PDA

View Full Version : Phage , the virus that cures


Pages : [1] 2

William Gaatjes
10-10-2009, 06:30 AM
I recently saw this documentary about bacteriophages.

Phage- The virus that cures (http://video.google.com/videoplay?docid=8887931967515748990&ei=4W3QSvatE4en-AbGqrDpDw&q=antibiotica+horizon#)

Bacteriophages (http://en.wikipedia.org/wiki/Bacteriophage)

Horizontal gene transfers (http://en.wikipedia.org/wiki/Horizontal_gene_transfer)

You ask perhaps why i posted this message, well i ask for opinions.

Long ago i bought a scientific american magazine (i think it was). There was some information about the possibility of horizontal gene transfers.

My Opinion is that through vertical gene transfers (aka offspring through sexual reproduction) and evolution a complex lifeform can loose genes. But with horizontal gene transfers a complex lifeform can gain genetic code. And not just a few basepairs but an entire sequence.

EDIT START : I think that it is entirely possible that this gene swapping can also occur between bacteria and viruses and cells of complex lifeforms. Most of the time our error detection/ error correction together with self destruction methods (cell apoptosis) and our immune system combat any change in dna code but radiation( or even cosmic radiation) and toxic materials can cause mailfunction to these error detection/correction systems and our immune system.

Cell apoptosis (http://en.wikipedia.org/wiki/Apoptosis)


EDIT END


Would this statement hold ?

http://upload.wikimedia.org/wikipedia/commons/thumb/4/4a/PhageExterior.svg/491px-PhageExterior.svg.png

Gibsons
10-10-2009, 08:35 AM
Originally posted by: William Gaatjes
I recently saw this documentary about bacteriophages.

Phage- The virus that cures (http://video.google.com/videoplay?docid=8887931967515748990&ei=4W3QSvatE4en-AbGqrDpDw&q=antibiotica+horizon#)

Bacteriophages (http://en.wikipedia.org/wiki/Bacteriophage)

Horizontal gene transfers (http://en.wikipedia.org/wiki/Horizontal_gene_transfer)

You ask perhaps why i posted this message, well i ask for opinions.

Long ago i bought a scientific american magazine (i think it was). There was some information about the possibility of horizontal gene transfers.

My Opinion is that through vertical gene transfers (aka offspring through sexual reproduction) and evolution a complex lifeform can loose genes. But with horizontal gene transfers a complex lifeform can gain genetic code. And not just a few basepairs but an entire sequence.

EDIT START : I think that it is entirely possible that this gene swapping can also occur between bacteria and viruses and cells of complex lifeforms. Most of the time our error detection/ error correction together with self destruction methods (cell apoptosis) and our immune system combat any change in dna code but radiation( or even cosmic radiation) and toxic materials can cause mailfunction to these error detection/correction systems and our immune system.

Cell apoptosis (http://en.wikipedia.org/wiki/Apoptosis)


EDIT END


Would this statement hold ?

Which statement?

The immune system can detect changes in the DNA indirectly, but it's far from foolproof. Also, if the change occurs in germline DNA, the immune system of the developing person will see these changes as "self" and not react to them. There are lots and lots of viral sequences in human DNA.

William Gaatjes
10-10-2009, 09:05 AM
Originally posted by: Gibsons

Which statement?

The immune system can detect changes in the DNA indirectly, but it's far from foolproof. Also, if the change occurs in germline DNA, the immune system of the developing person will see these changes as "self" and not react to them. There are lots and lots of viral sequences in human DNA.



Also, if the change occurs in germline DNA, the immune system of the developing person will see these changes as "self" and not react to them.
I agree. But to make things clear the error detection /correction inside the cell itself is responsible for reparing the dna. And if it fails the cell will execute apoptosis. This will then be seen by the immunesystem and the by macrophage engulfed cell is taken to the lymphatic system to begin it's journey in i think our bowls to be secreted.


This statement : :)

My Opinion is that through vertical gene transfers (aka offspring through sexual reproduction) and evolution a complex lifeform can loose genes. But with horizontal gene transfers a complex lifeform can gain genetic code. And not just a few basepairs but an entire sequence.

Gibsons
10-10-2009, 10:43 AM
Originally posted by: William Gaatjes
Originally posted by: Gibsons

Which statement?

The immune system can detect changes in the DNA indirectly, but it's far from foolproof. Also, if the change occurs in germline DNA, the immune system of the developing person will see these changes as "self" and not react to them. There are lots and lots of viral sequences in human DNA.



Also, if the change occurs in germline DNA, the immune system of the developing person will see these changes as "self" and not react to them.
I agree. But to make things clear the error detection /correction inside the cell itself is responsible for reparing the dna. And if it fails the cell will execute apoptosis. This will then be seen by the immunesystem and the by macrophage engulfed cell is taken to the lymphatic system to begin it's journey in i think our bowls to be secreted.


This statement : :)

My Opinion is that through vertical gene transfers (aka offspring through sexual reproduction) and evolution a complex lifeform can loose genes. But with horizontal gene transfers a complex lifeform can gain genetic code. And not just a few basepairs but an entire sequence.


Oh okay. I think both statements are correct.

Syncytin (http://www.ncbi.nlm.nih.gov/pubmed/10693809) is a pretty well documented case for gaining a sequence.

William Gaatjes
10-10-2009, 11:00 AM
Originally posted by: Gibsons

Oh okay. I think both statements are correct.


Syncytin (http://www.ncbi.nlm.nih.gov/pubmed/10693809) is a pretty well documented case for gaining a sequence.


Yay for me :)

I read the link you wrote. I had to look up the explanation of all the words in that article.
Correct me if i am wrong please :

In our dna their is a gene coding for a protein that is used to build the envelope (or skin) of the virus. And that the same gene is used in to form the envelope of cells that provide nutrients and protect the blastocyst ? These cells are called trophoblasts ?Later these cells form the placenta ?

If true, Wow. Might be common but very interesting indeed. Is this a human only feature of have all animals using a placenta exhibit this ?


EDIT :

HERV-W , It seems this virus is present in many cancer tissues ?

Herv-W (http://vir.sgmjournals.org/cgi/content/abstract/85/5/1203)

eggrolls
10-12-2009, 12:14 AM
Our genome encodes for the proteins embedded in the membrane and the enzymes for phospholipid synthesis.

Viruses with envelopes get their lipid envelopes from either the cellular cytoplasmic membrane or some membrane-bound organelle such as the endoplasmic reticulum or Golgi. They basically "steal" our cell membranes and embed virally-encoded proteins in them.

Some viruses don't have lipid envelopes, so their outermost layer is the capsid protein, which is virally encoded.

William Gaatjes
10-12-2009, 12:19 PM
Originally posted by: eggrolls
Our genome encodes for the proteins embedded in the membrane and the enzymes for phospholipid synthesis.

Viruses with envelopes get their lipid envelopes from either the cellular cytoplasmic membrane or some membrane-bound organelle such as the endoplasmic reticulum or Golgi. They basically "steal" our cell membranes and embed virally-encoded proteins in them.

Some viruses don't have lipid envelopes, so their outermost layer is the capsid protein, which is virally encoded.

So it is a chicken or the egg question. I wonder if we can ever find out what the oldest virus is. I know there is some research being done on bones and maybe tissues from extincted animals.

Although i think that with this virus it perhaps borrowed the cell membrane but gave us some genetic code in return ?

Something else :
It is proposed that part of life on earth originated from space and another part came from the earth it self.

I have some links here with theories and findings about life and how tough it can be.

Bacteria leaving earth (http://adsabs.harvard.edu/abs/2006hep.ph...12311G)

SAO/NASA ADS Astronomy Abstract Service

The questions of how did life arise and is there life on other planets are some of the most profound questions that humanity asks Although there has been controversial signs of past bacterial life in meteorites which originated on Mars and there are current claims of bacterial life high in the atmosphere the issues of origin by chemical process or contamination make these types of results arguable and they will likely remain that way until a comprehensive theory is developed to explain why the claims might be true This paper proposes a complete theory for the spread of bacterial life throughout the galaxy by combining current knowledge from the fields of bacteriology stellar evolution and space weather Here we show the possibility that the forces of uplift on a charged bacteria particle are sufficient bring at least some lighter types of bacteria high into the ionosphere and subsequently move the charged spore onto magnetic field lines The bacteria spore is then driven down the magnetotail where during a solar storm a structure known as a plasmoid is propelled radially outward into space at velocities exceeding solar system escape velocity From that point the plasmoids are capable of reaching Mars the outer planets and even others systems eventually depositing the bacterial spores either via comets or direct interaction with the receiving planet The solid observational evidence for the strength of the electric fields and the speeds that the plasmoids leave the magnetotail during geomagnetic storms provide a firm.



Bacteria living in the stratosphere (http://archives.cnn.com/2000/TECH/space/11/24/alien.microbe.claim/)

(CNN) -- An international team of scientists has recovered microorganisms in the upper reaches of the atmosphere that could have originated from outer space, a participant in the study said Friday.
The living bacteria, plucked from an altitude of 10 miles (16 km) or higher by a scientific balloon, could have been deposited in terrestrial airspace by a passing comet, according to the researchers.
The microorganisms are unlike any known on Earth, but the astrobiologists "want to keep the details under wraps until they are absolutely convinced that these are extraterrestrial," said study participant Chandra Wickramasinghe, a noted scientist at Cardiff University in Wales.
Could life on Earth have arrived on meteors and comets?
NASA's Ames Research Center posted a cautious reaction to the report on its Astrobiology Web site. NASA said the finding is likely to meet considerable skepticism in the scientific community.
"Aerobiologists might argue that 10 miles is not too high for Earth life to reside, a possibility that Wickramasinghe appears to accept," the statement said.
However, NASA said, a compelling case can be made for the transport of microorganisms through space aboard comets and meteors.
"A recent discovery indicates that microbes can remain dormant for millions of years -- enough time to travel from planet to planet," NASA said.
Disputing critics who suggest that the balloon was contaminated on the ground, Wickramasinghe said the experiment took place with strict controls. He does acknowledge the possibility that terrestrial bacteria could be kicked up into the stratosphere. Living fungal spores have been discovered at altitudes of 7 miles (11 km). But observations from this and a related study suggest the presence of living bacteria far too high in the atmosphere to have originated from the surface of the planet, according to Wickramasinghe. "What is present in the upper atmosphere, critics will say it came from the ground. That is a serious possibility at 15 kilometers, but at 40 or 85 kilometers, you can forget about it," he said Friday.
Wickramasinghe and colleague Sir Fred Hoyle published a report on the Web Friday about evidence that they say strengthens the hypothesis that unusual microbes float through the upper reaches of the atmosphere. Looking at spectral data from the 1999 Leonid meteorite shower, they detected a bacterial "fingerprint" as the tiny space rocks streaked across the sky at a height of 51 miles (83 km).
"The bacteria heated at temperatures high enough to radiate and shine in this (spectral) signature," Wickramasinghe said. Along with Hoyle, Wickramasinghe pioneered "panspermia," the theory that outer space seeded Earth with its first life forms about 4 billion years ago. Wickramasinghe holds that primitive life could still be arriving from space. "If we find microbes at great heights that are not contaminants from the ground, we have to wonder where they came from. One hundred tons of comet and meteor organic debris is deposited in the atmosphere every day."
Javant Narlikar of India lead the atmospheric bacteria sample study, which the Indian Space Research Organization coordinated. The location of the microbe is what most impressed Wickramasinghe, not the composition. It seems like a novel strain of a common bacteria genus on Earth, he said.




UV resisitant bacteria found, working together to shield themselves from UV radation. (http://www.jstage.jst.go.jp/article/bss/22/1/22_18/_article)


Yinjie Yang, Shiho Itahashi, Shin-ichi Yokobori and Akihiko Yamagishi

(Received: May 15, 2008)
(Accepted: September 18, 2008)

Abstract: Five bacterial strains have been isolated from dust samples collected from the upper troposphere and lower stratosphere during several aircraft flights. Most of them displayed much higher resistance to ultraviolet radiation (254 nm) than surface airborne isolates. The role of UV radiation combined with other conditions to determine survivability of bacterial species in the upper atmosphere is discussed. Two strains from the upper atmosphere (ST0316 and TR0125) exhibited extreme UV resistance and tend to form cell clumps or aggregates. Forming cell aggregation might be a strategy to enhance their survivability in the harsh conditions such as high dosage of UV at high altitude.



Bacteria might be in more control then we think, Some researches suggest it is bacteria that help form clouds as well. And a hibernating bacteria was found to be claimed to be 250 million years old reanimated when given nutrients.

spacefaring bacteria (http://georgewashington2.blogspot.com/2009/06/spacefaring-bacteria.html)

In 2002, several scientists claimed that bacteria high in Earth's atmosphere came from space.
Last year, scientists said that bacteria in the upper atmosphere may actually make rain. Specifically, they said that bacteria can freeze at fairly warm temperatures, so that the "biological ice nuclei" form condensation nuclei which triggers rain. Indeed, some scientists have speculated that bacteria cause rain as a means of transportation, so that they will "rain out" from the upper atmosphere to the surface of a planet. Now, scientists have discovered a "hibernating" bacteria in a salt mine in Utah which they believe has been in suspended animation for 250 million years. There is evidence that this ability to hibernate for long periods of time is also useful for travel through space by the bacteria:
Bacteria have the ability to go into a kind of semi-permanent hibernation, but survival for this long was unheard of. After lying dormant in the salt crystal for 250 million years, the scientists added fresh nutrients and a new salt solution, and the ancient bacteria "re-animated."
Dr. Russell Vreeland, one of the biologists who found the bacteria, pointed out that bacteria can survive the forces [of] acceleration via rubble thrown into space via a meteor impact. If it is possible for a bacteria to survive being [thrown] off the planet and to stay alive within a salt chunk for 250 million years, then in a sort of "reverse-exogenesis" it may be possible that earth's own microbes are already out there.
Indeed, there is a more down-to-earth analogy to the idea of spacefaring bacteria: the humble coconut. Coconuts can float across long distances of water in the ocean, and when they land on a hospitable island, start growing.



ice clouds (http://www.sciencecentric.com/news/article.php?q=09051706-first-direct-observations-biological-particles-high-altitude-ice-clouds)


A team of UC San Diego-led atmospheric chemistry researchers moved closer to what is considered the 'holy grail' of climate change science when it made the first-ever direct detection of biological particles within ice clouds.

The team, led by Kerri Pratt, a Ph.D. student of atmospheric chemistry Professor Kim Prather, who also holds appointments at Scripps Institution of Oceanography as well as the Department of Chemistry and Biochemistry at UCSD, sampled water droplet and ice crystal residues at high speeds from an aircraft flying through clouds in the skies over Wyoming in fall 2007. Analysis of the ice crystals revealed that they were made up almost entirely of either dust or biological particles such as bacteria, fungal spores and plant material. While it has long been known that microorganisms or parts of them get airborne and travel great distances, this study is the first to yield in-situ data on their participation in cloud ice processes.
Results of the Ice in Clouds Experiment - Layer Clouds (ICE-L), funded by the National Science Foundation (NSF) and the National Centre for Atmospheric Research (NCAR), appear 17 May in the advance online edition of the journal Nature Geoscience.
'If we understand the sources of particles that nucleate clouds and their relative abundance, then we can determine the impact of these different sources on climate,' said Pratt.
The effects of tiny airborne particles called aerosols on cloud formation have been some of the most difficult aspects of weather and climate for scientists to understand. In the climate change science field, which derives many of its projections from computer simulations of climate phenomena, the actions of aerosols on clouds represent what scientists consider the greatest uncertainty in modelling predictions for the future.
'By sampling clouds in real time from an aircraft, these investigators were able to get information about ice particles in clouds at an unprecedented level of detail,' said Anne-Marine Schmoltner of the NSF's Division of Atmospheric Sciences. 'By determining the chemical composition of the very cores of individual ice particles, they discovered that both mineral dust, and, surprisingly, biological particles play a major role in the formation of clouds.'
Aerosols, ranging from dust, soot, sea salt to organic materials, some of which travel thousands of miles, form the skeletons of clouds. Around these nuclei, water and ice in the atmosphere condense and grow leading to precipitation. Scientists are trying to understand how they form as clouds play a critical role by both cooling the atmosphere and affect regional precipitation processes.
ICE-L was the first aircraft-based deployment of the aircraft aerosol time-of-flight mass spectrometer (A-ATOFMS) nicknamed 'Shirley,' which was recently developed at UCSD with funding from NSF. The ICE-L team mounted the mass spectrometer and an ice chamber run by Colorado State University researcher Paul DeMott onto a C-130 aircraft operated by NCAR and made a series of flights through a type of cloud known as a wave cloud. The researchers performed in-situ measurements of cloud ice crystal residues and found that half were mineral dust and about a third contained nitrogen, phosphorus and carbon - the signature elements of biological matter.
The second-by-second analysis speed allowed the researchers to make distinctions between residues of water droplets and ice nuclei in real-time. Ice nuclei are rarer than droplet nuclei and are more likely to create precipitation.
The A-ATOFMS also allowed the unambiguous measurement of biological particles in the cloud ice, which scientists previously concluded serve as ice nuclei based on simulations in laboratory experiments and precipitation measurements. Based on modelling and the chemical composition of measured dust, the ICE-L team was able to identify the source of the dust as Asia or Africa. 'This has really been kind of a holy grail measurement for us,' said Prather. 'Understanding which particles form ice nuclei, which occur at extremely low concentrations and are inherently difficult to measure, means you can further understand processes that result in precipitation. Any new piece of information you can get is critical.'
The findings suggest that the biological particles that get swept up in dust storms help to induce the formation of cloud ice and that their region of origin makes a difference. Prather said initial evidence is increasingly suggesting that dust transported from Asia could be influencing precipitation in North America, for example. Researchers hope to use the ICE-L data to design future studies timed to events when such particles may be playing a bigger role in triggering rain- or snowfall.
Paper co-authors include Anthony Prenni from Colorado State University, Jeffrey French and Zhien Wang of the University of Wyoming, Douglas Westphal of the Naval Research Laboratory in Monterey, Calif., Andrew Heymsfield of the National Centre for Atmospheric Research and Cynthia Twohy of Oregon State University.


Bacteria controlling the airflow in a labexperiment (http://www.sciencedaily.com/releases/2009/07/090716134903.htm)

http://images.sciencedaily.com/2009/07/090716134903.jpg
ScienceDaily (July 16, 2009) — Bacteria know that they are too small to make an impact individually. So they wait, they multiply, and then they engage in behaviors that are only successful when all cells participate in unison. There are hundreds of behaviors that bacteria carry out in such communities. Now researchers at Rockefeller University have discovered one that has never been observed or described before in a living system.

In research published in the May 12 issue of Physical Review Letters, Albert J. Libchaber, head of the Laboratory of Experimental Condensed Matter Physics, and his colleagues, including first author Carine Douarche, a postdoctoral associate in the lab, show that when oxygen penetrates a sample of oxygen-deprived Escherichia coli bacteria, they do something that no living community had been seen to do before: The bacteria accumulate and form a solitary propagating wave that moves with constant velocity and without changing shape. But while the front is moving, each bacterium in it isn’t moving at all. “It’s like a soliton,” says Douarche. “A self-reinforcing solitary wave.”
Unlike the undulating pattern of an ocean wave, which flattens or topples over as it approaches the shore, a soliton is a solitary, self-sustaining wave that behaves like a particle. For example, when two solitons collide, they merge into one and then separate into two with the same shape and velocity as before the collision. The first soliton was observed in 1834 at a canal in Scotland by John Scott Russell, a scientist who was so fascinated with what he saw that he followed it on horseback for miles and then set up a 30-foot water tank in his yard where he successfully simulated it, sparking considerable controversy. The work began when Libchaber, Douarche and their colleagues placed E. coli bacteria in a sealed square chamber and measured the oxygen concentration and the density of bacteria every two hours until the bacteria consumed all the oxygen. (Bacteria, unlike humans, don’t die when starved for oxygen, but switch to a nonmotile state from which they can be revived.) The researchers then cracked the seals of the chamber, allowing oxygen to flow in.
The result: The motionless bacteria, which had spread out uniformly, began to move; first those around the perimeter, nearest to the seals, and then those further away. A few hours later, the bacteria began to spatially segregate into two domains of moving and nonmoving bacteria and pile up into a ring at the border of low-oxygen and no-oxygen. There they formed a solitary wave that propagated slowly but steadily toward the center of the chamber without changing its shape.
The effect, which lasted for more than 15 hours and covered a considerable distance (for bacteria), could not be explained by the expression of new proteins or by the addition of energy in the system. Instead, the creation of the front depends on the dispersion of the active bacteria and on the time it takes for oxygen-starved bacteria to completely stop moving, 15 minutes. The former allows the bacteria to propagate at a constant velocity, while the latter keeps the front from changing shape.
However, a propagating front of bacteria wasn’t all that was created. “To me, the biggest surprise was that the bacteria control the flow of oxygen in the regime,” says Libchaber. “There’s a propagating front of bacteria, but there is a propagating front of oxygen, too. And the bacteria, by absorbing the oxygen, control it very precisely.”
Oxygen, Libchaber explains, is one of the fastest-diffusing molecules, moving from regions of high concentration to low concentration such that the greater the distance it needs to travel, the faster it will diffuse there. But that is not what they observed. Rather, oxygen penetrated the chamber very slowly in a linear manner. Equal time, equal distance. “This pattern is not due to biology,” says Libchaber. “It has to do with the laws of physics. And it is organized in such an elegant way that the only thing it tells us is that we have a lot to learn from bacteria.”



I wonder if all these bacteria have phages as well...


And one more scary parasite to finish the behaviour control part.

Toxoplasma gondii (http://arstechnica.com/science/news/2007/04/how-a-parasite-can-help-a-cat-catch-its-mouse.ars)


EDIT: Bad links

Gibsons
10-13-2009, 08:18 AM
Originally posted by: William Gaatjes
Originally posted by: Gibsons

Oh okay. I think both statements are correct.


Syncytin (http://www.ncbi.nlm.nih.gov/pubmed/10693809) is a pretty well documented case for gaining a sequence.


Yay for me :)

I read the link you wrote. I had to look up the explanation of all the words in that article.
Correct me if i am wrong please :

In our dna their is a gene coding for a protein that is used to build the envelope (or skin) of the virus. And that the same gene is used in to form the envelope of cells that provide nutrients and protect the blastocyst ? These cells are called trophoblasts ?Later these cells form the placenta ?

If true, Wow. Might be common but very interesting indeed. Is this a human only feature of have all animals using a placenta exhibit this ?


EDIT :

HERV-W , It seems this virus is present in many cancer tissues ?

Herv-W (http://vir.sgmjournals.org/cgi/content/abstract/85/5/1203)

eggrolls covered most of the viral assembly stuff - enveloped viruses (usually but not always) use a bit of host membrane as their envelope.

As for syncytin in particular, it seems to be necessary for cell fusion at some developmental stages. This makes some sense, as enveloped viruses usually (maybe always) encode a gene that induces membrane fusion (fusion of the viral envelope with host cell or endosomal membrane).

Difficult for me to sort out just what animals have syncytin and which ones don't. There's more than one, and it's derived from a pretty large family of endogenous retroviruses, so there are homologs, orthologs etc. to worry about. I'd guess all placentals do, but just a guess. Too lazy to blast it right now. :P

The big picture of what's going on with all the endogenous retroviruses is largely unknown. Roughly 8% of the human genome is apparently derived from viral sequences (can't find the ref, it's in my notes). A lot of these seem to be inactive/degraded/degenerate... But some are not. Some of these do get transcribed in cancer, but I don't think anyone's figured out cause and effect. That doesn't mean that actual infectious virus is produced in those cancers, but it is possible.

For something interesting and scary, read about the Phoenix virus. (http://discovermagazine.com/2007/feb/phoenix-virus-retrovirus-dna)

William Gaatjes
10-13-2009, 02:04 PM
Originally posted by: Gibsons
Originally posted by: William Gaatjes
Originally posted by: Gibsons

Oh okay. I think both statements are correct.


Syncytin (http://www.ncbi.nlm.nih.gov/pubmed/10693809) is a pretty well documented case for gaining a sequence.


Yay for me :)

I read the link you wrote. I had to look up the explanation of all the words in that article.
Correct me if i am wrong please :

In our dna their is a gene coding for a protein that is used to build the envelope (or skin) of the virus. And that the same gene is used in to form the envelope of cells that provide nutrients and protect the blastocyst ? These cells are called trophoblasts ?Later these cells form the placenta ?

If true, Wow. Might be common but very interesting indeed. Is this a human only feature of have all animals using a placenta exhibit this ?


EDIT :

HERV-W , It seems this virus is present in many cancer tissues ?

Herv-W (http://vir.sgmjournals.org/cgi/content/abstract/85/5/1203)

eggrolls covered most of the viral assembly stuff - enveloped viruses (usually but not always) use a bit of host membrane as their envelope.

As for syncytin in particular, it seems to be necessary for cell fusion at some developmental stages. This makes some sense, as enveloped viruses usually (maybe always) encode a gene that induces membrane fusion (fusion of the viral envelope with host cell or endosomal membrane).

Difficult for me to sort out just what animals have syncytin and which ones don't. There's more than one, and it's derived from a pretty large family of endogenous retroviruses, so there are homologs, orthologs etc. to worry about. I'd guess all placentals do, but just a guess. Too lazy to blast it right now. :P

The big picture of what's going on with all the endogenous retroviruses is largely unknown. Roughly 8% of the human genome is apparently derived from viral sequences (can't find the ref, it's in my notes). A lot of these seem to be inactive/degraded/degenerate... But some are not. Some of these do get transcribed in cancer, but I don't think anyone's figured out cause and effect. That doesn't mean that actual infectious virus is produced in those cancers, but it is possible.

For something interesting and scary, read about the Phoenix virus. (http://discovermagazine.com/2007/feb/phoenix-virus-retrovirus-dna)



Amazing...

That virus is scary indeed. But what worries me is there are no enforced guidelines.
I am sure that the people who work with extinct viruses or lethal ones like polio or the 1918 flu virus do not need enforced guidelines , they know how dangerous the material is they work with. What do you think about this ? Are the precautions taken really that strict ?

My personal opinion is that almost all cancers must be virus related. I think that toxic materials that cause cancer, are not the primary cause, but a catalyst to jump start the process.

What was mentioned in the article was interesting :

Relics of the retrovirus are scattered throughout our genome but have long since lost their infectivity due to mutation. By comparing 10 or so of these dysfunctional relics, Heidmann and his colleagues puzzled out the components of the original virus that must have infected our ancestors eons ago. Using DNA cloning techniques, they then reconstructed a version that can infect human cells. Heidmann says this virus, which he calls Phoenix, is completely harmless. But he thinks it could play a role in cancer research because high levels of similar retroviral particles have been found in many different types of tumors, leading oncologists to suspect that they may help cancers grow.



Here are some more links about viruses and cancer. Might come in handy, however i would not be surprised you already know about them...

Cervical cancer (http://en.wikipedia.org/wiki/Cervical_cancer)

JC virus (http://www.annieappleseedproject.org/linvirandbra.html)

Virus inside brain tumors. (http://www.newsweek.com/id/178660)


EDIT : typing errors and link :

cache, main memory and mass storage (http://www.sciencedaily.com/releases/2009/10/091008142957.htm)

The researchers report two striking findings. First, the human genome is organized into two separate compartments, keeping active genes separate and accessible while sequestering unused DNA in a denser storage compartment. Chromosomes snake in and out of the two compartments repeatedly as their DNA alternates between active, gene-rich and inactive, gene-poor stretches.

active, gene-rich and inactive, gene-poor stretches

Now does that not sound like cache, main memory and mass storage ? :)

Gibsons
10-13-2009, 09:19 PM
Originally posted by: William Gaatjes
Originally posted by: Gibsons
Originally posted by: William Gaatjes
Originally posted by: Gibsons

Oh okay. I think both statements are correct.


Syncytin (http://www.ncbi.nlm.nih.gov/pubmed/10693809) is a pretty well documented case for gaining a sequence.


Yay for me :)

I read the link you wrote. I had to look up the explanation of all the words in that article.
Correct me if i am wrong please :

In our dna their is a gene coding for a protein that is used to build the envelope (or skin) of the virus. And that the same gene is used in to form the envelope of cells that provide nutrients and protect the blastocyst ? These cells are called trophoblasts ?Later these cells form the placenta ?

If true, Wow. Might be common but very interesting indeed. Is this a human only feature of have all animals using a placenta exhibit this ?


EDIT :

HERV-W , It seems this virus is present in many cancer tissues ?

Herv-W (http://vir.sgmjournals.org/cgi/content/abstract/85/5/1203)

eggrolls covered most of the viral assembly stuff - enveloped viruses (usually but not always) use a bit of host membrane as their envelope.

As for syncytin in particular, it seems to be necessary for cell fusion at some developmental stages. This makes some sense, as enveloped viruses usually (maybe always) encode a gene that induces membrane fusion (fusion of the viral envelope with host cell or endosomal membrane).

Difficult for me to sort out just what animals have syncytin and which ones don't. There's more than one, and it's derived from a pretty large family of endogenous retroviruses, so there are homologs, orthologs etc. to worry about. I'd guess all placentals do, but just a guess. Too lazy to blast it right now. :P

The big picture of what's going on with all the endogenous retroviruses is largely unknown. Roughly 8% of the human genome is apparently derived from viral sequences (can't find the ref, it's in my notes). A lot of these seem to be inactive/degraded/degenerate... But some are not. Some of these do get transcribed in cancer, but I don't think anyone's figured out cause and effect. That doesn't mean that actual infectious virus is produced in those cancers, but it is possible.

For something interesting and scary, read about the Phoenix virus. (http://discovermagazine.com/2007/feb/phoenix-virus-retrovirus-dna)
Amazing...

That virus is scary indeed. But what worries me is there are no enforced guidelines.
I am sure that the people who work with extinct viruses or lethal ones like polio or the 1918 flu virus do not need enforced guidelines , they know how dangerous the material is they work with. What do you think about this ? Are the precautions taken really that strict ?

My personal opinion is that almost all cancers must be virus related. I think that toxic materials that cause cancer, are not the primary cause, but a catalyst to jump start the process.

Pretty much a certainty that all cancers are not virus related.

Of course some are, and there are probably a few that are that we don't know about. But the data for some cancers is way too clean, imo, for their to still be a hidden virus lurking around playing a role.

Also there are restrictions and regulations on handling infectious material in every country that I'm aware of.

William Gaatjes
10-14-2009, 05:25 AM
<My personal opinion is that almost all cancers must be virus related. I think that toxic materials that cause cancer, are not the primary cause, but a catalyst to jump start the process.





Pretty much a certainty that all cancers are not virus related.

Of course some are, and there are probably a few that are that we don't know about. But the data for some cancers is way too clean, imo, for their to still be a hidden virus lurking around playing a role.

Also there are restrictions and regulations on handling infectious material in every country that I'm aware of.

I agree on that :)
Some cancers are virus related some are not.

I have been thinking more about toxic materials...
I do not know all the details when and how specific genes are expressed,
Can it be that certain toxic materials (causing cancer) cause parts of one gene and parts of the next gene to be expressed ? That codons are no longer seen as end or start codons but as part of a an expression ? Perhaps toxic materials cause havoc on a higher level. Perhaps these toxins influence proteins that certain genes are expressed to much , causing an chemical unbalance ?

Gibsons
10-14-2009, 07:21 AM
The vast majority of carcinogens are mutagens. They cause changes in the DNA sequence of a cell. Some genes cause or regulate cellular growth, and changes in those genes (the right kind of changes) can lead to cancer. There are a few other things that can contribute, but that's the basic idea.

For a start, look here (http://en.wikipedia.org/wiki/Oncogene) and here. (http://en.wikipedia.org/wiki/Tumor_suppressor_gene)

William Gaatjes
10-26-2009, 05:26 PM
Some information about talking bacteria by Bonnie Bassler :

talking bacteria (http://www.ted.com/index.php/talks/bonnie_bassler_on_how_bacteria_communicate.html)

Chriscross3234
11-03-2009, 07:38 PM
It's kind of a coincidence that I came across this thread. Tomorrow I meet with my research professor/mentor to discuss the details of my undergraduate research project that involves phage display technology. I guess I'll update when I know exactly what I'm going to do.

jagec
11-05-2009, 09:38 PM
Amazing...

That virus is scary indeed. But what worries me is there are no enforced guidelines.
I am sure that the people who work with extinct viruses or lethal ones like polio or the 1918 flu virus do not need enforced guidelines , they know how dangerous the material is they work with. What do you think about this ? Are the precautions taken really that strict ?

My personal opinion is that almost all cancers must be virus related. I think that toxic materials that cause cancer, are not the primary cause, but a catalyst to jump start the process.
It is foolish to put your faith in "regulations". As most smart people know (http://xkcd.com/651/), rules created by the ignorant leave huge gaps for the better-informed, and rules created by the well-informed require self-enforcement since the details are simply not understood by anyone else. The fact of the matter is that if a well-trained scientist working in a lab wanted to sneak out some dangerous material, it would simply be a matter of pipetting it into a tube and putting it in their pocket, and then walking right out of the lab. One tube with a clear liquid in it looks much the same as another.
Now, as far as brewing industrial batches of the stuff is concerned, that would be a little bit harder. But still achievable for someone determined.

It's only scary if you don't think about the fact that it would be easier and more effective to just buy a bunch of fertilizer and diesel fuel if you wanted to become a mass-murderer. Modern society has placed a great deal of potential power into each and every one of our hands. People rightly fear power, but it's not going away.

Gibsons
11-06-2009, 10:36 AM
It is foolish to put your faith in "regulations". As most smart people know (http://xkcd.com/651/), rules created by the ignorant leave huge gaps for the better-informed, and rules created by the well-informed require self-enforcement since the details are simply not understood by anyone else. The fact of the matter is that if a well-trained scientist working in a lab wanted to sneak out some dangerous material, it would simply be a matter of pipetting it into a tube and putting it in their pocket, and then walking right out of the lab. One tube with a clear liquid in it looks much the same as another.
Now, as far as brewing industrial batches of the stuff is concerned, that would be a little bit harder. But still achievable for someone determined.

It's only scary if you don't think about the fact that it would be easier and more effective to just buy a bunch of fertilizer and diesel fuel if you wanted to become a mass-murderer. Modern society has placed a great deal of potential power into each and every one of our hands. People rightly fear power, but it's not going away.

luv XKCD :)

yes, regulations and rules are only useful if they are enforced and enforceable. One of the scary scenarios is someone setting up a lab in a warehouse somewhere. They just have to know what they're doing, be a bit clever, and have some money. Assuming they don't make some fairly obvious mistakes, I don't see how anyone could catch them until they've done their damage. That's probably what happened with the anthrax attacks.

William Gaatjes
11-07-2009, 05:07 PM
luv XKCD :)

yes, regulations and rules are only useful if they are enforced and enforceable. One of the scary scenarios is someone setting up a lab in a warehouse somewhere. They just have to know what they're doing, be a bit clever, and have some money. Assuming they don't make some fairly obvious mistakes, I don't see how anyone could catch them until they've done their damage. That's probably what happened with the anthrax attacks.

Indeed.

The problem occurs the most when the materials used are so called "of the shelf" materials.
You need a big database to cross-reference what people buy. And that is privacy related.

To come back to my former posts :

I found this virus to be intriguing. : SV40.

http://en.wikipedia.org/wiki/SV40.

I quote:


Theorized role in human disease

The hypothesis that SV40 might cause cancer in humans has been a particularly controversial area of research.[3] Several different methods have been used to detect SV40 in a variety of human cancers, although how reliable these detection methods are, and whether SV40 has any role in causing these tumors, remains unclear.[4] As a result of these uncertainties, academic opinion remains divided, with some arguing that this hypothesis is not supported by the data,[5] and others arguing that some cancers may involve SV40.[6][7] However, the United States National Cancer Institute announced in 2004 that although SV40 does cause cancer in some animal models, "substantial epidemiological evidence has accumulated to indicate that SV40 likely does not cause cancer in humans".[8] This announcement is based on two recent studies.[9][10]
[edit]
p53 Damage and carcinogenicity

SV40 is believed to suppress the transcriptional properties of the tumor-suppressing p53 in humans through the SV40 Large T-antigen and SV40 Small T-antigen. p53 is responsible for initiating regulated cell death ("apoptosis"), or cell cycle arrest when a cell is damaged. A mutated p53 gene may contribute to uncontrolled cellular proliferation, leading to a tumor.

SV40 may act as a cocarcinogen with crocidolite to cause mesothelioma [11] (review [12])

When SV40 infects nonpermissive cells such as 3T3 mouse cells the dsDNA of SV40 becomes covalently integrated. In nonpermissive cells only the early gene expression occurs and this leads to transformation, or oncogenesis. The nonpremissive host needs the Large T antigen and the small t antigen in order to function. The small t antigen interacts with and integrates with the cellular phosphatase pp2A. This causes the cell to lose the ability to initiate transcription.



Melanocytes from fetuses seem to be affected by the sv40 virus and may hold an explanation to some melanocyte related cancers. That the chance occurs when the person affected is still in the womb can explain a lot.

Since not too long ago i learned that the human genome is not big enough to hold our basic blueprint. That not for every step of the process of development and maintenance and for just learning there is a seperate gene. The way we are "build" is by simultaneously switching different but multiple genes on and off.

It really seems if many of the virus related cancerous diseases are the result of multiple virus infections or a combination of a virus and carcinogen. That our error detection / error correction works great until that system is compromised as well in a cell. Other cancers may even be a combination of carcinogens

The p53 gene is in effect not the repair agent but the part that stops the cell division from completetion if an error is detected and must be corrected. If the p53 fails, the error correction can not occur and daughter cells with faulty DNA emerge. P53 stalls the cell division process until the dna damage is corrected.

EDIT: forgot to mention that the p53 also can activate cell apoptosis.

Amazing when it comes to smoking : Benzopyrene interference causes dna damage. But something must have altered the DNA sequence of p53 already. Because the p53 only halts the division, nothing else. That is , if i can assume that what i have read is correct. This is not really surprising because we inhale air and air is saturated with many particles from organic to inorganic. The air we breath is also filled with bacteria and viruses.





This may seem as pretty standard, but for me it is just an interest and i find it amazing to see how life works.


On a Side note, has anybody else encountered that the password system failed on them ?
I had to reset the password to be able to log in again.
And when i wanted to change my password, i never got to that specific page.
I guess there are a few bugs to be worked out. Although i would expect that some tests where done on a test environment prior before the roll out. Perhaps the problem occurred after a certain maximum number of users was encountered.

I understood that the dailytech forum and the anandtech forum are powered by the same system. My old password still works on dailytech even after the change to a new password for the anandtech forum. It seems the forum is a work in progress. When editting, i can not preview anymore.
I do find the old version of the forum a bit more relaxing. There are way to many buttons and double functions.

William Gaatjes
11-07-2009, 07:23 PM
It is foolish to put your faith in "regulations". As most smart people know (http://xkcd.com/651/), rules created by the ignorant leave huge gaps for the better-informed, and rules created by the well-informed require self-enforcement since the details are simply not understood by anyone else. The fact of the matter is that if a well-trained scientist working in a lab wanted to sneak out some dangerous material, it would simply be a matter of pipetting it into a tube and putting it in their pocket, and then walking right out of the lab. One tube with a clear liquid in it looks much the same as another.
Now, as far as brewing industrial batches of the stuff is concerned, that would be a little bit harder. But still achievable for someone determined.

It's only scary if you don't think about the fact that it would be easier and more effective to just buy a bunch of fertilizer and diesel fuel if you wanted to become a mass-murderer. Modern society has placed a great deal of potential power into each and every one of our hands. People rightly fear power, but it's not going away.

Indeed. Very true. That is why i am convinced that the only way the human race will survive is through knowledge and compassion. The knowledge is needed to know that you can do something wrong no matter what your hands will carry. The compassion is needed to know that you can hurt other living beings. Besides that, knowledge just comes in handy when you are encountering problems.
And compassion makes you feel good.

Just making people smarter will not make them better persons. I once have seen a documentary about one of the engineers of the H-bomb. He was at the end of his life but did not stop him hoping to see the H-bomb used. You would think that someone with the intelligence to build such a device would also be very human. I was wrong about that and saddened too. But at the same time it does explain human history, the present and unfortunately the future.

Gibsons
11-07-2009, 08:09 PM
Indeed.
Amazing when it comes to smoking : Benzopyrene interference causes dna damage. But something must have altered the DNA sequence of p53 already. Because the p53 only halts the division, nothing else. That is , if i can assume that what i have read is correct. This is not really surprising because we inhale air and air is saturated with many particles from organic to inorganic. The air we breath is also filled with bacteria and viruses.


p53 does a lot of things. I can't see why benzopyrene can't cause mutations in p53, there's pretty strong evidence it does. http://www.ncbi.nlm.nih.gov/pubmed/15206894?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed _ResultsPanel.Pubmed_RVDocSum&ordinalpos=2

William Gaatjes
11-07-2009, 09:04 PM
p53 does a lot of things. I can't see why benzopyrene can't cause mutations in p53, there's pretty strong evidence it does. http://www.ncbi.nlm.nih.gov/pubmed/15206894?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed _ResultsPanel.Pubmed_RVDocSum&ordinalpos=2


Grrrr.
I am seriously starting too lose my patience with this untested crap called vbulletin style forum. I just had to log in 7 times in a row while i was already logged in just to be able to post this message. Crapware in my opinion based on experience.


To come back to your post, I am wondering if the benzopyrene has a specific preference
to lock onto parts of the dna. This is what i retreived from your link :



It has been previously demonstrated that the diol epoxide metabolites of bay region polycyclic aromatic hydrocarbons present in tobacco smoke, e.g., benzo[a]pyrene diol epoxide (BPDE), preferentially bind to the most frequently mutated guanine nucleotides within p53 codons 157, 158, 248, and 273 [Denissenko, M. F., Pao, A., Tang, M., and Pfeifer, G. P. (1996) Science 274, 430-432].


and :


We found that all four N(2)-BPDE-dG diastereomers were formed preferentially at the methylated CG dinucleotides, including the frequently mutated p53 codons 157, 158, 245, 248, and 273.


If i read it correctly, it means that the benzopyrene binds to already mutated parts of p53.
Please correct me if i am wrong. If i am right the question is, what caused the mutation in the p53 gene ? Could it been benzopyrene ? Have there been tests performed that show that benzopyrene also binds preferentially to a working form of p53 ? Is it known that p53 can have naturally occurring mutations that do not interfere with it's function ? And does benzopyrene preferentially binds to the same spots in all these version of p53 ?

If i am wrong, then benzopyrene caused the mutation to form first and that this mutation made it easier for benzopyrene to bind to that specific part in the p53 gene.
That if it is the case i find strange but interesting.

I do find that interesting questions.
Sincerely awaiting your answer...

Me.

Gibsons
11-07-2009, 10:28 PM
If i read it correctly, it means that the benzopyrene binds to already mutated parts of p53.
p53 has been studied pretty intensely for a very long time. Lots of people have sequenced lots of p53 genes from many many different cancers and normal tissues. When you compile this data, you see some bases mutated very often in cancer samples (usually leading to specific amino acid changes), some not so much.

The general theory is that all the bases are, roughly, equally prone to mutation (this is never exactly true). So, when you sequence p53 from cancer cells, your data is selected - you're looking at mutations that lead to cancer (with some noise too, of course). If you see a few bases mutated over and over again, and a lot of other bases only rarely mutated, the conclusion is usually that those bases lead to cancer.

Another explanation though, is simply that cancer cells have a high mutation rate and there's some bias in these mutations. i.e. the mutations are an effect of cancer, not a cause.

Other data suggests that the former is correct - the mutations in p53 lead to cancer. When you look at the mutated proteins for instance, the common mutations lead to loss or change of function of the protein. Also, some unfortunate people are born with a mutated p53 and they get cancer early and often.
http://en.wikipedia.org/wiki/Li-Fraumeni_syndrome

What the article I linked is talking about is that they can detect a known mutagen/carcinogen binding to some of the specific sequences. I didn't read the whole paper, but they might be suggesting that benzopyrene has a higher than-you-might-expect propensity to cause the cancer associated mutations. i.e. it's not randomly mutating all bases, it's more prone to mutate the important ones than unimportant ones.

William Gaatjes
11-08-2009, 04:33 AM
p53 has been studied pretty intensely for a very long time. Lots of people have sequenced lots of p53 genes from many many different cancers and normal tissues. When you compile this data, you see some bases mutated very often in cancer samples (usually leading to specific amino acid changes), some not so much.

The general theory is that all the bases are, roughly, equally prone to mutation (this is never exactly true). So, when you sequence p53 from cancer cells, your data is selected - you're looking at mutations that lead to cancer (with some noise too, of course). If you see a few bases mutated over and over again, and a lot of other bases only rarely mutated, the conclusion is usually that those bases lead to cancer.


I wonder if it is tested what those preferred codons actually do.


Another explanation though, is simply that cancer cells have a high mutation rate and there's some bias in these mutations. i.e. the mutations are an effect of cancer, not a cause.



i think both explanations are relevant. The damage in p53 leads to dna damage which is not is no longer corrected. That means that mutation after mutation can arise without a mechanism to correct it. Especially since it is known what p53 has as function.


Other data suggests that the former is correct - the mutations in p53 lead to cancer. When you look at the mutated proteins for instance, the common mutations lead to loss or change of function of the protein. Also, some unfortunate people are born with a mutated p53 and they get cancer early and often.
http://en.wikipedia.org/wiki/Li-Fraumeni_syndrome


I have no doubt about that, knowing what p53 does : Stalling the cell division for dna repaires or setting off apoptosis when the dna damage can not be repaired.


What the article I linked is talking about is that they can detect a known mutagen/carcinogen binding to some of the specific sequences. I didn't read the whole paper, but they might be suggesting that benzopyrene has a higher than-you-might-expect propensity to cause the cancer associated mutations. i.e. it's not randomly mutating all bases, it's more prone to mutate the important ones than unimportant ones.

I still wonder if it can do that. Perhaps it latches on and causes the p53 gene to be interpreted wrong. Or that when the benzopyrene is latched on, that the reading mechanism accidently together with the benzopyrene changes the dna chemicals. I guess that is all in the realm of binding energy and chemistry /physics.

Not so long ago the name super atom was used for an artificially configuration of atoms that collectively behaved like an atom of another element depending on it's elektron configuration.

http://en.wikipedia.org/wiki/Superatom
http://www.sciencedaily.com/releases/2008/07/080701092153.htm

Perhaps nature uses a manipulation form similair as this one described in the link.



Grrrr. i have to enter my password multiple times again while i am logged in. It is only in this thread it seems.

tcsenter
11-08-2009, 04:59 AM
Very cool:

http://www.usnews.com/science/articles/2009/11/06/french-scientists-re-engineer-hiv-virus-to-halt-brain-disease.html

William Gaatjes
11-08-2009, 05:20 AM
Very cool:

http://www.usnews.com/science/articles/2009/11/06/french-scientists-re-engineer-hiv-virus-to-halt-brain-disease.html

Cool indeed.

Gene therapy is very promising. But in my opinion should be limited in use until it is actually known how life works. These are dangerous grounds to play on if you can not see the whole playing field. We are constantly invested by bacteria and viruses and recombining of dna happens often. Maybe i am over cautious.

Gibsons
11-10-2009, 08:29 AM
I wonder if it is tested what those preferred codons actually do.
big snip

In large part, yes. It's not really the codons that are preferred, it's the amino acids they code for. You can take these mutant p53s and compare their properties to wild type p53 and demonstrate biochemical differences. i.e. wild type binds DNA, mutant doesn't.

As for benzopyrene, after some metabolic processing, it covalently attaches to a base in the double helix. If nothing else, this makes it difficult to impossible for DNA polymerase to copy faithfully. (see pic, notice how the opposing bases don't pair up correctly).
http://en.wikipedia.org/wiki/File:Benzopyrene_DNA_adduct_1JDG.png

Finally, I'd bet a reproductive organ that superatoms have nothing whatsoever to do with any of this.

jagec
11-12-2009, 07:53 PM
Cool indeed.

Gene therapy is very promising. But in my opinion should be limited in use until it is actually known how life works. These are dangerous grounds to play on if you can not see the whole playing field. We are constantly invested by bacteria and viruses and recombining of dna happens often. Maybe i am over cautious.

FWIW, the only human gene therapy trials are done in cases where the disease itself is definitively worse than the cure, even if things go wrong.

For example, there was a French study where they used an integrating virus to deliver a corrected copy of a gene that was defective in children with SCID (Severe Combined ImmunoDeficiency, think "bubble boy syndrome"). Random integration is dangerous, and indeed some of the kids got cancer later, but having an immune system beats not having cancer, and cancer is treatable in many cases. So, a net win..but the initial disease was pretty terrible.

More modern ideas/approaches are being pursued for site-specific gene repair, but nothing has been conclusively demonstrated in humans.

William Gaatjes
11-13-2009, 12:28 PM
FWIW, the only human gene therapy trials are done in cases where the disease itself is definitively worse than the cure, even if things go wrong.

For example, there was a French study where they used an integrating virus to deliver a corrected copy of a gene that was defective in children with SCID (Severe Combined ImmunoDeficiency, think "bubble boy syndrome"). Random integration is dangerous, and indeed some of the kids got cancer later, but having an immune system beats not having cancer, and cancer is treatable in many cases. So, a net win..but the initial disease was pretty terrible.

More modern ideas/approaches are being pursued for site-specific gene repair, but nothing has been conclusively demonstrated in humans.


Not so long ago i read an article about that genes from genetic modified mais and other crops are found in mais that used to be "natural". I worry for such scenario's. I am all for gene manipulation and stemcell research to remove physical and / or mental suffering. But i fear for abuse of the technology. And for people neglecting serious issues for money and fame.

William Gaatjes
11-13-2009, 12:33 PM
In large part, yes. It's not really the codons that are preferred, it's the amino acids they code for. You can take these mutant p53s and compare their properties to wild type p53 and demonstrate biochemical differences. i.e. wild type binds DNA, mutant doesn't.

As for benzopyrene, after some metabolic processing, it covalently attaches to a base in the double helix. If nothing else, this makes it difficult to impossible for DNA polymerase to copy faithfully. (see pic, notice how the opposing bases don't pair up correctly).
http://en.wikipedia.org/wiki/File:Benzopyrene_DNA_adduct_1JDG.png




I see, thank you.


Finally, I'd bet a reproductive organ that superatoms have nothing whatsoever to do with any of this.

I am sure that in this specific scenario it is not used.
But It's the principle that i find interesting.
And it just does not let me go that it could be or is used in some chemical process.

William Gaatjes
02-24-2010, 07:49 AM
FWIW, the only human gene therapy trials are done in cases where the disease itself is definitively worse than the cure, even if things go wrong.

For example, there was a French study where they used an integrating virus to deliver a corrected copy of a gene that was defective in children with SCID (Severe Combined ImmunoDeficiency, think "bubble boy syndrome"). Random integration is dangerous, and indeed some of the kids got cancer later, but having an immune system beats not having cancer, and cancer is treatable in many cases. So, a net win..but the initial disease was pretty terrible.

More modern ideas/approaches are being pursued for site-specific gene repair, but nothing has been conclusively demonstrated in humans.


I assume there is now much more (thanks to ever improving technology, but in all honesty i do not know how these techologies works) testing done on contamination and scenario's where unforeseen consequences can arise. Back in the 1960's , Salk and others used monkey tissue cells to produce a polio vaccine. A polio vaccine given to millions of people around the world. Little did they know that these vaccines where contaminated with numerous monkey viruses. One of those viruses is the now well known SV40 virus. A virus that can cause cancer.

http://www.sv40foundation.org/

http://en.wikipedia.org/wiki/SV40

In my opinion though, genetic variance plays a role where SV40 becomes lethal . Or perhaps a combination of pathogens are needed.

But what i am writing is that when scientists overlook something they might create something devastating without intent. Knowing only of what they have done after the effects become apparent. This is what fears me, scientists are human too and can make mistakes too you know...
But i hope that since many of these events occurred , there is now a strict regulation system prevent serious errors...

EDIT :

Some more examples form the past ?

The cutter incident : a paralyzing polio vaccine.

http://en.wikipedia.org/wiki/Cutter_Laboratories


In 1955 Cutter Laboratories was one of several companies licensed by the United States government to produce Salk polio vaccine. In what came to be known as the Cutter Incident, a production error caused some lots of the Cutter vaccine to be tainted with live polio virus.The problem had not only been the carelessness of the Cutter company , but the lack of scrutiny from the Agency ( and its excessive trust in the polio foundation reports ) Ed. Shorter , The Health Century.

The Cutter incident was one of the worst pharmaceutical disasters in U.S. history and caused several thousand children to be exposed to live polio virus upon vaccination.[1] . It should be noted that NIH's Laboratory of Biologics Control ,which had certified the Salk vaccine, had received advance warnings of problems : in 1954 , one of its staff member, Dr Bernice Eddy had reported to her superiors that some of the inoculated monkeys were getting paralysed ( pictures were sent as well). William Sebrell,the director of NIH wouldn't hear of such a thing...Ed.


This is just 30 years ago...


In the 1980s Cutter Laboratories produced unsafe blood products to treat hemophilia. The pharmaceutical product, which was produced from blood given by donors all across the US, was contaminated with HIV. These problems were the subject of lawsuits over the next twenty years.[3].

A recent German documentary called "Toedlicher Ausverkauf: Wie BAYER AIDS nach Asien importierte" (Deadly Sale: How Bayer imported AIDS into Asia) researched the Koate product sold by Cutter Laboratories under full knowledge of its HIV contamination. Cutter ex-manager Merill Boyce expressed that the company should be made responsible and pay damages. Another ex-manager John H Hink, who was also in the responsible team for marketing Koate to Asia, express regret in the documentary, that management required that old stock should be sold despite the HIV contamination. Lexi J Hazan and Charles A Kozak are attorneys representing victims against Bayer AG in the Koate cases. Thomas C Drees is a consultant that researched the Koate Cutter case.

William Gaatjes
03-05-2010, 11:26 AM
This article also mentions just like Bonnie Bassler did in the video linked in another post in this thread below( or above) that the amount of microbial genes outnumber our own genes.


Two excerpts...

The thousands of bacteria, fungi and other microbes that live in our gut are essential contributors to our good health. They break down toxins, manufacture some vitamins and essential amino acids, and form a barrier against invaders. A study published in Nature shows that, at 3.3 million, microbial genes in our gut outnumber previous estimates for the whole of the human body.

From a bacterium's point of view, the human gut is not the best place to set up home, with low pH and little oxygen or light. Thus, bacteria have had to evolve means of surviving in this challenging environment, which this study now begins to unveil. The scientists identified the genes that each individual bacterium needs to survive in the human gut, as well as those that have to be present for the community to thrive, but not necessarily in all individuals, since if one species produces a necessary compound, others may not have to. This could explain another of the scientists' findings, namely that the gut microbiomes of individual humans are more similar than previously thought: there appears to be a common set of genes which are present in different humans, probably because they ensure that crucial functions are carried out. In the future, the scientists would like to investigate whether the same or different species of bacteria contribute those genes in different humans.

http://www.sciencedaily.com/releases/2010/03/100304075703.htm

EDIT :

http://www.ted.com/index.php/talks/bonnie_bassler_on_how_bacteria_communicate.html

beginner99
03-31-2010, 03:24 PM
My Opinion is that through vertical gene transfers (aka offspring through sexual reproduction) and evolution a complex lifeform can loose genes. But with horizontal gene transfers a complex lifeform can gain genetic code. And not just a few basepairs but an entire sequence.

Don't really get what you mean. That you can only gain by horizontal transfer?

What is a complex lifeform exactly in this context (in your statement)?


Of course you can "gain dna" both ways if something goes wrong in Meiosis. (eg building of eggs or sperms) and the horizontal way.
(Down-syndrome, 3 versions of chromosome 21). -> more dna.

That you can get new genes by horizontal transfer is especially in bacteria nothing else but normal. Easy seen with antibiotic resistance that usually passes different bacteria species.

Also bacterial genomes can be full of latent phages, eg phages that don't replicate but just integrate into the genome. Over time they can become part of the bacteria.

William Gaatjes
03-31-2010, 05:51 PM
Don't really get what you mean. That you can only gain by horizontal transfer?

What is a complex lifeform exactly in this context (in your statement)?


Of course you can "gain dna" both ways if something goes wrong in Meiosis. (eg building of eggs or sperms) and the horizontal way.
(Down-syndrome, 3 versions of chromosome 21). -> more dna.

That you can get new genes by horizontal transfer is especially in bacteria nothing else but normal. Easy seen with antibiotic resistance that usually passes different bacteria species.

Also bacterial genomes can be full of latent phages, eg phages that don't replicate but just integrate into the genome. Over time they can become part of the bacteria.


Well, i meant gaining fresh genes just like bacteria do it. But normally i doubt complex lifeforms as multicellular lifeforms would allow this to happen that easy. We have way to much protection in our cells to make sure dna does not alter. That is if everything works properly. Now if this alteration indeed would happen in sperm or an egg, it would have to be critical or the error detection and error correction of the cell must not work properly.

And it is the case to get different strands of dna from the mother and the father. If i remember correctly and i am right we get al our mitochondrial dna from the mother and most of the dna is a mix of a single dna strand from the mother and a single dna strand of the father ? Because i remember where a mutation on the dna of the father on the same location causes a different genetic disease then when the mutation is located on the same location but from the mother. .

That is very interesting what you mentioned about the phages. quite interesting indeed. I assumed these phages would destroy the bacteria but afcourse it is an endless war.
How to let evolution make a new bacteria ? Add some phages. But what would happen if we or any other lifeform would get infected by a bacteria that is filled with phages. Is it the phages that infect host cells and not the bacteria itself ? Or is the bacteria bursting open because of the phages and releasing its inner machinery into the cell where it interferes with the cell machinery ?

beginner99
04-01-2010, 06:40 AM
I actually studied microbiology but it's few years ago and i work in very different field (Chemistry - IT related). So what I say may not be 100 % even though but is sure is not far fetched either.

Human cells or any mammalian cells can take up dna just like bacteria. Still if this dna encodes one or many genes it's not sure they are actually expressed becase of many reasons like regulation of expression.

Our cells also contain alot of so called junk dna (= no function whatsoever based on current knowledge). Inserting new dna in these regions can't destroy any exisiting genes. Contrary to that bacteria contain more or less 0 junk dna. so any insertion might cause troubles.
So there is no reason why it should not work in humans. Already read something about gene therapy.

The reason is too simple you didn't see it. Bacteria are single-celled, you are not. If your livercells get new genes your children won't have them because they are made from sperms. So only "alterations" to sperms or eggs are transmitted to the offspring everything else is lost when you die. Cancer is a nice example of such alterations.

It's also common knowledge that certain viruses can cause cancer (increase chance you get a certain type of cancer). Can't tell you if it's known why.

Gibsons
04-01-2010, 08:09 AM
As I said in a previous post (#4), there are sequences in the human genome that originated from retroviruses, quite a few in fact.

There are at least three ways viruses can cause cancer. The simplest to explain is that viruses often express genes that cause the infected cells to grow (all viruses don't just simply reproduce and lyse the host cell). The E6 and E7 genes from HPV are pretty well described in lots of places.

The cancers caused from the viral gene therapy experiments are from a different mechanism.

William Gaatjes
04-01-2010, 01:17 PM
As I said in a previous post (#4), there are sequences in the human genome that originated from retroviruses, quite a few in fact.

There are at least three ways viruses can cause cancer. The simplest to explain is that viruses often express genes that cause the infected cells to grow (all viruses don't just simply reproduce and lyse the host cell). The E6 and E7 genes from HPV are pretty well described in lots of places.

The cancers caused from the viral gene therapy experiments are from a different mechanism.

You are right indeed. When i posted i was getting weary and my memory was letting me down. usually, a swift look at the posts is enough to revive memories.

William Gaatjes
04-01-2010, 04:55 PM
Time to add a post over parasite using behaviour control over there prey making them do what the parasite wants them to do, even if the prey will die from it :

Rabies the virus that makes it's prey afraid of water and makes it's prey bite you and in the course you get infected as well...
http://en.wikipedia.org/wiki/Rabies

Rabies (pronounced /ˈreɪbiːz/. From Latin: rabies) is a viral disease that causes acute encephalitis (inflammation of the brain) in warm-blooded animals.[1] It is zoonotic (i.e., transmitted by animals), most commonly by a bite from an infected animal but occasionally by other forms of contact. Rabies is almost invariably fatal if post-exposure prophylaxis is not administered prior to the onset of severe symptoms.

The rabies virus travels to the brain by following the peripheral nerves. The incubation period of the disease is usually a few months in humans, depending on the distance the virus must travel to reach the central nervous system.[2] Once the rabies virus reaches the central nervous system and symptoms begin to show, the infection is effectively untreatable and usually fatal within days.

Early-stage symptoms of rabies are malaise, headache and fever, progressing to acute pain, violent movements, uncontrolled excitement, depression, and hydrophobia.[1] Finally, the patient may experience periods of mania and lethargy, eventually leading to coma. The primary cause of death is usually respiratory insufficiency.[2] Worldwide, the vast majority of human rabies cases (approximately 97%) come from dog bites.[3] In the United States, however, animal control and vaccination programs have effectively eliminated domestic dogs as reservoirs of rabies.[4] In several countries, including the United Kingdom, Australia and Japan, rabies carried by ground dwelling animals has been eradicated entirely, they have not in fact been eradicated in airborne mammals such as bats.[citation needed]

The economic impact is also substantial, as rabies is a significant cause of death of livestock in some countries.


The parasite that makes rodents think cats are harmless :
http://arstechnica.com/science/news/2007/04/how-a-parasite-can-help-a-cat-catch-its-mouse.ars

Here's the interesting bit: Toxoplasma fixes the odds. A new study from Ajai Vyas and colleagues at Stanford University, published in PNAS this week, has discovered the mechanism by which the parasitic protozoa does this. Previous studies had shown that infected rodents lacked the instinctive aversion to cat urine; instead they had a vague preference for it. The work in this paper confirms those findings, and also shows how it happens.

By using genetically modified Toxoplasma that produced firefly luciferase (the enzyme fireflies use to glow), Dr. Vyas' team were able to track the sites of infection in animals. After a few days, the infection cleared up throughout the rodents with the exception of cysts localized to the amygdala. Although the infected animals no longer exhibited a fearful response to cat urine, they did still respond normally to learned fear, anxiety-like behavior, and other behavioral tests.

This data proves that the behavioral modification of rodents by Toxoplasma is incredibly specific for advancing the needs of the parasite without affecting many other brain processes, and makes a powerful case for the behavior manipulation hypothesis.


The fungus that makes ants do anything the fungus wants wants even kill itself :
http://www.scientificamerican.com/article.cfm?id=fungus-makes-zombie-ants

After the ant death, the fungus began growing hyphae inside the insect’s body; in a few days, the hyphae would emerge from the exoskeleton—"always … from a specific point at the back of the head," write the authors of the study, which was led by Sandra Andersen of the Center for Social Evolution at the University of Copenhagen in Denmark. Within a week, the fungus had grown to about twice the length of the host ant’s body and had started sexual reproduction. Meanwhile, "the ant cuticle is … remodeled into a protective case by reinforcing the weaker parts," and the parts of the fungus inside the ant’s body appear to differentiate into separate functions, write the researchers.


How about a parasite turns you into a nice juicy red berry. At least that's what your predator thinks. Because the parasite wants to be eaten by your predator :.
http://www.innovations-report.com/html/reports/life_sciences/report-101536.html

"It's phenomenal that these nematodes actually turn the ants bright red, and that they look so much like the fruits in the forest canopy," said co-author Stephen P. Yanoviak, an insect ecologist and assistant professor of biology at the University of Arkansas at Little Rock, who noted that numerous tropical plants produce small red, orange and pink berries. "When you see them in the sunlight, it's remarkable."

Or a parasitic hair worm that lets a grashopper jump into his death and as such the hairworm can travel on :
http://www.nytimes.com/2005/09/06/science/06hopp.html?_r=1

The hairworm seems to have perfected an equally intimate manipulation of its host by inducing a fantastical desire to swim, of which the grasshopper is scarcely more capable than the worm is of flying.

This is not the parasite's only trick. No one knows how, from its aquatic home, the hairworm manages to infect a terrestrial species. Dr. Thomas said he suspects that the larvae, minuscule on hatching, first infect aquatic insects like mosquito larvae and hide as cysts in their tissues.

When the adult mosquito flies away and when it dies, its body may be eaten by a grasshopper or cricket. The hairworm "will then develop, eating absolutely everything not essential to keep its host alive," Dr. Thomas said. The zombified grasshopper is reduced to just its head, legs and outer skeleton by the time it goes for its final swim.

There are some 300 species of hairworm found around the world. Their billions of larvae "will infect everything - frogs, fish, snails," Dr. Thomas said. But it is only in grasshoppers, crickets and katydids that these uninvited guests are able to usurp both the body and mind of their hosts.

How about a wasp that takes control of the movement of it's prey, a cock roach :
http://news.nationalgeographic.com/news/2007/12/071206-roach-zombie.html

The parasitic jewel wasp uses a venom injected directly into a cockroach's brain to inhibit its victim's free will, scientists have discovered.
The venom blocks a chemical substance called octopamine in the cockroach's brain that controls its motivation to walk, the study found.
Unable to fight back, the "zombie" cockroach can be pulled into the wasp's underground lair, where an egg is laid in its abdomen. The larva later hatches and eats the still living but incapacitated cockroach from the inside out.
"The whole thing takes about seven to eight days, during which the meat has to be fresh," said study co-author and neurobiologist Frederic Libersat of Ben-Gurion University of the Negev in Be'ér Sheva, Israel.
"If you kill a cockroach, it rots within a day."


A wasp that controls the web building ability of a spider :
http://www.simpletoremember.com/articles/a/wasp-manipulation/

The larva makes small holes in the spider’s abdomen to imbibe haemolymph1. As the spider continues to build the cocoon web even when the larva is removed shortly before construction would normally start, the changes in the spider’s behaviour must be induced chemically rather than by direct physical interference. The effects are both rapid (removal earlier in the evening did not result in the formation of typical cocoon webs) and long-lasting (spiders from which larvae were removed built similar webs the following night, although some slowly reverted to more normal orbs on subsequent nights).

A parasite that castrates you so all that energy of reproduction is instead used to make you grow larger and thus you will get eaten by the next prey of the parasite :
http://en.wikipedia.org/wiki/Microphallus

Several species are notable for manipulating or influencing their hosts. Microphallus piriformes causes its host, the rough periwinkle, to move upwards, making it more vulnerable to predation by herring gulls. Microphallus pseudopygmaeus chemically castrates (parasitic castration) its host, the snail Onoba aculeus, and causes it to grow larger than normal (it is not clear if this gigantism benefits the host or parasite or if it is a non-adaptive side-effect).[4] Microphallus papillorobustus causes its host, the lagoon sand shrimp (Gammarus insensibilis) to swim upwards, making it more vulnerable to predation.[5] Some species of this genus "hitch-hike" on the manipulations of other species; for example, Microphallus hoffmanni parasitizes the same sand shrimps as Microphallus papillorobustus but does not manipulate the shrimps itself, instead benefiting from the latter's manipulation of the host.

William Gaatjes
04-03-2010, 05:00 AM
I was curious if they discovered something new on the phoenix virus ...
Nothing so far it seems.

Human Endogenous Retroviruses are expected to be the remnants of ancestral infections of primates by active retroviruses that have thereafter been transmitted in a Mendelian fashion. Here, we derived in silico the sequence of the putative ancestral “progenitor” element of one of the most recently amplified family—the HERV-K family—and constructed it. This element, Phoenix, produces viral particles that disclose all of the structural and functional properties of a bona-fide retrovirus, can infect mammalian, including human, cells, and integrate with the exact signature of the presently found endogenous HERV-K progeny. We also show that this element amplifies via an extracellular pathway involving reinfection, at variance with the non-LTR-retrotransposons (LINEs SINEs) or LTR-retrotransposons, thus recapitulating ex vivo the molecular events responsible for its dissemination in the host genomes. We also show that in vitro recombinations among present-day human HERV-K loci can similarly generate functional HERV-K elements, indicating that human cells still have
the potential to produce infectious retroviruses.

Here is the link :

http://genome.cshlp.org/content/early/2006/10/31/gr.5565706.abstract

http://www.nytimes.com/2006/11/07/science/07virus.html?ei=5088&en=492dd1d370217836&ex=1320555600&adxnnl=1&partner=rssnyt&emc=rss&adxnnlx=1163032655-5nRqAOkgWGeKvh/qQcSYCg

tcsenter
04-03-2010, 05:16 AM
This has some interesting implications (potentially):

http://news.yahoo.com/s/afp/20100401/hl_afp/healthresearchusvirus_20100401180429

William Gaatjes
04-03-2010, 05:27 AM
This has some interesting implications (potentially):

http://news.yahoo.com/s/afp/20100401/hl_afp/healthresearchusvirus_20100401180429

That is interesting indeed.

In a study of monkeys, scientists at Oregon Health Sciences University found that the common cytomegalovirus (CMV), which has infected up to 80 percent of the adult population, can overcome the body's ability to clean out infected cells unlike most viruses.

"In essence, CMV is able to cutoff an infected cell's call for elimination. This allows CMV to overcome this critical immune barrier during re-infection," explained Klaus Frueh, a senior scientist at the university.


The cmv virus is also suspected of being the cause or at least an agent in cancer.

http://www.newsweek.com/id/178660
Two excerpts...

In 2002, UCSF neurosurgeon Charles Cobbs published a novel finding in a prominent cancer journal: nearly all of the two-dozen brain tumors he had analyzed were teeming with a common herpes virus called cytomegalovirus, or CMV. Normally, CMV is harmless—it lies dormant in roughly 80 percent of the population—but in Cobbs's tumor samples, the virus appeared to be actively replicating, even as it remained dormant in nearby healthy tissue. "When I first saw the data, I couldn't sleep for a week," says Cobbs. "I kept asking myself, 'can this be?'" If his findings were correct, they might shed light on the causes of brain cancer, or better yet, provide a new target for battling—maybe even preventing—the disease.



The findings have opened a new avenue of inquiry for one of the most intractable cancers—Glioblastoma Multiforme, an aggressive brain tumor, diagnosed in 10,000 new patients every year and fatal in virtually all cases. (Sen. Ted Kennedy was stricken with the disease last year). The alleged link between CMV and brain cancer may also represent the latest reversal of a decades-old consensus that generally speaking, viruses don't cause cancer. While some scientists are urging caution in interpreting this growing body of evidence, others say that a bias against "cancer-virus" research highlights a major flaw in the way science works. Ideas that challenge the conventional wisdom are often shunned in favor of "safer" hypotheses that stand a better chance of gaining acceptance and securing research dollars. "The powers that be are really opposed to funding this kind of research," says Cobbs who is now at California Pacific Medical Center. "They would rather put their money on more discreet projects where the outcomes are clear."



This would explain a lot.
A hypothetical situation :
Cell turns cancerous for some reason. CMV virus disable attention call for immune cells to come by and destroy the cancerous cell.
Cell keeps growing and dividing. A tumor arises...
That would add a piece to the puzzle. It could be then that the CMV virus does not make you sick, but does makes you more susceptible for cancer. How about that, if that is true... Nice evolutionary 1-2 punch. And another possible example of how 2 or more different and not connected variables match up for a most undesirable outcome.

And another link about the cmv virus possibly linked to some respect with colon cancer.
http://www.rense.com/general31/linked.htm

BIRMINGHAM, Ala. (UPI) -- A common human virus might have some role in the development of colon cancer, according to a new, small study released Thursday.

Preliminary findings from researched conducted at the University of Alabama in Birmingham suggest the cytomegalovirus, or CMV, a widespread organism particularly dangerous to people with weakened immune systems, could be associated with the cellular breakdown that leads to colon cancer.

"This virus is strongly associated with malignant brain tumors," lead researcher Dr. Charles S. Cobbs, also a neurosurgeon with the Birmingham VA Medical Center, told United Press International. "The more I learned about virus, the more I realized it had many properties important for cancer in general."

As described in the Nov. 16 issue of the British journal, The Lancet, Cobbs and his team took colorectal polyps, tumors and surrounding healthy cells from 29 patients. They found proteins from the cytomegalovirus in approximately 80 percent of the polyps and in about 85 percent of the colon cancer samples.

"I'm not trying to say this virus is causal in colon cancer," Cobbs said. "I've just made a preliminary observation ... whether or not it's influencing the cancer remains to be determined."

The virus might be inducing unwanted cell behavior that could lead later to uncontrollable cell growth or cancer, Cobbs explained, but more study is needed to confirm these findings.

Cytomegalovirus resides in about 50 to 80 percent of the U.S. population, Cobbs said, and age and socioeconomic status are risk factors. The virus also can cause ulcers, he explained. It is a relative of the herpes virus and, like herpes or chicken pox, when an individual contracts it, the virus cannot be eradicated. It can lie dormant in a person for years or even decades and not cause any harm.

William Gaatjes
06-17-2010, 12:27 PM
An interesting article over how 1 bacteria harmless to humans tricks the human inmmune system to attack another bacteria which is also harmless to humans. At least so it seems.

http://www.physorg.com/news195996047.html



"For many microbes, living in harmony with their host is the best option, so why do some suddenly turn nasty?" asks Dr Sam Brown, a Wellcome Trust Research Career Development Fellow at the University of Oxford. "Sometimes the answer is obvious - for example, the cold virus makes its host sneeze, helping it spread wider. But for other bacteria and viruses, which do not normally cause disease, the reason isn't at all clear."

In a study published today in Current Biology, scientists have modelled in mice how a commonly-found bacterium known as Streptococcus pneumoniae interacts with other bacteria, showing that competition for space between rival bacteria can cause deadlier forms of bacteria to evolve. S. pneumoniae usually exists in the nasal passage, where it sits quietly: as many as two in five people in some countries will carry the bug without being aware of it.

When S. pneumoniae is forced to share space with Haemophilus influenzae, another common and ordinarily asymptomatic bacterium, the two begin a tussle for space. But H. influenzae has an extra trick up its sleeve, calling on our immune system to help get rid of its competitor by recruiting white blood cells called neutrophils, which surround and attack the S. pneumoniae bacteria.

"Many bacteria are not a problem to our immune system, so can be left alone," explains Dr. Lysenko. "But the H. influenzae bacteria stir up trouble, saying to the body, 'S. pneumoniae are bad guys - beat them up'. The neutrophils respond, attacking the innocent bacteria and thus helping H.
influenzae to survive."

Many strains of S. pneumoniae exist, each coated with a thick sugar capsule. In some strains, the capsule is particularly protective, and appears to act as armour against the host's immune response. This allows the bacterium to enter the blood stream where it can go on to replicate and cause serious diseases such as pneumonia, bacteraemia (blood infection), septicaemia and meningitis.

William Gaatjes
06-17-2010, 01:50 PM
Post above this one is the new one.

I just thought this text was something that should be in this thread as well.

http://www.wired.com/wired/archive/11.04/quorum.html

The Bacteria Whisperer

Bonnie Bassler discovered a secret about microbes that the science world has missed for centuries. The bugs are talking to each other. And plotting against us.

By Steve Silberman

Trim and hyperkinetic at 40, Bonnie Bassler is often mistaken for a graduate student at conferences. Five mornings a week at dawn, she walks a mile to the local YMCA to lead a popular aerobics class. When a representative from the MacArthur Foundation phoned last fall, the caller played coy at first, asking Bassler if she knew anyone who might be worthy of one of the foundation's fellowships, popularly known as genius grants. "I'm sorry," Bassler apologized, "I don't hang out with that caliber of people."

The point of the call, of course, was that Bassler - an associate professor of molecular biology at Princeton - is now officially a genius herself. More than a decade ago, she began studying a phenomenon that even fellow biologists considered to be of questionable significance: bacterial communication. Now she finds herself at the forefront of a major shift in mainstream science.

The notion that microbes have anything to say to each other is surprisingly new. For more than a century, bacterial cells were regarded as single-minded opportunists, little more than efficient machines for self-replication. Flourishing in plant and animal tissue, in volcanic vents and polar ice, thriving on gasoline additives and radiation, they were supremely adaptive, but their lives seemed, well, boring. The "sole ambition" of a bacterium, wrote geneticist Fran�ois Jacob in 1973, is "to produce two bacteria."

New research suggests, however, that microbial life is much richer: highly social, intricately networked, and teeming with interactions. Bassler and other researchers have determined that bacteria communicate using molecules comparable to pheromones. By tapping into this cell-to-cell network, microbes are able to collectively track changes in their environment, conspire with their own species, build mutually beneficial alliances with other types of bacteria, gain advantages over competitors, and communicate with their hosts - the sort of collective strategizing typically ascribed to bees, ants, and people, not to bacteria.

Last year, Bassler and her colleagues unlocked the structure of a molecular language shared by many of nature's most fearsome particles of mass destruction, including those responsible for cholera, tuberculosis, pneumonia, septicemia, ulcers, Lyme disease, stomach cancer, and bubonic plague. Now even Big Pharma, faced with a soaring number of microbes resistant to existing drugs, is taking notice of her work.

What Bassler and other pioneers in her field have given us, however, is more than a set of potential drug targets. Their discoveries suggest that the ability to create intricate social networks for mutual benefit was not one of the crowning flourishes in the invention of life. It was the first.

The bobtail squid lives in the knee-deep coastal shallows in Hawaii, burying itself in the sand during the day and emerging to hunt after dark. On moonlit nights, the squid's shadow on the sand should make it visible to predators, but it possesses a "light organ" that shines with a blue glow, perfectly matching the amount of light shining down through the water.

The secret of the squid's ability to simulate moonlight is a densely packed community of luminescent bacteria called Vibrio fischeri. Minutes after birth, a squid begins circulating seawater through a hollow chamber in its body. The water contains millions of species of microbes, but cilia in the squid's light organ expel all but the V. fischeri cells. Fed with oxygen and amino acids, they multiply and begin to emit light. Sensors on the squid's upper surface detect the amount of illumination in the night sky, and the squid adjusts an irislike opening in its body until its shadow on the sand disappears. Each morning, the squid flushes out most of its cache of glowing vibrios, leaving enough cells to start the cycle anew.

In the early '60s, Woody Hastings, a microbiologist at the University of Illinois, noticed a curious thing about the V. fischeri grown in his lab. The bacterial population would double every 20 minutes, but the amount of the cells' light-producing enzyme, called luciferase, would stay the same for four or five hours, dispersed among more and more cells. Only when the bacterial population had vastly increased would the flask begin to glow brightly.

From the perspective of a single V. fischeri cell, delaying light production makes sense. The emission of photons is metabolically expensive, as biologists say, and the puny glow of a lone organism is apt to be overlooked in the vastness of the ocean. So how do the cells know when they have reached critical mass? One of Hastings' students, Ken Nealson, theorized that they were secreting a chemical that accumulates in their environment until the group reaches some threshold density. He christened this unknown molecule an "autoinducer." Nealson's hunch turned out to be correct, and the chemical process by which V. fischeri keep track of their own numbers - determining, like a group of senators, that enough members are present to take a vote - was eventually dubbed "quorum sensing."

More recently, scientists have begun to understand that the importance of cell-to-cell communication goes far beyond mere head counting. Many things that bacteria do, it turns out, are orchestrated by cascades of molecular signals. One such behavior is the formation of spores that make bacteria more resistant to antibiotics. Another is the unleashing of virulence. For disease-causing pathogens like Staphylococcus aureus, waiting for a quorum to assemble before getting down to business has distinct benefits. A few microbes dribbling out toxins in a 200-pound host will succeed only in calling down the furies of the immune system. En masse, they can do serious damage. The first "sleeper cells" were bacterial cells.

Hastings, who is now at Harvard, admits that he underestimated the significance of what he saw in his lab. He assumed that quorum sensing was limited to the marine microbes he was studying. "I accepted the view that these bacteria were in a very specific situation," he says, with a burr of regret. "It doesn't take much reflection to think this must occur elsewhere."

The conclusion that only highly evolved organisms have the ability to act collectively proved to be a stubborn prejudice, however. On several occasions, Nealson tried to publish a diagram in microbiology journals illustrating cell-to-cell signaling in V. fischeri, but peer reviewers rejected it. Bacteria just don't do this, the critics told him.

Bassler proved that they did, by discovering that V. fischeri were not the only chatty microbes in the sea.

As an undergraduate at UC Davis, Bassler decided that she wanted to become a veterinarian. But there was a problem: Dissections in biology class made her faint. She also loathed the rote memorization of lists of muscles and bones. Then she volunteered to work in a biochemistry lab. "I was planning to cure cancer," she recalls, smiling, "then I discovered that bacteria were these totally fantastic creatures."

In 1990, she joined geneticist Mike Silverman for postdoctoral work at the Agouron Institute in La Jolla, California. Microbial light was in the water; the institute was located on a cliff above the Pacific Ocean, where luminescent organisms sparkled on balmy nights. It was Silverman and a graduate student, Joanne Engebrecht, who had mapped the quorum-sensing circuit in Vibrio fischeri by cloning the genes that made luciferase.

At Agouron, Bassler turned her attention to another marine organism, Vibrio harveyi. Unlike V. fischeri, these cells live in the open ocean or in the gut tracts of fish, in bacterial consortia composed of many different species. While the pampered existences of symbiotic V. fischeri are dully predictable, the lives of cosmopolitan V. harveyi are more like ours - having to make sense, minute to minute, of swarms of changing conditions.

Like V. fischeri cells, V. harveyi light up when their own population reaches quorum density. But if a "soup" made of extracts of other species of bacteria is introduced into a V. harveyi culture, they glow as well.

Bassler determined that what looked like one signaling system was actually two: The first sensed the presence of other V. harveyi cells, and the second received signals from many other kinds of bacteria. She and her colleagues created mutant "reporter strains" of V. harveyi - capable of responding to only one signal or the other - to tease the two circuits apart.

The work required an intensity perfectly suited to Bassler, who obsesses about everything - her weight, her guilt that she hasn't put in enough hours at the lab, and especially her bacteria, which she speaks of with unabashed awe. "Did you know that 'vibrio' means vibrate? Unlike E. coli, which are fat and sleepy, these guys zip around under the microscope," she gushes. "Each bacterium in a species is perfect for the niche in which it resides, and if one survives, the whole species survives. They're better than us. They're the ultimate, stripped-down version of life."

Silverman, who is now retired, recalls that while Bassler was "starry-eyed and deferential" to him when she first arrived at his lab, she was soon advancing the research further than he had hoped. "Once she got some traction, she really started pulling," he says.

But in part because Bassler's cute glow-in-the dark microbes seemed to have little impact on the health or commercial success of humankind, her discoveries were considered a sideline curiosity in the world of mainstream science. Just before Bassler left Agouron, she recalls, "I was in the lab, streaking out my bacteria, and I thought, 'I love this job. But I'm gonna be selling shoes at Thom McAnn's next year, because Mike and I are the only people who care about this.'"

Bassler had more reasons to be optimistic than she knew. In 1994, she was hired as an associate professor at Princeton. Thomas Silhavy, who chaired the search committee, admired how far she had pushed the young science of quorum sensing in such a short time. "Figuring out that there were two circuits was a difficult problem, and Bonnie solved it," he says. "It was a gutsy move. Now the whole field rests on it."

That field is expanding at an astonishing rate. In the early '90s, papers were published describing cell-to-cell signaling in Agrobacterium tumefaciens, which causes gall tumors in plants, in Erwinia carotovora, the architect of soft rot in carrots, and in a particularly nasty bug called Pseudomonas aeruginosa, which accounts for 10 percent of all infections contracted in hospitals. Often deadly for cystic fibrosis patients, burn victims, and others with impaired immune systems, P. aeruginosa makes itself impervious to antibiotics by surrounding itself with a biofilm - the bacterial equivalent of a fortress. University of Iowa researcher E. Peter Greenberg, whose daughter has cystic fibrosis, determined that the manufacture of biofilms in P. aeruginosa is mobilized by molecular signals.

Some exceptionally opportunistic bugs have learned to hack the network. The staph microbes responsible for toxic shock, for instance, send out molecular signals in order to compete against nearby staph colonies, disabling their rivals' quorum-sensing circuits before they become virulent.

Quorum sensing has profound implications in the war against disease. With the Age of Antibiotics, we launched a brute force assault on pathogenic bacteria, emphasizing drugs that outright kill. This monolithic approach has brought what geneticists call maximum selective pressure to bear on pathogens. In essence, we have given a 50-year course in antibiotic resistance to an enemy that reproduces every 20 minutes. Bassler's research points to new ways of fighting disease that will aim not to kill but to scramble data in the bacterial network. One approach would be to block the receptors that receive the molecular signals so that cells never become virulent; another would target the DNA-replication mechanisms set in motion inside cells when the signals are received.

Once at Princeton, Bassler turned to identifying the elusive molecule that enabled V. harveyi to communicate with other species. In 2002, her team finally nailed it, christening it AI-2 (autoinducer 2). With the help of Princeton's chemistry department, they determined that the AI-2 molecule contains the element boron, trace amounts of which lurk everywhere in the biosphere, though few biological roles for it have ever been found. When they cloned the gene that makes AI-2, they discovered that at least 50 bacterial species possess the genetic machinery to produce the molecule.

To Bassler, AI-2 is bacterial Esperanto: a molecular language for interspecies conversation and conspiracy that has been spoken on earth for more than a million years.

Not everyone is convinced. Last year, Nottingham University's Paul Williams published a paper titled "Bacterial Cell-to-Cell Communication: Sorry, Can't Talk Now - Gone to Lunch!" Williams claims that while AI-2 plays the role of a signaling molecule in V. harveyi, in most organisms, it's garbage - a metabolic byproduct.

As recently as the late '90s, the National Institutes of Health routinely rejected Bassler's grant applications, politely suggesting that she apply again to a different committee the following year. Her most dependable sources of funding were the National Science Foundation and the Office of Naval Research, which is tracking quorum sensing carefully because biofilms degrade naval steel, foul water lines, and slow the progress of ships at sea. "The good news was that you weren't competing with anyone for money," Bassler recalls. "The bad news was that there was no money."

Papers published over the past year by researchers around the world, however, suggest that Bassler is right about AI-2. And now there's a little more money. Bassler's lab got its first NIH grant this year. She may use some of her $500,000 MacArthur windfall to bring scientists from other fields to study the implications of cell-to-cell communication at Princeton. Quorum-sensing research groups are sprouting up in the UK, Germany, Singapore, Sweden, and Brazil, as well as several dozen universities in the US.

For a growing number of researchers, the term "quorum sensing" already feels too narrowly defined. They favor the use of the broader phrase "cell-to-cell signaling" to stress that communication seems to be the rule, rather than the exception, in every domain of life. Some propose that molecular discourse may even have been one of the things that propelled us up the ladder toward becoming the complex creatures we are; the mechanisms that orchestrate the division of labor in bacterial colonies are similar to the signals that regulate the growth and specialization of animal tissues. "How does your heart know itself from your liver?" asks Bassler. "This may be how multicellular organisms evolved in the first place."

While the post-MacArthur buzz has elevated Bassler from an obscure academic into (in her own half-ironic hyperbole) "the queen of quorum sensing," she is refreshingly unpretentious about her new celebrity. She's grateful that her Advanced Genetics course is as popular as her aerobics classes at the Y, but she's still happiest in the lab, among her bioassays and pipettes, where, as she says, there's a surprise in the incubator every morning.

Through Bassler's discoveries, we're learning that those on the lowest rungs of the Darwinian ladder share one of the traits that has, until recently, been thought of as distinctly human: the propensity to create a continuous stream of commentary about the world. As Bassler puts it, for microbial communities, the advent of the cell-to-cell network made "the difference between subsistence farming and living in Manhattan. These guys know self and other, friend and foe, and have been doing biological warfare for over a million years."

William Gaatjes
06-19-2010, 01:07 PM
A short movie of a neutrophil that chases a bacteria.


http://www.youtube.com/watch?v=OWUmXx5V_wE&feature=related

William Gaatjes
06-23-2010, 12:57 AM
For the sake of gathering and storing, i added this as well.

A bit superficial (not to me, to be honest) but ...
Since many chemicals in our daily life can cause changes in our body. It is not surprising that bacteria can do the same while producing chemicals.



http://www.physorg.com/news94707017.html

http://www.physorg.com/news193928997.html


These findings, identified by researchers at the University of Bristol and colleagues at University College London, aid the understanding of why an imbalance in the immune system leaves some individuals vulnerable to mood disorders like depression.

Dr Chris Lowry, lead author on the paper from Bristol University, said: "These studies help us understand how the body communicates with the brain and why a healthy immune system is important for maintaining mental health. They also leave us wondering if we shouldn’t all be spending more time playing in the dirt."

Interest in the project arose after human cancer patients being treated with the bacteria Mycobacterium vaccae unexpectedly reported increases in their quality of life. Lowry and his colleagues reasoned that this effect could be caused by activation of neurons in the brain that contained serotonin.

When the team looked closely at the brains of mice, they found that treatment with M. vaccae activated a group of neurons that produce the brain chemical serotonin. The lack of serotonin in the brain is thought to cause depression in people, thus M. vaccae’s effects on the behavior of mice may be due to increasing the release of serotonin in parts of the brain that regulate mood.

The new research supports this hypothesis, but future studies will be designed to determine if M. vaccae, other bacteria, or pharmaceutical compounds have antidepressant properties through activation of this group of serotonin neurons.



"Mycobacterium vaccae is a natural soil bacterium which people likely ingest or breath in when they spend time in nature," says Dorothy Matthews of The Sage Colleges in Troy, New York, who conducted the research with her colleague Susan Jenks.

Previous research studies on M. vaccae showed that heat-killed bacteria injected into mice stimulated growth of some neurons in the brain that resulted in increased levels of serotonin and decreased anxiety.

"Since serotonin plays a role in learning we wondered if live M. vaccae could improve learning in mice," says Matthews.

Matthews and Jenks fed live bacteria to mice and assessed their ability to navigate a maze compared to control mice that were not fed the bacteria.

"We found that mice that were fed live M. vaccae navigated the maze twice as fast and with less demonstrated anxiety behaviors as control mice," says Matthews.

In a second experiment the bacteria were removed from the diet of the experimental mice and they were retested. While the mice ran the maze slower than they did when they were ingesting the bacteria, on average they were still faster than the controls.

A final test was given to the mice after three weeks' rest. While the experimental mice continued to navigate the maze faster than the controls, the results were no longer statistically significant, suggesting the effect is temporary.

"This research suggests that M. vaccae may play a role in anxiety and learning in mammals," says Matthews. "It is interesting to speculate that creating learning environments in schools that include time in the outdoors where M. vaccae is present may decrease anxiety and improve the ability to learn new tasks."

Provided by American Society for Microbiology

William Gaatjes
06-29-2010, 12:26 PM
Research about the link between bacteria "Enterococcus faecalis " and colon cancer.


The research, published in the October issue of the Journal of Medical Microbiology, sheds light on the way gut bacteria can cause colon cancer.

There are more bacteria in our bodies than there ever have been people on the Earth. In fact, there are more bacteria in the colon than there are human cells in our bodies. Most of the bacteria in our guts are harmless and many are beneficial to our health. However, for several decades scientists have thought that some microbes living in the gut may play a role in the formation of sporadic colorectal cancer.

Enterococcus faecalis is a normal gut bacterium. Unlike most gut bacteria, it can survive using two different types of metabolism: respiration and fermentation. When the bacteria use fermentation they release by-products. One of these is a kind of oxygen molecule called superoxide, which can damage DNA and may play a role in the formation of colon tumours.

"We wanted to investigate how colon cells respond to normal gut bacteria that can damage DNA, like E. faecalis," said Professor Mark Huycke from the Department of Veterans Affairs Medical Center in Olklahoma City, USA. "We found that superoxide from E. faecalis led to strong signalling in immune cells called macrophages. It also altered the way some cells in the gut grew and divided and even increased the productivity of genes that are associated with cancer."

The team found that 42 genes in epithelial cells in the gut are involved in the regulation of the cell cycle, cell death and signalling based on the unique metabolism of E. faecalis. This suggests that cells of the lining of the colon are rapidly affected when E. faecalis switches to fermentation. It also indicates that E. faecalis may have developed novel mechanisms to encourage colon cells to turn cancerous.

Intestinal cancers occur almost exclusively in the colon where billions of bacteria are in contact with the gut surface. For years scientists have tried to identify links between gut bacteria and people who are at risk of colon cancer. This has been made difficult by the enormous complexity of the microbial communities in the intestine.

"Our findings are among the first to explore mechanisms by which normal gut bacteria damage DNA and alter gene regulation in the colon that might lead to cancer," said Professor Huycke. "This research puts n to perspective the complexity of the effects normal gut bacteria can have on the health of an individual."


http://www.sciencedaily.com/releases/2008/09/080921201716.htm

EDIT:

Forgot to mention we have the common cytomegalovirus (CMV) virus that can suppress immune system calls( See posts above) and a bacteria that can turn cells cancerous in the colon. Seemingly not related to each other. But a most undesirable outcome is possible. I wonder if this virus and bacteria if these 2 could combined cause cancer. Reading this i would think so.

Could this be true ?
The bacteria Enterococcus faecalis would then be the cause and the virus cytomegalovirus would be the reason the immune system can not properly destroy the cancerous turned cell. Thus the cancer can grow.

The good researchers mentioned :
In essence, CMV is able to cutoff an infected cell's call for elimination. This allows CMV to overcome this critical immune barrier during re-infection," explained Klaus Frueh, a senior scientist at the university.

As described in the Nov. 16 issue of the British journal, The Lancet, Cobbs and his team took colorectal polyps, tumors and surrounding healthy cells from 29 patients. They found proteins from the cytomegalovirus in approximately 80 percent of the polyps and in about 85 percent of the colon cancer samples.

"I'm not trying to say this virus is causal in colon cancer," Cobbs said. "I've just made a preliminary observation ... whether or not it's influencing the cancer remains to be determined."

William Gaatjes
06-30-2010, 01:54 AM
I noticed the link to the CMV virus article does not work anymore.

I have acquired a more detailed version of text :


http://www.ncbi.nlm.nih.gov/pmc/articles/PMC538736/

Here is an abstract :

Human cytomegalovirus (HCMV) has evolved multiple strategies for suppression of the antiviral response of the infected cell. DNA array technology has revealed that HCMV clearly regulates host gene expression during the course of a productive infection by enhancing, sustaining, or suppressing steady-state levels of cellular transcripts. Interleukin-6 (IL-6) is a pleiotropic cytokine that plays a central role in the immune response to infection. Here we report a detailed study of the effects of HCMV infection on IL-6 expression by human fibroblasts. UV-inactivated virus was found to induce high levels of IL-6 mRNA and protein expression, and IL-6 mRNA remained abundant in cells 16 h after inoculation even though the level of ongoing IL-6 transcription was not significantly enhanced. In lytic HCMV infections, the onset of viral gene expression resulted in two apparently antagonistic effects on IL-6 expression: (i) transcriptional activation, mediated at least in part by the IE2p86 protein, and (ii) posttranscriptional suppression mediated by destabilization of IL-6 mRNA. Transcriptional activation was outweighed by the suppressive effect, such that cells undergoing productive infection produced less IL-6 than cells challenged with inactivated virus. Suppression of IL-6 expression was independent of the viral IL-10 homologue, cmvIL-10. Destabilization of IL-6 mRNA was observed to coincide with the enhanced expression and aberrant intracellular localization of HuR, an mRNA-binding protein known to interact with IL-6 and other mRNAs containing 3′ AU-rich elements. Our data suggest a novel mechanism for gene regulation by HCMV at the posttranscriptional level.

Human cytomegalovirus (HCMV) is a ubiquitous, clinically important herpesvirus. Following primary infection, HCMV persists throughout the lifetime of the host, during which the virus must avoid elimination by host immune mechanisms. Thus, HCMV has become a paradigm for viral immune evasion (1, 35, 44). In recent years a remarkable series of HCMV immune evasion or modulation systems have been elucidated, including the following: down-regulation of surface MHC-I expression (1), evasion of natural killer (NK) cell-mediated killing (60), and altered expression of immune signaling molecules and interferon response genes (1, 6, 47). Furthermore, these studies have shown that the virus has acquired or evolved in its genome a number of homologues of immune regulators, including chemokines and chemokine receptors (35, 58). The assumption that such molecules play a direct role in persistence and pathogenesis in the host is supported by the fact that attenuated laboratory strains (AD169 and Towne) lack a set of additional genes, associated with immunomodulatory functions, that are present in virulent clinical or low-passage isolates of HCMV (10, 42). Thus, HCMV has a direct impact on normal immune signaling, to promote an infection associated with a wide range of life-threatening conditions in the immune-compromised host (41).
Interleukin-6 (IL-6) plays a central role in both innate and acquired immune responses. IL-6 is the predominant inducer of the acute-phase response, an innate immune mechanism which is triggered by infection and inflammation (45). IL-6 also plays multiple roles during subsequent development of acquired immunity against incoming pathogens, including regulation of cytokine and chemokine gene expression, stimulation of antibody production by B cells (45), regulation of macrophage and dendritic cell differentiation (12), and response of regulatory T cells to microbial infection (40). In addition to these roles in pathogen-specific inflammation and immunity, IL-6 levels are elevated in chronic inflammatory conditions, such as rheumatoid arthritis, and indeed antibodies against IL-6 and the soluble form of its receptor have been used therapeutically for this condition (30). The inflammatory effects of IL-6 have also been implicated as a factor in the failure of organ and tissue grafts; moreover, elevated levels of the cytokine have been reported to accompany HCMV replication in transplanted lungs and bone marrow during episodes of inflammation or rejection (18, 28, 48, 55, 56). Given the ability of HCMV to persist in the infected host, it might be anticipated that the virus has evolved mechanisms to modulate the expression or signaling of IL-6 as part of the viral armory of immune evasion strategies. However, the effects of productive HCMV infection on IL-6 expression are not well understood.
Transcription of the IL-6 gene can be induced by several cellular factors in response to a range of physiological stimuli; moreover, the mRNA is subject to extensive regulation at the posttranscriptional level. Some inducers, such as IL-1, induce both transcription and stabilization of IL-6 mRNA, whereas tumor necrosis factor alpha induces transcription but not stabilization of the mRNA (39). Regulation of IL-6 mRNA stability is mediated through the 3′ untranslated region (UTR), which contains a number of AU-rich elements (AREs). AREs occur in the mRNAs of many genes involved in inflammation, immune signaling, and cell growth and proliferation (4). Their presence in an mRNA generally promotes its degradation in the unstimulated cell but can confer stability in response to appropriate—typically inflammatory—stimuli such as IL-1; these effects on mRNA stability are mediated by a number of both positive (stabilizing) and negative (destabilizing) proteins in the cell, although the precise mechanism of action of ARE-binding proteins has not yet been elucidated fully.
The effects of HCMV infection on cellular gene expression are initiated with binding of the virion to the cell surface (22), with interaction between glycoprotein B and Toll-like receptor 2 playing a major role in this process (13). The binding of virions, or even glycoprotein B in isolation, leads to the induction of inflammatory cytokines and interferon-responsive genes (3, 47, 61). IL-6 mRNA expression is up-regulated by HCMV infection in the absence of de novo expression of viral genes (6, 8, 24, 62, 63), although the IL-6 promoter does not contain recognized interferon response elements. However, virion binding activates multiple intracellular signal transduction pathways, including the phosphatidylinositol kinase, mitogen-associated protein/extracellular signal-regulated kinase, and protein kinase C pathways, all of which lead to the activation of nuclear factors such as NF-κB and p38 (13, 22), which are known inducers of IL-6 gene transcription (45). Since the prolonged expression of inflammatory and antiviral genes would likely be detrimental to viral replication, HCMV has evolved mechanisms to counter the host cell's innate antiviral defenses: another virion protein, the matrix protein pp65, has recently been shown to inhibit expression of many of the interferon-responsive genes that are induced by HCMV infection (5). Nevertheless, wild-type HCMV virions still induce up-regulation of a substantial number of proinflammatory genes, showing that the presence of pp65 is not sufficient to completely overcome the innate immune response. Indeed, elevated levels of prostaglandins appear to be required to activate viral gene expression (64). Thus, the induction of many inflammatory cytokines and interferon response genes is transient (6, 27), and de novo expression of virus-encoded genes acts in concert with incoming pp65 to suppress cellular antiviral gene functions (5).
While HCMV infection is known to produce profound changes in the regulation of cellular genes, published studies provide only limited insight into the control of IL-6 gene expression in the productively infected cell. Although the 72-kilodalton HCMV immediate-early (IE) protein 1 (IE1p72) can mediate transcriptional activation of the IL-6 promoter in monocytic cells (24), expression of IE genes is limited in undifferentiated monocytes (49), and it is not known whether such activation occurs during productive infection. Moreover, most previous work has been carried out in the presence of serum, which has profound effects on the expression of cytokines and induces IL-6 expression in fibroblasts (29). In this study, we analyzed in detail the regulation of IL-6 expression in HCMV-infected primary human fibroblasts, in both the absence and the presence of serum. Fibroblasts remain the best-characterized cell system for the study of productive HCMV replication and are a potential source of IL-6 during localized episodes of viral replication in vivo. Our data reveal a hitherto-unsuspected level of complexity in the regulation of IL-6 expression in the infected cell and an apparently novel mode of gene regulation by HCMV at the posttranscriptional level.

Ancalagon44
06-30-2010, 02:04 AM
My Opinion is that through vertical gene transfers (aka offspring through sexual reproduction) and evolution a complex lifeform can loose genes.

Lose genes, not loose genes.

William Gaatjes
06-30-2010, 04:59 AM
Lose genes, not loose genes.

True, my spell checker only checks for errors and not the actual meaning of the word.
Time to refresh with a good old dictionary.

Ancalagon44
06-30-2010, 05:44 AM
Sorry for being anal - its just a very common grammar mistake and irritates the crap out of me.

tcsenter
06-30-2010, 05:52 AM
Sorry for being anal - its just a very common grammar mistake and irritates the crap out of me.
It's = it is (contraction).

And probably more appropriate to use that rather than and to join those two phrases. e.g.

"....it's just a very common grammar mistake THAT irritates the crap out of me."

Gibsons
06-30-2010, 07:41 AM
Not gonna even attempt to comment on the wall of text, but point out one thing. The immune avoidance mechanisms noted for CMV aren't uncommon, EBV has a few tricks as do most herpes viruses.

Given any immune defense against viruses, there's usually a viral means of avoiding it. They don't work perfectly however, or we might all be dead.

For instance, CMV has a really neat way of avoiding NK cells, so it might seem that NK cells wouldn't be effective as part of a response to CMV. However, people with defects in NK cell function tend to have much worse outcomes from CMV infections.

William Gaatjes
06-30-2010, 07:57 AM
Not gonna even attempt to comment on the wall of text, but point out one thing. The immune avoidance mechanisms noted for CMV aren't uncommon, EBV has a few tricks as do most herpes viruses.

Given any immune defense against viruses, there's usually a viral means of avoiding it. They don't work perfectly however, or we might all be dead.

For instance, CMV has a really neat way of avoiding NK cells, so it might seem that NK cells wouldn't be effective as part of a response to CMV. However, people with defects in NK cell function tend to have much worse outcomes from CMV infections.

Oh, i agree that my post above might seem as the answer but it is not.
I do think and that is my intention is that when it comes to some of the diseases that accumulate and kill fast or kill slowly like for example cancer that the wrong combination of viruses and bacteria might be the reason or the wrong combination of bacteria and toxins or a combination of viruses , bacteria, toxins, and other pathogens like fungi, yeast...

But as you state yourself, many viruses have these tricks up their viral sleeves. Now you can imagine, that it is the consensus in the medical world that most viruses are harmless. I do think that in a solitary situation as for example lab experiments nothing will happen because of the isolated nature. But in real life, we are infected often by multiple pathogens and we carry more microbes in and on our body then we have body cells. We live in symbiosis. Now the real bad bugs are aggressive and kill humans quick. But a life long of having the wrong balance of gut microbes and living in a toxic environment and eating the wrong food. I am amazed how resilient the human body is. But i wonder if there is an epigenetic effect to be discovered here as well, that is as soon as the consensus is adjusted.

William Gaatjes
07-01-2010, 12:30 PM
Sorry for being anal - its just a very common grammar mistake and irritates the crap out of me.

Do not worry.

Here something funny to watch 2:20 to 2:50 :
The series is great though and she is a very good comedienne...
And makes you laugh when she is laughing.
:^_^


http://www.youtube.com/watch?v=yjJ5B7xcfbI

ModestGamer
07-01-2010, 12:45 PM
Amazing...

That virus is scary indeed. But what worries me is there are no enforced guidelines.
I am sure that the people who work with extinct viruses or lethal ones like polio or the 1918 flu virus do not need enforced guidelines , they know how dangerous the material is they work with. What do you think about this ? Are the precautions taken really that strict ?

you think the polio virus is extinct ? Far from it.



My personal opinion is that almost all cancers must be virus related. I think that toxic materials that cause cancer, are not the primary cause, but a catalyst to jump start the process.

actually a poor immune system is the biggest offender of cancers.a healthy immune system spots and removes cancers. Odd that cancer rates sky rocket alongside immunization rates. Disturbing trend.



What was mentioned in the article was interesting :





Here are some more links about viruses and cancer. Might come in handy, however i would not be surprised you already know about them...

Cervical cancer (http://en.wikipedia.org/wiki/Cervical_cancer)

JC virus (http://www.annieappleseedproject.org/linvirandbra.html)

Virus inside brain tumors. (http://www.newsweek.com/id/178660)


EDIT : typing errors and link :

cache, main memory and mass storage (http://www.sciencedaily.com/releases/2009/10/091008142957.htm)



active, gene-rich and inactive, gene-poor stretches

Now does that not sound like cache, main memory and mass storage ? :)


Well obviously a poorly performing immune system will not catch the virus that cuases the cell mutation that leads to cancer. It is common sense.

William Gaatjes
07-01-2010, 01:53 PM
you think the polio virus is extinct ? Far from it.


I do not think it is extinct. It is very much alive.
Life is never that easy to kill. I am sure variants of the polio virus still exist in some remote area.



actually a poor immune system is the biggest offender of cancers.a healthy immune system spots and removes cancers. Odd that cancer rates sky rocket alongside immunization rates. Disturbing trend.

What do you mean by this ? Can you clarify, please ?
This that you mention reminds me of SV40.



Well obviously a poorly performing immune system will not catch the virus that cuases the cell mutation that leads to cancer. It is common sense.

By your perspective people would either be sick forever or never sick.
It is a lot more complicated then that.

For example, a lot of "harmless" viruses are transmitted by intimate contact.
From that perspective, the best practice would be to avoid viruses transmitted through intimate contact, is to find one partner and stay with that partner for life, not even kissing. With such discipline a lot of viruses and their effects would be eradicated from a large part of humanity, but accidents will always happen. However, can you ask people such a way of life ? Even through the use of religion, people cannot be forced and will find a way and a scapegoat. People have to decide for themselves what is best.

Another example is that some pathogens have novel ways to prevent alarming the human immune system. The phrase "You do not care about what you do not know." works very well for the immune system.

ModestGamer
07-01-2010, 03:13 PM
I do not think it is extinct. It is very much alive.
Life is never that easy to kill. I am sure variants of the polio virus still exist in some remote area.



What do you mean by this ? Can you clarify, please ?
This that you mention reminds me of SV40.



By your perspective people would either be sick forever or never sick.
It is a lot more complicated then that.

You are always technically sick. You have virus loads right now. The difference is do they overwhelm you or not ? for instance most adults today carry chicken pox. The varserillas virus. It is however inactive even though it is always there.

So how does that work again ?

there are several strains of Polio. Only one of which is paralitic and the other strains pose no more symptoms then the flu with one strain cuasing severe to mild respritory distress.

which one is extinict.




For example, a lot of "harmless" viruses are transmitted by intimate contact.
From that perspective, the best practice would be to avoid viruses transmitted through intimate contact, is to find one partner and stay with that partner for life, not even kissing. With such discipline a lot of viruses and their effects would be eradicated from a large part of humanity, but accidents will always happen. However, can you ask people such a way of life ? Even through the use of religion, people cannot be forced and will find a way and a scapegoat. People have to decide for themselves what is best.

a well practiced immune system is a healthy body. My family survived the great plague, only family in the village. Virus's are not fundementaly a bad thing. They can and do cuase positive mutation "as well as negative mutations" and also serve the pupose of trimming the herd for healthier more capable producing stock.

We are just fancy animals after all.





Another example is that some pathogens have novel ways to prevent alarming the human immune system. The phrase "You do not care about what you do not know." works very well for the immune system.


not really. we might be poisoning ourselves.

Gibsons
07-01-2010, 04:55 PM
sigh...

I just don't have time for this.

William Gaatjes
07-01-2010, 06:20 PM
sigh...

I just don't have time for this.


Although i do not know much about this as you do, i will give it a try.




You are always technically sick. You have virus loads right now. The difference is do they overwhelm you or not ? for instance most adults today carry chicken pox. The varserillas virus. It is however inactive even though it is always there.

So how does that work again ?


What do you think inactive means ?
You have not received an alive and healthy version of the virus. That is the whole idea. Because if you did receive a fully healthy version, you might as well have died if you did, but not necessarily.
(Was confused with small pox)



a well practiced immune system is a healthy body. My family survived the great plague, only family in the village. Virus's are not fundementaly a bad thing. They can and do cuase positive mutation "as well as negative mutations" and also serve the pupose of trimming the herd for healthier more capable producing stock.

We are just fancy animals after all.

You make the same mistake about Darwins principle of evolution as the next.
It has nothing to do with being the strongest overall. For some people in your family all the variables where right to survive. They where lucky.

For example , the physically stronger lion gets bitten by a snake. Is weakened but is not dying. Now in a fight for a troop of females he looses from a lion that is far less powerful but has the advantage of not having snake venom in his veins. And as such the weaker lion spreads his genes.
Another example is a physically stronger lion and a physically weaker lion where both get bitten by a snake. The weaker lion however has a built in advantage to recover from snake venom faster and is almost not affected. And such the physically stronger and superior lion loses from the physically weaker lion in a fight for a troop of females because in that special case the physically weaker lion had the advantage. In a normal situation he had lost.

You have a false view of supremacy and do not understand how nature works. Nature cannot be divided into separate cases.
Some real life examples :

http://www.nih.gov/news/pr/may98/niaid-06.htm

http://www.news.harvard.edu/gazette/1998/07.09/CysticFibrosisG.html

http://www.newscientist.com/article/dn10013-cystic-fibrosis-gene-protects-against-tuberculosis.html

Cystic fybrosis and typhoid or or cholera tubercolosis.

A genetic mutation that protects against the disease typhoid but expected is that tubercolosis was the major contributor to the spreading of the genetic mutation..
But when you aquire this mutation from both parents, you get the very awful disease called cystic fybrosis.

Millions of people in the United States, Canada, and Europe carry a ticking time bomb in their cells -- a mutated copy of a gene known as CFTR. If both mother and father possess the mutation, each of their children has a one in four chance of dying before age 30.

A single copy of the mutated CFTR gene is present in one out of every 20 people of European origin. The 25 percent of those children who inherit two mutant copies get cystic fibrosis, a lethal disease that attacks the lungs. Until the 1950s, almost all such newborns died in early childhood.

Cystic fibrosis sufferers produce unusually salty sweat, a trait used to detect the disease. In the past, if a baby tasted salty when kissed, people knew the infant would die before its second birthday. Even today, when lung infections can be controlled with antibiotics, most victims of cystic fibrosis, 30,000 people in the United States, die before age 30.

Men with cystic fibrosis are usually sterile, and only recently have women with the disease been able to become pregnant.

This lethality and sterility present medical scientists with a mystery. Why does the mutation persist when, until quite recently, those who got the disease perished before passing it on? To survive the ruthless culling of evolution, the mutation must provide some advantage. But what is it?

Researchers at Harvard University and their colleagues at the universities of Bristol and Cambridge in England have found a likely answer.

"People with only one copy of the mutated gene apparently gain protection from infection by the bacterium that causes typhoid," says Gerald Pier, professor of medicine at Harvard Medical School.

Typhoid comes from eating food or drinking water contaminated with Salmonella typhi, a bacterium common in places with poor sanitation. Carried into the gut with corrupted water or food, the bug gets into the intestinal wall, then moves into the bloodstream. People with one copy of the mutated CFTR gene gain protection against such infection.

In lungs, a protein produced by the CFTR gene binds to another bacterium, usually Pseudomonas aeruginosa, and causes the germ to be expelled by coughing, sneezing, or expectoration. But cystic fibrosis patients lack this protein and thus suffer infections that clog airways and destroy lung tissue.

Sickle cell anemia.

A mutation in the production of red blood cells creates a barrier for the plasmodium parasite.

http://en.wikipedia.org/wiki/Malaria#Genetic_resistance_to_malaria

http://sickle.bwh.harvard.edu/malaria_sickle.html

The same type of benefit occurs in people of African descent who carry mutations in the gene responsible for making hemoglobin, a vital blood protein that carries oxygen. If genes from both parents are mutated, each offspring has a 25 percent chance of getting sickle-cell anemia, a painful, disabling disease that affects approximately 4,000 African-American babies born every year in the United States.

Those with only one mutated gene, however, gain resistance to the parasite that causes malaria. Such resistance gives blacks a big advantage in Africa, where malaria kills about one million children a year. However, this resistance is not so advantageous in this country, where the mosquito-borne disease is well controlled.

About the black death and protection against HIV1:

http://www.pbs.org/wnet/secrets/previous_seasons/case_plague/index.html

http://www.wellsphere.com/hiv-aids-article/selective-pressures-on-ccr5-delta-32-in-the-european-population/439163

Recent research into the HIV pandemic has focused on the presence of individuals who do not become infected by HIV when exposed to the virus. So-called co receptors, which are essential for viral docking and infection, are thought to play a role in this immunity. One such co receptor is the protein CCR5, a chemokine receptor on the surface of T4 cells (Galvani et al.). Individuals who lack functional CCR5 protein do not become infected when exposed to HIV-1. A gene mutation, CCR5-&Delta;32, which causes a deletion of the allele for making CCR5, is present in about 10% of the European population (Galvani et al.). Homozygous individuals are completely immune to HIV-1 and heterozygotes while still susceptible to viral transmission, show slower progression of infection (Galvani et al.). A study done by Doctors Alison P. Galvani and. Montgomery Slatkin published in the December 9th, 2003 Proceedings of the National Academy of The Sciences in the United States, suggests that the higher rate of CCR5-&Delta;32 in European populations is the direct result of selection pressure caused by Small Pox epidemics.
Previous studies have tried to correlate the augmented prevalence of CCR5-&Delta;32 in Europe with the intense selection pressure caused by Bubonic Plague. Galvani et al. propose that a correlation between CCR5-&Delta;32 and Small Pox is a more likely scenario (Galvani et al.). To back this up, a population genetics model was set up using derivations of Hardy-Weinberg equations. These models assume that the CCR5-&Delta;32 is at least 700 years old and measure selection pressure caused by both diseases on CCR5-&Delta;32 since 1300 (Galvani et al.). Derivations of the Hardy-Weinberg equation, which factor in the frequency of outbreaks, percentage of mortality and age of the victims, were used to calculate the selection pressure of each disease on CCR5-&Delta;32. These models were used to determine whether or not each disease exerted enough selection pressure to cause 10% prevalence of CCR5-&Delta;32 in the European population over a 700 year period (Galvani et al.). This model shows conclusively that the Bubonic Plague did not exert enough selection pressure over 700 years to cause 10% prevalence of CCR5-&Delta;32 in the population while Small Pox did (Galvani et al.)..
Small Pox exerted higher selection pressure than Plague for a variety of reasons. Small Pox appeared in the population as early as 1,300 years before the first outbreak of Plague. Small Pox outbreak cycles were more frequent than Plague, correlating to a greater mortality (Galvani et al.). Finally, children, who had the greatest reproductive potential, were most susceptible to death by Small Pox while Bubonic Plague tended to eliminate people indiscriminately (Galvani et al.). All of these factors were included in the mathematical model, which showed that Small Pox was enough of a selecting force in Europe to cause the prevalence of CCR5-&Delta;32 to increase from 0-10% over 700 years.
There were two other pieces of evidence used by the authors to support their claim. The first came from noting that CCR5-&Delta;32 was present in a higher percentage of the population (14%) in Scandinavia, where Small Pox epidemics were most severe (Galvani et al.). When examined at the molecular level, the mechanism for infection by Small Pox virus involves the use of chemokine receptors, like CCR5, while Y. pestis infection in Plague is independent of these receptors (Galvani et al.).
The implications of this study on the future the HIV-1 pandemic are alarming. At least 700 years of fairly high selective pressure on a population by Small Pox conferred only 10% immunity (Galvani et al.). Since jumping species, HIV has already evolved into two subtypes, three groups and nine clades. In addition, co-infection with different clades is producing recombinant viruses, which are resistant to drug treatments and have stronger binding affinities for immune cells (Avert). HIV is evolving faster than the human race, which from a Darwinian perspective, does not bode well for our species. An interesting application of this data would be to run the same sort of population models in Africa. The selection pressure there on CCR5-&Delta;32 and other genes, which confer immunity to HIV, theoretically will be high. A measurement of the evolution of HIV immunity would be a helpful tool in determining the prospects for this embattled continent.


Now could you please continue this in another new thread about your genetic superiority. I try to accumulate information in this thread. Thank you.

William Gaatjes
07-02-2010, 01:59 PM
I was wondering if the CCR5 delta 32 mutation would make people more susceptible to a genetic disease. I have not found information about that. But it seems that people who have the CCR5 delta 32 mutation are more likely to not survive an encounter with the west nile virus.

CCR5 Δ32 (delta 32) is a non-functional CCR5 receptor and is characterized by a deletion of 32 base pairs in the open reading frame. Individuals with CCR5 delta 32 have a perfectly normal phenotype except for a heightened risk of West Nile virus.

http://www.trofileassay.com/Natural_History.html

This is another example that these mutations are not steered by some intelligence. Symbolic speaking : We just run from one threat in the arms of another threat. And adjusting in the progress. This is happening all over the planet. I do not know of any life form that is able to not mutate over time.
If there is, i would gladly read about it..

ModestGamer
07-02-2010, 04:53 PM
Although i do not know much about this as you do, i will give it a try.






What do you think inactive means ?
You have not received an alive and healthy version of the virus. That is the whole idea. Because if you did receive a fully healthy version, you might as well have died if you did, but not necessarily.
(Was confused with small pox)



You make the same mistake about Darwins principle of evolution as the next.
It has nothing to do with being the strongest overall. For some people in your family all the variables where right to survive. They where lucky.

.

First off you make a false premise about virus behavior. They are not living creatures such as bacteria. They are essentially for lack of a better term a hacking agent. a virus hacks the DNA of a host cell and then convert the host cell into a reproduction facility that creates either more DNA or cells to create more virus. They don't really do anything else. The symptomology of each virus is different to some extent but the function is all the same.

Most virus's can most likely be traced to cell mutations as a point of origin. Wiat for it the research will ferret this out.

There is no genetic superiority. Only genetic traits that allow some individuals to survive certain enviromental difference more or less sucessfully. In the case of my family it is resistance to many types of viral strains but issue with dealing with bacteria and alergens and having a hyper immune system.

sickle cell is though to provide protection against Milaria.


On the immunization front.

Why are we infecting ourselves ? Do you think those DNA/RNA fragments totally leave ? har har har they are simply incorporated into our bodys in some fashion or another only to cuase cancer or other immune system related problems later. Do you think it is coincedance that cancer rates have sky rocketed alongside immunization rates. Where is all of the genetic virus trash they are finding comming from ?

chicken pox become dormant but it can also become active later in life. shingles is the example of this. The reason it stays dormant is becuase the immune system can suppress it. However in periods of high stress or illness chickenpox can often reappear and cuase shingles or even another high level infection.

The arrogance of man is in beliving we can do anything about the situation.

Polio is a great example.

in the 1930's we ran nearly 1,000,000 cases annualy of the repritory strain. By the early 1950's the indedance rate dropped to under 50,000 annually.

there was no medical intervention no vaccines to help fight the disease.ultimately the thing that really seemed to help was the improvements in sanitation and the treating of the drinking water supply with cholrine.



So for all the hyperbole about advances in using virus's and immuniation to cure disease, it is just that. Hyperbole. If time is a test in the next 10 years we shall see a rampant increase in auto immune disease as we have been for the last 3 decades although and I will predict this based on todays data. We shall see a 10 fold increase in diabete mellitis " auto immune attack on the pancreas"

It is already happening. It is most likely being driven by the chickenpox immunizations. Which many european and canadian researchers have pointed to the chickpox virus itself being a preindicator for developing Diabete mellitis.

Your pretty ignorant on what the effect of our meddeling is.

Gibsons
07-02-2010, 05:13 PM
First off you make a false premise about virus behavior.

Why are we infecting ourselves ? Do you think those DNA/RNA fragments totally leave ? har har har they are simply incorporated into our bodys in some fashion or another only to cuase cancer or other immune system related problems later. Do you think it is coincedance that cancer rates have sky rocketed alongside immunization rates. Where is all of the genetic virus trash they are finding comming from ?

Based on the above quote, I think you have a lot to learn about what a vaccination is or how the immune system works. Or biology in general.

I'll ask you a question or two: What "DNA/RNA fragments" are you worried about?

How are they "incorporated into our bodys in some fashion or another?" What does that even mean?

Anyway, increased cancer rates are mostly due to increased longevity. So in some sense, you're right, vaccinations have led to increased cancer rates. People are dying of cancer at age 70 instead of say, small pox at age 20.


The arrogance of man is in beliving we can do anything about the situation.

You can form an opinion on whether it's arrogant or not, but in many cases it's a fact.

William Gaatjes
07-03-2010, 05:20 AM
First off you make a false premise about virus behavior. They are not living creatures such as bacteria. They are essentially for lack of a better term a hacking agent. a virus hacks the DNA of a host cell and then convert the host cell into a reproduction facility that creates either more DNA or cells to create more virus. They don't really do anything else. The symptomology of each virus is different to some extent but the function is all the same.


It is the combination of viruses and bacteria that is the basis of life. Viruses cannot survive in a changing environment without bacteria. Bacteria cannot survive in a changing environment without viruses. It is this basic concept that is the start for more diversity and for more complex forms. Without viruses, life would have to depend on mutagens like radiation or chemicals or heavy elements for dna changes to occur. With viruses, life has a very powerful tool to speed up evolution. I would almost admit that viruses are very elegant tools to create new forms of life.

EDIT:
Forgot to mention that this was primarily the case when life in this solar system and in particular on the planet Earth was evolving. Through evolution, many viruses where incorporated and as such a build in means of adaptation was evolved. But i have to admit this and the text above is my opinion based on some information
i found so far.
/EDIT:


Most virus's can most likely be traced to cell mutations as a point of origin. Wiat for it the research will ferret this out.

Doubt that.


There is no genetic superiority. Only genetic traits that allow some individuals to survive certain enviromental difference more or less sucessfully. In the case of my family it is resistance to many types of viral strains but issue with dealing with bacteria and alergens and having a hyper immune system.

From this i would think that you have some auto immune system issue in the family. Not to be a mean person, but as i told you before, change in one direction makes a lifeform more susceptible for a certain situation in another direction. But i am happy to read that you agree that genetic superiority only exist in one certain situation at the right place and time. And as such does not last. I would personally call this the law of evolution.


sickle cell is though to provide protection against Milaria.


On the immunization front.

Why are we infecting ourselves ? Do you think those DNA/RNA fragments totally leave ? har har har they are simply incorporated into our bodys in some fashion or another only to cuase cancer or other immune system related problems later. Do you think it is coincedance that cancer rates have sky rocketed alongside immunization rates. Where is all of the genetic virus trash they are finding comming from ?

chicken pox become dormant but it can also become active later in life. shingles is the example of this. The reason it stays dormant is becuase the immune system can suppress it. However in periods of high stress or illness chickenpox can often reappear and cuase shingles or even another high level infection.

The arrogance of man is in beliving we can do anything about the situation.

Polio is a great example.

in the 1930's we ran nearly 1,000,000 cases annualy of the repritory strain. By the early 1950's the indedance rate dropped to under 50,000 annually.

there was no medical intervention no vaccines to help fight the disease.ultimately the thing that really seemed to help was the improvements in sanitation and the treating of the drinking water supply with cholrine.



So for all the hyperbole about advances in using virus's and immuniation to cure disease, it is just that. Hyperbole. If time is a test in the next 10 years we shall see a rampant increase in auto immune disease as we have been for the last 3 decades although and I will predict this based on todays data. We shall see a 10 fold increase in diabete mellitis " auto immune attack on the pancreas"

It is already happening. It is most likely being driven by the chickenpox immunizations. Which many european and canadian researchers have pointed to the chickpox virus itself being a preindicator for developing Diabete mellitis.

Your pretty ignorant on what the effect of our meddeling is.

I am not ignorant at all. I think i know pretty much about the dangerous side effects of not having proper procedures. If you have read this thread fully, you might have read that i am very concerned about the lack of looking from different perspectives at the same time, at a certain solution used now or has been used in the past. Solutions such as genetic modifications or using vaccines while not checking what the vaccine is actually comprised of. I agree that some people have been meddling out of greed and a limited intelligence. And such is the burden of the human race. We are all doing our best to change that. The easiest change is eradication and start new. But that is against the believes of many and as such a more difficult, more labour intensive , more time consuming approach is happening. You reap what you sow or better known as karma. It is the fundamental rule, so much ignored and forgotten. But i am wondering off... :hmm:

But you make the same mistake and that is looking from one perspective at a time : Less stress, better food, more sleep, children that are fed properly and have a save place to sleep. All this affects the human body greatly. That humanity in the western world lives longer is because of common sense. Simple things we still try to deliver to other countries like clean water make an enormous amount of difference.

A few centuries ago, people in some countries in Europe realized that water makes you sick. As such, they never bathed and drank as little water as possible because they argued that not using water keeps you healthy. That is afcourse a very simple view but i do think you understand what i mean. While cooking the water or purifying it in another way makes it perfectly save to drink and use to wash with.

Life is not that simple, my friend. It is very complicated. But the more of those variables the equation of life is comprised of you can see, the more beautiful life becomes and you start to treasure it more.

EDIT:
You really need to view this, it will explain a lot :

http://www.ted.com/index.php/talks/bonnie_bassler_on_how_bacteria_communicate.html

William Gaatjes
07-03-2010, 05:50 PM
There is another new way discovered/identified about how viruses can be incorporated into the genome of for example mammals.


Published this week in the online journal BMC Evolutionary Biology, the paper ("Filoviruses are ancient and integrated into mammalian genomes") demonstrates for the first time that mammals have harbored filoviruses for at least tens of millions of years, in contrast to the existing estimate of a few thousand.

It suggests that these species, which maintain a filovirus infection without negative health consequences, could have selectively maintained these so-called "fossil" genes as a genetic defense.

The work has important implications for the development of potential human vaccines, as well as for the modeling of disease outbreaks and the discovery of emerging diseases, including new filoviruses.

"This paper identifies the first captured 'fossil' copies of filovirus-like genes in mammalian genomes," says Derek J. Taylor, PhD, associate professor of biological sciences in the UB College of Arts and Sciences and co-author. "Our results confirm for the first time that several groups of mammals, including groups such as marsupials that never colonized Africa, have had an association with filoviruses."

The UB co-authors say that if the rarely captured genes represent antiviral defenses or genomic scars from persistent infections, then the work opens up new possibilities for identifying reservoir species for filoviruses, which harbor the virus but remain asymptomatic.

"The reservoir for filovirus has remained a huge mystery," says Jeremy A. Bruenn, PhD, UB professor of biological sciences and co-author. "We need to identify it because once a filovirus hits humans, it can be deadly."

When the UB researchers studied samples from the fur of a wallaby at the Buffalo Zoo and a brown bat caught on the UB campus, they found that the genomes of both animals as well as some other small mammals contain "fossil" copies of the gene for these deadly viruses, and thus could be candidate reservoir species for them.

"Who knew that the bats in the attic as well as modern marsupials harbored fossil gene copies of the group of viruses that is most lethal to humans," asks Taylor.

The research also demonstrates a new mechanism by which different species of mammals can acquire genes, through non-retroviral integrated RNA viruses, which the UB scientists had previously identified in eukaryotes but was unknown in mammals.

The UB scientists note that it is well-known that RNA retroviruses, like HIV-AIDS, can be integrated into mammal genomes.

"But because filoviruses infect only the cytoplasm of cells and not the nucleus and because they have no means of making DNA copies that might be integrated into the genome -- as retroviruses do -- it was never thought gene transfer could occur between non-retroviral RNA viruses and hosts," says Bruenn. "This paper shows that it does and it may prove to be a far more general phenomenon than is currently known."

The research also reveals that existing estimates that filoviruses originated in mammals a few thousand years ago were way off the mark.

"Our findings demonstrate that filoviruses are, at a minimum, between 10 million and 24 million years old, and probably much older," says Taylor. "Instead of having evolved during the rise of agriculture, they more likely evolved during the rise of mammals."

Although this text would suggest that a complete virus is encoded into the dna of the marsupials. I do not think that it is possible for some form of coordinated gene expressions to become active and that some part or organ of the animal would start to produce a complete and functional filovirus. If it was however, we can stop watching science fiction movies. Because this would be i think the holy grail. :eek:
Another thing that i ask myself, is how does the virus get incorporated in the dna of the animal ? I think that perhaps infection of multiple viruses from different families may help. An RNA virus together with a filo virus. I do not know if that is possible though. It is just an idea.

http://www.physorg.com/news197298768.html


What are filoviruses :

Filoviruses belong to a virus family called Filoviridae and can cause severe hemorrhagic fever in humans and nonhuman primates. So far, only two members of this virus family have been identified: Marburg virus and Ebola virus. Four species of Ebola virus have been identified: Ivory Coast, Sudan, Zaire, and Reston. Ebola-Reston is the only known filovirus that does not cause severe disease in humans; however, it can be fatal in monkeys.

Structurally, filovirus virions (complete viral particles) may appear in several shapes, a biological feature called pleomorphism. These shapes include long, sometimes branched filaments, as well as shorter filaments shaped like a "6", a "U", or a circle. Viral filaments may measure up to 14,000 nanometers in length, have a uniform diameter of 80 nanometers, and are enveloped in a lipid (fatty) membrane. Each virion contains one molecule of single-stranded, negative-sense RNA. New viral particles are created by budding from the surface of their hosts’ cells; however, filovirus replication strategies are not completely understood.


It appears that filoviruses are zoonotic, that is, transmitted to humans from ongoing life cycles in animals other than humans. Despite numerous attempts to locate the natural reservoir or reservoirs of Ebola and Marburg viruses, their origins remain undetermined. However, because the virus can be replicated in some species of bats, some types of bats native to the areas where the virus is found may prove to be the viruses’ carriers.How are filoviruses spread?

In an outbreak or isolated case among humans, just how the virus is transmitted from the natural reservoir to a human is unknown. Once a human is infected, however, person-to-person transmission is the means by which further infections occur. Specifically, transmission involves close personal contact between an infected individual or their body fluids, and another person. During recorded outbreaks of hemorrhagic fever caused by filovirus infection, persons who cared for (fed, washed, medicated) or worked very closely with infected individuals were especially at risk of becoming infected themselves. Nosocomial (hospital) transmission through contact with infected body fluids – via reuse of unsterilized syringes, needles, or other medical equipment contaminated with these fluids – has also been an important factor in the spread of disease. When close contact between uninfected and infected persons is minimized, the number of new filovirus infections in humans usually declines. Although in the laboratory the viruses display some capability of infection through small-particle aerosols, airborne spread among humans has not been clearly demonstrated.



http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/filoviruses.htm

ModestGamer
07-03-2010, 11:09 PM
Based on the above quote, I think you have a lot to learn about what a vaccination is or how the immune system works. Or biology in general.

I'll ask you a question or two: What "DNA/RNA fragments" are you worried about?

How are they "incorporated into our bodys in some fashion or another?" What does that even mean?

Anyway, increased cancer rates are mostly due to increased longevity. So in some sense, you're right, vaccinations have led to increased cancer rates. People are dying of cancer at age 70 instead of say, small pox at age 20.


You can form an opinion on whether it's arrogant or not, but in many cases it's a fact.


Actually it is the common misconception about what is taught in the medical sciences field as to how virus's work that is really the key problem.

Do you know what cancer ultimately is ?

a fialure of the immune system to stop a cell that has mutated "non beneficially" from reproducing. IE cancers grow becuase the immue system cells have difficulty distingushing the difference between friend and foe. How could this have happened in a 10-12 year old child.

what would cuase the immune system in a otherwise healthy person to attacks its own body and kill the pancreas ?

MisIdentification.

Now how does that mechanism become broken. All the micro celluar issues aside.

BTW look at cancer in chlidren and people under 50 . compares those numbers to 30-40-50 years ago.

When you take a vaccination you have aquried the very illness you in fact were attempting to avoid.

ModestGamer
07-03-2010, 11:23 PM
I am not ignorant at all. I think i know pretty much about the dangerous side effects of not having proper procedures. If you have read this thread fully, you might have read that i am very concerned about the lack of looking from different perspectives at the same time, at a certain solution used now or has been used in the past. Solutions such as genetic modifications or using vaccines while not checking what the vaccine is actually comprised of. I agree that some people have been meddling out of greed and a limited intelligence. And such is the burden of the human race. We are all doing our best to change that. The easiest change is eradication and start new. But that is against the believes of many and as such a more difficult, more labour intensive , more time consuming approach is happening. You reap what you sow or better known as karma. It is the fundamental rule, so much ignored and forgotten. But i am wondering off... :hmm:

But you make the same mistake and that is looking from one perspective at a time : Less stress, better food, more sleep, children that are fed properly and have a save place to sleep. All this affects the human body greatly. That humanity in the western world lives longer is because of common sense. Simple things we still try to deliver to other countries like clean water make an enormous amount of difference.

A few centuries ago, people in some countries in Europe realized that water makes you sick. As such, they never bathed and drank as little water as possible because they argued that not using water keeps you healthy. That is afcourse a very simple view but i do think you understand what i mean. While cooking the water or purifying it in another way makes it perfectly save to drink and use to wash with.

Life is not that simple, my friend. It is very complicated. But the more of those variables the equation of life is comprised of you can see, the more beautiful life becomes and you start to treasure it more.

EDIT:
You really need to view this, it will explain a lot :

http://www.ted.com/index.php/talks/bonnie_bassler_on_how_bacteria_communicate.html

I disagree on that aspect. Had I taken the narrow view of health I would have concluded based on current infection rates that vaccinations provide a margin of immunity against diseases. Instead I looked at the data in its totality including data from periods of high and low disease rates and looked at things in totality. What outside factors may have influenced outbreaks and rates of infection.

The #1 factor in almost every instance is that hygene in terms of water, fleas etc is the primary indicator of overall infection rates.

If you doubt this. Look at measles in the UK. immunizations have fialed to end the infection rates. In fact the new mesales strains are resistant to immunizations if the data is correct.If the immunizations ever really had any effect anyway??? Maybe the herd gianed a natural immunity due to repeated infection that eventually became prevelant and ended the problem of infection anaywas. Measales had pretty much gone away on its own. Infections rates had dropped prior to the MMR shots and other mesales immunizations.

So on that front. If we consider all data "not data from the current age of medicine" but data from say the last 100 years versus the last say 30 we find that most of the prominent diseaes we immunize for went away without any vaccines.

BTW having had measales I will enjoy my permamnent immunity for life.

William Gaatjes
07-04-2010, 03:53 AM
I disagree on that aspect. Had I taken the narrow view of health I would have concluded based on current infection rates that vaccinations provide a margin of immunity against diseases. Instead I looked at the data in its totality including data from periods of high and low disease rates and looked at things in totality. What outside factors may have influenced outbreaks and rates of infection.

The #1 factor in almost every instance is that hygene in terms of water, fleas etc is the primary indicator of overall infection rates.

If you doubt this. Look at measles in the UK. immunizations have fialed to end the infection rates. In fact the new mesales strains are resistant to immunizations if the data is correct.If the immunizations ever really had any effect anyway??? Maybe the herd gianed a natural immunity due to repeated infection that eventually became prevelant and ended the problem of infection anaywas. Measales had pretty much gone away on its own. Infections rates had dropped prior to the MMR shots and other mesales immunizations.

So on that front. If we consider all data "not data from the current age of medicine" but data from say the last 100 years versus the last say 30 we find that most of the prominent diseaes we immunize for went away without any vaccines.

BTW having had measales I will enjoy my permamnent immunity for life.

I give you the benefit of the doubt.
Can you explain how antibodies work for me ?
And how the immune system stores information about pathogens in the body ?
And how this affects the immunity for pathogen x version a and pathogen x version b. Same pathogen, different version.


http://www.cellsalive.com/antibody.htm

The whole problem is that you still look from one perspective.
You have to understand we are all a bit different from each other, unique.
(If humans would know this from childhood on, they maybe no longer would have the desire to differentiate themselves from others because they already are) But i am wondering of...

You have to understand we are all a bit different from each other, unique.
Because of this, pathogen a is normally not going to have much affect on person a when compared to person b or person c, etcetera. Now what the whole idea is, give the group of people a vaccination. Most will benefit, some will get sick because of a wrong reaction. At the time, people wanted to save lives, others wanted to make money so these people just accepted the risks. And your right in that way, they unknowingly steered human evolution in a certain direction. That is where you are right and i agree about meddling. But you have to understand that if nothing was done, there would have been a lot more deaths.Talking about survival of the fittest is easy until you have to helplessly witnessing how your children suffer and you have to bury your own children. This is what i mean with different perspectives. No story has 1 side.

What you probably mean is that the vaccination is contaminated with by products. This is the real issue. It is not the actual desired (for the vaccine)pathogen parts that make you sick. It is the contamination of vaccines. At page 2 of this thread, i mention the SV40 virus. You should really the read links i provided about how those polio vaccines where created and how there was one scientist (Bernice Eddy) ignored that the vaccines would be contaminated. However, the managers did not listen and millions of people got more then 40 (SV40 was number 40 identified and the list kept on growing) alive and kicking pathogens( different kind of monkey viruses) and 1 disabled and weakened polio virus. Now you could say, that we are not affected by monkey viruses. But evolution has a nasty side as well. When multiple of these viruses infect a cell and viruses that are lethal infect the same cell, the possibility arises and probability increases that a new virus will be created that will be lethal to humans. A new virus. Since we cannot scan all the cells of every individual on this planet or at least in a city, we will never know what virus is new and what virus is old. We can only assume based on indirect findings.
Remember about influenza and how pigs, chickens, ducks and humans are all infected with viruses and these viruses recombine when these animals and humans live close together ?
The 1918 infuenza epidemic ? Perhaps there is a reason why many people in the middle east do not want to eat pig meat. Because pigs are the biological equivalent of the melting oven for viruses. And the western world even has food recipes with raw or hardly cooked or baked pig meat. :eek:
How about a medium done steak where the blood still comes pouring out ! :eek:
I know steak is bovine or cow meat but anyway...

It is the contamination that causes more problems then the weakened vaccination it self.
Here is a link :
http://www.sv40foundation.org/Chronology.html


The human immune system can be deadly in a few minutes if it would turn in full aggression against the human body.The human immune system is incredibly powerful. But the human immune system does not come pre-compiled with a database. The human immune system is learned what is friend and foe by chance and because of little bacteria spies that help our immune system pointing out agressive pathogens. The chance factor is greatly increased because when you are born, you get breast milk. In this breastmilk, a lot of bacteria are present you need. At the same time you get all the bacteria from your mother and father because of the cuddling and hugging and kissing. As such, your immune system is learning and gathering information while you are a little infant. You already have a large part of the bacteria that you need because you where in the womb. The placenta shields and filters a lot, but it is not perfect. If too clean means you do not have friendly bacteria on you or inside you, then too clean is not good in a world where you are surrounded with microscopic life looking for a home and food...


The friends :
In general the thymus, it is a special test system where the new cells(T-lymphocytes or T cells) of the immune system are being tested if they will recognize body cells as enemies. If so, these t-cells must be destroyed.

The friends part 2 :
You have 10 times as much bacteria living on and inside you as you have body cells. Your immune system is fighting not all these bacteria, Some (probably a pretty large part)bacteria work in a cooperative manner with your immune system. In a few posts above is solid evidence of a bacteria warning the immune system about an dangerous imposter the immune system itself can not recognize.

The friends part 3 :
These bacteria are the first line of defense , for example on your skin their exist bacteria that fight of other pathogens when your skin is damaged. And because these friendly bacteria fill up the wound, it is for the human immune system more easy to get rid of them again because these friendly bacteria are in the database of your immune system, while a new unknown pathogen would need to learned first. And learning takes time.

The human immune system acts in reality more like a balance to keep cooperative cells and cooperative bacteria at a proper level. Everything that does not cooperate must be destroyed to make sure the body as a whole is not compromised. You can understand, we really are redundantly made up of tiny little biological devices. Because everything is efficient, there is hardly any waste.

Now imagine all these little bacteria also have phages. ^_^

The foe's :
Every pathogen that wants to get inside and causes havoc in your body and distorts the balance. The Article and the video about Bonnie Bassler, explains much about quorum sensing or the molecular language between bacteria. Bacteria talk to each other. And the immune system is connected to this communication network as well.


EDIT :

Some more information about how important the right balance is between the organisms living in your gut.:
http://forums.anandtech.com/showthread.php?t=2084791

http://forums.anandtech.com/showthread.php?t=2051807&highlight=genetics




About the placenta :
( I am not fond of using to much wikipedia but i am getting tired)
http://en.wikipedia.org/wiki/Placenta#Cloaking_from_immune_system_of_mother

The placenta and fetus may be regarded as a foreign allograft inside the mother, and thus must evade from attack by the mother's immune system.For this purpose, the placenta uses several mechanisms:It secretes Neurokinin B containing phosphocholine molecules. This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host.[6]
Also, there is presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2.[7]
However, the placental barrier is not the sole means to evade the immune system, as foreign fetal cells also persist in the maternal circulation, on the other side of the placental barrier.[8]




And something else : epigenetics :

And a documentary about epi genetics :
I cannot find the link to the thread anymore thus i will just add it as link to google video :

A BBC horizon documentary about epi genetics :

http://video.google.com/videoplay?docid=1128045835761675934#docid=92084774 61799586076


And the deletion of the same gene on the same location of chromosome 15 causes a different disease depending if the deletion is on the dna strand from the father or on the dna strand from the mother.
It is genomic imprinting : http://ghr.nlm.nih.gov/chromosome/15

Humans normally have 46 chromosomes in each cell, divided into 23 pairs. Two copies of chromosome 15, one copy inherited from each parent, form one of the pairs. Chromosome 15 spans about 100 million DNA building blocks (base pairs) and represents more than 3 percent of the total DNA in cells.

http://en.wikipedia.org/wiki/Angelman_syndrome

http://en.wikipedia.org/wiki/Prader–Willi_syndrome

William Gaatjes
07-04-2010, 06:45 AM
I learn every day :)
I was reading about the singer Sonique and read that she was ill with breast cancer in 2009. Naturally i did a quick search and i never knew this, but it seems there is a link between breast cancer and a virus found in cancerous breast tissue.

The MMTV virus is a cause of breast cancer in mice. But it seems this virus is found as well in human breast tissue that turned cancerous.

Now it may not be the sole cause, but it is interesting what the connection may be...

http://news.bbc.co.uk/2/hi/health/3879783.stm

http://www.webmd.com/breast-cancer/news/20061214/mouse-virus-link-breast-cancer

Tests by researchers in the United States have found signs of a virus called MMTV in tissue taken from women with the disease.
But writing in the journal Cancer, they said there were geographical variations in the numbers testing for the virus.
The UK charity Breast Cancer Care said more research is needed to determine if there is a link. Dr Paul Levine and colleagues from The George Washington University School of Public Health carried out tests on tissue samples taken from breast cancer patients in Europe, North and South America and North Africa. They found that 74% of the samples taken from patients in Tunisia showed signs of MMTV.
This study adds to existing research suggesting there may be a link between the MMTV virus and the development of breast cancer.
This compared to 42% of the samples from Australia, 38% of those from Italy, 36% of those from the United States and 31% of those from Argentina.
Tests on samples from women from Vietnam found that less than 1% showed signs of the virus.

MMTV or mouse mammary tumour virus is known to cause breast cancer in mice. Previous studies have found signs of the virus in breast cancer tissue taken from women.

The researchers said animal studies have found high levels of this virus in aggressive cancer tumours. But they said: "Whether this can be extrapolated to humans remains to be demonstrated." The researchers suggested the geographical variations may be directly related to MMTV in mice.
"The geographic differences were compatible with studies of MMTV in wild mice," they said. Helen Graham, a breast health nurse specialist at Breast Cancer Care said: "This study adds to existing research suggesting there may be a link between the MMTV virus and the development of breast cancer.
"The study had a very small sample and it is clear that more extensive research is needed into the possible link between MMTV and breast cancer.
"Many of the women Breast Cancer Care talk to are anxious to understand the causes of breast cancer but it is very important for all to remember that the single most significant risk factor for breast cancer is age. "Therefore, every woman should be breast aware throughout her adult life."

Mouse mammary tumor virus (MMTV) is a milk transmitted retrovirus like the HTL viruses, HI viruses and BLV. It belongs to the genus betaretroviruses. MMTV was formerly known as Bittner virus, and previously the 'milk factor' referring to the extra-chromosomal vertical transmission of murine breast cancer by adoptive nursing, demonstrated in 1936, by Dr. John Joseph Bittner, while working at the Jackson Laboratory in Bar Harbor, Maine. Dr. Bittner, a geneticist and cancer biologist, established the theory that a cancerous agent, or "milk factor", could be transmitted by cancerous mothers to young mice from a virus in their mother's milk Medicine: Cancer Virus The majority of mammary tumors in mice are caused by mouse mammary tumor virus (MMTV).

http://en.wikipedia.org/wiki/Mouse_mammary_tumor_virus

William Gaatjes
07-04-2010, 01:58 PM
For those interested in music :

This is singer/DJ Sonique :

http://www.youtube.com/watch?v=z1XCBqxgak0

And the very first single :
http://www.youtube.com/watch?v=1tuQ6AkOdGY&feature=related

ModestGamer
07-04-2010, 03:43 PM
I give you the benefit of the doubt.
Can you explain how antibodies work for me ?
And how the immune system stores information about pathogens in the body ?
And how this affects the immunity for pathogen x version a and pathogen x version b. Same pathogen, different version.


http://www.cellsalive.com/antibody.htm

The whole problem is that you still look from one perspective.
You have to understand we are all a bit different from each other, unique.
(If humans would know this from childhood on, they maybe no longer would have the desire to differentiate themselves from others because they already are) But i am wondering of...




I understand the celluar interaction issue but I lack the communication skills to effectively describe what I take in. It is a disability and a very anoying one.

Anyways to adress your points.

The very systems you describe later in your post about the immune systm are interesting in 2 facets.

1. We bypass those response mechanisms by introvenously injecting "anti bodies" which is a misnomer.

Vaccine delibrately give a person a infection, typically with a non human genome parent cell. This almost always creates a massive response as a forgien cell. Now similar things do occur with normal infection but the vaccine itself is not even the same disease we are immunizing for.

Virus + host cell equals different disease. IE a human polio cell is genetically different then a monkey polio cell. So even IF we can avoid complications from the delibrate infection by the virus,what we are immunizing for is already genetically different from the human version. In fact all the human versions while relatively similar are different due to the fact that the Host DNA in some fashion is retained by the virus to help it disguise itself from the immune system in a virus infection.

So the very premise of the vaccine is False on its face.

2. I am not worried about the contimination so much as the fact that we have no way to prove IF vaccines are effective.

IE if you look at comparative data and set aside medical research. Infections come and go.

There was a great case in ohion some 3 years agoe where 400 kids got measales. Upon investigation all 4000 young adults had not only been properly immunized but had had the needed boosters as well.

So obviously when 100% of the infected population is immunized. It speas volumes about the effectiveness of the immunizations on its face.

BTW the data for that infection group has been curiously removed from the FDA website. I don't know why.

3. Immunizations will not work for a substantial portion of the population. due to genetic variances vaccines may only be effective in at best 10% of the population.

Thanx to the wonderful genetic manipulation of virus's every infectee creates a new strain of the virus simply by becoming infected.

4. We are learning more about virus's. This will hopefully change the future of how these vaccines are developed. Maybe they will become effective.

Just a foot note.

Polio was generally transmitted by water in swimming pools and misquitos.

ModestGamer
07-04-2010, 03:43 PM
Cancer in and of itself is a virus by the best definition.



I learn every day :)
I was reading about the singer Sonique and read that she was ill with breast cancer in 2009. Naturally i did a quick search and i never knew this, but it seems there is a link between breast cancer and a virus found in cancerous breast tissue.

The MMTV virus is a cause of breast cancer in mice. But it seems this virus is found as well in human breast tissue that turned cancerous.

Now it may not be the sole cause, but it is interesting what the connection may be...

http://news.bbc.co.uk/2/hi/health/3879783.stm

http://www.webmd.com/breast-cancer/news/20061214/mouse-virus-link-breast-cancer





http://en.wikipedia.org/wiki/Mouse_mammary_tumor_virus

William Gaatjes
07-04-2010, 03:57 PM
Cancer in and of itself is a virus by the best definition.

I do not know if that is the case.

But i do know that viruses are the reason why we exist.

I mean, if you want to make a sterile environment, that is fine. But then you first have to completely change how the human body works. Because we are part of our environment and our environment is part of us. And when you succed you still have to create defenses against bacteria.

ModestGamer
07-04-2010, 04:03 PM
I do not know if that is the case.

But i do know that viruses are the reason why we exist.

I mean, if you want to make a sterile environment, that is fine. But then you first have to completely change how the human body works. Because we are part of our environment and our environment is part of us. And when you succed you still have to create defenses against bacteria.


I don't worry about it. They come and they go regardless of what we do. We can take some commons sense steps to reduce deaths and infections but beyond that. We are at the planets mercy.

do you know how few people died of polio vs the total number of infections.

about as bad as the flu in reality.

William Gaatjes
07-04-2010, 04:07 PM
I understand the celluar interaction issue but I lack the communication skills to effectively describe what I take in. It is a disability and a very anoying one.

Anyways to adress your points.

The very systems you describe later in your post about the immune systm are interesting in 2 facets.

1. We bypass those response mechanisms by introvenously injecting "anti bodies" which is a misnomer.

Vaccine delibrately give a person a infection, typically with a non human genome parent cell. This almost always creates a massive response as a forgien cell. Now similar things do occur with normal infection but the vaccine itself is not even the same disease we are immunizing for.

Virus + host cell equals different disease. IE a human polio cell is genetically different then a monkey polio cell. So even IF we can avoid complications from the delibrate infection by the virus,what we are immunizing for is already genetically different from the human version. In fact all the human versions while relatively similar are different due to the fact that the Host DNA in some fashion is retained by the virus to help it disguise itself from the immune system in a virus infection.

So the very premise of the vaccine is False on its face.

2. I am not worried about the contimination so much as the fact that we have no way to prove IF vaccines are effective.

IE if you look at comparative data and set aside medical research. Infections come and go.

There was a great case in ohion some 3 years agoe where 400 kids got measales. Upon investigation all 4000 young adults had not only been properly immunized but had had the needed boosters as well.

So obviously when 100% of the infected population is immunized. It speas volumes about the effectiveness of the immunizations on its face.

BTW the data for that infection group has been curiously removed from the FDA website. I don't know why.

3. Immunizations will not work for a substantial portion of the population. due to genetic variances vaccines may only be effective in at best 10% of the population.

Thanx to the wonderful genetic manipulation of virus's every infectee creates a new strain of the virus simply by becoming infected.

4. We are learning more about virus's. This will hopefully change the future of how these vaccines are developed. Maybe they will become effective.

Just a foot note.

Polio was generally transmitted by water in swimming pools and misquitos.

The FDA has some strange behaviour sometimes. I do not think the FDA is fully independent.
And i do think sometimes people have been used as guinea pigs.

There is a theory for example that multiple scleroses originated from biological experiments in the USSR. But i do not know to believe that. This man claimed he created a disease by manipulating dna from viruses and bacteria that is exactly the same as MS. The rabbits that where used as test subjects got a fewer first and a few days later these rabbits where healthy. But a few weeks later the rabbits started to behave strange. The rabbits acquired an auto immune disease that affected the myelin sheats of the nerves... The name of the doctor is Sergei Popov. I do not know if it is true though...

http://www.pbs.org/wgbh/nova/bioterror/biow_popov.html
http://www.youtube.com/watch?v=AX67YtDjPms
And a 50 minuted documentary where Sergei Popov speaks.
http://www.youtube.com/watch?v=xpz-f-DgDK4&feature=related





I agree that we could not give the human polio virus at the time in the 19 century. But with todays technology we can actually learn our immune system about specific virus proteins. The only problem is that before we can do such a thing, we must perform the same function as the thymus does. And that is to check if this is not a body protein because then we might create an auto immune disease. Now most proteins are encased in lipids when they travel around in the bloodstream because other wise the immune systems assume these as hostile, if i am not mistaken. Perhaps Gibsons can explain it better if he has the time...

But what do you think then what has happened during the first vaccination that started all this :Edward Jenner was the first to use the vaccination technique because he noticed the girls who took care of the cows did not get sick.

Jenner worked in a rural community and most of his patients were farmers or worked on farms with cattle. In the 18th century smallpox was a very common disease and was a major cause of death. The main treatment was by a method which had brought success to a Dutch physiologist Jan Ingenhaus and was brought to England in 1721 from Turkey by Lady Mary Wortly Montague. This method involved inoculating healthy people with substances from the pustules of those who had a mild case of the disease, but this often had fatal results.In 1788 an epidemic of smallpox hit Gloucestershire and during this outbreak Jenner observed that those of his patients who worked with cattle and had come in contact with the much milder disease called cowpox never came down with smallpox. Jenner needed a way of showing that his theory actually worked.Jenner was given the opportunity on the 14 May 1796, when a young milkmaid called Sarah Nelmes came to see him with sores on her hands like blisters. Jenner identified that she had caught cowpox from the cows she handled each day.
Jenner now had the opportunity to obtain the material try out his theories. He carefully extracted some liquid from her sores and then took some liquid from the sores of a patient with mild smallpox.
Jenner believed that if he could inject someone with cowpox, the germs from the cowpox would make the body able to defend itself against the dangerous smallpox germs which he would inject later.
Jenner approached a local farmer called Phipps and asked him if he could inoculate his son James against smallpox. He explained to the farmer that if his theory was correct, James would never contract smallpox. Surprisingly, the farmer agreed.Jenner made two small cuts on James's left arm. He then poured the liquid from Sarah's cowpox sores into the open wounds which he bandaged.James went down with cowpox but was not very ill. Six weeks later when James had recovered, Jenner vaccinated him again, this time with the smallpox virus.This was an extremely dangerous experiment. If James lived Jenner would have found a way of preventing smallpox. If James developed smallpox and died he would be a murderer.To Jenner's relief James did not catch smallpox. His experiment had worked.In 1798 after carrying out further successful tests, he published his findings: An Inquiry into the Causes and Effects of the Variolae Vaccinae, a Disease Known by the Name of Cow Pox. Jenner called his idea " vaccination" from the word vaccinia which is latin for cowpox. Jenner also introduced the term virus.Jenner found a great deal of scepticism to his ideas and was subject to much ridicule. A cartoon was drawn, showing cows coming out of various parts of people's bodies after they had been vaccinated with cowpox.


After this he used it on many people who did not die. I do think vaccination is not a bad method. But it all depends on what is being used.


http://www.zephyrus.co.uk/edwardjenner.html

Mr. Pedantic
07-04-2010, 04:17 PM
I agree that we could not give the human polio virus at the time in the 19 century. But with todays technology we can actually learn our immune system about specific virus proteins. The only problem is that before we can do such a thing, we must perform the same function as the thymus does. And that is to check if this is not a body protein because then we might create an auto immune disease. Now most proteins are encased in lipids when they travel around in the bloodstream because other wise the immune systems assume these as hostile, if i am not mistaken. Perhaps Gibsons can explain it better if he has the time...
That is not true. The lymphocytes that make up the body's cell-mediated immunity do not inherently recognize the difference between self and non-self antigens. Though lymphocytes recognize only peptides, the body does not need lipids to disguise the presence of proteins. Instead, all the lymphocytes that could possibly be activated by self antigens in the body are screened during maturation by the bone marrow and thymus, and destroyed.

Also, as far as I know there is no effective way to teach the immune system to recognize a new antigen. Unless the genotype HLA complement of an individual were missing a combination that allowed a certain lymphocyte to bind said antigen with any affinity, there is no point - the body can already do this on its own. Vaccines and inoculation do not enhance this, they simply prepare the body for the reinfection with this virus by causing an immune response, which in turn causes the production of memory lymphocytes that can produce a much quicker secondary response in the case of reinfection.

ModestGamer
07-04-2010, 04:27 PM
That is not true. The lymphocytes that make up the body's cell-mediated immunity do not inherently recognize the difference between self and non-self antigens. Though lymphocytes recognize only peptides, the body does not need lipids to disguise the presence of proteins. Instead, all the lymphocytes that could possibly be activated by self antigens in the body are screened during maturation by the bone marrow and thymus, and destroyed.

Also, as far as I know there is no effective way to teach the immune system to recognize a new antigen. Unless the genotype HLA complement of an individual were missing a combination that allowed a certain lymphocyte to bind said antigen with any affinity, there is no point - the body can already do this on its own. Vaccines and inoculation do not enhance this, they simply prepare the body for the reinfection with this virus by causing an immune response, which in turn causes the production of memory lymphocytes that can produce a much quicker secondary response in the case of reinfection.

Thanx you so much for explianing what I was trying to get at.

When you get a vaccine fo say measales. We are giving Measales to the person being vaccinated. givin that the virus is genetically altered it no longer represents the actual virus in the wild. Ergo the vaccine will not be effective.

BTW getting the mseaes is a 100% effective guarentee against reinfection. Given the data on the measales vaccine that I have seen on and off over the years. the vaccine does not work with modern strains.

Also measales just isn't that bad. Really no worse then chicken pox excpet for the high fever. Which if left alone poses no significant threat. Mot of the complications with measales are cuaed by overly aggresive treatment altering the normal path of the bodys immune response.

William Gaatjes
07-04-2010, 04:45 PM
That is not true. The lymphocytes that make up the body's cell-mediated immunity do not inherently recognize the difference between self and non-self antigens. Though lymphocytes recognize only peptides, the body does not need lipids to disguise the presence of proteins. Instead, all the lymphocytes that could possibly be activated by self antigens in the body are screened during maturation by the bone marrow and thymus, and destroyed.

Also, as far as I know there is no effective way to teach the immune system to recognize a new antigen. Unless the genotype HLA complement of an individual were missing a combination that allowed a certain lymphocyte to bind said antigen with any affinity, there is no point - the body can already do this on its own. Vaccines and inoculation do not enhance this, they simply prepare the body for the reinfection with this virus by causing an immune response, which in turn causes the production of memory lymphocytes that can produce a much quicker secondary response in the case of reinfection.

I am bit weary. How do auto immune diseases start then ?
I for example learned from a colleague that he acquired diabetes after he had a virus infection which then caused his immune system to attack the islets of Langerhans. My memory is failing on me because i vaguely remember that someone in Canada who had diabetes had an experimental treatment, where his bone marrow was destroyed. And when he had his transplant, the memory of his immune system was erased and he no longer had diabetes. The same version of diabetes my colleague has.

http://en.wikipedia.org/wiki/Islets_of_Langerhans

If he is in, i will ask about it tomorrow.

I think it where the measles , what he aquired. After that he became a diabetic type 1. I will verify it when he is in.

There is some mention about this virus :
http://en.wikipedia.org/wiki/Coxsackie_B4_virus

Gibsons
07-04-2010, 08:58 PM
Cancer in and of itself is a virus by the best definition.

This is wrong.

Mr. Pedantic
07-04-2010, 09:01 PM
I'm no expert on immunology, I only know what we've been taught. But I would guess that something would interfere with the primary immune organs' ability to screen these lymphocytes out, causing lymphocytes with HLA receptors that bind to self antigens.

Gibsons
07-04-2010, 09:07 PM
I am bit weary. How do auto immune diseases start then ?

Autoimmune diseases are among the most heavily studied and poorest understood things I can think of.

As Mr. Pedantic said, there are mechanisms that eliminate self reactive lymphocytes during the maturation process. But these mechanisms aren't perfect. You can find self reactive lymphocytes in most individuals, but they are usually quiescent (anergic is the proper term).

In some cases, what seems to happen is that something triggers them out of their unreactive state. It might be a failure of the mechanism that supposed to suppress them (genetic or maybe something else), it might be a disease, or whatever.

There's an enormous amount of literature on autoimmunity, but very few clear answers, even in the case of what seem to be clear cut genetic problems.

ModestGamer
07-05-2010, 10:42 AM
This is wrong.


Is it ? By definition of behavior a cancer cell is basically a virus. It grows out of control and without purpose. A cancer cell is basically just a regular cell that has genetic flaw that cuase reproduction without need and cancer cells typically do not serve the function of the original cell. For all intensive purposes they are a virus like cell.

Gibsons
07-05-2010, 12:09 PM
Is it ? By definition of behavior a cancer cell is basically a virus. It grows out of control and without purpose. A cancer cell is basically just a regular cell that has genetic flaw that cuase reproduction without need and cancer cells typically do not serve the function of the original cell. For all intensive purposes they are a virus like cell.

haha, okay you had me going for a while there, but now I know you're just trolling. Pretty good job, I must say.

edit: on the off chance you were serious, a virus is an infectious obligate intracellular parasite. Cancer doesn't fit that description. Eukaryotic cells are not viruses.

Mr. Pedantic
07-05-2010, 02:42 PM
Is it ? By definition of behavior a cancer cell is basically a virus. It grows out of control and without purpose. A cancer cell is basically just a regular cell that has genetic flaw that cuase reproduction without need and cancer cells typically do not serve the function of the original cell. For all intensive purposes they are a virus like cell.
A virus does not grow. A virus has no organization. A virus has no purpose other than reproduction. Whereas cancer cells do. They grow, they organize themselves into structures reminiscent of some of those present in the human body, they perform other functions than just growth and division. Viruses are very small, on the scale of nanometers wide. Cells are typically around 1000x bigger. Viruses necessarily contain only a few pieces of nucleic acid and a protein coat, whereas cells contain so much more. Viruses require a host cell to replicate.

Also, cancer cells have far more than a single genetic "flaw". Cells require several different cellular 'switches' to be deactivated before they can become cancerous. And along every step of the way, a precancerous cell is liable to be picked up by the immune system and destroyed. If getting cancer were as simple as you made out, none of us would survive birth.

Next time, I suggest you look up your words and make sure you know what they mean before saying something like this.

ModestGamer
07-05-2010, 04:18 PM
A virus does not grow. A virus has no organization. A virus has no purpose other than reproduction. Whereas cancer cells do. They grow, they organize themselves into structures reminiscent of some of those present in the human body, they perform other functions than just growth and division. Viruses are very small, on the scale of nanometers wide. Cells are typically around 1000x bigger. Viruses necessarily contain only a few pieces of nucleic acid and a protein coat, whereas cells contain so much more. Viruses require a host cell to replicate.

Also, cancer cells have far more than a single genetic "flaw". Cells require several different cellular 'switches' to be deactivated before they can become cancerous. And along every step of the way, a precancerous cell is liable to be picked up by the immune system and destroyed. If getting cancer were as simple as you made out, none of us would survive birth.

Next time, I suggest you look up your words and make sure you know what they mean before saying something like this.

a virus left unchecked will simply grow by infecting more host cells to increase its numbers. when the host dies it also dies.

Cancer and virus's behave in the same fashion.

Next time you open your yapper consider that some people are not entrained into the specific thinking of the medical industry and view problem from the outside in. Not the inside out.

BTW I am aware of the difference between a cancer and a virus. My point is that they behave in the same fashion.

no cancer grows with any meaningful structure.

ModestGamer
07-05-2010, 04:20 PM
haha, okay you had me going for a while there, but now I know you're just trolling. Pretty good job, I must say.

edit: on the off chance you were serious, a virus is an infectious obligate intracellular parasite. Cancer doesn't fit that description. Eukaryotic cells are not viruses.


your entirely to blinded by the "legalees " of the medical field to see it for what it is.

Gibsons
07-05-2010, 04:38 PM
your entirely to blinded by the "legalees " of the medical field to see it for what it is.
A virus isn't cancer. Cancer isn't a virus.

Mr. Pedantic
07-05-2010, 05:15 PM
no cancer grows with any meaningful structure.
That's not quite true. It obviously depends on what you call 'meaningful', but adenocarcinomas, for example, form in gland-like structures, hence the name.

BTW I am aware of the difference between a cancer and a virus. My point is that they behave in the same fashion.
No, they don't.

ModestGamer
07-05-2010, 05:26 PM
That's not quite true. It obviously depends on what you call 'meaningful', but adenocarcinomas, for example, form in gland-like structures, hence the name.


No, they don't.

Yes they do.

admittedly in your own research they are finding virus fragments in cancer cells. Well one might ask

Why is that ?

so are cancer and virus's interelated ?

hmmmm.

Gibsons
07-05-2010, 05:30 PM
Yes they do.

admittedly in your own research they are finding virus fragments in cancer cells. Well one might ask

Why is that ?

so are cancer and virus's interelated ?

hmmmm.

Viruses can cause cancer, so yes, there is some relationship. This is well known and fully accepted science.

But they don't as you put it, "behave in the same fashion." It's like saying a great white shark is a hemorrhage. There is a causal relationship in some instances, but they are very different things.

ModestGamer
07-05-2010, 05:33 PM
Viruses can cause cancer, so yes, there is some relationship. This is well known and fully accepted science.

But they don't as you put it, "behave in the same fashion." It's like saying a great white shark is a hemorrhage. There is a causal relationship in some instances, but they are very different things.


without all the menusha.

define in as few words as possiable the behavior of

a virus

and a cancer

Gibsons
07-05-2010, 06:45 PM
without all the menusha.

define in as few words as possiable the behavior of

a virus

and a cancer

I hesitate to say either "behaves."

Virus: Infectious, filterable particle.

Cancer: Non infectious, unregulated growth of host cells.

beginner99
07-06-2010, 07:57 AM
Thanx you so much for explianing what I was trying to get at.

When you get a vaccine fo say measales. We are giving Measales to the person being vaccinated. givin that the virus is genetically altered it no longer represents the actual virus in the wild. Ergo the vaccine will not be effective.

BTW getting the mseaes is a 100% effective guarentee against reinfection. Given the data on the measales vaccine that I have seen on and off over the years. the vaccine does not work with modern strains.

Also measales just isn't that bad. Really no worse then chicken pox excpet for the high fever. Which if left alone poses no significant threat. Mot of the complications with measales are cuaed by overly aggresive treatment altering the normal path of the bodys immune response.

Yes they do.

Next time you open your yapper consider that some people are completley clueless like me but don't know it.



fixed.

Please select one or more answers:

[] Troll
[] religious/ anti-vaccination fanatic
[x] no clue what he is talking about

ModestGamer
07-06-2010, 10:14 AM
I am a raving idtiot




Please select one or more answers:

[] Incapable of critical thinking
[] Sheep
[x] fialed biology 101 in high school

ModestGamer
07-06-2010, 10:18 AM
I hesitate to say either "behaves."

Virus: Infectious, filterable particle.

Cancer: Non infectious, unregulated growth of host cells.

Well behavior is the hall mark of diagnosis.

Funny you call a virus a particle. Which it is not. usually it comes over in a cell nasal,oral etc as a host and the virus itself is the equivalent of a hacker. It hacks the host cell and alters the host cells behavior by changing the dna of the host cell.

Are cancers non infectious ? I would disagree with that statement. Provided with food and nutrition and they will infect the host and grow without purpose.

The only purpose either virus's or cancer have is continued reproduction.

So the behavior is the same.

Work from there how they might be interelated.

Gibsons
07-06-2010, 11:19 AM
Well behavior is the hall mark of diagnosis.

Funny you call a virus a particle. Which it is not. usually it comes over in a cell nasal,oral etc as a host and the virus itself is the equivalent of a hacker. It hacks the host cell and alters the host cells behavior by changing the dna of the host cell.

Are cancers non infectious ? I would disagree with that statement. Provided with food and nutrition and they will infect the host and grow without purpose.

The only purpose either virus's or cancer have is continued reproduction.

So the behavior is the same.

Work from there how they might be interelated.

Wrong, wrong, sort of right, wrong, and you don't know what infectious means.

ModestGamer
07-06-2010, 12:05 PM
Wrong, wrong, sort of right, wrong, and you don't know what infectious means.


A virus is not infectious either. It simply has a medium of transmission.

beginner99
07-06-2010, 12:22 PM
Wrong, wrong, sort of right, wrong, and you don't know what infectious means.

he is a troll. also trolling in most L&R Threads. just look at his post. -> ignore

ModestGamer
07-06-2010, 12:30 PM
he is a troll. also trolling in most L&R Threads. just look at his post. -> ignore


I just like fucking with ignorant people. There is a massive amount of ignorance and fial here.

Mr. Pedantic
07-06-2010, 02:32 PM
Love this thread. There are already so many medical misconceptions I've moved on from the facepalm now to just amused exasperation.

William Gaatjes
07-08-2010, 04:06 AM
Time to raise the level of information of this polluted thread :


http://www.physorg.com/news197731732.html

Now scientists have found that the vitamin D receptor is a key player amid the gut bacteria - what scientists refer to matter-of-factly as the "gut flora" - helping to govern their activity, responding to their cues, and sometimes countering their presence. The work was published online recently in the American Journal of Pathology.

The findings deliver a new lead to scientists investigating how bacteria might play a role in the development of inflammatory bowel diseases such as Crohn's disease or ulceractive colitis. The work complements studies suggesting that Salmonella infection can increase the risk of inflammatory bowel disease.

"Vitamin D deficiency is a known factor in the pathology of inflammatory bowel disease and colon cancer," said microbiologist Jun Sun, Ph.D., of the University of Rochester Medical Center, "but there have been very few reports about how bacteria might play a role by targeting the vitamin D receptor. Our work suggests one possible mechanism, by working through the vitamin D receptor, a sensor and regulator for the majority of functions of vitamin D."

Sun specializes in the actions of bacteria in the body and how their interactions within the body contribute to disease. She has shown that bacteria often found in the human intestine affect molecular signals known to contribute to inflammatory response and cell growth.

Her work with the vitamin D receptor takes place at a time when the molecule is coming under increasing scrutiny. Scientists have associated vitamin D and the receptor with many types of cancer, as well as osteoporosis, heart disease, diabetes, inflammatory bowel disease, and infection.

Sun's team took a close look at the vitamin D receptor in mice and its interactions with bacteria in the colon. The team studied normal mice; mice in which the vitamin D receptor had been knocked out; and mice that were completely free of any germs. Scientists observed how the mice responded to infection with either a harmless strain of E. coli or a pathogenic strain of Salmonella Typhimurium.


The team found that Salmonella is able to regulate the vitamin D receptor, increasing its activity and determining where in the colon the receptor is active. In the presence of Salmonella, the receptor was more prevalent than usual deep within folded intestinal structures known as crypts.

Sun's team also discovered that the vitamin D receptor plays a key role in defending the body from assault by Salmonella and squelching inflammation. The receptor stops a molecule known as NF-Kappa B, a well-known master player in the world of inflammation, by binding to it and preventing it from activating other inflammatory molecules. While scientists have known that the receptor interacts with NF-Kappa B, details of the interaction modulated by bacteria in the colon are new.

The scientists found that Salmonella was much more virulent and aggressive in mice in which the vitamin D receptor had been turned off. These mice showed higher levels of activity of inflammatory molecules, and they lost weight more quickly and were much more likely to die in response to infection.

"We live together in a mutually beneficial state with most of the bacteria in our gut," said Sun, assistant professor in the Gastroenterology and Hepatology Division of the Department of Medicine. "They help us digest foods like fruits and vegetables, and we provide them a place to live and thrive. We co-exist peacefully - most of the time.

"But we aren't able to culture most of these bacteria in the laboratory, and we don't know what most of them are doing. We need to understand our gut flora much more than we do. This is particularly important for understanding how we might manipulate the natural gut flora to stop an invader like Salmonella," added Sun, who also has appointments in the James P. Wilmot Cancer Center and the Department of Microbiology and Immunology.


About Salmonella :

Salmonella (S.) is the genus name for a large number (over 2,500) of types of bacteria. Each type is distinctly identifiable by its specific protein coating. The types are otherwise closely related. Salmonella bacteria are rod-shaped, flagellated, Gram stain-negative, and are known to cause disease in humans, animals, and birds (especially poultry) worldwide.

The terminology that identifies the particular protein coats, or serovars, is not well settled, and what previously were thought to be various species of the genus Salmonella are now thought to be serovars of only two species by many researchers, S. enterica and S. bongori. However, these designations are not always accepted in the scientific literature and so common serovars that have been named in the past are still used (for example, S. typhi, S. typhimurium, S. enteritidis, S. cholerasuis, S. saintpaul). The serovars are identified by the Kauffman-White classification that uses two major types of antigens (somatic O and flagellar H) to distinguish the over 2,500 types of Salmonella bacteria. Sometimes laboratories or other reporting agencies identify isolates simply as Salmonella spp (species) and do not identify the serovars.

William Gaatjes
07-08-2010, 04:16 AM
Autoimmune diseases are among the most heavily studied and poorest understood things I can think of.

As Mr. Pedantic said, there are mechanisms that eliminate self reactive lymphocytes during the maturation process. But these mechanisms aren't perfect. You can find self reactive lymphocytes in most individuals, but they are usually quiescent (anergic is the proper term).

In some cases, what seems to happen is that something triggers them out of their unreactive state. It might be a failure of the mechanism that supposed to suppress them (genetic or maybe something else), it might be a disease, or whatever.

There's an enormous amount of literature on autoimmunity, but very few clear answers, even in the case of what seem to be clear cut genetic problems.

I was thinking about what you have written and had to think about the diabetes 1 my colleague has. He is on holiday for a few weeks and as such i can not confirm until then.

Another possibility is that a dormant virus infection is the cause. (doh, diabetes 1...)
For some reason the virus becomes active after a while or periodically.

Maybe parts of that virus where the immune system responds too have become a part of those cells meaning that expression takes place where parts of the virus where antigens lock on too are created. Maybe the complete virus is not expressed but parts of proteins are. If these proteins would be recognized as hostile by the immune system, then the immune system would start to attack those cells and protein structures.

Another possibility may be that in the process of a virus infection a protein is created that looks like a protein used in the human body in an entirely different part of the human body. As such, one could acquire an auto immune disease. I do not think that auto immune diseases are all a defect in genetic code. That would be to perfect and clean. Nature does not work with closely guarded boundaries.

William Gaatjes
07-08-2010, 07:30 AM
Research in multiple sclerosis :

http://www.sciencedaily.com/releases/2010/06/100611093613.htm

A virus infection can incite the body to attack its own nerve tissue by activating unusual, disease-fighting cells with receptors for both viral and nerve proteins. The dual-receptor observation suggests a way brain and spinal cord nerve damage might be triggered in susceptible young adults afflicted with multiple sclerosis (MS).

University of Washington Department of Immunology scientists Qingyong "John" Ji, Antoine Perchellet, and Joan M. Goverman conducted the study, which was published June 6 in Nature Immunology.

This is thought to be the first study to reveal a mechanism for autoimmune disease that depends on destroyer immune cells expressing dual receptors for a normal protein made by the body and a pathogen.

Multiple sclerosis is one of many autoimmune disorders in which the body's lines of defense become misguided and start damaging normal tissue. In the case of multiple sclerosis, the protective sheath around major nerves -- the myelin -- in the brain and spinal cord disintegrates. Like a frayed electrical cord, the nerves no longer transmit a clear signal.

People with multiple sclerosis might lose their ability to see, walk, or use their arms, depending on which nerves are affected. The symptoms can appear, disappear, and re-appear. The disease is more common in women than in men.

In healthy people, the immune system is kept in check to tolerate the usual proteins and cells in the body, much like an eager watch dog is put on a leash and trained to ignore friends and neighbors, yet still protect the family.

"Autoimmunity is believed to arise from an accidental breakdown in this tolerance of the body's own proteins. This breakdown is triggered by something in the environment, most likely a pathogen," noted Goverman, professor and acting chair of immunology whose research concentrates on the origins of autoimmune disease. Her lab is studying mechanisms that maintain tolerance, as well as the "tripping" mechanisms that defeat it.

In their most recently published study, her research team genetically engineered mice that over-produce a certain type of white blood cell from a group known as killer T cells. The normal function of killer cells is to attack tumor cells or cells infected with viruses or other pathogens. These T cells have receptors that recognize specific proteins that infected cells display to them, much like holding up a target in a window.

The specific killer T cells examined in this study were CD8+ T cells. The Goverman lab engineered mice to over-produce CD8+cells that recognized myelin basic protein, a predominant protein in the myelin sheath that covers nerves. The major question investigated in the study was whether the genetically engineered mice would exhibit a disease that resembled multiple sclerosis.

The researchers infected the mice with a virus that has itself been engineered to produce myelin basic protein. This infection should activate the CD8+T cells to first attack the virally infected cells making myelin basic protein to eliminate the virus, then kill other cells that make myelin basic protein to wrap around nerves. Killing those cells would destroy the myelin sheath.

As expected, the mice developed a multiple sclerosis-like disease. But the researchers were surprised when viruses lacking the myelin basic protein also triggered the disease.

Additional cross-breeding experiments revealed the existence of two receptors on a few of the CD8+T cells. These cells, engineered specifically to bind to myelin basic protein, also built their own receptors for viruses, and could recognize both. When exposed to cells infected with viruses, they would bind to and destroy them using one receptor. Geared up as if they were beserk, some of these double-agent cells then would head elsewhere to bind their other receptor to cells producing myelin basic protein and ruin the coats on nerve cells.

"These results," the authors noted, "demonstrate a role for dual-receptor cells in autoimmunity." The study also points to why a ubiquitous viral infection could leave most people without any lasting effects, but trigger autoimmunity in genetically predisposed individuals.

The findings open a new perspective on the proposal that multiple sclerosis is virally induced, despite the inability to detect infectious virus in the central nervous system of multiple sclerosis patients. Data from other studies show that CD8+T cells can cross the blood-brain barrier, and also that multiple sclerosis patients have more central nervous system protein-specific CD8+T cells, compared to healthy people.

In the dual-receptor model, the autoimmune activity against nerve protein can continue after the virus is wiped out. Multiple sclerosis patients usually have high levels of antibodies indicating past infectious from several common viruses, but a live virus associated with multiple sclerosis has not been consistently observed. Therefore, to date, no specific virus has been confirmed as a causative agent for multiple sclerosis.

The authors explained that it's possible that multiple viruses could influence susceptibility to multiple sclerosis. The ability of any particular virus to contribute to the disease could depend on an individual's own repertoire of other predisposing genes, exposure to other predisposing environmental factors, and the random chance that T cells had been generated that recognize a myelin protein and a pathogen.

Receptors on T cells are randomly generated during their development. This observation helps explain why multiple sclerosis is partly a matter of chance. Some people with a genetic predisposition and environmental exposure develop the disease, while others with similar genetic predisposition and environmental exposure do not.

It's uncertain how common these dual-receptor T cells are, according to the researchers, although there are reports that up to one-third of human T cells express dual receptors. Goverman and her group plan to test samples from multiple sclerosis patients and see how many have dual-receptor T-cells.

A grant from the National Institutes of Health supported the study.


There also seems to be a link between multiple sclerosis and HPV or human papillomavirus. Also between multiple sclerosis and the herpes viruses family.
multiple sclerosis is an autoimmune disease where the immune system attacks the myelin sheath of nerves from the nervous system. All these diseases are sexually transmitted diseases and can cause no harm according to the medical world. But it is admitted that at least the HPV virus can cause cancer. And the link between multiple sclerosis and herpes is not clear but it seems the virus uses the nerves as a means of transport and that this virus hides out in groups of neurons called ganglia ? This seems to much of an coincidence. Although i do admit that there must be more variables and genetic disposition can be one of them.

Herpes viruses in neurons and link between myelin sheets and herpes simplex 1:
http://www.springerlink.com/content/1g3kx6m7mk82eh7h/

This study presents the first direct evidence for herpes simplex virus type 1 (HSV-1) infection in the neurons of the vestibular ganglion. Although many investigators have reported electron microscopic evidence of HSV-1 infection in sensory ganglia, HSV-1 infection in the vestibular ganglion has not been described. Vestibular ganglion neurons have a unique structure, with a loose myelin sheath instead of the satellite cell sheath that is seen in other ganglia. This loose myelin is slightly different from compact myelin which is known as too tight for HSV-1 to penetrate. The role of loose myelin in terms of HSV-1 infection is completely unknown. Therefore, in an attempt to evaluate the role of loose myelin in HSV-1 infection, we looked for HSV-1 particles, or any effects mediated by HSV-1, in the vestibular ganglion as compared with the geniculate ganglion. At the light microscopic level, some neurons with vacuolar changes were observed, mainly in the distal portion of the vestibular ganglion where the communicating branch from the geniculate ganglion enters. At the electron microscopic level, vacuoles, dilated rough endoplasmic reticulum and Golgi vesicles occupied by virus were observed in both ganglia neurons. In contrast, viral infections in Schwann and satellite cells were observed only in the geniculate ganglion, but not in the vestibular ganglion. These results suggest that loose myelin is an important barrier to HSV-1 infection, and it must play an important role in the prevention of viral spread from infected neurons to other cells.

About multiple sclerosis :
http://www.mult-sclerosis.org/howms.html

EDIT:
Forgot this quote :

During periods of multiple sclerosis activity, white blood cells (leukocytes) are drawn to regions of the white matter. These initiate and take part in what is known as the inflammatory response. The resulting inflammation is similar to what happens in your skin when you get a pimple.

During the inflammation, the myelin gets stripped from the axons in a process known as demyelination. The effect of this bears many parallels to the rubber insulation on wire perishing - some or all of the electricity in the wire will short out and the efficient conductivity of the wire will be reduced. When the myelin sheath is damaged, the transmission of nerve impulses is slowed, stopped or can jump across into other demyelinated axons.

Additionally, the inflammation can also damage the underlying axonal membrane. This membrane is a sophisticated structure that enables the nerve transmission (the action potential) to travel along the nerve.

It seems that the inflammation also kills the mainenance glial cells, in particular it seems to kill the myelin-producing oligodendrocytes, which are lost in great numbers. Almost no oligodendrocytes persist in the middle of chronic MS lesions.

At least, this has been the prevailing theory for the past few years. Now, however, several pieces of experimental work have produced results which challenge this model. Inflammation and oligodendrocyte loss are both found together in multiple sclerosis but which comes first? Does inflammation cause oligodendrocyte death, does oligodendrocyte death cause inflammation or are they both caused by a third process, perhaps a virus?

Recent research has looked at the brains of people who have died in the very early stages of MS lesion development and found that oligodendrocyte death actually precedes inflammation [Prineas et al, 2004]. It must be emphasised that these are the results of a very small study which have not yet been reproduced. Although few would deny that the inflammation contributes to MS damage, this work has the potential to turn the world of MS research upside-down. It suggests that looking for an autoimmune cause for MS may be misguided. It also challenges the current anti-inflammatory focus of most MS therapies. Are we, by analogy, treating a broken pipe by sticking a bucket under it rather than fixing the leak? That's not to say that these therapies don't produce results, just that tackling inflammation may not be the optimal stategy. For people with MS, this is a space to watch eagery.


http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T06-485RN87-GT&_user=10&_coverDate=10%2F31%2F1979&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=48471944c5c7e543924f460c9c19e1ae

Mice were inoculated with herpes simplex virus (HSV) type 1 by gently scraping the skin of the nose with a fine needle. About 80% of the animals developed latent inapparent HSV infections in trigeminal ganglia. Virus was demonstrable for at least 6 months post inoculation (p.i.) by cocultivation of ganglionic tissue with GMK cells. Histologically, trigeminal ganglia revealed infiltrations of inflammatory cells even 6 months p.i. In addition, lesions occurred in the brainstem corresponding to the entry of trigeminal roots, trigeminal tracts and nuclei. Inflammatory cell infiltration, disruption of myelin sheaths and macrophages laden with myelin degradation products were observed 7 days p.i. Fourteen to 30 days p.i. electron microscopy demonstrated completely naked axons. In the transitional region of the trigeminal root denuded axons occurred in the central part of the region while the peripheral myelin, bordering the demyelinated central segments, was intact. Small areas of demyelination were still detectable 3 and 6 months p.i. but there were then also signs of remyelination. Possible mechanisms causing the demyelination are discussed.

William Gaatjes
07-08-2010, 07:47 AM
To support modestgamer with his claim that vaccinations can be a serious risk :

It seems some people acquired an autoimmune disease similar to multiple sclerosis after an HPV vaccination in Australia. The Gardasil vaccin is used to prevent a possible cancer of the cervix or other parts of the female reproductive system.
http://www.tga.gov.au/alerts/medicines/gardasil.htm

The TGA is also aware of a small number of cases in which neurological symptoms, similar to those experienced in patients with a demyelinating disorder such as multiple sclerosis, have been reported shortly after HPV vaccination. In some of these cases symptoms were present prior to the vaccination. These reports have been actively investigated by an independent panel of clinical and scientific experts in immunology, neurology, epidemiology and paediatrics. Based on the available reported cases, the incidence of demyelinating disorders amongst recipients of Gardasil is not demonstrably higher than would be expected to occur by chance.
I do not feel comfortable with the results.


How are vaccines made today ?
Are there still animals used or are there cultured cells used as in for example petri dishes ?

Gibsons
07-08-2010, 08:11 AM
Another possibility may be that in the process of a virus infection a protein is created that looks like a protein used in the human body in an entirely different part of the human body. As such, one could acquire an auto immune disease. I do not think that auto immune diseases are all a defect in genetic code. That would be to perfect and clean. Nature does not work with closely guarded boundaries.

What you're referring to is called mimicry. Seems to happen with Strep, or at least that's the theory (google rheumatic fever). Probably some other cases out there but not so well understood. I'd guess they're very rare though.

As I said before, there are definitely genetic/inherited components to some autoimmune diseases as well as some environmental contributions. For some really odd stuff, look at the geographic associations (37th parallel) with Multiple Sclerosis.

William Gaatjes
07-08-2010, 08:27 AM
What you're referring to is called mimicry. Seems to happen with Strep, or at least that's the theory (google rheumatic fever). Probably some other cases out there but not so well understood. I'd guess they're very rare though.


Interesting : mimicry, also known as cross reactivity. I have not fully read or understood the mechanism. But that does seem to worry me. I think research to find out how the immune system can be strengthened and partially reset on a certain group of antibodies or antigens if necessary will be a very good advancement.


As I said before, there are definitely genetic/inherited components to some autoimmune diseases as well as some environmental contributions. For some really odd stuff, look at the geographic associations (37th parallel) with Multiple Sclerosis.

I did, but what i read, is that everything can be blamed.
Metals in the soil to low radioactivity to low hygiene in houses.

This could however be once again a combination problem. Heavy metals or chemicals or radiation would weaken the immune system. Then the virus would be able to do it's damage more easy and in the end multiple sclerosis as a result. Maybe even more variables have to be met though. Multiple infections with different viruses perhaps or bacteria... Past events from infections.

EDIT:
However, if the soil has a certain chemical or elemental composition, then it must also have a certain bacterial composition and a certain virus composition.

Gibsons
07-08-2010, 06:39 PM
To support modestgamer with his claim that vaccinations can be a serious risk :

You're better off ignoring modestgamer if you want to understand anything. He's either a drooling moron or a very persistent troll.

I suspect the article you're linking is referring to Guillain Barre syndrome. Chances of it occurring are about one in a million. Vaccination might raise that chance slightly, and a viral infection might raise it as well.

The rest of what you're talking about is just too speculative to specifically discuss. Yes, it could be this or that, and we also could be in the matrix.

Mr. Pedantic
07-08-2010, 08:20 PM
I do not feel comfortable with the results.
Did you read your own exerpt? "Based on the available reported cases, the incidence of demyelinating disorders amongst recipients of Gardasil is not demonstrably higher than would be expected to occur by chance."

How are vaccines made today ?
Are there still animals used or are there cultured cells used as in for example petri dishes ?
The nucleic acid coding for surface proteins (or any other antigen that can be used by the immune system to identify the virus) is extracted from the virus and reinserted into another, attenuated virus - one with all virulence factors removed, or one cultured to infect at above or below body temperature, etc.

tcsenter
07-08-2010, 08:23 PM
I suspect the article you're linking is referring to Guillain Barre syndrome. Chances of it occurring are about one in a million. Vaccination might raise that chance slightly, and a viral infection might raise it as well. Its about one in 1000 for persons who have a bout of Campylobacteriosis. Campylobacter is one of the most common (often cited as THE most common) types of food poisoning or causes of invasive diarrhea (in the developed world).

William Gaatjes
07-09-2010, 05:30 AM
You're better off ignoring modestgamer if you want to understand anything. He's either a drooling moron or a very persistent troll.

I suspect the article you're linking is referring to Guillain Barre syndrome. Chances of it occurring are about one in a million. Vaccination might raise that chance slightly, and a viral infection might raise it as well.

The rest of what you're talking about is just too speculative to specifically discuss. Yes, it could be this or that, and we also could be in the matrix.

I wil look it up, thank you.

Babylonical translation errors are the burden of human society.
I do not agree with that cancer is an virus.
But i understand what he is trying to write about vaccination.
However, i personally think contamination of vaccination serums is the real problem.


EDIT:

The rest of what you're talking about is just too speculative to specifically discuss. Yes, it could be this or that, and we also could be in the matrix.

Well, then you have a future for you. ^_^
Don't be silly. The matrix... That is the most worst idea to generate electricity i have ever seen.

William Gaatjes
07-09-2010, 05:35 AM
Did you read your own exerpt? "Based on the available reported cases, the incidence of demyelinating disorders amongst recipients of Gardasil is not demonstrably higher than would be expected to occur by chance."


Afcourse i read it.
I did. But i do not always like the results of data massage. When smoothing the unknown, there might be something hidden as well.
When somebody tells me that it is statistical insignificant, what he or she is actually meaning that he/she does not know. I am difficult sometimes i know.



The nucleic acid coding for surface proteins (or any other antigen that can be used by the immune system to identify the virus) is extracted from the virus and reinserted into another, attenuated virus - one with all virulence factors removed, or one cultured to infect at above or below body temperature, etc.

That is interesting. But in what are the weakened viruses with desired antigen injected to, to make more copies ? Bacteria ? Animals ? Special cultured human cells ?

Mr. Pedantic
07-09-2010, 05:59 AM
Afcourse i read it.
I did. But i do not always like the results of data massage. When smoothing the unknown, there might be something hidden as well.
When somebody tells me that it is statistical insignificant, what he or she is actually meaning that he/she does not know. I am difficult sometimes i know.
It does not mean he/she does not know. It means that the results are sufficiently similar that given the experimental error involved it is likely that any differences are due to chance. There is a difference. An important difference.

That is interesting. But in what are the weakened viruses with desired antigen injected to, to make more copies ? Bacteria ? Animals ? Special cultured human cells ?
Chicken embryos, as far as I'm aware. This is expensive, since 1 embryo provides roughly 3 doses of vaccine, so something else is probably used now.

Gibsons
07-09-2010, 08:12 AM
That is interesting. But in what are the weakened viruses with desired antigen injected to, to make more copies ? Bacteria ? Animals ? Special cultured human cells ?


Okay, I guess I'll try to clear this up.

Vaccines can be divided into two categories, passive and active. We're talking about active vaccines in this case.

Active vaccines can be divided further into two categories, generally called attenuated and inactivated.

An inactivated vaccine is denatured (sometimes called "killed" although a virus isn't technically alive by some standards). The common flu vaccine is this kind. Virus is grown up in chick embryos, then denatured. The viral proteins are then injected into the vaccinee. The immune response to this is usually solely antibody based, specifically serum IgG. This isn't the strongest immune response around, but for some diseases it's enough. The failure rates from this approach can be pretty high, but they're generally safe.

An attenuated vaccine is one where the vaccine agent is 'alive' or capable of infecting, maybe even reproducing. The classic example of this is the cowpox-chickenpox story. The cowpox and smallpox viruses are closely related, so an immune reaction against one is effective against the other. When cowpox infects a human, it's a very mild disease, zero percent mortality assuming a normal immune system. But the immune response against it is extremely effective against smallpox. Smallpox has a ~30% mortality rate. Attenuated vaccines tend to be more effective than inactivated, they raise different 'arms' of the immune response as well as the serum IgG response, usually a much better memory response.

Nature isn't always kind enough to provide us with a closely related animal version of a particular virus however, so we have to attenuate it ourselves. This usually means growing it at a lower temperature, and maybe in other animal cells for several generations. Basically, you let evolution take its course and the virus adapts to the new cells and temperature, such that when it is later introduced into humans at a higher temperature, it's no longer pathogenic. Can't use it in the immunocompromised, and there's some chance that it can revert to pathogenic. So, it's more effective, but less safe.

We are getting much more sophisticated now though. Different variations on this approach with hybrid viruses, single cycle viruses etc are being tested and show some promise against some previously intractable diseases. DNA vaccines are another matter. DC vaccinations might be the best approach of all but they're too expensive for widespread use.

Regarding my matrix comment - yes, humans as living batteries is a very dumb idea. But are we all a computer simulation? It's an interesting question. link (http://www.simulation-argument.com/) As with your more speculative ideas - yes it's possible, but so are lots of things that aren't worth worrying about.

William Gaatjes
07-09-2010, 11:33 AM
Okay, I guess I'll try to clear this up.

Vaccines can be divided into two categories, passive and active. We're talking about active vaccines in this case.

Active vaccines can be divided further into two categories, generally called attenuated and inactivated.

An inactivated vaccine is denatured (sometimes called "killed" although a virus isn't technically alive by some standards). The common flu vaccine is this kind. Virus is grown up in chick embryos, then denatured. The viral proteins are then injected into the vaccinee. The immune response to this is usually solely antibody based, specifically serum IgG. This isn't the strongest immune response around, but for some diseases it's enough. The failure rates from this approach can be pretty high, but they're generally safe.

An attenuated vaccine is one where the vaccine agent is 'alive' or capable of infecting, maybe even reproducing. The classic example of this is the cowpox-chickenpox story. The cowpox and smallpox viruses are closely related, so an immune reaction against one is effective against the other. When cowpox infects a human, it's a very mild disease, zero percent mortality assuming a normal immune system. But the immune response against it is extremely effective against smallpox. Smallpox has a ~30% mortality rate. Attenuated vaccines tend to be more effective than inactivated, they raise different 'arms' of the immune response as well as the serum IgG response, usually a much better memory response.

Nature isn't always kind enough to provide us with a closely related animal version of a particular virus however, so we have to attenuate it ourselves. This usually means growing it at a lower temperature, and maybe in other animal cells for several generations. Basically, you let evolution take its course and the virus adapts to the new cells and temperature, such that when it is later introduced into humans at a higher temperature, it's no longer pathogenic. Can't use it in the immunocompromised, and there's some chance that it can revert to pathogenic. So, it's more effective, but less safe.

We are getting much more sophisticated now though. Different variations on this approach with hybrid viruses, single cycle viruses etc are being tested and show some promise against some previously intractable diseases. DNA vaccines are another matter. DC vaccinations might be the best approach of all but they're too expensive for widespread use.

Regarding my matrix comment - yes, humans as living batteries is a very dumb idea. But are we all a computer simulation? It's an interesting question. link (http://www.simulation-argument.com/) As with your more speculative ideas - yes it's possible, but so are lots of things that aren't worth worrying about.

Well, i for large part know about this in a rudimentary, but i a have some questions anyway.
I was interested in the chicken embryos, are these grown/born in a sterile environment or is the vaccine a combination of the inactivated virus and other viruses naturally present in the chicken ?
Denatured, does that mean process the alive viruses with formaldehyde ?


An attenuated virus, that sound like let it adapt to another host or another species. Then use that same virus to infect humans. I am interested in the hosts for the same reason that no animal is possibly free of viruses. Because this reminds of the poliovirus accident from the 1960s.
We both would agree sterile hosts are needed, yes ?

You mention temperature. Why is temperature so important to viruses ? I know that an increase in temperature speeds up chemical reactions. Must i see it in that direction ?

Gibsons
07-09-2010, 12:02 PM
Well, i for large part know about this in a rudimentary, but i a have some questions anyway.
I was interested in the chicken embryos, are these grown/born in a sterile environment or is the vaccine a combination of the inactivated virus and other viruses naturally present in the chicken ?
Denatured, does that mean process the alive viruses with formaldehyde ?


An attenuated virus, that sound like let it adapt to another host or another species. Then use that same virus to infect humans. I am interested in the hosts for the same reason that no animal is possibly free of viruses. Because this reminds of the poliovirus accident from the 1960s.
We both would agree sterile hosts are needed, yes ?

You mention temperature. Why is temperature so important to viruses ? I know that an increase in temperature speeds up chemical reactions. Must i see it in that direction ?

Chicken embryos = eggs, more or less. They grow the virus, purify it, then heat+formaldehyde denature it. Other viruses aren't a big concern with chicken eggs (not saying it should be ignored however). But, the heat and formaldehyde, if properly done, will denature any virus, so there's not much issue with another virus anyway. No real concerns with 'bits of RNA and DNA' here either since formaldehyde was used.

dunno exactly what you mean by a "sterile" host. That's hard to quantify when you get concerns with endogenous viruses. The attenuated polio vaccine is/has been grown in monkey cells. Some other virus running around there is a possibility. Need to be very careful in choosing host cells, for sure. And, you can learn a bit from testing the vaccine in the right animal host. Finally, if there is some other virus in there, it should be specific for the other animal, but of course you can't be certain of that.

Temperature is important because you can grow the virus at a low temperature for many generations. This will allow the whole viral population to accumulate temperature-sensitive mutations. i.e. the mutated gene now encodes a protein that works fine at 30C, but at an elevated temperature (37C) it tends to misfold and function poorly or not at all. Thus the virus has a very difficult time reproducing in a human host. With the attenuated version of the influenza vaccine, it can mean that it reproduces in the nasal passages, but not deeper in the respiratory tract.

William Gaatjes
07-09-2010, 12:50 PM
Chicken embryos = eggs, more or less. They grow the virus, purify it, then heat+formaldehyde denature it. Other viruses aren't a big concern with chicken eggs (not saying it should be ignored however). But, the heat and formaldehyde, if properly done, will denature any virus, so there's not much issue with another virus anyway. No real concerns with 'bits of RNA and DNA' here either since formaldehyde was used.

dunno exactly what you mean by a "sterile" host. That's hard to quantify when you get concerns with endogenous viruses. The attenuated polio vaccine is/has been grown in monkey cells. Some other virus running around there is a possibility. Need to be very careful in choosing host cells, for sure. And, you can learn a bit from testing the vaccine in the right animal host. Finally, if there is some other virus in there, it should be specific for the other animal, but of course you can't be certain of that.

Temperature is important because you can grow the virus at a low temperature for many generations. This will allow the whole viral population to accumulate temperature-sensitive mutations. i.e. the mutated gene now encodes a protein that works fine at 30C, but at an elevated temperature (37C) it tends to misfold and function poorly or not at all. Thus the virus has a very difficult time reproducing in a human host. With the attenuated version of the influenza vaccine, it can mean that it reproduces in the nasal passages, but not deeper in the respiratory tract.


Ah thank you.
The bold part i find very amazing. It is so obvious that i would not think about it. The temperature has effect on the folding. I learn every day something new. :)


I do worry about contamination though. I find it very likely that the human immune system has no problem with weakened viruses. But alive and kicking viruses from another species ? This would be creating a situation where a virus can jump between species. And that is not an impossible scenario, taking into account food habits, diseases, inoculation from contaminated vaccines, the environment, genetic make up. When taking epi-genetics into account, most of the above mentioned variables have an epi-genetic influence it seems, maybe even all of them. And i am sure that certain rules can be laid out that one can predict that a certain stimulus would cause a genetic mutation or epi - genetic change in a certain direction...:hmm:



I did some reading, and some people are worried about the use of formaldehyde. They claim this can have an effect when received in the blood through inoculation. But i find it hard to believe that a small amount could have such an effect on the immune system. I would think the heart especially would not be so happy about it. But then again, i am not a chemist or biologist. I do not know how much is needed for a serious effect. And there is a linkage between formaldehyde and food. If the people who got an inoculation also ate prepared food where high concentration of formaldehyde would be present, then this would seem that it is the inoculation responsible for the elevated levels of formaldehyde found in the body. It is once again all very complex.

Mr. Pedantic
07-09-2010, 03:50 PM
I do worry about contamination though. I find it very likely that the human immune system has no problem with weakened viruses. But alive and kicking viruses from another species ? This would be creating a situation where a virus can jump between species. And that is not an impossible scenario, taking into account food habits, diseases, inoculation from contaminated vaccines, the environment, genetic make up. When taking epi-genetics into account, most of the above mentioned variables have an epi-genetic influence it seems, maybe even all of them. And i am sure that certain rules can be laid out that one can predict that a certain stimulus would cause a genetic mutation or epi - genetic change in a certain direction...
It's what happens every time we get a flu 'outbreak'. Influenza A is mainly an avian virus, except we get outbreaks every couple of years when the NA and HG receptors mutate so that the virus can infect human cells. Of course, this is far more likely to happen if you are actively feeding the virus new material by packaging it in with a vaccine.

William Gaatjes
07-10-2010, 07:36 AM
It's what happens every time we get a flu 'outbreak'. Influenza A is mainly an avian virus, except we get outbreaks every couple of years when the NA and HG receptors mutate so that the virus can infect human cells. Of course, this is far more likely to happen if you are actively feeding the virus new material by packaging it in with a vaccine.

I know. But if the biological researchers are going to create a virus, i prefer they create one that is easily recognized and defeated by the human immune system. Maybe one day it will be possible to steer mutations towards a direction where it is easily to control the mutation of the virus. Viruses will mutate and recombine and some diseases will be the result. If it would be possible to create a means to steer the lethality from the virus into a direction where it is not as dangerous anymore. I have read in the past about that some advanced and expensive chemical cocktails do just that with HIV. HIV starts to mutate into a certain direction when the body is flood with certain chemicals.

I found what Gibson mentioned about viruses and temperature very interesting.

There is temperature (body temperature) that limits the amount of possible reactions.
There is a certain chemical make up.
If we know about the exact details how the recombination of DNA occurred, there might be a way to severely limit the amount of possible mutations. One can never fully rule out all options to one single candidate but still. Ruling out viruses or bacteria, forget it. It is not going to happen. But steer them in a way that they are non lethal and possibly even more beneficial then they already are. That is a good thing. Combine that with full control over the immune system with respect to alarming it or resetting it for a certain chemical. Most of the sickness that exist will no longer be present.

Grrr. I hate the low infrasonic sounds of helicopters. :mad:

Gibsons
07-10-2010, 08:11 AM
I know. But if the biological researchers are going to create a virus, i prefer they create one that is easily recognized and defeated by the human immune system. Maybe one day it will be possible to steer mutations towards a direction where it is easily to control the mutation of the virus. Viruses will mutate and recombine and some diseases will be the result. If it would be possible to create a means to steer the lethality from the virus into a direction where it is not as dangerous anymore. I have read in the past about that some advanced and expensive chemical cocktails do just that with HIV. HIV starts to mutate into a certain direction when the body is flood with certain chemicals.

I found what Gibson mentioned about viruses and temperature very interesting.

There is temperature (body temperature) that limits the amount of possible reactions.
There is a certain chemical make up.
If we know about the exact details how the recombination of DNA occurred, there might be a way to severely limit the amount of possible mutations. One can never fully rule out all options to one single candidate but still. Ruling out viruses or bacteria, forget it. It is not going to happen. But steer them in a way that they are non lethal and possibly even more beneficial then they already are. That is a good thing. Combine that with full control over the immune system with respect to alarming it or resetting it for a certain chemical. Most of the sickness that exist will no longer be present.

Grrr. I hate the low infrasonic sounds of helicopters. :mad:
There's no "steering" of mutations, not in the sense you're describing anyway. It's right next to impossible, even in theory, as long as you're talking about nucleic acid based reproduction.

There are some sophisticated approaches being developed right now. One idea is to take a harmless virus and engineer it to express a protein or three from your target virus. The immune reaction to this will target everything, and can be effective against the real thing. Look up RV 144. The idea I've always liked is DNA vaccines, they just haven't worked too well in the real world, at least not yet.

William Gaatjes
07-10-2010, 08:46 AM
There's no "steering" of mutations, not in the sense you're describing anyway. It's right next to impossible, even in theory, as long as you're talking about nucleic acid based reproduction.

There are some sophisticated approaches being developed right now. One idea is to take a harmless virus and engineer it to express a protein or three from your target virus. The immune reaction to this will target everything, and can be effective against the real thing. Look up RV 144. The idea I've always liked is DNA vaccines, they just haven't worked too well in the real world, at least not yet.

Ok, what are your thoughts then about what i mentioned about HIV and the cocktails ? According to research at the time the virus seemed to mutate to a certain direction depending on the composition of the chemical cocktail. This was not a petri dish experiment. But the results of an experiment with real life infected humans.

Gibsons
07-10-2010, 08:52 AM
Ok, what are your thoughts then about what i mentioned about HIV and the cocktails ? According to research at the time the virus seemed to mutate to a certain direction depending on the composition of the chemical cocktail. This was not a petri dish experiment. But the results of an experiment with real life infected humans.

HIV has a high mutation rate, and the mutations are mostly random. What happens with the drug treatments is you then get selection of those mutants that are resistant. Basic evolution.

William Gaatjes
07-10-2010, 09:28 AM
HIV has a high mutation rate, and the mutations are mostly random. What happens with the drug treatments is you then get selection of those mutants that are resistant. Basic evolution.

Exactly. And what they found out is that you can push evolution to make the virus mutate in such a way it becomes more sensitive to other chemicals in the next cocktail. The resistance for chemical A made the virus more sensitive for chemical B. where chemical B would kill or at least disable the virus.

Now here is my theory :
Afcourse when using chemical B, mutation starts the other way around. Now this was not clear about what i read then, but i would think myself that the virus would have become resistant to chemical B but once again became more sensitive for chemical A. Now if that is the case, which i am willing to bet it is (And i do not like to bet) There is a pattern to be found. And that pattern is hidden in what you mentioned with temperature and the chemical composition. The chemical composition itself is depend on what atoms are used and on the sequence of RNA/DNA and enzymes used. Now i do not know all the details but i think this can be the case. Now afcourse this would still mean there are a lot more variables to account for like simultaneous infections of other viruses. But i truly think something can be found here. If one could reduce the number of possible mutations from for example 1000.0000.0000 to 1000.000 (just a random number as an example). That means a lot in favour of the immune system.

Gibsons
07-10-2010, 10:37 AM
Exactly. And what they found out is that you can push evolution to make the virus mutate in such a way it becomes more sensitive to other chemicals in the next cocktail. The resistance for chemical A made the virus more sensitive for chemical B. where chemical B would kill or at least disable the virus.

link? something peer reviewed preferably? I think I know what's going on here, but it's still random, not directed, mutations.

William Gaatjes
07-10-2010, 11:36 AM
link? something peer reviewed preferably? I think I know what's going on here, but it's still random, not directed, mutations.

It was some news item in a science magazine a year or 3 ago.
I do not know if it was peer reviewed. I was hoping you would have something.
But that should not be a major concern since most ground breaking science is ridiculed at first every time.
Although it is possible that it was just chance.

I will see if i can google something about it from the web.

If i remember correctly it was something about that first drug that inhibited something with the RNA to DNA transcription ?
Later on the virus adapted. After that they found another chemical that worked but the virus adapted to that too. But it became sensitive again to the first drug.

I remember a bit more :
reverse transcriptase, protease AZT.
Integrase


Yahooo :
I found something similar i think :

http://www.ncbi.nlm.nih.gov/pubmed/7679778

Wild-type reverse transcriptase has evolved for the survival of human immunodeficiency virus type 1 (HIV-1) by natural selection. In contrast, therapy relying on inhibitors of reverse transcriptase by nucleosides like zidovudine (AZT) or dideoxyinosine (ddI), and by non-nucleosides like pyridinones or nevirapine, may exert different selection pressures on this enzyme. Therefore the acquisition of resistance to reverse transcriptase inhibitors by selection of mutations in the pol gene may require compromises in enzyme function that affect viral replication. As single mutations are unlikely to confer broad resistance when combinations of reverse transcriptase inhibitors are used, multiple mutations may occur that result in further compromises. Certain drug combinations may prevent the co-existence of adequate reverse transcription function and multi-drug resistance (MDR). Unlike bacterial or eukaryotic drug resistance, retroviral drug resistance is conferred only by mutations in its own genome and is limited by genome size. Combining drugs directed against the same essential viral protein may thus prevent HIV-1 MDR, whereas the conventional approach of targeting different HIV-1 proteins for combination therapy may not, because genomes with resistance mutations in different HIV-1 genes might recombine to develop MDR. Here we show that several mutations in the HIV-1 reverse transcriptase gene that confer resistance to inhibitors of this enzyme can attenuate viral replication. We tested whether combinations of mutations giving rise to single-agent resistance might further compromise or even abolish viral replication, and if multidrug-resistant viruses could be constructed. Certain combinations of mutations conferring resistance to AZT, ddI and pyridinone are incompatible with viral replication. These results indicate that evolutionary limitations exist to restrict development of MDR. Furthermore, a therapeutic strategy exploiting these limitations by using selected multidrug regimens directed against the same target may prevent development of MDR. This approach, which we call convergent combination therapy, eliminated HIV-1 replication and virus breakthrough in vitro, and may be applicable to other viral targets. Moreover, elimination of reverse transcription by convergent combination therapy may also limit MDR.

I found some more information but while reading this website i had to acknowledge this is where it ends for me. Perhaps you can make sense of it. It is to detailed and to warm outside for me to decode what they mean.


http://jvi.asm.org/cgi/content/full/79/18/11981

William Gaatjes
07-11-2010, 12:12 PM
Another example of how beneficial symbiosis with the right bacteria can be :

Now, in a paper to be published in the journal Science, University of Rochester biologist John Jaenike and colleagues document a clear example of a new mechanism for evolution. In previous well documented cases of evolution, traits that increase an animal's ability to survive and reproduce are conferred by favorable genes, which the animal passes on to its offspring. Jaenike's team has chronicled a striking example of a bacteria infecting an animal, giving the animal a reproductive advantage, and being passed from mother to children. This symbiotic relationship between host animal and bacteria gives the host animal a readymade defense against a hazard in its environment and thus has spread through the population by natural selection, the way a favorable gene would.

Jaenike provides the first substantial report of this effect in the wild in his paper "Adaptation via Symbiosis: Recent Spread of a Drosophila Defensive Symbiont," but he says it may be a common phenomenon that has been happening undetected in many different organisms for ages.

Aside from shedding light on an important evolutionary mechanism, his findings could aid in developing methods that use defensive bacteria to stave off diseases in humans.

Jaenike studied a species of fly, Drosophila neotestacea, which is rendered sterile by a parasitic worm called a nematode, one of the most abundant, diverse, and destructive parasites of plants and animals in the world. Nematodes invade female flies when they are young by burrowing through their skin and prevent them from producing eggs once they mature. However, when a female fly is also infected with a bacteria species called Spiroplasma, the nematodes grow poorly and no longer sterilize the flies, Jaenike found. He also discovered that, as a result of the Spiroplasma's beneficial impact, the bacteria have been spreading across North America and rapidly increasing in frequency in flies as they are passed from mother to offspring. Testing preserved flies from the early 1980s, Jaenike found that the helpful bacteria were present in only about 10% of flies in the eastern United States. By 2008, the frequency of Spiroplasma infection had jumped to about 80%.

"These flies were really getting clobbered by nematodes in the 1980s, and it's just remarkable to see how much better they are doing today. The spread of Spiroplasma makes me wonder how much rapid evolutionary action is going on beneath the surface of everything we see out there," Jaenike said.

He reasoned that the substantial increase in Spiroplasma infection was an evolutionary response to the recent colonization of North America by nematodes. As the nematodes invaded the continent, the bacteria proved to be a convenient and potent defense against the nematodes' sterilizing effect. Now, the majority of flies in eastern North America carry the bacteria, and the bacterial infection appears to be spreading west. Without any mutation in their own genes, the flies have rapidly developed a defense against an extremely harmful parasite simply by co-opting another organism and passing it on from generation to generation.

"This is a beautiful case showing that the main reason these Spiroplasma are present in these flies is for their defensive role," said Nancy Moran, the Fleming Professor of Ecology and Evolutionary Biology at Yale University. Moran studies the role of defensive symbionts in aphids. "These heritable symbionts are a way for an animal host to acquire a new defense very quickly. One way to get a truly novel defense is to get a whole organism rather than mutating your own genes that aren't that diverse to begin with."

Jaenike's work could also have implications for disease control. Nematodes carry and transmit severe human diseases, including river blindness and elephantiasis. By uncovering the first evidence of a natural, bacterial defense against nematodes, Jaenike's work could pave the way for novel methods of nematode control. He plans to investigate that prospect further.

Jaenike's coauthors on the paper are Robert Unckless and Lisa Boelio from the University of Rochester, and Steve Perlman and Sarah Cockburn from the University of Victoria in British Columbia. The work was funded by the National Science Foundation.

http://www.sciencedaily.com/releases/2010/07/100708141533.htm

William Gaatjes
07-11-2010, 12:19 PM
How to become protected against viruses if you are a single cell organism ?

http://www.sciencedaily.com/releases/2008/10/081026094351.htm



These results enable a clearer understanding of the origin of, and reasons for, sexual reproduction in eukaryotes (1).

The researchers studied the impact of marine viruses on Emiliania huxleyi, one of the most abundant unicellular eukaryotes in oceans that significantly influences the carbon cycle and climates. In their diploid form, i.e. when they contain a pair of chromosomes (2N), Emiliania huxleyi produce mineral scales and form gigantic populations that are visible from space. But when attacked by marine viruses, they transform into haploid cells which only contain a single chromosome (N). These new, non-calcifying, highly motile cells are totally invisible to viruses (and undetectable on satellite photos) so that the species can live in peace to await safer times.

These scientists have called this the "Cheshire Cat" strategy, in homage to Lewis Carroll's novel " Alice in Wonderland". In this book, the crafty and philosophical Cheshire Cat escapes being beheaded on the order of the Red Queen by rendering his body transparent. In the same way, by changing their form during the haploid phase, eukaryotes can evade biotic pressure and reinvent themselves within their own species.

Our ancestors, unicellular eukaryotes, appeared in oceans some one billion years ago and "invented" sexuality. These species are characterized by a life cycle where haploid individuals (carrying a single copy of the genome, like gametes(2)) unify to form diploid individuals that will subsequently generate haploid cells once again. During this eukaryote "double life", humans and other multicellular eukaryotes whose haploid gametes remain imprisoned within a diploid body, tend to be the exception. Originally, and in most eukaryotes, haploid cells multiply in their environment to form independent populations. Sexuality has allowed eukaryotes to evade constant attacks by viruses so that they could evolve towards more complex, high-performance organisms, the ecological importance of which is still markedly underestimated.

Notes:

1) Cells where genetic material is preserved within a nucleus

2) Reproductive cells

The bolded part is interesting for climate research. What happens when the water gets colder or warmer ?


EDIT:

These cells have an impact on the carbon cycle with respect to the sea it seems.

I wonder if pollution could force these cells into their haploid cell state.
Or if pollution would make it easier for the viruses to infect these organisms called Emiliania huxleyi.

Gibsons
07-12-2010, 07:57 AM
I found something similar i think :
http://www.ncbi.nlm.nih.gov/pubmed/7679778

The idea here is about what happens during antibiotic selection. A particular target of an antibiotic (in this case reverse transcriptase, RT) acquires mutations and in many cases a single point mutation renders the target resistant to the antibiotic, but still functional. it might not work quite as well as the the wild type enzyme, but it works well enough to get the job done.

You can then work at least two ways from there. 1. Treat (preferably at the same time) with a second drug that works by binding a different site on the enzyme. The enzyme now needs a second mutation in order to be resistant to both drugs. Also, the enzyme with two mutations might be even less efficient than the one mutation version. HAART therapy works along this strategy. It's usually a cocktail that includes two RT inhibitors and they bind at different sites on the enzyme. It's not so much the idea of 'making the enzyme less efficient,' it's that finding a virus with both mutations is less likely than finding a virus with either one. Thus at least one drug is effective against every virus in an infected person. (for the nit pickers - yes, HAART usually includes a protease inhibitor as well)

2. Treat with a second drug that's designed to be effective against the most common resistance mutation, but works in the same way (i.e. binding to the same site on the enzyme). Problem here is that you need to know the mutation(s), and be relatively certain that there's not a third mutation that's resistant to both. This isn't used too much or at all. Well sort of in bacteria, but not in a combination type approach. We find resistant bacteria, we develop a new drug that works against them, then we find bacteria resistant the that, we develop a new drug, etc. We're on like the 5th or 6th generation of cephalosporins for example.

Now, none of this involves 'guiding' evolution, that's kind of bizarre weird and I can't imagine how it might be done in any thing outside of Star Trek. It's really pretty standard stuff. And a point that can't be stressed enough, b/c sooo many people get it wrong: antibiotic treatments don't cause the mutations. They select for naturally occurring mutations. Given a large enough population, the mutations are already there. The antibiotic treatment just selects for them. Note there are a a few antibiotics out there that are mutagens in some sense, but it doesn't have much relevance here.

William Gaatjes
07-12-2010, 10:53 AM
The idea here is about what happens during antibiotic selection. A particular target of an antibiotic (in this case reverse transcriptase, RT) acquires mutations and in many cases a single point mutation renders the target resistant to the antibiotic, but still functional. it might not work quite as well as the the wild type enzyme, but it works well enough to get the job done.

You can then work at least two ways from there. 1. Treat (preferably at the same time) with a second drug that works by binding a different site on the enzyme. The enzyme now needs a second mutation in order to be resistant to both drugs. Also, the enzyme with two mutations might be even less efficient than the one mutation version. HAART therapy works along this strategy. It's usually a cocktail that includes two RT inhibitors and they bind at different sites on the enzyme. It's not so much the idea of 'making the enzyme less efficient,' it's that finding a virus with both mutations is less likely than finding a virus with either one. Thus at least one drug is effective against every virus in an infected person. (for the nit pickers - yes, HAART usually includes a protease inhibitor as well)

2. Treat with a second drug that's designed to be effective against the most common resistance mutation, but works in the same way (i.e. binding to the same site on the enzyme). Problem here is that you need to know the mutation(s), and be relatively certain that there's not a third mutation that's resistant to both. This isn't used too much or at all. Well sort of in bacteria, but not in a combination type approach. We find resistant bacteria, we develop a new drug that works against them, then we find bacteria resistant the that, we develop a new drug, etc. We're on like the 5th or 6th generation of cephalosporins for example.

Now, none of this involves 'guiding' evolution, that's kind of bizarre weird and I can't imagine how it might be done in any thing outside of Star Trek. It's really pretty standard stuff. And a point that can't be stressed enough, b/c sooo many people get it wrong: antibiotic treatments don't cause the mutations. They select for naturally occurring mutations. Given a large enough population, the mutations are already there. The antibiotic treatment just selects for them. Note there are a a few antibiotics out there that are mutagens in some sense, but it doesn't have much relevance here.

I see, you are right. ^_^
The mutations where already present. That makes sense, now i think of it, because if the medicines would cause heavy mutations on these enzymes the virus and the host uses or on the DNA /RNA, then the host would very likely experience such serious effects as well.
But the selection method still has a lot of opportunity i would think. Meaning you can still steer the selection in a way. And thus you could say you are indirectly controlling evolution, because you are laying out a path of survival for those pathogens that will survive. And those survivors must have a weakness as well. It might not be an direct way. But for now it is still the way.

William Gaatjes
07-20-2010, 07:27 AM
A gut bacteria that affect multiple sclerosis in mice.


http://www.sciencedaily.com/releases/2010/07/100719162643.htm

he work -- led by Sarkis K. Mazmanian, an assistant professor of biology at Caltech, and postdoctoral scholar Yun Kyung Lee -- appears online the week of July 19-23 in the Proceedings of the National Academy of Sciences.

Multiple sclerosis results from the progressive deterioration of the protective fatty myelin sheath surrounding nerve cells. The loss of myelin hinders nerve cells from communicating with one another, leading to a host of neurological symptoms including loss of sensation, muscle spasms and weakness, fatigue, and pain. Multiple sclerosis is estimated to affect about half a million people in the United States alone, with rates of diagnosis rapidly increasing. There is currently no cure for MS.

Although the cause of MS is unknown, microorganisms seem to play some sort of role. "In the literature from clinical studies, there are papers showing that microbes affect MS," Mazmanian says. "For example, the disease gets worse after viral infections, and bacterial infections cause an increase in MS symptoms."

On the other hand, he concedes, "it seems counterintuitive that a microbe would be involved in a disease of the central nervous system, because these are sterile tissues."

And yet, as Mazmanian found when he began examining the multiple sclerosis literature, the suggestion of a link between bacteria and the disease is more than anecdotal. Notably, back in 1993, Caltech biochemist Leroy Hood -- who was then at the University of Washington -- published a paper describing a genetically engineered strain of mouse that developed a lab-induced form of multiple sclerosis known as experimental autoimmune encephalomyelitis, or EAE.

When Hood's animals were housed at Caltech, they developed the disease. But, oddly, when the mice were shipped to a cleaner biotech facility -- where their resident gut bacterial populations were reduced -- they didn't get sick. The question was, why? At the time, Mazmanian says, "the authors speculated that some environmental component was modulating MS in these animals." Just what that environmental component was, however, remained a mystery for almost two decades.

But Mazmanian -- whose laboratory examines the relationships between gut microbes, both harmful and helpful, and the immune systems of their mammalian hosts -- had a hunch that intestinal bacteria were the key. "As we gained an appreciation for how profoundly the gut microbiota can affect the immune system, we decided to ask if symbiotic bacteria are the missing variable in these mice with MS," he says.

To find out, Mazmanian and his colleagues tried to induce MS in animals that were completely devoid of the microbes that normally inhabit the digestive system. "Lo and behold, these sterile animals did not get sick," he says.

Then the researchers decided to see what would happen if bacteria were reintroduced to the germ-free mice. But not just any bacteria. They inoculated mice with one specific organism, an unculturable bug from a group known as segmented filamentous bacteria. In prior studies, these bacteria had been shown to lead to intestinal inflammation and, more intriguingly, to induce in the gut the appearance of a particular immune-system cell known as Th17. Th17 cells are a type of T helper cell -- cells that help activate and direct other immune system cells. Furthermore, Th17 cells induce the inflammatory cascade that leads to multiple sclerosis in animals.

"The question was, if this organism is inducing Th17 cells in the gut, will it be able to do so in the brain and central nervous system?" Mazmanian says. "Furthermore, with that one organism, can we restore to sterile animals the entire inflammatory response normally seen in animals with hundreds of species of gut bacteria?"

The answer? Yes on all counts. Giving the formerly germ-free mice a dose of one species of segmented filamentous bacteria induced Th17 not only in the gut but in the central nervous system and brain -- and caused the formerly healthy mice to become ill with MS-like symptoms.

"It definitely shows that gut microbes have a strong role in MS, because the genetics of the animals were the same. In fact, everything was the same except for the presence of those otherwise benign bacteria, which are clearly playing a role in shaping the immune system," Mazmanian says. "This study shows for the first time that specific intestinal bacteria have a significant role in affecting the nervous system during MS -- and they do so from the gut, an anatomical location very, very far from the brain."

Mazmanian and his colleagues don't, however, suggest that gut bacteria are the direct cause of multiple sclerosis, which is known to be genetically linked. Rather, the bacteria may be helping to shape the immune system's inflammatory response, thus creating conditions that could allow the disease to develop. Indeed, multiple sclerosis also has a strong environmental component; identical twins, who possess the same genome and share all of their genes, only have a 25 percent chance of sharing the disease. "We would like to suggest that gut bacteria may be the missing environmental component," he says.

For their part, Th17 cells are needed for the immune system to properly combat infection. Problems only arise when the cells are activated in the absence of infection -- just as disease can arise, Mazmanian and others suspect, when the species composition of gut bacteria become imbalanced, say, by changes in diet, because of improved hygiene (which kills off the beneficial bacteria as well as the dangerous ones), or because of stress or antibiotic use. One impact of the dysregulation of normal gut bacterial populations -- a phenomenon dubbed "dysbiosis" -- may be the rising rate of multiple sclerosis seen in recent years in more hygienic societies.

"As we live cleaner, we're not just changing our exposure to infectious agents, but we're changing our relationship with the entire microbial world, both around and inside us, and we may be altering the balance between pro- and anti-inflammatory bacteria," leading to diseases like MS, Mazmanian says. "Perhaps treatments for diseases such as multiple sclerosis may someday include probiotic bacteria that can restore normal immune function in the gut… and the brain."

tcsenter
07-20-2010, 01:11 PM
Since there is no definitive diagnosis for MS and its etiology is almost completely unknown, it creates the potential for 'many like things' to get diagnosed as MS (or something else) which do not have the same underlying etiology. e.g.

http://en.wikipedia.org/wiki/Chronic_cerebrospinal_venous_insufficiency

http://www.hbotreatment.com/The%20Etiology%20of%20Multiple%20Sclerosis-%20A%20New%20and%20Extended%20Vascular-%20Ischemic%20Model.pdf

William Gaatjes
07-20-2010, 02:10 PM
Since there is no definitive diagnosis for MS and its etiology is almost completely unknown, it creates the potential for 'many like things' to get diagnosed as MS (or something else) which do not have the same underlying etiology. e.g.

http://en.wikipedia.org/wiki/Chronic_cerebrospinal_venous_insufficiency

http://www.hbotreatment.com/The%20Etiology%20of%20Multiple%20Sclerosis-%20A%20New%20and%20Extended%20Vascular-%20Ischemic%20Model.pdf

Oh, i agree. There are many different perspectives to research from. The interesting part is that the immune system can be "controlled" or at least informed by bacteria. I am still wondering if the human immune system can listen in on the quorum sensing language of bacteria. Some researchers suggest that the language of bacteria is a bit more complex then just voting and keeping track of votes. Bacteria may have more to say then we think. From a certain perspective, one can say that the human body after birth is conditioned by bacteria to stay alive in nature. More and more research in this direction seems to reveal so... In this thread is a lot of information to be found about examples. And that is just what i collected when i have nothing to do. There must be so much more information out there waiting to be collected.... ^_^

Forgot, thank you for the pdf. I stored it.

William Gaatjes
08-01-2010, 01:25 PM
Virus time ! 4 articles .^_^

http://www.sciencedaily.com/releases/2010/01/100107103621.htm

About eight percent of human genetic material comes from a virus and not from our ancestors, according to researchers in Japan and the U.S.
The study, and an accompanying News & Views article by University of Texas at Arlington biology professor Cédric Feschotte, is published in the journal Nature.The research showed that the genomes of humans and other mammals contain DNA derived from the insertion of bornaviruses, RNA viruses whose replication and transcription takes place in the nucleus.

Feschotte wrote on recent research led by Professor Keizo Tomonaga at Osaka University in Japan. Feschotte said this virally transmitted DNA may be a cause of mutation and psychiatric disorders such as schizophrenia and mood disorders.In his article, Feschotte speculates about the role of such viral insertions in causing mutations with evolutionary and medical consequences.
The assimilation of viral sequences into the host genome is a process referred to as endogenization. This occurs when viral DNA integrates into a chromosome of reproductive cells and is subsequently passed from parent to offspring. Until now, retroviruses were the only viruses known to generate such endogenous copies in vertebrates. But Feschotte said that scientists have found that non-retroviral viruses called bornaviruses have been endogenized repeatedly in mammals throughout evolution.Bornavirus (BDV) owes its name to the town of Borna, Germany, where a virus epidemic in 1885 wiped out a regiment of cavalry horses. BDV infects a range of birds and mammals, including humans. It is unique because it infects only neurons, establishing a persistent infection in its host's brain, and its entire life cycle takes place in the nucleus of the infected cells. Feschotte said this intimate association of BDV with the cell nucleus prompted researchers to investigate whether bornaviruses may have left behind a record of past infection in the form of endogenous elements. They searched the 234 known eukaryotic genomes (those genomes that have been fully sequenced) for sequences that are similar to that of BDV. "The researchers unearthed a plethora of endogenous Borna-like N (EBLN) elements in many diverse mammals, " Feschotte said.The scientists also were able to recover spontaneous BDV insertions in the chromosomes of human cultured cells persistently infected by BVD.Based on these data, Feschotte proposes that BDV insertions could be a source of mutations in the brain cells of infected individuals."These data yield a testable hypothesis for the alleged, but still controversial, causative association of BDV infection with schizophrenia and mood disorders," Feschotte said. The research in Feschotte 's laboratory, which largely focuses on transposable elements, the genetic elements that are able to move and replicate within the genomes of virtually all living organisms, is representative of the research under way at UT Arlington, an institution of 28,000 students on its way to becoming a nationally recognized, top-tier research university.


http://www.sciencedaily.com/releases/2008/06/080624111015.htm

Viruses can travel around cells they infect by hitching a ride on a microscopic transport system, according to new research.
Cells are exposed to foreign DNA and RNA and it is understood that some of this genetic material can be integrated into the host genome. Using modern microscopic techniques, scientists have been able to see how virus DNA is transported in the cell.Professor Dr Urs Greber from the University of Zurich will describe interactions between viruses and the cell cytoskeleton on June 24 2008 at the new SGM-RMS satellite meeting, part of the MICROSCIENCE 2008 conference being held at the ExCeL conference centre in London.
"We have been using human adenoviruses (Ads) to investigate transport processes of foreign DNA in the cytoplasm of human cells," said Professor Dr Greber. "Adenoviruses are a diverse family of agents that replicate their DNA genome in the cell nucleus. We wanted to find out how the virus gets to the nucleus to replicate. To do this we have been using live cell fluorescence microscopy, which means we can literally watch the virus travelling inside the cell."Human adenoviruses can cause respiratory, urinary and digestive infections. They occasionally cause epidemic conjunctivitis, and can be fatal in immunocompromised patients. Adenoviruses can aggravate asthmatic conditions, and are associated with deadly gastroenteritis in babies. This research improves our knowledge of how the virus replicates in host cells.
"Virus DNA is transported from the edge of the cell to the nucleus in the middle by attaching to microtubules. These are microscopic tubes that form part of the cytoskeleton, keeping the cell in shape and carrying molecules around in the cytoplasm," said Professor Dr Greber. "We found an unexpected new link between microtubule-based transport in the cytoplasm of the cell and the import of virus DNA to the nucleus."Other talks at the one-day SGM meeting will concentrate on the 'tussle' that takes place when a host cell tries to fight back against an invading pathogen. Sir David King will start the day by talking about the 'Twenty first century challenges of sustainability and wellbeing'. Professor Timo Hyypia (University of Turku) will speak on 'Cellular interactions of enteroviruses' and Dr Mark Jepson (University of Bristol) will look at the way in which bacteria invade cells. The manipulation of cellular compartments by the SARS coronavirus for replication purposes will also be discussed by Dr Marjolein Kikkert (Leiden University Medical Centre).


http://www.sciencedaily.com/releases/2010/07/100729172330.htm


Over millions of years, retroviruses, which insert their genetic material into the host genome as part of their replication, have left behind bits of their genetic material in vertebrate genomes.
In a recent study, published July 29 in the open-access journal PLoS Pathogens, a team of researchers have now found that human and other vertebrate genomes also contain many ancient sequences from Ebola/Marburgviruses and Bornaviruses -- two deadly virus families.Because neither virus family inserts their genetic material into the host genome during replication, as retroviruses do, the discovery was all the more unexpected."This was a surprise for us," says author Anna Marie Skalka, Ph.D., Director Emerita of the Institute for Cancer Research at Fox Chase Cancer. "It says that the source of our genetic material is considerably wider than we thought. It includes our own genes and unexpected viral genes as well."The team, which included lead author Vladimir A. Belyi, Ph.D., and co-author Arnold J. Levine, Ph.D., both at the Institute for Advanced Study in Princeton, compared 5,666 viral genes from all known non-retroviral families with single-stranded RNA genomes to the genomes of 48 vertebrate species, including humans. In doing so, they uncovered 80 separate viral sequence integrations into 19 different vertebrate species. Interestingly, nearly all of the viral sequences come from ancient relatives of just two viral families, the Ebola/Marburgviruses and Bornaviruses, both of which cause hemorrhagic fevers and neurological disease."These viruses are RNA viruses," Skalka says. "They replicate their RNA and are not known to make any DNA. And they have no known mechanism for getting their genetic material integrated into the DNA of the host genome. Indeed, some of them don't even enter the nucleus when they replicate."That the sequences, some of which may have been integrated into the genomes more than 40 million years ago, have been largely conserved over evolutionary time suggests that they give the host a selective advantage, perhaps protecting them from future infections by viruses from those families. The study shows that integration of the ancient viral sequences was probably mediated by movable elements, LINEs, which are abundant in mammalian genomes."In a way, one might even think of these integrations as genomic vaccinations," says Skalka.Demonstrating conclusively that the viral sequences have some biological function will take additional work. However, the team has noted that expression of some of these viral open reading frames has been detected in human tissues, which supports the possibility that they are biologically active in host species.


http://www.sciencedaily.com/releases/2008/05/080531090353.htm

A Weizmann Institute study provides important new insights into the process of viral infection. The study, reported in the online journal PLoS Biology, reveals certain mechanisms by which mimivirus – a virus so called because it was originally thought to mimic bacteria in various aspects of their behavior – invades amoeba cells.

Living cells become infected by viruses in two steps. First, the virus penetrates the cell. Next, in the second and crucial step, the cell starts producing new viruses, which spread and infect additional cells. At the beginning of this production process, the cell makes the outer wall of the virus, which is a container of sorts composed of proteins and known as the capsid. The cell then makes copies of viral DNA and inserts it into the capsid. The result is a new, functioning virus that is ready to leave the host cell and infect more cells.Understanding how viruses infect cells and how new viruses are produced in the course of the infection allows scientists to interrupt the infection cycle, blocking viral diseases. One of the difficulties, however, is that the invasion strategies of different viruses greatly vary from one another.
The mimivirus, known, among other things, for its exceptional size – it is five to ten times larger than any other known virus – poses an interesting challenge in this respect. This virus was discovered only in the late twentieth century, as its extraordinary size made it impossible to identify it by regular means. In addition, it contains much more genetic material than other viruses, a feature that forces the mimivirus to develop particularly efficient methods for introducing its viral DNA into the host cell and for inserting the genetic “parcel” into the protein container during the production of new viruses in the host cell.The Weizmann Institute’s Prof. Abraham Minsky and graduate students Nathan Zauberman and Yael Mutsafi of the Organic Chemistry Department, together with Drs. Eugenia Klein and Eyal Shimoni of Chemical Research Support, have now revealed the details of some of the methods used by this virus. In their new study, the scientists have obtained, for the first time, three-dimensional pictures of the openings through which the viral genetic material is injected into an infected cell, and of the process by which this genetic material is inserted into the protein capsid.In all previously studied viruses, viral genetic material was shown to be injected into the cell (during the cell’s infection) and to enter the newly formed protein container (during the production of new viruses inside the cell) through the same channel, which was created in the viral container. In contrast, the Institute scientists discovered that the giant mimivirus uses a different channel – located in a different part of its capsid – for each of these two goals. The scientists also discovered that the DNA helix in both these processes does not form a long thread, as in other viruses, but rather is organized into a densely packed block. The researchers believe that these unique traits serve to specifically facilitate both the injection into the host cell and the insertion of the large quantity of genetic material in the mimivirus.
In the Weizmann study, electron microscope images of the mimivirus invading an amoeba cell showed that just after invasion, the walls of the protein capsid – a polygon composed of 20 triangles – separate from one another and open up like flower petals to create a large, star-shaped entry nicknamed the “stargate.” The viral membrane underneath the stargate fuses with the amoeba cell membrane, creating a broad channel that leads into the amoeba. The pressure released with the sudden opening of the walls – which is 20 times greater than the pressure pushing the cork out of a Champagne bottle – pushes the viral DNA into the channel, whose large dimensions allow the genetic material to pass quickly into the amoeba cell.Additional images show how the viral genetic material is inserted into the newly formed protein container when new viruses are produced in the host cell. In this process, the viral genetic material is delivered to its destination through an opening in the new container’s wall opposite the stargate. The insertion must overcome the pressure inside the container and is probably driven by an “engine” located within the wall that harbors the opening.
The scientists believe that the study of the mimivirus’s life cycle, from cellular infection to the production of new viruses, may yield valuable insights into the mechanisms of action of numerous other viruses, including those that cause human diseases.


http://www.sciencedaily.com/releases/2010/05/100528210736.htm


Nihal Altan-Bonnet, assistant professor of cell biology, Rutgers University in Newark, and her research team have made a significant new discovery about RNA (ribonucleic acid) viruses and how they replicate themselves.

Certain RNA viruses -- poliovirus, hepatitis C virus and coxsackievirus -- and possibly many other families of viruses copy themselves by seizing an enzyme from their host cell to create replication factories enriched in a specific lipid, explains Altan-Bonnet. Minus that lipid -- phosphatidylinositol-4-phosphate (Pl4P) -- these RNA viruses are not able to synthesize their viral RNA and replicate. The key structural components on cell membranes, lipids often serve as signaling molecules and docking sites for proteins.Viral replication is the process by which virus particles make new copies of themselves within a host cell. Those copies then can go on to infect other cells. An RNA virus is a virus that has RNA, rather than DNA, as its genetic material. Many human pathogens are RNA viruses, including SARS virus, West Nile virus, HIV, and the ones Altan-Bonnet has been studying.As reported in the May 28, 2010 issue of Cell, Altan-Bonnet and her co-researchers for the first time have uncovered that certain RNA viruses take control of a cellular enzyme to design a replication compartment on the cell's membrane filled with PI4P lipids. Those lipids, in turn, allow the RNA viruses to attract and stimulate the enzymes they need for replication. In uninfected cells, the levels of PI4P lipids are kept low, but in virally infected cells those levels increase dramatically. The findings by Altan-Bonnet and her colleagues not only open several possibilities for preventing the spread of various viral infections, but also may help to shed new light on the regulation of RNA synthesis at the cellular level and potentially on how some cancers develop."The goal of the virus is to replicate itself," notes Altan-Bonnet. "For its replication machines to work, the virus needs to create an ideal lipid environment which it does by hijacking a key enzyme from its host cell."Altan-Bonnet and her team also were able to identify the viral protein (the so-called 3A protein in poliovirus and coxsackievirus infections) that captures and recruits the cellular enzyme (phosphatidylinositol-4-kinase III beta). Additionally, her lab was able to impede the replication process by administering a drug that blocked the activity of the cellular enzyme once it had been hijacked. Drug therapies to prevent viral replication potentially also could be targeted to prevent the hijacking of the enzyme.
Once that enzyme is hijacked, cells are prevented from normally operating their secretory pathway, the process by which they move proteins to the outside of the cell. In many cases, the impeding of that process can result in the slow death of the cell, leading to such problems as cardiac and vascular complications in those infected with the coxsackievirus and neurological damage in those with poliovirus.
Utilizing their recent findings, Altan-Bonnet and her team now plan to investigate PI4P dependence in other viruses as well as the role other lipids may play in different virus families. For example, the SARS virus also requires a lipid-rich environment for its replication, so her lab now is working with SARS researchers on determining what lipid is necessary for that virus's replication. In addition, they will be examining the role of lipids in regulating RNA synthesis in cells, potentially providing new insight into some of the cellular mutations that occur in cancer.
"Given that a lot of what we know about cellular processes historically comes from the study of viruses, our studies may provide insight into the novel roles lipids play in regulating the expression of genetic material in cells," notes Altan-Bonnet.Altan-Bonnet's research into RNA replication is supported with grants from the National Science Foundation and the Busch Foundation.

William Gaatjes
08-04-2010, 01:08 PM
Just a strange question. But is Herpes simplex virus not infecting Schwann cells ?

I was wondering about the coincidence between the Devil facial tumour disease
in tasmanian devils. This disease is an parasitic cancer. And the hypothesis is that it originated inside schwann cells.

Parasitic cancers or transmissible cancers are very rare but i find it very interesting that the immunesystem from tasmanian devils does not seem to mind that an foreign cell can just start to grow like a tumor. Perhaps this has something to do with the fact that tasmanian devils are isolated as an species. Interbreeding might occur and may cause unwanted side effects as for example that the immune system becomes dumbed down. I do not know.

William Gaatjes
08-14-2010, 09:23 AM
To return to the interesting subject of autoimmune diseases...

I posted here about diabetes mellitus type 1 and the islets of Langerhans.
And that a suspected virus infection causes this. Probably through antigen mimicry as Gibsons mentioned.

My colleague is back. And i had the story about the experimental treatment a bit wrong. As it turns out, the experimental treatment in Canada was about :
Transplantation of tissue containing the islets of Langerhans. The patient was given immune suppression medicines to prevent tissue rejection. After a while they noticed the immune system did not attack the islets of Langerhans and the person no longer suffered from diabetes type 1.
The interesting part is that this was not a result of the immune suppression medicines, but as is suspected a result of a transplantation where the donor tissue was not virus infected. The original Langerhans tissue produced viruses or partial virus particles and where as such destroyed by the immune system. And the result was diabetes type 1. It was the virus infection that caused the auto immune disease. I did some research and it seems that the lymphocytic choriomeningitis virus which can be present inside the house mouse might be the cause. At least in some situations it has been found to be the case. There is lot of this information on the internet.
I find it interesting that it seems that a lot of rodents or similar mammals are carriers of viruses causing dangerous diseases.



I myself have been researched in the recent past for Bechterew disease also known as ankylosing spondylitis. And i luckily do not have this disease.
But it is an auto immune disease with an interesting hypothesis :
Almost all Bechterew patients have the HLA-B27 protein. And this protein is very similar to proteins found on the outside of the bacteria klebsiella pneumoniae. If this bacteria comes in contact with the immune system, the immune system will attack the body protein HLA-B27 inside bones and eyes because of antigenic mimicry if all conditions are met.

ModestGamer
08-16-2010, 01:09 AM
To return to the interesting subject of autoimmune diseases...

I posted here about diabetes mellitus type 1 and the islets of Langerhans.
And that a suspected virus infection causes this. Probably through antigen mimicry as Gibsons mentioned.

My colleague is back. And i had the story about the experimental treatment a bit wrong. As it turns out, the experimental treatment in Canada was about :
Transplantation of tissue containing the islets of Langerhans. The patient was given immune suppression medicines to prevent tissue rejection. After a while they noticed the immune system did not attack the islets of Langerhans and the person no longer suffered from diabetes type 1.
The interesting part is that this was not a result of the immune suppression medicines, but as is suspected a result of a transplantation where the donor tissue was not virus infected. The original Langerhans tissue produced viruses or partial virus particles and where as such destroyed by the immune system. And the result was diabetes type 1. It was the virus infection that caused the auto immune disease. I did some research and it seems that the lymphocytic choriomeningitis virus which can be present inside the house mouse might be the cause. At least in some situations it has been found to be the case. There is lot of this information on the internet.
I find it interesting that it seems that a lot of rodents or similar mammals are carriers of viruses causing dangerous diseases.



I myself have been researched in the recent past for Bechterew disease also known as ankylosing spondylitis. And i luckily do not have this disease.
But it is an auto immune disease with an interesting hypothesis :
Almost all Bechterew patients have the HLA-B27 protein. And this protein is very similar to proteins found on the outside of the bacteria klebsiella pneumoniae. If this bacteria comes in contact with the immune system, the immune system will attack the body protein HLA-B27 inside bones and eyes because of antigenic mimicry if all conditions are met.


Now here is a great question. How would artificial immune system stimulation via vaccination affect this immune response in predisposed but non symptopmatic patients ?

IE look at the pandemic of type 1 diabetes.

Mr. Pedantic
08-16-2010, 03:55 AM
There's a pandemic of Type 1 diabetes?

ModestGamer
08-16-2010, 03:31 PM
There's a pandemic of Type 1 diabetes?


here in the USA. absofuckinglutely effects as many as 1 in 20 children. Up from 1-1000

number of vaccinations by age 3 is as high as 45. That rediculous.

William Gaatjes
08-23-2010, 03:53 PM
here in the USA. absofuckinglutely effects as many as 1 in 20 children. Up from 1-1000

number of vaccinations by age 3 is as high as 45. That rediculous.

Well, I think it is a good idea to start to do some biological tests on the rodents living near by those cases of diabetes -1. What are the relations between the children. What do they have in common ? Age, quality of living, quality of houses, geographic locations, rodent infestation, do they have cats that bring mouses in the house as prey ? Perhaps the cats have carried the viruses for a short while.
Maybe a cat that starts to spin and rubs it's scent while producing slime can transmit the virus while being infected for a short time. Maybe there is an indirect link to be found with Toxoplasma gondii and lymphocytic choriomeningitis virus.

http://en.wikipedia.org/wiki/Toxoplasma_gondii



Maybe you are partially right when you mentioned that viruses come from cells.
Maybe viruses do not only spread in the wild but also become inserted completely in the genome of the host. Now when a certain trigger( other virus or bacteria or just a chemical molecule) starts that part of dna to become expressed, a virus would be produced. The host would then need to be in a situation where the infected tissue or it's blood (where the viruses can roam around freely because maybe the immune system of the host see the viruses no longer as foreign because the viruses have been incorporated many generations before) would be shared with other possible hosts(can be from different species). I am just mentioning a few possibilities.

William Gaatjes
08-23-2010, 04:03 PM
I will just add these post here as well for the usual reason of collecting information :

Deinococcus radiodurans

http://www.usuhs.mil/pat/deinococcus/index_20.htm

Bacteria belonging to the family Deinococcaceae are some of the most radiation-resistant organisms yet discovered. Deinococcus (Micrococcus) radiodurans strain R1 (ATCC BAA-816) was first reported in 1956 by A. W. Anderson and coworkers of the Oregon Agricultural Experimental Station, Corvalis, Oregon. This obligate aerobic bacterium typically grows in rich medium as clusters of two cells (diplococci) in the early stages of growth, and as clusters of four cells (tetracocci) in the late stages of growth, is non-pathogenic, and best known for its ability to survive extremely high doses of acute ionizing radiation (10,000 Gy) without cell-killing. For comparison, 5 Gy is lethal to the average human, and 2,000 Gy can sterilize a culture of Escherichia coli. D. radiodurans is capable of growth under chronic radiation (60 Gy/hour) and resistant to other DNA damaging conditions including exposure to desiccation, ultraviolet (UV) light, and hydrogen peroxide. The genes and cellular pathways underlying the survival strategies of D. radiodurans are under investigation, and its resistance characteristics are being exploited in the development of bioremediation processes for cleanup of highly radioactive US Department of Energy waste sites, and in the development of radioprotectors.

Death By Protein Damage

The modern founding concept of radiation biology that deals with X-rays and g-rays is that ionizing radiation is dangerous because of its damaging effects on DNA. Mounting experimental evidence does not fit into this theoretical framework, instead supporting that radiation resistance is governed by protein damage. Recent studies from several independent labs implicate protein damage as the major probable cause of death in irradiated cells. Whereas DNA lesion-yields in cells exposed to a given dose of radiation appear to be fixed, protein-lesion yields are variable and closely related to survival. There are profound practical implications to this new view of radiation toxicity � Basically, if you want to survive radiation, protect your proteins! D. radiodurans has shown us how to protect proteins from radiation and other sources of reactive oxygen species (ROS), which is the subject of several experimental manuscripts working their way to press. For a history which led to this emerging paradigm shift in radiation biology, see Nat Rev Microbiol, 2009; 7(3):237-45, as well as others.

One original goal of radiobiology was to explain why cells are so sensitive to ionizing radiation (IR). Early studies in bacteria incriminated DNA as the principal radiosensitive target, an assertion that remains central to modern radiation toxicity models. More recently, the emphasis has shifted to understanding why bacteria such as Deinococcus radiodurans are extremely resistant to IR (1), by focusing on DNA repair systems expressed during recovery from high doses of IR (2). Unfortunately, as key features of DNA-centric hypotheses of extreme resistance have grown weaker (3), the study of alternative cellular targets has lagged far behind, mostly because of their relative biological complexity. Recent studies have shown that extreme levels of bacterial IR resistance correlate with high intracellular Mn(II) concentrations (4), and resistant and sensitive bacteria are equally susceptible to IR-induced DNA damage (~0.005 DSB/Gy/haploid genome). Our recent work has established a mechanistic link between the orthophosphate complex of Mn2+ and protection of proteins from radiation damage (5a, 5b). In contrast to resistant bacteria, naturally sensitive bacteria are highly susceptible to IR-induced protein oxidation. We have proposed that sensitive bacteria sustain lethal levels of protein damage at radiation doses that elicit relatively little DNA damage, and that extreme resistance in bacteria is dependent on protein protection (6).

In the months ahead, published papers that deal with "Death by Protein Damage" in irradiated cells will be listed on this site. Most important, we will show the critical role of combining orthophosphate (Pi) complexes of Mn2+ with common metabolites (e.g., uridine and peptides) in the protection of enzymes from extreme oxidative damage caused during irradiation. These complexes are immensely radioprotective of proteins but not DNA. For more information contact Michael Daly (mdaly@usuhs.mil).


Image overlay of transmission electron microscopy, light microscopy, and x-ray fluorescence microprobe analyses of Deinococcus radiodurans. Depth-average abundance of Mn (blue, green, pink) and Fe (red) are shown within a single D. radiodurans diplococcus.

http://www.usuhs.mil/pat/deinococcus/FrontPage_DR_Web_work/front_pictures/XANEX.jpg


http://www.sciencedaily.com/releases/2010/08/100816095719.htm

A team of marine microbiologists at Newcastle University have discovered for the first time that bacteria have a molecular "nose" that is able to detect airborne, smell-producing chemicals such as ammonia.

Published in Biotechnology Journal, their study shows how bacteria are capable of 'olfaction' -- sensing volatile chemicals in the air such as ammonia produced by rival bacteria present in the environment.

Led by Dr Reindert Nijland, the research also shows that bacteria respond to this smell by producing a biofilm -- or 'slime' -- the individual bacteria joining together to colonise an area in a bid to push out any potential competitor.

Biofilm is a major cause of infection on medical implants such as heart valves, artificial hips and even breast implants. Also known as 'biofouling' it costs the marine industry millions every year, slowing ships down and wasting precious fuel. But it also has its advantages. Certain biofilms thrive on petroleum oil and can be used to clean up an oil spill.

Dr Nijland, who carried out the work at Newcastle University's Dove Marine Laboratory, said the findings would help to further our understanding of how biofilms are formed and how we might be able to manipulate them to our advantage.

"This is the first evidence of a bacterial 'nose' capable of detecting potential competitors," he said.

"Slime is important in medical and industrial settings and the fact that the cells formed slime on exposure to ammonia has important implications for understanding how biofilms are formed and how we might be able to use this to our advantage.

"The next step will be to identify the nose or sensor that actually does the smelling."

This latest discovery shows that bacteria are capable of at least four of the five senses; a responsiveness to light -- sight -- contact-dependent gene expression -- touch -- and a response to chemicals and toxins in their environment either through direct contact -- taste -- or through the air -- smell.

Ammonia is one of the simplest sources of nitrogen -- a key nutrient for bacterial growth. Using rival bacteria Bacillus subtilis and B.licheniformus, both commonly found in the soil, the team found that each produced a biofilm in response to airborne ammonia and that the response decreased as the distance between the two bacterial colonies increased.

Project supervisor Professor Grant Burgess, director of the Dove Marine Laboratory, said that understanding the triggers that prompt this sort of response had huge potential.

"The sense of smell has been observed in many creatures, even yeasts and slime moulds, but our work shows for the first time that a sense of smell even exists in lowly bacteria.

"From an evolutionary perspective, we believe this may be the first example of how living creatures first learned to smell other living creatures.

"It is an early observation and much work is still to be done but, nevertheless, this is an important breakthrough which also shows how complex bacteria are and how they use a growing number of ways to communicate with each other.

"Bacterial infections kill millions of people every year and discovering how your bacterial enemies communicate with each other is an important step in winning this war. This research provides clues to so far unknown ways of bacterial communication."

William Gaatjes
08-23-2010, 04:44 PM
p53 has been studied pretty intensely for a very long time. Lots of people have sequenced lots of p53 genes from many many different cancers and normal tissues. When you compile this data, you see some bases mutated very often in cancer samples (usually leading to specific amino acid changes), some not so much.

The general theory is that all the bases are, roughly, equally prone to mutation (this is never exactly true). So, when you sequence p53 from cancer cells, your data is selected - you're looking at mutations that lead to cancer (with some noise too, of course). If you see a few bases mutated over and over again, and a lot of other bases only rarely mutated, the conclusion is usually that those bases lead to cancer.

Another explanation though, is simply that cancer cells have a high mutation rate and there's some bias in these mutations. i.e. the mutations are an effect of cancer, not a cause.

Other data suggests that the former is correct - the mutations in p53 lead to cancer. When you look at the mutated proteins for instance, the common mutations lead to loss or change of function of the protein. Also, some unfortunate people are born with a mutated p53 and they get cancer early and often.
http://en.wikipedia.org/wiki/Li-Fraumeni_syndrome

What the article I linked is talking about is that they can detect a known mutagen/carcinogen binding to some of the specific sequences. I didn't read the whole paper, but they might be suggesting that benzopyrene has a higher than-you-might-expect propensity to cause the cancer associated mutations. i.e. it's not randomly mutating all bases, it's more prone to mutate the important ones than unimportant ones.

I just read this post again and for some reason i had to think about the prion first. The benzopyrene may not be a prion. But maybe the mechanisms are similar. When it is subjected to the dna, it forces another electron distribution in the sequence. Causing the sequence to behave different. That is also why i had to think about quantum mirages principles and super atoms principles as the basic mechanisms of life in the first place :


http://www.almaden.ibm.com/almaden/media/mirage.html


To create the quantum mirage, the scientists first moved several dozen cobalt atoms on a copper surface into an ellipse-shaped ring. As Michael Crommie (who is now a professor at the University of California-Berkeley), Lutz and Eigler had shown in 1993, the ring atoms acted as a "quantum corral" -- reflecting the copper's surface electrons within the ring into a wave pattern predicted by quantum mechanics.

The size and shape of the elliptical corral determine its "quantum states" -- the energy and spatial distribution of the confined electrons. The IBM scientists used a quantum state that concentrated large electron densities at each focus point of the elliptical corral. When the scientists placed an atom of magnetic cobalt at one focus, a mirage appeared at the other focus: the same electronic states in the surface electrons surrounding the cobalt atom were detected even though no magnetic atom was actually there. The intensity of the mirage is about one-third of the intensity around the cobalt atom.

"We have become quantum mechanics -- engineering and exploring the properties of quantum states," Eigler said. "We're paving the way for the future nanotechnicians."

The operation of the quantum mirage is similar to how light or sound waves is focused to a single spot by optical lenses, mirrors, parabolic reflectors or "whisper spots" in buildings. For example, faint sounds generated at either of the two "whisper spots" in the Old House of Representatives Chamber (now called Statuary Hall) in the U.S. Capitol Building in Washington, D.C., can be heard clearly far across the chamber at the other whisper spot.

"The quantum mirage technique permits us to do some very interesting scientific experiments such as remotely probing atoms and molecules, studying the origins of magnetism at the atomic level, and ultimately manipulating individual electron or nuclear spins," said Dr. Manoharan. "But we must make significant improvements before this method becomes useful in actual circuits. Making each ellipse with the STM is currently impractically slow. They would have to be easily and rapidly produced, connections to other components would also have to be devised and a rapid and power-efficient way to modulate the available quantum states would need to be developed."

tcsenter
08-23-2010, 05:41 PM
I posted here about diabetes mellitus type 1 and the islets of Langerhans. And that a suspected virus infection causes this. Probably through antigen mimicry as Gibsons mentioned.See HLA DQB1*0602 allele, which is strongly protective against Type 1 IDDM, even among Islet cell antibody-positive first-degree relatives of patients with IDDM. So much, that investigational studies on IDDM typically exclude any subjects with DQB1*0602.

Only reason I know about it is because DQB1*0602 was previously implicated in narcolepsy and cataplexy, which mounting evidence strongly suggests is an auto-immune disease (or results from one).

William Gaatjes
08-23-2010, 06:31 PM
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%
See HLA DQB1*0602 allele, which is strongly protective against Type 1 IDDM, even among Islet cell antibody-positive first-degree relatives of patients with IDDM. So much, that investigational studies on IDDM typically exclude any subjects with DQB1*0602.

Only reason I know about it is because DQB1*0602 was previously implicated in narcolepsy and cataplexy, which mounting evidence strongly suggests is an auto-immune disease (or results from one).

I found some information about a small number study :

http://diabetes.diabetesjournals.org/content/44/6/608.abstract

HLA-DQB1 alleles confer susceptibility and resistance to insulin-dependent diabetes mellitus (IDDM). We investigated whether the susceptibility alleles DQB1*0302 and DQB1*0201 affect progression to diabetes among islet cell antibody-positive (ICA+) first-degree relatives of IDDM patients and whether the protective allele DQB1*0602 can be found and is still protective among such relatives. We human leukocyte antigen-typed and periodically tested beta-cell function (first-phase insulin release [FPIR] during the intravenous glucose tolerance test) in 72 ICA+ relatives, of whom 30 became diabetic on follow-up (longest follow-up 12 years); 54 (75%) relatives carried DQB1*0302 and/or DQB1*0201. The frequency of DQB1*0302 and DQB1*0201 and of the high-risk genotype DQB1*0302/DQB1*0201 did not differ significantly between diabetic relatives and those remaining nondiabetic. On follow-up, progression to IDDM was not statistically different for relatives with or without the DQB1*0302/DQB1*0201 genotype. However, those relatives with the DQB1*0302/DQB1*0201 genotype had a tendency to develop diabetes at an earlier age (log-rank P = 0.02). We found DQB1*0602 in 8 of 72 (11.1%) ICA+ relatives. Relatives with DQB1*0602 did not develop diabetes or show any decline of FPIR versus 28 of 64 DQB1*0602- relatives who developed IDDM (log-rank P = 0.006; Wilcoxon's P = 0.02). The protective allele DQB1*0602 is found in ICA+ relatives who have minimal risk of progression to IDDM. Therefore, DQB1*0602 is associated with protection from IDDM both in population studies and among relatives with evidence of autoimmunity who should not enter prevention trials.

If i understand correctly, when you carry the DQB1*0602 allele you do not get IDDM. But why ? Is the immune system when having DQB1*0602 blind for the lymphocytic choriomeningitis virus ? For particular viral parts ? Or is the immune system more effective in killing the virus before the virus can infect the cells of the pancreas ?


The reason why i mention this is because the IDDM does not happen after birth. Acquiring IDDM always seem to happen at a later age when the child can run around, move freely and interact with others. Thus becoming prone to infection.

EDIT :

I found some information about narcolepsy.

http://med.stanford.edu/school/Psychiatry/narcolepsy/faq1.html

What is the cause of narcolepsy?
Recent studies have shown that narcolepsy with cataplexy is usually caused (>90%) by the lack of two related brain chemicals called "hypocretin-1" and "hypocretin-2". The cause of narcolepsy without cataplexy is still under investigation.

What are these so-called hypocretin (orexin) molecules?
Hypocretins (orexins) were discovered by two groups of researchers almost simultaneously, hence the two names "hypocretins" and "orexins". The first group called them "hypocretin-1" and "hypocretin-2" after discovering that the molecules were found only in the hypothalamus and had some weak resemblance with the gut hormone secretin. Only 10,000-20,000 cells in the entire human brain (out of many billions) secrete these specific hypocretin molecules. The hypothalamus, a region localized deep in the base of the brain, regulates many basic functions such as the release of hormones, blood pressure, sex, food intake regulation and sleep. The subregion of the hypothalamus containing the hypocretin cells was known to be especially important for the regulation of feeding. These molecules were thus first hypothesized to be important in feeding regulation. In fact, the second group that discovered the hypocretin molecules called them "orexin A and orexin B" (from orexis=appetite in grec) and suggested that they stimulated appetite. Orexins and hypocretins are thus interchangeable terms and the scientific community is divided on what is the best name to use.

How can I have my hypocretin levels measured?
Hypocretin-1 (but not 2) can be measured in the cerebrospinal fluid (CSF) but not in the blood or in any other peripheral tissue. A lumbar puncture is required to collect CSF. Most patients with narcolepsy-cataplexy have no hypocretin-1 molecules in their CSF. If you are interested in having your CSF hypocretin levels measured, please contact Mali Einen at the Center for Narcolepsy.

How do you collect cerebrospinal fluid (CSF)?
To draw CSF requires a lumbar puncture (spinal tap). This is a safe but not completely insignificant procedure (the main problem is that temporary headaches can occur in about 5% of the cases following the procedure). The procedure is a little similar to an epidural anesthesia (actually safer and easier), is used a lot by neurologists to exclude many neurological problems such as brain hemorrhage, brain infections, multiple sclerosis, etc... We have tried to measure hypocretins in other tissues such as blood but this molecule probably exists in sufficient amount only in the brain and the CSF. Clearly, some effort should be devoted in measuring hypocretin levels more easily.

What is HLA?
HLA stands for " Human Leukocyte Antigens". HLA antigens are molecules produced by the HLA genes. HLA molecules are expressed on the surface of white blood cells to coordinate the immune response. DR and DQ are two different types of HLA molecules. HLA genes are very important systems to keep the immune system in check. The HLA molecules are very particular in that different individuals generally carry different HLA "subtypes" (for example DR1, DR2, subtypes of HLA-DR; DQ1, DQB1*0602, subtypes of HLA-DQ). The fact HLA molecules are slightly different from one individual to another makes our immune system slightly different from each other.

What is the best HLA marker in narcolepsy?
The best HLA marker for narcolepsy is HLA-DQB1*0602. Over 90% of patients with narcolepsy-cataplexy carry HLA-DQB1*0602. This marker is more specific and sensitive than the old marker HLA-DR2, especially in African Americans.

Can HLA testing be used to diagnosed narcolepsy?
Absolutely not. About 20% of the general population carry the exact same HLA subtypes (HLA-DR2, DQB1*0602, etc). Furthermore, many patients without cataplexy do not have HLA-DQB1*0602. The HLA subtypes are only predisposing factors but are not sufficient by themselves to cause narcolepsy.

How is HLA involved in narcolepsy?
No one knows for sure. A large number of other diseases (>80) like Multiple sclerosis or Juvenile Onset (type I) Insulin Dependent Diabetes Mellitus are also associated with specific HLA subtypes. Most of these diseases are autoimmune disorders.

I did not quote all text.
But i wonder if there is a pathogen to be found in those hypocretin producing cells.

what is narcolepsy ?

http://en.wikipedia.org/wiki/Narcolepsy

Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive daytime sleepiness (EDS) in which a person experiences extreme fatigue and possibly falls asleep at inappropriate times, such as while at work or at school. Narcoleptics usually experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which is often confused with insomnia. When a narcoleptic falls asleep they generally experience the REM stage of sleep within 10 minutes; whereas most people do not experience REM sleep until after 90 minutes. There is no evidence to suggest that narcoleptics tend to have a shorter life span.

Another problem that some narcoleptics experience is cataplexy, a sudden muscular weakness brought on by strong emotions (though many people experience cataplexy without having an emotional trigger).[1] It often manifests as muscular weaknesses ranging from a barely perceptible slackening of the facial muscles to the dropping of the jaw or head, weakness at the knees, or a total collapse. Usually only speech is slurred, vision is impaired (double vision, inability to focus), but hearing and awareness remain normal. In some rare cases, an individual's body becomes paralyzed and muscles become stiff.

William Gaatjes
08-23-2010, 07:01 PM
%%%%%%%%%%%%%%%%%%%%%%%%%%%%%%

A post about parts of the ebola virus (a filovirus) being embedded in bats and wallabies.

http://www.sciencecodex.com/wallabies_and_bats_harbor_fossil_genes_from_the_mo st_deadly_family_of_human_viruses

BUFFALO, N.Y. -- Modern marsupials may be popular animals at the zoo and in children's books, but new findings by University at Buffalo biologists reveal that they harbor a "fossil" copy of a gene that codes for filoviruses, which cause Ebola and Marburg hemorrhagic fevers and are the most lethal viruses known to humans.

Published this week in the online journal BMC Evolutionary Biology, the paper ("Filoviruses are ancient and integrated into mammalian genomes") demonstrates for the first time that mammals have harbored filoviruses for at least tens of millions of years, in contrast to the existing estimate of a few thousand.

It suggests that these species, which maintain a filovirus infection without negative health consequences, could have selectively maintained these so-called "fossil" genes as a genetic defense.

The work has important implications for the development of potential human vaccines, as well as for the modeling of disease outbreaks and the discovery of emerging diseases, including new filoviruses.

"This paper identifies the first captured 'fossil' copies of filovirus-like genes in mammalian genomes," says Derek J. Taylor, PhD, associate professor of biological sciences in the UB College of Arts and Sciences and co-author. "Our results confirm for the first time that several groups of mammals, including groups such as marsupials that never colonized Africa, have had an association with filoviruses."

The UB co-authors say that if the rarely captured genes represent antiviral defenses or genomic scars from persistent infections, then the work opens up new possibilities for identifying reservoir species for filoviruses, which harbor the virus but remain asymptomatic.

"The reservoir for filovirus has remained a huge mystery," says Jeremy A. Bruenn, PhD, UB professor of biological sciences and co-author. "We need to identify it because once a filovirus hits humans, it can be deadly."

When the UB researchers studied samples from the fur of a wallaby at the Buffalo Zoo and a brown bat caught on the UB campus, they found that the genomes of both animals as well as some other small mammals contain "fossil" copies of the gene for these deadly viruses, and thus could be candidate reservoir species for them.

"Who knew that the bats in the attic as well as modern marsupials harbored fossil gene copies of the group of viruses that is most lethal to humans," asks Taylor.

The research also demonstrates a new mechanism by which different species of mammals can acquire genes, through non-retroviral integrated RNA viruses, which the UB scientists had previously identified in eukaryotes but was unknown in mammals.

The UB scientists note that it is well-known that RNA retroviruses, like HIV-AIDS, can be integrated into mammal genomes.

"But because filoviruses infect only the cytoplasm of cells and not the nucleus and because they have no means of making DNA copies that might be integrated into the genome -- as retroviruses do -- it was never thought gene transfer could occur between non-retroviral RNA viruses and hosts," says Bruenn. "This paper shows that it does and it may prove to be a far more general phenomenon than is currently known."

The research also reveals that existing estimates that filoviruses originated in mammals a few thousand years ago were way off the mark.

"Our findings demonstrate that filoviruses are, at a minimum, between 10 million and 24 million years old, and probably much older," says Taylor. "Instead of having evolved during the rise of agriculture, they more likely evolved during the rise of mammals."

I think integration can happen when the host is infected by multiple different types of viruses.
But i must stress that the mutation must happen in dna that ends up in reproductive cells as sperm or eggs.

But does this mean that the the specific animals can produce life complete filo viruses ?
Or is again another pathogen needed to complement the missing genes ?


Another link :
http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1001030

tcsenter
08-23-2010, 07:39 PM
Mouse virus link to chronic fatigue is studied (http://news.yahoo.com/s/ap/20100823/ap_on_he_me/us_med_chronic_fatigue)

William Gaatjes
08-23-2010, 08:12 PM
Mouse virus link to chronic fatigue is studied (http://news.yahoo.com/s/ap/20100823/ap_on_he_me/us_med_chronic_fatigue)

Interesting.

It seems i cannot find my other post anymore where i posted my worries about that rodents might be the carrier of a lot of viruses. It was also about marsupials.

But what i find strange is that the CDC did not do a larger screening for different viruses.

William Gaatjes
08-23-2010, 09:14 PM
To remove forum parser issue : %%%%%%%%%%%%%%%%%%%%


I read your post and did some research about the virus :

The XMRV virus mentioned in the text is associated with prostate cancer.
Interesting, another cancer candidate caused by i expect multiple virus infections or a virus together with a bacteria infection.
It is only known since 2006 it seems. It is suggested to be responsible for the chronic fatigue syndrome.

We have the Murine leukemia virus.
And we have the Xenotropic murine leukemia virus-related virus. Both found in humans.

http://news.sciencemag.org/sciencenow/2010/08/second-paper-supports-viral-link.html

There's a new twist in the ongoing battle over whether a virus is linked to chronic fatigue syndrome (CFS). After the journal held it for 2 months, a study supporting a link between a mouse retrovirus and CFS was published today in the Proceedings of the National Academy of Science (PNAS). Many are still doubtful of the link, but they're impressed by the authors' efforts to ensure accuracy.

In the new study, conducted by scientists at the National Institutes of Health (NIH), the U.S. Food and Drug Administration (FDA), and Harvard University, researchers scanned for traces of a virus known as XMRV in samples taken from 37 CFS patients, collected by Harvard Medical School CFS specialist Anthony Komaroff in the mid-1990s. They found evidence for the virus in 32 (87%) of the patients, but in only three out of 44 healthy controls (6.8%). It remains to be seen whether the infection causes the disease or vice versa, says NIH virologist and co-author Harvey Alter—but he's "confident" that the findings are correct.

XMRV—less succinctly known as xenotropic murine leukemia virus-related virus—was first implicated for its potential involvement in prostate cancer, a link that's still under intense debate. Then, in a Science paper published last year, a team led by retrovirologist Judy Mikovits of the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada, found evidence of infection in 67% of CFS patients, compared with just 3.4% of healthy controls. But since then, four other papers failed to find the link, or any evidence of XMRV infection in humans at all. The last of the four, by researchers at the U.S. Centers for Disease Control and Prevention (CDC), was also held for a while, at the researchers' request, while they tried to figure out how government labs could come to such opposite conclusions. The CDC paper was eventually published on 1 July in Retrovirology.

Skeptics were concerned that the XMRV Mikovits had found might be the result of contamination by mouse DNA in the lab. To address this, the new study's first author—FDA virologist Shyh-Ching Lo—and his colleagues tested every positive sample for murine mitochondrial DNA. They found none.

While the paper was on hold—also because of conflicts with other studies—the team ran additional checks that bolstered the data further, says Alter. "I felt we needed to do more to prove our case," Alter says, in part because an additional, third reviewer, had looked at the paper at PNAS's request. For instance, the researchers took fresh samples from eight of the patients and found that, 15 years on, they were still infected and that the virus had evolved, "just as we would expect from a retrovirus," says Alter. The wait was "time well spent," he adds.

The data do seem solid, admits Steve Monroe, who co-authored the conflicting CDC paper. "It's simply a good paper," adds Reinhard Kurth, the former director of the Robert Koch Institute in Germany, who helped test some of CDC's samples and did not find the virus either. Alter—a widely respected virologist and winner of the Albert Lasker Award for Clinical Medical Research—"clearly knows what he is doing. They did everything correctly," says Kurth, who nonetheless says he remains skeptical.

So too does virologist Robin Weiss of Imperial College London (ICL), who says he's seen too many instances of proposed new human retroviruses that fell apart on closer inspection, including one he reported in arthritis and lupus patients in 1999 that turned out to be an innocuous rabbit virus. (In a 40-page review that he co-authored in 2008, Weiss called such mishaps "human rumor viruses.") "You can have a very good reputation and be very careful and still get it wrong," Weiss says.

Part of the problem, skeptics say, is that the researchers didn't exactly replicate the Science paper. XMRV is a so-called xenotropic murine virus, which means it can no longer enter mouse cells but can infect cells of other species. (Murine means "from mice.") The researchers in the PNAS paper say the viral sequences they find are more diverse than that and resemble more closely the so-called polytropic viruses, which is why they adopted the term MLV-related virus, for murine leukemia virus. "Let's be clear: This is another virus. They did not confirm [Mikovits's] results," says retrovirologist Myra McClure of ICL, a co-author of one of the four negative studies.

Still, "in the grand scheme of things," the viral sequence found in the PNAS paper closely resembles those of XMRV, says Celia Witten, the director of FDA's Office of Cellular, Tissue and Gene Therapies, who was not an author of the paper herself but spoke on Lo's behalf. Witten adds that the data "support" the Science paper. Mikovits—who is "delighted" by the new paper—says the difference is not important. In as-yet-unpublished results, her group finds more genetic diversity in the virus as well, she says.

Meanwhile, a working group coordinated by the National Heart, Lung, and Blood Institute (NHLBI) is coordinating an effort to answer the most baffling question: Why some labs find the virus in both patients and healthy people, and others find it in neither. Initially, some believed there might be geographical reasons, because the first three negative studies were all from Europe—but that theory seems unlikely after the CDC paper, whose patients were from Kansas and Georgia. Patient selection could play a role: Different studies have used different diagnostic and recruitment criteria. But even given this messiness, it's hard to explain why four studies wouldn't have included a single infected patient.

The discordant results may also stem from subtle differences in handling the samples or performing the tests that would have led the four labs to miss the virus. But CDC's Monroe says he's confident that the lab can identify the virus. As part of the NHLBI program, researchers at FDA, CDC, WPI, and other labs have all blindly tested a panel of samples, some of them "spiked" with different amounts of the virus; all of them performed well. Further exchange of samples and reagents is now under way to understand where the differences came from. "They should be able to clear this up by Christmas," says Kurth.

Many of the main players in the controversy plan to attend a workshop organized by NIH on 7 and 8 September. Mikovits, who is on the scientific committee, says she has seen the abstracts of two presentations confirming her findings. "I think it will be fun," she says.

http://en.wikipedia.org/wiki/Xenotropic_murine_leukemia_virus-related_virus

http://en.wikipedia.org/wiki/Murine_leukemia_virus

William Gaatjes
08-25-2010, 01:28 PM
Plasmids must be added as well :

Can plasmids and viruses exchange dna ?
I would say yes. I just read that the Epstein barr virus turns itself into a plasmid after entering the cell.
Epstein barr virus is a herpes virus that can cause cancer.
I would think viruses started out as plasmids when looking at the way bacteria exchange plasmids...

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/R/RecombinantDNA.html

Plasmids are molecules of DNA that are found in bacteria separate from the bacterial chromosome.
They:
are small (a few thousand base pairs)
usually carry only one or a few genes
are circular
have a single origin of replication

Plasmids are replicated by the same machinery that replicates the bacterial chromosome. Some plasmids are copied at about the same rate as the chromosome, so a single cell is apt to have only a single copy of the plasmid. Other plasmids are copied at a high rate and a single cell may have 50 or more of them.

Genes on plasmids with high numbers of copies are usually expressed at high levels. In nature, these genes often encode proteins (e.g., enzymes) that protect the bacterium from one or more antibiotics.

Plasmids enter the bacterial cell with relative ease. This occurs in nature and may account for the rapid spread of antibiotic resistance in hospitals and elsewhere. Plasmids can be deliberately introduced into bacteria in the laboratory transforming the cell with the incoming genes.

http://upload.wikimedia.org/wikipedia/commons/thumb/c/cf/Plasmid_(english).svg/320px-Plasmid_(english).svg.png

http://en.wikipedia.org/wiki/Plasmid

Mr. Pedantic
08-26-2010, 03:53 AM
I would think it unlikely that viruses originated as plasmids given out by bacteria; generally, evolution tends towards complexity; simplicity is very hard to do. Also, I find it unlikely that any bacterial genome would have the functions that a virus would need to function.

William Gaatjes
08-26-2010, 07:42 AM
I would think it unlikely that viruses originated as plasmids given out by bacteria; generally, evolution tends towards complexity; simplicity is very hard to do. Also, I find it unlikely that any bacterial genome would have the functions that a virus would need to function.

Well, maybe it is not , maybe it is :
Maybe it is the other way around.
Here i have some more information from a discussion.

http://www.bio.net/bionet/mm/virology/1996-January/005314.html
The distinction between viruses and plasmids is further blurred
by the habit of some viruses of converting into plasmid form
upon entry to the cell. For example, Eptein-Barr virus will
circularise in the cell to form a stable plasmid that replicates
in phase with the cell. Expression of latency-associated proteins
allows the virus to persist without lysing the cell.

Circularisation of DNA is also not sufficient to distinguish a
plasmid from a virus, since some viruses, for example baculoviruses
(Nucleopolyhedrovirus, Granulovirus), circoviruses (Circovirus) and
corticoviruses (Corticovirus) have circular genomes.

The ability of a virus to package its DNA (or RNA) into a protein
capsid would be a feature that no plasmid shares; in other words,
plasmid DNA outside the cell would be "naked". However, given the
complex means that bacteria have developed for transferring plasmids
between themselves, I would not be surprised if some bacteria have
developed packaging systems for plasmids. However, this packaging
would not have been coded by the plasmid. Also, it is possible for
some viruses to integrate into the genome of the host cells and be
transmitted vertically from a parent to its progeny without the
need for expression of viral structural proteins. The retrovirus
mouse mammary tumour virus is such an example.

William Gaatjes
12-18-2010, 07:15 AM
The mimivirus.
A virus that can be infected by another virus "sputnik", a so called virophage.

http://www.microbiologybytes.com/virology/Mimivirus.html

Mimivirus is one of the largest and most complex viruses known. The virus was first isolated in 1992 from amoebae growing in a water tower in Bradford. La Scola, B. et al. (2003) A giant virus in amoebae. Science 299: 2033.

Both the particle size and the genome size of mimivirus is larger than that of some small bacteria. The 1.2 Mbp genome, which contains 911 protein coding genes, provides sufficient information to allow the virus to perform most (but not quite all) of the functions of living cells. The complexity and magnitude of the Mimivirus genome, combined with the large size of the virus, calls into question some of the established divisions between viruses and single-celled organisms, as well as raising questions about their evolution. Suzan-Monti M. (2005) Genomic and evolutionary aspects of Mimivirus. Virus Res.

Examination using cryo-electron microscopy has shown that the particle has a capsid with a diameter of 750 nm, including an array of 125 nm long closely packed fibres projecting out from the capsid surface. Based on a large number of open reading frames with collagen triple helix repeats in the viral genome, these fibers might consist of collagen. The dense, 200 thick base of these fibers might be formed by cross-linking. The capsid itself appeared to contain three layers of dense matter, probably representing two successive 4 nm thick lipid membranes inside a protein shell approximately 7 nm thick (Mimivirus and the emerging concept of giant virus. Claverie JM. et al. 2006 Virus Res. 117: 133-144). Similar double lipid membrane layers have been found in some poxviruses and in African swine fever virus (ASFV), another very large virus. Mimivirus particles also have a unique protruding vertex similar to that seen in tailed bacteriophages.

Mimivirus has many characteristics which put it at the boundary between living organisms and non-living entities. It is as large as several bacteria, such as Rickettsia conorii and Tropheryma whipplei, has a genome larger than a number of bacteria, and encodes some genetic products previously not known to be possessed by any virus. In particular, mimivirus contains genes coding for nucleotide and amino acid synthesis which even some small obligate intracellular bacteria lack. This means that unlike these bacteria, mimivirus is not dependent on the host cell genome for coding the metabolic pathways for these products. It does however, lack genes for ribosomal proteins, making mimivirus dependent on a host cell for protein synthesis and energy metabolism.

So, is mimivirus alive? Like all viruses, mimivirus particles do not reproduce by division, but are replicated by the self-assembly of preformed components. This differentiates it from cellular living organisms such as bacteria.

Patients with pneumonia have shown positive serological tests for mimivirus, and a laboratory technician working with the virus developed pneumonia and seroconverted. However, neither of these observations was definitive proof that mimivirus can cause disease, so experimental infections have been carried out in mice, which also developed pneumonia (Khan M. et al.

http://www.nature.com/news/2008/080806/full/454677a.html

An excerpt :
Closer inspection showed the microbe to be a huge virus with, as later work revealed, a genome harbouring more than 900 protein-coding genes3 — at least three times more than that of the biggest previously known viruses and bigger than that of some bacteria. It was named Acanthamoeba polyphaga mimivirus (for mimicking microbe), and is thought to be part of a much larger family. “It was the cause of great excitement in virology,” says Eugene Koonin at the National Center for Biotechnology Information in Bethesda, Maryland. “It crossed the imaginary boundary between viruses and cellular organisms.”

Now Raoult, Koonin and their colleagues report the isolation of a new strain of giant virus from a cooling tower in Paris, which they have named mamavirus because it seemed slightly larger than mimivirus. Their electron microscopy studies also revealed a second, small virus closely associated with mamavirus that has earned the name Sputnik, after the first man-made satellite.

With just 21 genes, Sputnik is tiny compared with its mama — but insidious. When the giant mamavirus infects an amoeba, it uses its large array of genes to build a ‘viral factory’, a hub where new viral particles are made. Sputnik infects this viral factory and seems to hijack its machinery in order to replicate. The team found that cells co-infected with Sputnik produce fewer and often deformed mamavirus particles, making the virus less infective. This suggests that Sputnik is effectively a viral parasite that sickens its host — seemingly the first such example.

The team suggests that Sputnik is a ‘virophage’, much like the bacteriophage viruses that infect and sicken bacteria. “It infects this factory like a phage infects a bacterium,” Koonin says. “It’s doing what every parasite can — exploiting its host for its own replication.”

Sputnik’s genome reveals further insight into its biology. Although 13 of its genes show little similarity to any other known genes, three are closely related to mimivirus and mamavirus genes, perhaps cannibalized by the tiny virus as it packaged up particles sometime in its history. This suggests that the satellite virus could perform horizontal gene transfer between viruses — paralleling the way that bacteriophages ferry genes between bacteria.





And 3 old news items how the immune system of bacteria can work.

http://www.sciencedaily.com/releases/2009/12/091231153907.htm
For the entire post click the link.

I find this most interesting :
In response to the unlimited number of foreign antigens (bits of microbes, chemicals and other substances) that can invade our bodies, the immune system must be able to tailor-make an unlimited number of antibodies. However, the amount of DNA in a cell is limited, so antibody-producing B cells must mutate and re-arrange their antibody genes to step up to the challenge (using processes called somatic hypermutation and class switch recombination, respectively).

In collaboration with the Papavasiliou lab, Dunnick discovered that mice carrying the artificial chromosomes with the antibody genes behave in ways that are indistinguishable from unmanipulated mice: they recombine and mutate their antibody genes to generate highly specific attacks on foreign invader. But for that, they absolutely need their enhancers: without them, the cell's machinery can transcribe and translate the antibody genes, but can't rearrange or mutate them, suggesting that the enhancers function as a loading dock for a common initiator molecule, which is then hauled to the antibody genes.

The experiments show that the enhancers of antibody genes are vital in springing the immune system to action, and suggest that mutations in the enhancers may make an individual more susceptible to infections, even infections for which he should have been vaccinated. "The main goal of vaccination is to produce, in a short amount of time, antibodies that are diversified to be most effective against a particular virus or bacterium," says Dunnick. "We were fortunate to identify the control elements that are critical for this antibody diversification."


http://www.sciencedaily.com/releases/2009/11/091125134703.htm

Still, bacteria and another class of microorganisms called archaea (first discovered in extreme environments such as deep-sea volcanic vents) manage just fine, thank you, in part because they have a built-in defense system that helps protect them from many viruses and other invaders.

A team of scientists led by researchers at the University of Georgia has now discovered how this bacterial defense system works, and it could lead to new classes of targeted antibiotics, new tools to study gene function in microorganisms and more stable bacterial cultures used by food and biotechnology industries to make products such as yogurt and cheese.

The research was published November 26 in the journal Cell.

"Understanding how bacteria defend themselves gives us important information that can be used to weaken bacteria that are harmful and strengthen bacteria that are helpful," said Michael Terns, a professor of biochemistry and molecular biology in UGA's Franklin College of Arts and Sciences. "We also hope to exploit this knowledge to develop new tools to speed research on microorganisms."

Other authors on the Cell paper include Rebecca Terns, a senior research scientist in biochemistry and molecular biology at UGA; Caryn Hale, a graduate student in the Terns lab at UGA; Lance Wells, an assistant professor of biochemistry and molecular biology and Georgia Cancer Coalition Scholar at UGA and his graduate student Peng Zhao; and research associate Sara Olson, assistant professor Michael Duff and associate professor Brenton Graveley of the University of Connecticut Health Center.

The system, whose mechanism of action was uncovered in the Terns lab (Michael and Rebecca Terns are a husband-wife team), involves a "dynamic duo" made up of a bacterial RNA that recognizes and physically attaches itself to a viral target molecule, and partner proteins that cut up the target, thereby "silencing" the would-be cell killer.

The invader surveillance component of the dynamic duo (an RNA with a viral recognition sequence) comes from sites in the genomes of bacteria and archaea, known technically as "clustered regularly interspaced short palindromic repeats" or more familiarly called CRISPRs. (A palindrome is a word or sentence that reads the same forward and backward.) CRISPR RNAs don't work alone in fighting invaders, though.

Their partners in invader defense are Cas proteins that arise from a suite of genes called "CRISPR-associated" or Cas genes. Together, they form the "CRISPR-Cas system," and the new paper describes this dynamic duo and how they protect bacteria from viruses.

"You can look at one as a police dog that tracks down and latches onto an invader, and the other as a police officer that follows along and `silences' the offender," said Rebecca Terns. "It functions like our own immune system, constantly watching for and neutralizing intruders. But the surveillance is done by tiny CRISPR RNAs rather than antibodies."

What the team discovered was that a particular complex of CRISPR RNAs and a subset of the Cas proteins termed the RAMP module recognizes and destroys invader RNAs that it encounters.

"This work has uncovered intriguing parallels between the bacterial CRISPR-Cas system and the human immune system, suggesting a novel way to target disease-causing bacteria," said Laurie Tompkins, Ph.D., who oversees genetic mechanisms grants at the National Institutes of Health's National Institute of General Medical Sciences. "It may be possible to turn CRISPR-Cas into a suicide machine, killing pathogenic bacteria by an attack on their own molecules, similar to the self-destruction seen in human autoimmune diseases."

Understanding how the system silences invaders opens up opportunities to exploit it. So far, CRISPRs have been found in about half of the bacterial genomes that have been mapped or sequenced and in nearly all sequenced archaeal genomes. Such pervasiveness indicates that an ability to manipulate the CRISPR-Cas system could yield a broad range of applications. For example, using the knowledge that they have obtained in this work, the Terns now envision being able to design new CRISPR RNAs that will take advantage of the system to selectively cleave target RNAs in bacterial cells.

"These could target viruses that wipe out cultures of bacteria used by industry to produce enzymes," said Michael Terns, "or could target the gene products of the bacteria themselves. With this set of Cas proteins, we now know how to cut a target RNA at the site we choose."

"Believe it or not, we have only recently recognized that these microorganisms have a heritable immune system [because it is so different from our own]," added Rebecca Terns.

Remarkably, scientists are already in a position to begin to capitalize on their rapidly growing knowledge of this bacterial immune system.

http://www.sciencedaily.com/releases/2010/09/100915171531.htm




The team led by Professor Sylvain Moineau of Université Laval's Department of Biochemistry, Microbiology, and Bioinformatics showed that this mechanism, called CRISPR/Cas, works by selecting foreign DNA segments and inserting them into very specific locations in a bacterium's genome. These segments then serve as a kind of immune factor in fighting off future invasions by cleaving incoming DNA.

The researchers demonstrated this mechanism using plasmids, DNA molecules that are regularly exchanged by bacteria. The plasmid used in the experiment, which contained a gene for antibiotic resistance, was inserted into bacteria used in making yogurt, Streptococcus thermophilus. Some of the bacteria integrated the segments of DNA from the resistance gene into their genome, and subsequent attempts to reinsert the plasmid into these bacteria failed. "These bacteria had simply been immunized against acquiring the resistance gene, commented Professor Moineau. This phenomenon could explain, among other things, why some bacteria develop antibiotic resistance while others don't."

The CRISPR/Cas immune system also protects bacteria from bacteriophages, a group of viruses that specifically target bacteria. This makes Professor Moineau's discovery particularly interesting for food and biotechnology sectors that use bacterial cultures, such as the yogurt, cheese, and probiotics industries. Bacterial culture contamination by bacteriophages is a serious concern with considerable financial implications for those industries.

wirednuts
12-18-2010, 09:14 AM
i have had acute chrons disease for 10 years. it took at least 5 years before i was able to find a way to regulate it a bit. and now it doesnt effect me often, and even when it does im not completely disabled like i used to be.

bacteria in the gut is the absolute key. the relationship between beneficial bacterial and your body's immune system is CRUCIAL. i am living proof of this. all the meds the doctors gave me only cured symptoms like pain and fatigue. my body was still wasting away, until i started taking probiotics. and every time i go south and i dont start taking the beneficial bacteria it simply never gets better. the longer you let the disease have free reign, the longer it takes to come back from it. i still have spurts of 3-5 months where i am not as healthy as i should be, but thats better then the 6 months of diarrhea and days of hospital stays that i used to have.

i have read countless articles on anything that might relate to chrons, so this one in OP is interesting to me too. there was one article i read that told of brainwave experiments focused on the intestines. same tests they do on the brain, only pointed on the gut. they were absolutely shocked when they found the same exact types of brainwaves that we have in our head. they now believe the stomach is actually a sub-brain, that controls the physical parts of our bodies like muscle control and immune system. it makes sense too, like a car's main ecm computer and its sub-computer on the transmission, or the body's ecm that controls the lights and buttons. the main computer (our brains) dictate actual descision making, while the sub-computer (our gut) controls the actual parts of our bodies into doing what our brain wants.

this is why it seems VITAL to have the proper organisms in your stomach. right now, sterile is not so great because we cant evolve away quick enough from our thousands of years of being connected to the outside environment. this is why probiotics help, because they reintroduce those organisms that our body manipulates into fighting the bad bacteria that is always trying to grow inside of us.

and if our stomach is healthy, our immune system is healthy. which means our bodies are healthy... which helps the brain function properly. its all tightly interconnected and were only starting to figure out the details, but its fascinating none the less.

William Gaatjes
12-18-2010, 09:48 AM
Good for you that you discovered the link between your disease and the bacteria inside your gut.

I do not know if i would call the bowls a brain. But i do think that the brain and the digestive system keep good contact with each other as does the immunesystem. A triangle of power generation, protection and command structure.


I do not have chrone disease but i did discover that any processed food product or advised normal amounts of sugar gives me pain , bowl movement problems or constipation changing rapidly into diarrhea for days in a row. And as a side effect acne like skin problems.
Since i make my own food recipes with reduced sugar and eat healthy this has improved for me :
My physical strength and stamina has increased.
Fighting of common diseases like flu or common cold in a matter of 4 hours while only feeling tired and a hunger for protein rich diet, after consuming i can sleep immediately. When awake i am no longer feeling feverish and the next day cured. I account this to that my body can stop the infection from spreading because i already have a lot of antibodies (public transport advantage) and because of my protein/vitamin/essential elements rich(low carbon hydrate) diet my immune system works better.
while i eat apparently the same, my bloated belly has gone.
My vertebrate problem hurts a lot less.

I do not take supplements. I just eat healthy and normal and moderate.

I too believe that the modern medical world underestimates the importance of a healthy diverse bacteria culture in the gut. But we need the right bacteria and wrong food can cause the wrong balance of bacteria.
The old true asian ways ( not that fake rhino horn or tiger penis bullshit) but using the right plants and roots (with accompanying bacteria) can help solve or relieve many problems by restoring the balance in the gut.

EDIT:
The old middle east and the old celtics and germanic tribes had similar knowledge about the healing powers of plants and roots( without knowing that bacteria existed on these plants and roots). Unfortunately the roman catholic church destroyed the knowledge because this knowledge was seen as heresy.
The old islam renaissance ( or islamic golden age) saved the asian version of this knowledge but got lost as well when the religion got divided by power hungry people. Until unfortunately the islam became similar as the roman catholic church dogma. Knowledge lost, lies gained.

Fun to know is that during the islamic golden age people theorized that there existed living creatures that can make you sick but where to small to see with the eye ? That is around the same time when quarantine was discovered/invented.

William Gaatjes
12-28-2010, 04:30 PM
I had not added this yet. Different types of bacteria movement :

http://forums.anandtech.com/showthread.php?t=2091742

Picture of a phage, and a photo about a model how an bacteria flagellum works.

A video about how it works :

http://www.youtube.com/watch?v=Ey7Emmddf7Y

And research that seem to suggest that bacteriophages can be responsible for the fine tuning of interaction between bacteria and their host :

Our data suggest that horizontal transfer of type III dependent effector proteins by lysogenic infection with bacteriophages (lysogenic conversion) may provide an efficient mechanism for fine-tuning the interaction of Salmonella spp. with their hosts.

William Gaatjes
12-29-2010, 05:02 AM
Alzheimer's disease and the HVS1.

This option has been researched since 1988 and more and more prove stacks on that this is the case since the last 20 years.

http://www.nytimes.com/1988/07/23/us/research-suggests-virus-link-to-alzheimer-s-disease.html

http://www.sciencedaily.com/releases/2008/12/081207134109.htm

They believe the herpes simplex virus is a significant factor in developing the debilitating disease and could be treated by antiviral agents such as acyclovir, which is already used to treat cold sores and other diseases caused by the herpes virus. Another future possibility is vaccination against the virus to prevent the development of the disease in the first place.

Alzheimer's disease (AD) is characterised by progressive memory loss and severe cognitive impairment. It affects over 20 million people world-wide, and the numbers will rise with increasing longevity. However, despite enormous investment into research on the characteristic abnormalities of AD brain - amyloid plaques and neurofibrillary tangles - the underlying causes are unknown and current treatments are ineffectual.

Professor Ruth Itzhaki and her team at the University's Faculty of Life Sciences have investigated the role of herpes simplex virus type 1 (HSV1) in AD, publishing their very recent, highly significant findings in the Journal of Pathology.

Most people are infected with this virus, which then remains life-long in the peripheral nervous system, and in 20-40% of those infected it causes cold sores. Evidence of a viral role in AD would point to the use of antiviral agents to stop progression of the disease.

The team discovered that the HSV1 DNA is located very specifically in amyloid plaques: 90% of plaques in Alzheimer's disease sufferers' brains contain HSV1 DNA, and most of the viral DNA is located within amyloid plaques. The team had previously shown that HSV1 infection of nerve-type cells induces deposition of the main component, beta amyloid, of amyloid plaques. Together, these findings strongly implicate HSV1 as a major factor in the formation of amyloid deposits and plaques, abnormalities thought by many in the field to be major contributors to Alzheimer's disease.

The team had discovered much earlier that the virus is present in brains of many elderly people and that in those people with a specific genetic factor, there is a high risk of developing Alzheimer's disease.

The team's data strongly suggest that HSV1 has a major role in Alzheimer's disease and point to the usage of antiviral agents for treating the disease, and in fact in preliminary experiments they have shown that acyclovir reduces the amyloid deposition and reduces also certain other feature of the disease which they have found are caused by HSV1 infection.

Professor Itzhaki explains: "We suggest that HSV1 enters the brain in the elderly as their immune systems decline and then establishes a dormant infection from which it is repeatedly activated by events such as stress, immunosuppression, and various infections.

http://brainblogger.com/2010/12/15/alzheimer’s-disease-vaccine-on-the-horizon/

HSV1 is ubiquitous, identified in approximately 90% of adults. Normally, an infection with HSV1 occurs in infancy, but the virus remains lifelong in the peripheral nervous system in a latent, inactive state. HSV1 can be reactivated later in life by stress, immunosuppression, fever or ultraviolet light exposure; HSV1 is the virus that causes cold sores. Researchers postulate that if HSV1 reaches the brain, the virus could cause damage consistent with AD. Likewise, HSV1 is already identified as the cause of herpes simplex encephalitis, a rare but serious brain disorder, which leaves survivors with memory loss and a loss of cognitive function, just as AD does.

HSV1 does not cause AD on its own. There are likely host factors that alter the risks for developing AD. Interestingly, a genetic component — the type 4 allele of the apolipoprotein E gene, which normally transports lipids in the body and repairs tissue damage — confers a high risk of AD when associated with HSV1. (The same genetic component is an increased risk factor for cold sores.)

Two hallmarks of AD are the presence of amyloid plaques and neurofibrillary tangles in the brain. Beta-amyloid, the primary component of the plaques, accumulates in the presence of HSV1 infections. Further, 90% of plaques evaluated from AD brains contained HSV1, and 72% of the virus DNA was associated with plaques; in normal, aged brains, which contain amyloid plaques at a much lower frequency than AD brains, 80% of the plaques contained HSV1, but only 24% of the viral DNA was plaque-associated. In normal brains, it is likely that there is a lesser production or greater removal of beta-amyloid, so it is less likely that HSV1 would be able to interact destructively inside the brain. Basically, HSV1 infection likely induces changes in gene expression in the brain, through its inflammatory and oxidative processes, that are damaging to the brain.

The only current pharmacological therapies approved for AD are acetylcholinesterase inhibitors and N-methyl-D-aspartic acid receptor inhibitors, which demonstrate symptomatic improvement, but do not treat the underlying cause of AD. The proposed involvement of HSV1 in AD has led to the possibility of the first potentially disease-modifying treatments in AD. Antiviral agents, such as acyclovir and valacyclovir, may be beneficial in preventing disease progression in AD patients. These agents inhibit the synthesis of viral DNA, preventing its spread throughout the body and the damage it causes. (Acyclovir is also being evaluated in the treatment of multiple sclerosis, owing to another herpes virus implicated in the development of that disease.) Alternatively, a vaccine to prevent the reactivation of HSV1 and prevent AD altogether is being evaluated in human trials. Anti-viral agents are the first attempt to prevent the pathogenesis of AD, rather than just treat the symptoms, offering hope to millions of current and future AD sufferers and their families.



Chackerian B (2010). Virus-like particle based vaccines for Alzheimer disease. Human vaccines, 6 (11) PMID : 20864801

Chackerian B, Rangel M, Hunter Z, & Peabody DS (2006). Virus and virus-like particle-based immunogens for Alzheimer’s disease induce antibody responses against amyloid-beta without concomitant T cell responses. Vaccine, 24 (37-39), 6321-31 PMID : 16806604

Hill JM, Zhao Y, Clement C, Neumann DM, & Lukiw WJ (2009). HSV-1 infection of human brain cells induces miRNA-146a and Alzheimer-type inflammatory signaling. Neuroreport, 20 (16), 1500-5 PMID : 19801956

Itzhaki RF, & Wozniak MA (2006). Herpes simplex virus type 1, apolipoprotein E, and cholesterol: a dangerous liaison in Alzheimer’s disease and other disorders. Progress in lipid research, 45 (1), 73-90 PMID : 16406033

Lukiw WJ, Cui JG, Yuan LY, Bhattacharjee PS, Corkern M, Clement C, Kammerman EM, Ball MJ, Zhao Y, Sullivan PM, & Hill JM (2010). Acyclovir or Abeta42 peptides attenuate HSV-1-induced miRNA-146a levels in human primary brain cells. Neuroreport, 21 (14), 922-7 PMID : 20683212

Sabbagh, M., & Berk, C. (2010). Latrepirdine for Alzheimer’s disease: trials and tribulations Future Neurology, 5 (5), 645-651 DOI: 10.2217/fnl.10.53

Wozniak MA, Mee AP, & Itzhaki RF (2009). Herpes simplex virus type 1 DNA is located within Alzheimer’s disease amyloid plaques. The Journal of pathology, 217 (1), 131-8 PMID : 18973185

Wozniak, M., & Itzhaki, R. (2010). Antiviral agents in Alzheimer’s disease: hope for the future? Therapeutic Advances in Neurological Disorders, 3 (3), 141-152 DOI: 10.1177/1756285610370069

William Gaatjes
03-04-2011, 09:08 AM
In my conquest of understanding the proliferation of diseases, i noticed something interesting. That cancer of the large intestines is relatively common while cancer of the small intestines is relatively rare.

When looking from the perspective of carrying bacteria in the large intestines, the small intestines are almost sterile with respect to the amounts of bacteria present in the small intestines. I found so far that cancer from the small intestines seems to start in nearby tissue and then spread out towards the small intestines. Afcourse there is always an exception. That exception seems to be Crohn's disease. Crohn's disease seems to be an auto immune system disease. From what i have read, this does not seem to be a genetic disorder. However, there has been research done that suggests that having a certain type of gene makes a person more susceptible to Crohn's disease but is not the primary cause. Crohn's disease also seems to be a family trait(duh :rolleyes: to myself : Genes.).

But i was thinking, the bacterial culture is also passed along from mother and father to child. I wonder if every isolated family have their own specific bacteria ? It makes sense. That some diseases are not just genetic (meaning in this special scenario more susceptible towards a certain disease) But that the bacterial culture also plays a role. If i think about it, i would expect diversification because of school and playgrounds would level out bacterial differences between young children. But maybe this is not entirely the case. Because when the children are home with their parents again, they are exposed again to the home environment (aka the family bacterial culture).

Now i mentioned that the small intestines are almost sterile meaning almost no bacteria. Maybe i am wrong, but Crohn's disease seems to start mostly at the ileum. The ileum is the last part of the small intestines and advances into the large intestines at the cecum. Here the appendix is also connected.

I read once in some journal although i do not know if this is true , that the appendix could be a bacterial reservoir.

Does Anybody have more interesting opinions or news ?

William Gaatjes
03-04-2011, 10:04 AM
Forgot to mention this :
Celiac disease, i do not understand this disease. Sometimes it is invoked by a gluten rich diet caused by gliadin found in the gluten.


Perhaps there is another interesting factor. I do not know for sure and here is an idea :
Simply put, gluten is a combination of proteins found in wheat made from the endosperm of grains. Fungi are very common in wheat. In the past a lot of demon sightings and witch burning happened because of local wheat from local villages was invested with certain fungi. When consumed, the byproducts of these fungi would cause people to hallucinate and have violent spasms and pain cramps. Giving the illusion to be possessed while in reality to be poisoned. But hey these where mid evil times and the churches where fond of spreading lies.

I do wonder if a prolonged exposure to a certain type of fungi in the intestines could cause an immune response that would attack seemingly random tissues throughout the entire body. The fungi would not cause any symptoms. But if the fungi would have been consumed while being infected by a fungi virus, this would make a seemingly unrelated cause and effect.
The virus could spread unnoticed until it is too late. The immune system starts to attack every tissue where viral proteins are found. The key factor here would be that the viral proteins resemble the gliadin peptide found to be the cause of Celiac disease.

William Gaatjes
08-19-2011, 04:00 AM
This is certainly an interesting view :

http://www.wired.com/medtech/health/news/2004/10/65252


Most of the cells in your body are not your own, nor are they even human. They are bacterial. From the invisible strands of fungi waiting to sprout between our toes, to the kilogram of bacterial matter in our guts, we are best viewed as walking "superorganisms," highly complex conglomerations of human cells, bacteria, fungi and viruses.

That's the view of scientists at Imperial College London who published a paper in Nature Biotechnology Oct. 6 describing how these microbes interact with the body. Understanding the workings of the superorganism, they say, is crucial to the development of personalized medicine and health care in the future because individuals can have very different responses to drugs, depending on their microbial fauna.

The scientists concentrated on bacteria. More than 500 different species of bacteria exist in our bodies, making up more than 100 trillion cells. Because our bodies are made of only some several trillion human cells, we are somewhat outnumbered by the aliens. It follows that most of the genes in our bodies are from bacteria, too.

Luckily for us, the bacteria are on the whole commensal, sharing our food but doing no real harm. (The word derives from the Latin meaning to share a table for dinner.) In fact, they are often beneficial: Our commensal bacteria protect us from potentially dangerous infections. They do this through close interaction with our immune systems.

"We have known for some time that many diseases are influenced by a variety of factors, including both genetics and environment, but the concept of this superorganism could have a huge impact on our understanding of disease processes," said Jeremy Nicholson, a professor of biological chemistry at Imperial College and leader of the study. He believes the approach could apply to research on insulin-resistance, heart disease, some cancers and perhaps even some neurological diseases.

Following the sequencing of the human genome, scientists quickly saw that the next step would be to show how human genes interact with environmental factors to influence the risk of developing disease, the aging process and drug action. But because environmental factors include the gene products of trillions of bacteria in the gut, they get very complex indeed. The information in the human genome itself, 3 billion base pairs long, does not help reduce the complexity.

"The human genome provides only scant information. The discovery of how microbes in the gut can influence the body's responses to disease means that we now need more research into this area," said Nicholson. "Understanding these interactions will extend human biology and medicine well beyond the human genome and help elucidate novel types of gene-environment interactions, with this knowledge ultimately leading to new approaches to the treatment of disease."

Nicholson's colleague, professor Ian Wilson from Astra Zeneca, believes the "human super-organism" concept "could have a huge impact on how we develop drugs, as individuals can have very different responses to drug metabolism and toxicity."

"The microbes can influence things such as the pH levels in the gut and the immune response, all of which can have effects on the effectiveness of drugs," Wilson said.

The Imperial College research demonstrates what many -- from X Files stalwarts to UFO fanatics -- have long claimed: We are not alone. Specifically, the human genome does not carry enough information on its own to determine key elements of our own biology.



Imagine what the environment for an effect might have if pollution is part of that environment.
New strains arise because of evolutionary survival. New strains the body may not be able to cope with. The balance distorted. The symbiotic structure unstable.
If you live wrongly, only seeking worldly pleasures, then you are destroying your own environment. And in the end destroying yourself or by means of karma, your offspring. Greed and selfishness is not a good thing.

William Gaatjes
08-30-2011, 03:42 PM
This research seems to provide more proof that there is a link between the mind and the micro organisms in our gut.

http://medicalxpress.com/news/2011-08-probiotics-brain-functioning.html


(Medical Xpress) -- It was just last year that a certain company selling a special probiotic enhanced yogurt was ordered by a U.S. court to stop suggesting in its advertisements that it's product had health benefits that went beyond the norm. Now, new evidence by Javier Bravo and colleagues at University College Cork, suggests the company may have been on to something. In their paper, published in the Proceedings of the National Academy of Science, the team describes how mice given the prbiotic Lactobacillus rhamnosus, showed signs of being less anxious and depressed and even had lowered levels of stress hormones.

Building on recent research that suggests there may be more of a gut-mind link than scientists have realized (such as depression and anxiety linked to bowel problems) Bravo and his team decided to look into probiotics and their possible impact on mood. In their research, they focused on Lactobacillus rhamnosus, a probiotic bacterium normally found in the gut, and which is also commonly found in various kinds of yogurt and other types of dairy products.

To find out if ingesting L. rhamnosus did indeed have any impact beyond normal nutritional value, the team fed half of a group of mice a broth heavily laden with the bacterium for a period of time; the other half were given the same broth without the probiotic. Afterwards, the mice were tested to see if any discernible behavioral changes resulted.

Bravo et al found that the mice that had been given the probiotic demonstrated less anxious type behaviors, such as more of a willingness to traverse narrow walkways or to venture out into wide open spaces, activities that are known to cause stress in mice. They also found that the mice that had eaten the probiotic were less likely give in to the sensation of drowning when put in water, a sign that normally indicates depressive behavior. And finally, they found that the treated mice also had lower levels of stress hormones in their blood.

To find more proof of the connection, the team then severed the vagus nerve in the test mice and found the behaviors and hormone levels reverted back to their norms. The Vagus nerve transmits information from the gut and other organs to the brain, thus having it severed removes any means of communication between the two.

The team also found that the brain neurotransmitter gamma-aminobutyric acid (GABA) was also changed in the mice that had been fed the probiotic, with higher levels found in some areas of the brain associated with depression and lower levels in some areas associated with anxiety.

All in all the team feels confident that they’ve found a clear link between probiotics and mood and behavioral changes in mice; the next step of course will be to find out if the same is true for people.

More information: Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve, PNAS, Published online before print August 29, 2011, doi: 10.1073/pnas.1102999108

Abstract
There is increasing, but largely indirect, evidence pointing to an effect of commensal gut microbiota on the central nervous system (CNS). However, it is unknown whether lactic acid bacteria such as Lactobacillus rhamnosus could have a direct effect on neurotransmitter receptors in the CNS in normal, healthy animals. GABA is the main CNS inhibitory neurotransmitter and is significantly involved in regulating many physiological and psychological processes. Alterations in central GABA receptor expression are implicated in the pathogenesis of anxiety and depression, which are highly comorbid with functional bowel disorders. In this work, we show that chronic treatment with L. rhamnosus (JB-1) induced region-dependent alterations in GABAB1b mRNA in the brain with increases in cortical regions (cingulate and prelimbic) and concomitant reductions in expression in the hippocampus, amygdala, and locus coeruleus, in comparison with control-fed mice. In addition, L. rhamnosus (JB-1) reduced GABAAα2 mRNA expression in the prefrontal cortex and amygdala, but increased GABAAα2 in the hippocampus. Importantly, L. rhamnosus (JB-1) reduced stress-induced corticosterone and anxiety- and depression-related behavior. Moreover, the neurochemical and behavioral effects were not found in vagotomized mice, identifying the vagus as a major modulatory constitutive communication pathway between the bacteria exposed to the gut and the brain. Together, these findings highlight the important role of bacteria in the bidirectional communication of the gut–brain axis and suggest that certain organisms may prove to be useful therapeutic adjuncts in stress-related disorders such as anxiety and depression.

William Gaatjes
09-07-2011, 03:33 AM
Researcher at the university of Michigan have found out how our little friends deal with uranium. The pili seem to play an important role.

http://www.physorg.com/news/2011-09-bacteria-immobilize-uranium.html



(PhysOrg.com) -- For several years, researchers have known that certain kinds of bacteria are able to "feed" off certain metals by either adding or removing electrons from their structure, but until now, haven’t really understood how they do it. Now, new research by Gemma Reguera and her team at Michigan State University have shown that the bacteria do so by means of protein nanowires, called pili, which are hair-like appendages with electrical conductivity. They have reported their findings in the Proceedings of the National Academy of Sciences.

The team specifically set out to find out how a specific type of bacterium known as a Geobacter, in this case, G. sulfurreducens, are able to clean up nuclear waste left behind by the cold war in such places as Colorado mines. They, like other researchers, believed that the bacteria were able to do its work through use of pili. In order to find out for sure, they had to induce the specimens to actually grow some in the lab, something that had stumped others before them. To force them, Reguera and her team subjected G. sulfurreducens, to much more harsh conditions than had been done before, presuming that the bacteria wouldn’t resort to using its pili unless pressed.

The tactic worked and the team was able to cause G. sulfurreducens to grow a mass of pili, which allowed them to study how they interacted with uranium. They found that the pili served as a buffer of sorts, protecting the cell structure of the bacterium as they also allowed for adding electrons to uranium ions which causes it to become more water soluble and thus safer to handle and clean up.

The pili grow to enormous lengths (though they are very then - only a few nanometers) relative to the bacteria that produce them, forming a conductive and protective barrier that allows the bacteria to thrive in truly hostile environments.

The study, part of ongoing research into so-named bioremediation; using organisms to remove unwanted substances from soil and water, adds to the growing body of knowledge that scientists hope will one day soon provide a means for dealing with a wide variety of environmental pollutants.

As for Reguera and her team, they hope their research eventually leads to getting away from using biological bugs to clean up toxic environments and more towards creating tiny little programmed robots that can mimic their actions but can be more easily manipulated into doing exactly what is needed in particular circumstances.


More about pili :


A pilus (Latin for 'hair'; plural : pili) is a hairlike appendage found on the surface of many bacteria.[1][2] The terms pilus and fimbria (Latin for 'thread' or 'fiber'; plural: fimbriae) can be used interchangeably, although some researchers reserve the term pilus for the appendage required for bacterial conjugation. All pili are primarily composed of oligomeric pilin proteins.

Pili connect a bacterium to another of its species, or to another bacterium of a different species, and build a bridge between the interior of the cells. This enables the transfer of plasmids between the bacteria. An exchanged plasmid can code for new functions, e.g., antibiotic resistance. The pilus is made up of the protein pilin.

Dozens of these structures can exist on the bacteria. Some bacterial viruses or bacteriophages attach to receptors on sex pili at the start of their reproductive cycle.

Pili are antigenic. They are also fragile and constantly replaced, sometimes with pili of different composition, resulting in altered antigenicity. Specific host responses to old pili structure are not effective on the new structure. Recombination genes of pili code for variable (V) and constant (C) regions of the pili (similar to immunoglobulin diversity).


http://en.wikipedia.org/wiki/Pilus

William Gaatjes
09-18-2011, 10:20 AM
Epi genetics.

EDIT:
I almost forgot to write that although the research from physorg is about plants, it is not unique to plants.
/EDIT


A simplified explanation.
What i understand of it, is that humans (and possibly all mammals) do not posses enough genes where each gene separately encodes for a certain function. The solution is to use multiple genes at the same time and for a certain amount of time. The idea is that the environment also has control on the use of multiple genes and the time these genes are active.

Here is my opinion :
Remember quorum sensing of bacteria ?
Remember also that the bacteria on the human body are also part of the environment but also live in symbiosis with the cells in our body. And that we have more bacteria living inside us and on our skin then we have human cells. Remember also that all these bacteria together have more dna then humans do. I would not be surprised if the bacteria can also influence human gene expression by use of epigenetics.
For example if a human family lives on an isolated location. Then that human family will over time evolve differently depending on the environment when compared to other human families that live on other locations on the planet with different environments. I would think it is possible that each human family does not only have their own specific family genes, but also their own specific bacterial culture. The idea is that human dna does not change that quickly. But bacterial dna changes and evolves a lot faster( in matter of hours). If bacteria that live in symbiosis with humans can adapt faster to a changing environment, then these bacteria might also be able to adapt humans faster by use of epigenetics. Instead of letting the complex human dna evolve with all the issues that rise with it(diseases because of genetic disposition), we have epigenetics where the smaller microorganisms evolve and we adapt automagically. However, this works by the grace that the microorganisms do not evolve into something that will kill us. That can happen when the environment is seriously polluted. Cancer victims will rise for example. Miscarriages and stillbirth and birth defects will rise in number then as well.

I do think it is save to say we are the result of the symbiosis between the cells of our bodies and the bacteria that live in it and on it.


http://www.physorg.com/news/2011-09-genes-destiny-hidden-code-dna.html


A "hidden" code linked to the DNA of plants allows them to develop and pass down new biological traits far more rapidly than previously thought, according to the findings of a groundbreaking study by researchers at the Salk Institute for Biological Studies.

The study, published today in the journal Science, provides the first evidence that an organism's "epigenetic" code - an extra layer of biochemical instructions in DNA - can evolve more quickly than the genetic code and can strongly influence biological traits.

While the study was limited to a single plant species called Arabidopsis thaliana, the equivalent of the laboratory rat of the plant world, the findings hint that the traits of other organisms, including humans, might also be dramatically influenced by biological mechanisms that scientists are just beginning to understand.

"Our study shows that it's not all in the genes," said Joseph Ecker, a professor in Salk's Plant Molecular and Cellular Biology Laboratory, who led the research team. "We found that these plants have an epigenetic code that's more flexible and influential than we imagined. There is clearly a component of heritability that we don't fully understand. It's possible that we humans have a similarly active epigenetic mechanism that controls our biological characteristics and gets passed down to our children. "

With the advent of techniques for rapidly mapping the DNA of organisms, scientists have found that the genes stored in the four-letter DNA code don't always determine how an organism develops and responds to its environment. The more biologists map the genomes of various organisms (their entire genetic code), the more they are discovering discrepancies between what the genetic code dictates and how organisms actually look and function.

In fact, many of the major discoveries that led to these conclusions were based upon studies in plants. There are traits such as flower shape and fruit pigmentation in some plants that are under the control of this epigenetic code. Such traits, which defy the predictions of classical Mendelian genetics, are also found in mammals. In some strains of mice, for instance, a tendency for obesity can pass from generation to generation, but no difference between the genetic code of fat mice and thin mice explains this weight difference.

Scientists have even found that identical human twins exhibit different biological traits, despite their matching DNA sequences. They have theorized that such unexplained disparities could be the work of epigenetic variation.

"Since none of these patterns of variation and inheritance match what the genetic sequence says should happen, there is a clearly a component of the 'genetic' heritability that is missing," Ecker said.

Ecker and other scientists have traced these mysterious patterns to chemical markers that serve as a layer of genetic control on top of the DNA sequence. Just as genetic mutations can arise spontaneously and be inherited by subsequent generations, epigenetic mutations can emerge in individuals and spread into the broader population.

Although scientists have identified a number of epigenetic traits, very little was known about how often they arose spontaneously, how quickly they could spread through a population and how significant an influence they could have on biological development and function.


"Perception of the extent of epigenetic variation in plants from generation to generation varies widely within our scientific community," said Robert Schmitz, a post-doctoral research in Eckers' laboratory and the lead author on the paper. "We actually did the experiment, and found that overall there is very little change between each generation, but spontaneous epimutations do exist in populations and arise at a rate much higher than the DNA mutation rate, and at times they had a powerful influence over how certain genes were expressed."

In their study, the Salk researchers and collaborators at Scripps Research Institute mapped the epigenome of a population of Arabidopsis plants then observed how this biochemical landscape had changed after 30 generations. This mapping consisted of recording the state of all locations on the DNA molecule that could undergo a chemical modification known as methylation, a key epigenetic change that can alter how certain underlying genes are expressed. They then watched how methylation states of these sites evolved over the generations.

The plants were all clones of a single ancestor, so their DNA sequences were essentially identical across the generations. Thus any changes in how the plants expressed certain genetic traits were likely to be a result of spontaneous changes in their epigenetic code - variations in the methylation of the DNA sites- not the result of variations in the underlying DNA sequences.

"You couldn't do this kind of study in humans, because our DNA gets shuffled each generation," Ecker said. "Unlike people, some plants are easily cloned, so we can see the epigenetic signature without all the genetic noise."

The researchers discovered that as many as a few thousand methylation sites on the plants' DNA were altered each generation. Although this represents a small proportion of the potentially six million methylation sites estimated to exist on Arabidopsis DNA, it dwarfs the rate of spontaneous change seen at the DNA sequence level by about five orders of magnitude.

This suggests that the epigenetic code of plants - and other organisms, by extension - is far more fluid than their genetic code.

Even more surprising was the extent to which some of these changes turned genes on or off. A number of plant genes that underwent heritable changes in methylation also experienced substantial alterations in their expression - the process by which genes control cellular function through protein production.

This meant that not only was the epigenome of the plants morphing rapidly despite the absence of any strong environmental pressure, but that these changes could have a powerful influence on the plants' form and function.

Ecker said the results of the study provide some of the first evidence that the epigenetic code can be rewritten quickly and to dramatic effect. "This means that genes are not destiny," he said. "If we are anything like these plants, our epigenome may also undergo relatively rapid spontaneous change that could have a powerful influence on our biological traits."

Now that they have shown the extent to which spontaneous epigenetic mutations occur, the Salk researchers plan to unravel the biochemical mechanisms that allow these changes to arise and get passed from one generation to the next.

They also hope to explore how different environmental conditions, such as differences in temperature, might drive epigenetic change in the plants, or, conversely, whether epigenetic traits provide the plants with more flexibility in coping with environmental change.

"We think these epigenetic events might silence genes when they aren't needed, then turned them back on when external conditions warrant," Ecker said. "We won't know how important these epimutations are until we measure the effect on plant traits, and we're just now to the point where we can do these experiments. It's very exciting."



Here is a horizon documentary about epigenetics ( i know, i posted in this thread before) :

http://video.google.com/videoplay?docid=4942166965081178368


And a song, it has something...

SH3 - Letters From The Lost Day

http://www.youtube.com/watch?v=0BDu7Sa5GDE

William Gaatjes
09-23-2011, 04:53 AM
http://medicalxpress.com/news/2011-09-gut-bacteria-immune-cells-friendly.html


Yahooo. Continued progress ?



Researchers find gut bacteria teaches immune cells to see them as friendly

(Medical Xpress) -- Most people know that the gut (human or otherwise) has bacteria in it that helps in the proper digestion of food. But how these bacteria manage to evade destruction by the immune system has been a mystery. Now, new research by a group working out of Washington University in St. Lois, as described in their paper published in the journal Nature, shows that such bacteria mange to survive by teaching T cells to see them as friends, rather than foes.

In the study, led by Chyi-Song Hsieh, the team first sought to discern whether the there was something going on in the development of T cells themselves that would account for them ignoring bacteria in the gut. To do this, they implanted some of the special T cell genes found only in the gut, into the bone marrow of a mouse that had been genetically modified to not produce T cells (which is where they normally come from). And though the T cells did grow, they didn’t have the same properties as the gut T cells and thus it was deduced that it wasn’t the environment in which they were spawned that led to them ignoring gut bacteria.

Next, the team looked at the mice they had just studied - one group had donated normal gut T cells genes, the other had genetically modified bone marrow and genes added from the first. The first group had gut bacteria, while the second did not. They discovered however, that when the two groups of mice were allowed to exist in the same cage, the mice with the modified bone marrow soon also had the special T cells that allowed the foreign bacteria to exist in its gut, clearly demonstrating that the bacteria in the normal mouse had somehow (after transferring via shared water and food dishes, etc.) trained the T cells in the guts of the modified mice (and changed them in the process) to ignore them. The question now, is how.

In an addendum to the research, the team also found that in studying mice with colitis, a condition generally associated with problems regarding helpful bacteria in the gut, there appeared to be problems in maintaining the regulatory T cells needed for proper digestion.

Now that researchers have a better understanding of which agent is responsible for allowing good bacteria to exist in the gut, new treatments might soon be on the way for those suffering from such gut ailments as colitis and Crohn's disease. They’ll also quite naturally, be trying to figure out how the bacteria trains gut T cells to abide them.

More information: Peripheral education of the immune system by colonic commensal microbiota, Nature (2011) doi:10.1038/nature10434

Abstract
The instruction of the immune system to be tolerant of self, thereby preventing autoimmunity, is facilitated by the education of T cells in a specialized organ, the thymus, in which self-reactive cells are either eliminated or differentiated into tolerogenic Foxp3+ regulatory T (Treg) cells1. However, it is unknown whether T cells are also educated to be tolerant of foreign antigens, such as those from commensal bacteria, to prevent immunopathology such as inflammatory bowel disease2, 3, 4. Here we show that encounter with commensal microbiota results in the peripheral generation of Treg cells rather than pathogenic effectors. We observed that colonic Treg cells used T-cell antigen receptors (TCRs) different from those used by Treg cells in other locations, implying an important role for local antigens in shaping the colonic Treg-cell population. Many of the local antigens seemed to be derived from commensal bacteria, on the basis of the in vitro reactivity of common colon Treg TCRs. These TCRs did not facilitate thymic Treg-cell development, implying that many colonic Treg cells arise instead by means of antigen-driven peripheral Treg-cell development. Further analysis of two of these TCRs by the creation of retroviral bone marrow chimaeras and a TCR transgenic line revealed that microbiota indigenous to our mouse colony was required for the generation of colonic Treg cells from otherwise naive T cells. If T cells expressing these TCRs fail to undergo Treg-cell development and instead become effector cells, they have the potential to induce colitis, as evidenced by adoptive transfer studies. These results suggest that the efficient peripheral generation of antigen-specific populations of Treg cells in response to an individual’s microbiota provides important post-thymic education of the immune system to foreign antigens, thereby providing tolerance to commensal microbiota.

William Gaatjes
10-11-2011, 05:35 AM
More progress...


World class scientist Professor Willem M. de Vos will explain next Monday how the microbes that are closest to our hearts – gut microbes – could underpin a new way of thinking about human biology. As well as looking at our own genes, we can now include those of our microbes in studies of human health and disease. This is a significant shift in the way we approach human biology.


Gut microbes affect our health by producing vitamins, priming our immune system and contributing to resistance to pathogens. For example, recent studies have shown that the insulin resistance of patients with type 2 diabetes is linked to the intestinal microbiota composition and can be beneficially altered by replacing it with the microbiota of healthy donors.

The genes of our gut microbes, also known as the microbiome, act as a personalized organ that can be modified by diet, lifestyle and antibiotics. This organ is fed partly by us and partly by our diets. Professor de Vos and colleagues have classified the human microbiome into three enterotypes: clusters of microbiomes with similar compositions and nutrient-processing preferences. These enterotypes are characterized by bacteria with different capacities to degrade carbohydrate and mucin (a gel-forming protein which produces mucus). Our gut microbes get carbohydrates partly from our diet, whereas the mucin is produced by our own body.

Although these enterotypes are separated by species composition, it doesn't necessarily follow that abundant functions are provided by abundant species. To investigate the relationship between the microbiome and health, scientists must establish the functions of the products of their microbiomes.

"We have evolved with the microbes in our gut, our microbes inside, and have discovered that they talk to us and we feed them with, among other things, the mucins we produce. We now are trying to unravel their functions and understand exactly what these microbes and their products mean to human health" said Professor de Vos.

The size of one microbial metagenome (one host's microbiome) is 150 times larger than the human genome and encodes 100 times more genes than our own genome. This extensive gene catalogue could enable us to study potential associations between microbial genes and human phenotypes and even environmental factors like diet, throughout the length of our lifetime.

More information: On 10 October 2011, Professor Willem M. de Vos will present the fourth Environmental Microbiology Lecture: "Microbes Inside"



http://www.physorg.com/news/2011-10-gut-microbiome-human-health-disease.html

William Gaatjes
10-11-2011, 02:28 PM
There is a virus discovered in 2010 that is huge. It is so big, that it can be seen with a normal visual light magnifying microscope. It is called Megavirus chilensis.

http://news.bbcimg.co.uk/media/images/55958000/jpg/_55958338_55958337.jpg

http://www.bbc.co.uk/news/science-environment-15242386


The largest virus yet discovered has been isolated from ocean water pulled up off the coast of Chile.

Called Megavirus chilensis, it is 10 to 20 times wider than the average virus.

It just beats the previous record holder, Mimivirus, which was found in a water cooling tower in the UK in 1992.

Scientists tell the journal PNAS that Megavirus probably infects amoebas, single-celled organisms that are floating free in the sea.

The particle measures about 0.7 micrometres (thousandths of a millimetre) in diameter.

"It is bigger than some bacteria," explained Prof Jean-Michel Claverie, from Aix-Marseille University, Marseille, France.

"You don't need an electron microscope to see it; you can see it with an ordinary light microscope," he told BBC News.

Viruses cannot copy themselves; they need to invade a host cell if they want to replicate.

Like Mimivirus, Megavirus has hair-like structures, or fibrils, on the exterior of its shell, or capsid, that probably attract unsuspecting amoebas looking to prey on bacteria displaying similar features.

A study of the giant virus's DNA shows it to have more than a thousand genes, the biochemical instructions it uses to build the systems it requires to replicate once inside its host.

In the lab experiments conducted by Professor Claverie and colleagues, in which they infected fresh-water amoebas, Megavirus was seen to construct large trojan organelles - the "cells within cells" that would produce new viruses to infect other amoebas.

"Everything is initiated from a single particle, and then grows and grows to become this virion factory," explained Prof Claverie. "That's why it needs all these genes."

Megavirus was found off the coast of Las Cruces, central Chile. It was recovered as part of a general trawl in the ocean for biology of interest.

"This is a new way of doing virology," said Prof Claverie.

"Previously, we only discovered viruses because they caused disease in humans, or animals and plants. But now we are initiating what might be called environmental virology and we are looking for viruses everywhere.

"You just go to lakes, seas and oceans and pick up the water, and then you filter it, and try to rescue the virus by co-cultivating it with some potential host."

More generally, there is interest in ocean viruses because they have a major influence on populations of plankton, the microscopic organisms that form the base of many marine food chains. And when they kill plankton, viruses are also helping to regulate the planet's geochemical cycles as the dead organisms sink into the deep, locking away their carbon for aeons.

Prof Claverie said the megavirus would not be hazardous to humans.


http://en.wikipedia.org/wiki/Megavirus

William Gaatjes
10-31-2011, 06:53 AM
There is new research that suggests that bacteria are exchanges genes at a faster rate then expected.

http://www.physorg.com/news/2011-10-bacteria-readily-swap-beneficial-genes.html


(PhysOrg.com) -- Much as people can exchange information instantaneously in the digital age, bacteria associated with humans and their livestock appear to freely and rapidly exchange genetic material related to human disease and antibiotic resistance through a mechanism called horizontal gene transfer (HGT).

In a paper appearing in Nature online Oct. 30, researchers — led by Eric Alm of MIT’s Department of Civil and Environmental Engineering and Department of Biological Engineering — say they’ve found evidence of a massive network of recent gene exchange connecting bacteria from around the world: 10,000 unique genes flowing via HGT among 2,235 bacterial genomes.

HGT is an ancient method for bacteria from different lineages to acquire and share useful genetic information they didn’t inherit from their parents. Scientists have long known about HGT and known that when a transferred gene confers a desirable trait, such as antibiotic resistance or pathogenicity, that gene may undergo positive selection and be passed on to a bacterium’s own progeny, sometimes to the detriment of humans. (For example, the proliferation of antibiotic-resistant strains of bacteria is a very real threat, as seen in the rise of so-called “superbugs.”)

But until now, scientists didn’t know just how much of this information was being exchanged, or how rapidly. The MIT team’s work illustrates the vast scale and rapid speed with which genes can proliferate across bacterial lineages.

“We are finding [completely] identical genes in bacteria that are as divergent from each other as a human is to a yeast,” says Alm, the Karl Van Tassel Associate Professor. “This shows that the transfer is recent; the gene hasn’t had time to mutate.”

“We were surprised to find that 60 percent of transfers among human-associated bacteria include a gene for antibiotic resistance,” adds computational systems biology graduate student Chris Smillie, one of the lead authors of the paper.

These resistance genes might be linked to the use of antibiotics in industrial agriculture: The researchers found 42 antibiotic-resistance genes that were shared between livestock-associated and human-associated bacteria, demonstrating a crucial link connecting pools of drug resistance in human and agricultural populations.

“Somehow, even though a billion years of genome evolution separate a bacterium living on a cow and a bacterium living on a human, both are accessing the same gene library,” Alm says. “It’s powerful circumstantial evidence that genes are being transferred between food animals and humans.”

Moreover, the team identified 43 independent cases of antibiotic-resistance genes crossing between nations. “This is a real international problem,” says microbiology graduate student Mark Smith, another lead author of the study. “Once a trait enters the human-associated gene pool, it spreads quickly without regard for national borders.”

The practice of adding prophylactic antibiotics to animal feed to promote growth and prevent the spread of disease in densely housed herds and flocks is widespread in the United States, but has been banned in many European countries. According to the Federal Drug Administration, more than 80 percent of the 33 million pounds of antibiotics sold in the United States in 2009 was for agricultural use, and 90 percent of that was administered subtherapeutically through food and water. This includes antibiotics such as penicillins and tetracyclines commonly used to treat human illness.

The MIT researchers found that HGT occurs more frequently among bacteria that occupy the same body site, share the same oxygen tolerance or have the same pathogenicity, leading them to conclude that ecology — or environmental niche — is more important than either lineage or geographical proximity in determining if a transferred gene will be incorporated into a bacterium’s DNA and passed on to its descendants.

“This gives us a rulebook for understanding the forces that govern gene exchange,” Alm says.

The team applied these rules to find genes associated with the ability to cause meningitis and other diseases, with the hope that transferred traits and the genes encoding those traits might make especially promising targets for future drug therapies.

“This is a very interesting piece of work that really shows how the increasing databases of complete genome sequences, together with detailed environmental information, can be used to discover large-scale evolutionary patterns,” says Rob Knight, associate professor of chemistry and biochemistry at the University of Colorado at Boulder. “The availability of vast datasets with excellent environmental characterization will give us an unprecedented view of microbes across the planet.”

Continuing the work, the researchers are now comparing rates of exchange among bacteria living in separate sites on the same person and among bacteria living on or in people with the same disease. They’re also studying an environmentally contaminated site to see which swapped genes might facilitate microbial cleanup by metal-reducing bacteria.

Other co-authors of the Nature paper are graduate student Jonathan Friedman, postdoc Otto Cordero and former graduate student Lawrence David, now at Harvard University.

Provided by Massachusetts Institute of Technology (news : web)

William Gaatjes
11-05-2011, 05:31 AM
There is more research done in finding the causes of tumors in the colon.
The only strange from this research is that hydrogen peroxide causes a strong immune system response. Thus i personally think they got it backwards. I doubt that it is the immune response and the hydrogen peroxide that is the cause of colon tumors. I think it is more a response to the actual cause. There is more going on here. What these researchers claim here is that the immune response must be weakened. And that is wrong.


http://medicalxpress.com/news/2011-11-common-bacteria-colon-tumors-peroxide-producing.html


Working with lab cultures and mice, Johns Hopkins scientists have found that a strain of the common gut pathogen Bacteroides fragilis causes colon inflammation and increases activity of a gene called spermine oxidase (SMO) in the intestine. The effect is to expose the gut to hydrogen peroxide – the caustic, germ-fighting substance found in many medicine cabinets -- and cause DNA damage, contributing to the formation of colon tumors, say the scientists.

"Our data suggest that the SMO gene and its products may be one of the few good targets we have discovered for chemoprevention," says Robert Casero, Ph.D., professor of oncology at the Johns Hopkins Kimmel Cancer Center.

In a study, Casero and his colleagues introduced B. fragilis to two colon cell lines and measured SMO gene activity. In both cell lines, SMO gene activity increased two to four times higher than cells not exposed to the bacteria. The scientists also observed similar increases in enzymes produced by the SMO gene. The scientists successfully prevented DNA damage in these cells by blocking SMO enzyme activity with a compound called MDL 72527.

The Johns Hopkins team also tested their observations in a mouse model, created by Hopkins infectious disease specialist Cynthia Sears, M.D., to develop colon tumors. Mice exposed to the bacteria had similar increases in SMO. Mice treated with MDL 72527 had far fewer tumors and lower levels of colon inflammation than untreated mice. Results of the experiments were published online in the Proceedings of the National Academy of Sciences in August.

Casero says hydrogen peroxide can freely distribute through and into other cells. "It roams around, and can damage the DNA in cells," he says.

Rising levels of hydrogen peroxide and DNA damage in the colon are clear steps to tumor development, says Andrew Goodwin, Ph.D., who spearheaded the studies while performing graduate work in Johns Hopkins' Cellular and Molecular Medicine Program and Casero's laboratory.

B. fragilis strains that secrete a toxin are widely known to cause diarrhea in children and adults, and previous studies, including those at Johns Hopkins, have linked the toxin-producing bacteria to inflammation and colon cancer. Casero and collaborators previously linked the SMO gene to inflammation and cancer of the prostate and stomach.

Using MDL 72527 in humans is not advised, Casero says, because the compound blocks another enzyme in addition to SMO. Investigators hope to develop a drug that targets only the SMO enzyme. Candidates for such prevention strategies may include people with a history of colon polyps, which increases risk for colon cancer, and those with inflammatory bowel disease.




hydrogen peroxide and white blood cells.

http://news.sciencemag.org/sciencenow/2009/06/03-03.html



Anyone who has felt the sting as hydrogen peroxide foams and fizzes on a scraped knee knows about the compound's antiseptic properties. But new research suggests that hydrogen peroxide does more than just kill microbes. It may also call for reinforcements, summoning an army of bacteria-fighting cells to cuts and wounds.

Punctured skin sets off a chain reaction of chemical signals that activates blood-clotting and attracts an array of immune cells to guard against intruding microbes. Some of these cells, known as leukocytes, or white blood cells, kill by initiating a "respiratory burst," which releases highly reactive antimicrobial molecules, including hydrogen peroxide produced by the body itself.

Biologist Philipp Niethammer, a postdoctoral researcher at Harvard Medical School in Boston, was trying to coax such a hydrogen peroxide burst out of a nicked zebrafish tail when he noticed something odd. "I saw something bursting at the wound," he says, "but I didn't see leukocytes there." That bursting, experiments revealed, was hydrogen peroxide--appearing an average of 17 minutes before the arrival of the white blood cells that are supposed to produce it. To Niethammer, it appeared as if hydrogen peroxide was bringing leukocytes to the wound rather than the other way around.

To confirm the theory, Niethammer and his colleagues bathed zebrafish larvae in compounds known to inhibit the production of hydrogen peroxide. When researchers nicked larvae tails in the presence of the inhibitors, leukocytes stayed away: An average of fewer than one per larvae appeared at the cut within 42 minutes, compared with four to six under normal conditions. Next, the team used genetic manipulation to pinpoint the enzyme responsible for producing hydrogen peroxide. The culprit, a protein known as duox, is also found in the thyroid, digestive tract, and lungs of humans. Asthma and other disorders result from excessive inflammation in these tissues, so duox may play a role in those conditions, the researchers report tomorrow in Nature.

Paul Martin, a cell biologist at the University of Bristol in the United Kingdom, says the work identifies a key time point in wound healing. "Now we know the first step," he says. So, can that brown drugstore bottle of hydrogen peroxide also bring leukocytes to a wound? That's an open question, says Niethammer. He's now investigating whether white blood cells detect hydrogen peroxide directly or whether the compound is part of a longer signaling chain.


3 pictures of hydrogen peroxide in a wound and the migration of white blood cells towards the wound.


Sliced. A zebrafish larvae tail 3 minutes, 17 minutes, and 61 minutes (top to bottom) after being cut. Hydrogen peroxide (red) emanates from the wound, fading to yellow and green as it dissipates through tissue.
Credit: Philipp Niethammer

http://news.sciencemag.org/sciencenow/assets_c/2010/02/200960331-thumb-200xauto-2113.jpg

William Gaatjes
11-11-2011, 01:35 PM
The mystery of resistance to the malaria parasite Plasmodium falciparum has been solved and explained. This is good news, because understanding these mechanisms will allow for better treatments against malaria and may be helpful in other diseases.

http://medicalxpress.com/news/2011-11-mystery-resistance-malaria.html


(Medical Xpress) -- Malaria is a disease caused by parasites passed to humans via the bites of infected mosquitoes. Globally, the disease causes over a million deaths every year, and is especially rife in parts of Africa and Asia. The parasites infect red blood corpuscles (the hemoglobin-containing cells that carry oxygen around the body) and hijack the support structure within the cells. Some people are known to be naturally resistant to the serious effects of malaria, and scientists have wondered for decades exactly how their resistance functions. Now new research gone a long way to solving the mystery.

It has been known for decades that some people in Africa and elsewhere who have a mutated gene that causes sickle cell anemia also have resistance to malaria because their red blood corpuscles contain an unusual form of hemoglobin―hemoglobin S, which results in the hemoglobin aggregating within the cell. Possessing only one copy of the mutated hemoglobin S makes the person a largely asymptomatic carrier, while two copies produces symptomatic sickle-cell anemia. In both cases the mutation gives some protection against malaria. Another mutation, hemoglobin C, causes hemolytic anemia when two copies of the mutation are present, and this form also protects against malaria.


http://s.ph-cdn.com/newman/gfx/news/hires/2011/plasmodiumfa.png

In a paper published in Science, researcher Marek Cyrklaff, of Heidelberg University in Germany, and colleagues in Germany and Burkina Faso, report that the unusual forms of hemoglobin in the red cells prevent the malaria parasite, Plasmodium falciparum, from hijacking the actin filaments that provide the skeleton scaffolding within the cell. They compared healthy and infected red corpuscles containing 'normal' hemoglobin with healthy and infected cells containing hemoglobin S or hemoglobin C. Using powerful cryoelectron tomography, the scientists discovered that in normal healthy cells the filaments of actin protein are short and located beneath the outer cell membrane , where they provide a support structure for the cell and makes it strong but pliable enough to pass through the tiniest blood vessels.

In infected cells with normal hemoglobin they found the actin protein was in long filaments, which the parasite used to build a cytoskeleton, or intracellular bridge, within the cell to transport its own manufactured protein, adhesin, to the surface of the cell. The effect of adhesin, as its name suggests, is to make adjoining cells stick together and to stick the cells to the blood vessel walls, causing the inflammation responses characteristic of malaria. In the hemoglobin S and C cells, the bridge could not be completed and the adhesin could not be effectively transported to the cell surface, thus reducing cell stickiness.

The scientists also found, after further experiments, that hemoglobin C and S are more easily oxidized than the unmutated form, and when actin filaments were placed with the hemoglobin, the C and S forms resulted in shorter actin filaments than normal hemoglobin, as did oxidized hemoglobin.

Malaria is most often treated with quinine, but clinical trials of a vaccine are now being carried out in Africa by GlaxoSmithKline, and the results look promising, with a 65% effectiveness rate. The new research suggests that further drugs could eventually be developed that interfere with the parasite's ability to use the actin filaments for its own purposes.

More information: Hemoglobins S and C Interfere with Actin Remodeling in Plasmodium falciparum–Infected Erythrocytes, Science, DOI: 10.1126/science.1213775

ABSTRACT
The hemoglobins S and C protect carriers from severe Plasmodium falciparum malaria. Here, we found that these hemoglobinopathies affected the trafficking system that directs parasite-encoded proteins to the surface of infected erythrocytes. Cryoelectron tomography revealed that the parasite generated a host-derived actin cytoskeleton within the cytoplasm of wild-type red cells that connected the Maurer's clefts with the host cell membrane and to which transport vesicles were attached. The actin cytoskeleton and the Maurer's clefts were aberrant in erythrocytes containing hemoglobin S or C. Hemoglobin oxidation products, enriched in hemoglobin S and C erythrocytes, inhibited actin polymerization in vitro and may account for the protective role in malaria.





About the parasite :
http://en.wikipedia.org/wiki/Plasmodium_falciparum

thaugen
12-07-2011, 04:07 PM
I'm not technically well-versed to enter the conversation. In fact I tried to write a short paper for lay persons on a different website with my understanding about how diet could prevent or help reverse cancer. It had to be short, not too technical, but hit all the major points. I'd appreciate any feedback to better develop it.


There are thousands of advocates of raw foods and eating healthy who say it may prevent cancer and it may be a helpful adjuvant when treating cancer, along with supplements and vitamins. Their evidence is not based on your beloved scientific studies/clinical trials but rather on case studies, individual outcomes where the persons survived after changing their diet. Like the original poster, they are still alive so they have no need to propose a mechanism of action, do lab tests, find appropriate clinical trial participants, or wait five years for the results to be published in a scholarly journal.

Those infected with scientism would now be frothing at the mouth and screaming "anecdotal, anecdotal, anecdotal!" I'm not a scientist, but I'll do some homework for you:

Inflammatory bowel disease: a model of chronic inflammation-induced cancer.
Chronic inflammation is a well-recognized risk factor for the development of human cancer. Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, is a typical longstanding inflammatory disease of the colon with increased risk for the development of colorectal carcinoma. Several molecular events involved in chronic inflammatory process may contribute to multistage progression of human cancer development, including the overproduction of reactive oxygen and nitrogen species, overproduction/activation of key arachidonic acid metabolites and cytokines/growth factors, and immunity system dysfunction. Multiple animal models of IBD have been established, and in general, these models can be mainly categorized into chemically induced, genetically engineered (transgenic or gene knock-out), spontaneous, and adoptive transferring animal models.
http://www.ncbi.nlm.nih.gov/pubmed/19347299

From this I get that chronic inflammation is a bad thing and inflammatory bowel disease (IBD) is a bad thing and immune system dysfunction is a bad thing. So let's look at whether a cancer diet could affect any of these. Dannon yogurt advertising tells us that 70% of our immune system is located in the digestive tract. I found no scholarly article contesting that figure. So the theory is that a damaged digestive tract might also include immune system damage, and together they could lead to cancer. If a cancer diet could help mend the digestive tract and the immune system, that would be a good thing. I'm not saying, cure cancer, I'm just saying give the person a means to help influence a positive outcome.

BTW, the government's main cancer agency doesn't bother to tell you that a good portion of your immune system is located in the digestive tract:
What is biological therapy? http://www.cancer.gov/cancertopics/treatment/biologicaltherapy
Biological therapy (BYE-o-loj-ee-cal THER-ah-py) is a type of treatment that works with your immune system. It can help fight cancer or help control side effects (how your body reacts to the drugs you are taking) from other cancer treatments like chemotherapy.
What is the difference between biological therapy and chemotherapy?
Biological therapy and chemotherapy are both treatments that fight cancer. While they may seem alike, they work in different ways. Biological therapy helps your immune system fight cancer. Chemotherapy attacks the cancer cells directly.
How does biological therapy fight cancer?
Doctors are not sure how biological therapy helps your immune system fight cancer. But they think it may:
Stop or slow the growth of cancer cells.
Make it easier for your immune system to destroy, or get rid of, cancer cells.
Keep cancer from spreading to other parts of your body.
What is my immune system and how does it work?
Your immune system includes your spleen, lymph nodes, tonsils, bone marrow, and white blood cells. These all help protect you from getting infections and diseases. [spleen is the only part of the digestive tract mentioned]

Anyways, let's get back to the cancer diet theory. "Antioxidants are natural biochemical substances that protect living cells from harmful free radicals. Free radicals are unstable molecules formed as result of normal metabolic processes in the body. Viruses, bacteria, stress and pollution can also cause free radical production. When left unchecked, free radicals can cause our DNA to mutate, leading to cancer and other degenerative diseases.
The vitamins A, C and E, beta-carotene and oligomeric proanthocyanidins (OPC) obtained from wholesome foods are some examples of antioxidants.

Antioxidants and phytochemicals give fruits and vegetables their color, flavor and aroma. Phytochemicals, or plant chemicals, are compounds unique to each fruit, vegetable and herb. Phytochemicals protect plants from sunlight and also ensure their survival. Research has shown phytochemicals to possess enormous healing and disease-preventing properties because of their amazing ability to nourish and strengthen the immune system."

Colon cancer linked to bacteria: Bacterium Linked to Colorectal Cancer in Two Independent Studies http://www.cancer.gov/ncicancerbulletin/101811/page3

In the digestive tract resident microflora (good bacteria, yeasts, fungi, etc.) contain a number of components able to activate innate and adaptive immunity. Disruptions of the normal gastrointestinal microflora, such as overgrowth of harmful bacteria or yeasts like Candida, can damage the digestive system and possibly lead to not only harming the immune system but also enabling toxic products from those nasty bacteria and yeasts to enter the bloodstream. Furthermore, the immune system gets mobilized to try to stop these invaders and also to assist in dealing with the digestive system damage. The results: the immune system causes inflammation as a necessary part of the attack and repair processes and we have inflammatory bowel disease and the chronic inflammation that can facilitate cancer, including cancers located distant from the digestive system.

in the last 48 months, a growing body of research is underscoring a very significant relationship between gut microflora, systemic low-grade inflammation, metabolism, blood lipids and fat storage
http://www.gutpathogens.com/content/3/1/1

Dysregulation of the intestinal immune response to normal bacterial flora was suggested to play a crucial role in several inflammatory and autoimmune diseases.
http://www.sciencedirect.com/science/article/pii/S0165247804000379

Some of the damage resulting from small bowel bacterial overgrowth is produced by the action of bacterial proteases which degrade pancreatic and intestinal brush border enzymes causing pancreatic insufficiency, mucosal damage and malabsorption. In more severe cases the intestinal villi are blunted and broadened and mononuclear cells infiltrate the lamina propria. Increased fecal nitrogen leads to hypoalbuminemia. Bacterial consumption of cobalamin lowers blood levels of vitamin B12. Med Hypoth 1986, 20:125-132.

OK, here is where the oncologists and the cancer diet advocates part ways. As recently as 2003, the Journal of Clinical Oncology, discussing patients who use alternative therapies, stated:

"A widely disseminated literature on unorthodox treatments exists in print and on the Web for patients interested in seeking alternative therapies. There has been a two-decade-long movement toward more natural methods to treat a host of diseases, including cancer, and there is a significant degree of magical thinking about the role of the bowel in contributing to malignant disease ..."

Maybe that's why Spellman and other oncodocs are clinging to the outdated notion that most cancers have no relationship to dysfunction in the digestive system.

Here we need to bring in the famous "leaky gut syndrome." You might want to read up on the controversy surrounding it: http://en.wikipedia.org/wiki/Leaky_gut_syndrome but regardless, what you need to know is that scientific researchers now study it as "increased gastrointestinal permeability." Physicians may diagnose it as small intestine bacterial overgrowth (SIBO), or systemic candidiasis.

As of 2008 many doctors and researchers had accepted leaky gut as a fact:

The gut-brain barrier in major depression: intestinal mucosal dysfunction with an increased translocation of LPS from gram negative enterobacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression.
There is now evidence that major depression is accompanied by an activation of the inflammatory response system and that pro-inflammatory [products of bad intestinal bacteria] may induce depressive symptoms.
The results show that intestinal mucosal dysfunction characterized by an increased translocation of gram-negative bacteria (leaky gut) plays a role in the inflammatory pathophysiology of depression. It is suggested that the increased translocation may mount an immune response and thus inflammatory response system activation in some patients with major depression ... It is suggested that patients with major depression should be checked for leaky gut by means of the IgM and IgA panel used in the present study and accordingly should be treated for leaky gut. http://www.ncbi.nlm.nih.gov/pubmed/18283240

So while you're getting cancer due to inflammatory response system activation (Spellman's chronic inflammation) you may also be getting majorly depressed due to the same bacteria problems.

C'mon, get to the point you say. OK, eating an anti-cancer diet and including probiotics (the good bacteria in yogurt) can sometimes clear up leaky gut syndrome all on its own. In the case of small intestine bacterial overgrowth (SIBO), the infection may be so bad as to need certain antibiotics along with the probiotics. But wait a minute you say, what about those cancers that are distant from the gut? A recent study of probiotics used to control acne found:

Recent studies have shown that orally consumed pre and probiotics can reduce systemic markers of inflammation and oxidative stress [49-51]. Since the local burden of lipid peroxidation in acne is high, such that it appears to place a great demand upon blood-derived antioxidants [52], the ability of oral probiotics to limit systemic oxidative stress [53] may be an important therapeutic pathway. Oral probiotics can regulate the release of inflammatory cytokines within the skin [54], and a specific reduction in interleukin-1 alpha (IL-1-α), noted under certain experimental conditions [55], would certainly be of potential benefit in acne. In line with observations of internal antibiotic use, it is also true that oral encapsulated probiotics have the potential to change the microbial community at sites far removed from the gastrointestinal tract [56].
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038963/?tool=pubmed

That last sentence, "change the microbial community at sites far removed from the gastrointestinal tract" is important if you believe that several cancers are caused by microbes. Researchers have already proven that bacteria and viruses cause certain cancers. The jury is still out as to how many more cancers result from bacteria, viruses, fungi, parasites or other microbes. Notice also they mentioned cytikines, which Spellman referred to:

"Many cancers produce something called cytokines which shut down our immune system from recognizing them as different and acting on that."

Since probiotics can regulate the release of inflammatory cytokines, is it possible they could interfere with that cancer mechanism? Another mechanism they might affect is apoptosis (cancer cell death.) Ceramides are signaling molecules that alert cells to perform apostosis, programming a cell to die.

Recently, relatively simple sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate, have been shown to be important mediators in the signaling cascades involved in apoptosis, proliferation, and stress responses. Specifically, researchers showed that the lactic acid bacteria Streptococcus thermophilus, a species found in most yogurts, can increase ceramide production.
A Textbook of Molecular Biotechnology by Ashok K. Chauhan, Ajit Varma

Phytosphingosine lipids inhibit micro-organisms and their second-messenger function, and are therefore considered part of the body's natural defense system, and have bacteria-killing properties. Not only does this enable Phytosphingosine to prevent acne from forming, but recent studies in France have also shown it to act as an anti-inflammatory at concentrations as low as 1%

So there you have it. Eat a good anti-cancer diet, take probiotics, and stay away from the stuff Spellman said causes cancer.

Gibsons
12-07-2011, 08:08 PM
I really don't have the time to sort this out, but.

You're overgeneralizing when it suits you, and nitpicking the other side when it suits you.

One specific thing I have to point out re the "digestive system" comprising the immune system. Lymphoid tissue is part of the digestive system. Your statement implying we're being misled is telling, and frankly, wrong.

I don't think there's anything wrong with your general conclusion and advice, but the construction of the argument just bugs me.

William Gaatjes
12-08-2011, 01:36 PM
There is another breakthrough in research about how heliobacter pylori can survive in stomach acid. Now imagine, that when you have multiple pathogens, that while bacteria share genes through horizontal gene transfer, one of those harmful bacteria acquires for a short while the ability to survive stomach acid... And then ends up in the digestive system... It is a case of throwing the dice, but even throwing dice has a finite number of possibilities and thus shall occur sooner or later.

http://www.physorg.com/news/2011-12-ulcer-cancer-causing-bacterium.html



A research team led by scientists at the Chinese University of Hong Kong is releasing study results this week showing how a bacterium, Helicobacter pylori, that causes more than half of peptic ulcers worldwide and that has been implicated in stomach cancer has managed for eons to turn the acidic environment of the human gut into one in which it can thrive.


Writing in a Journal of Biological Chemistry "Paper of the Week," the scientists say the information they have obtained about the pathogen's clever employment of acid neutralizers may inform those who are designing new drugs to blunt H. pylori's effects across the globe.

H. pylori are the only bacteria known to thrive in the human stomach. It remains unclear how the pathogens are transmitted, although researchers suspect they could be spread through contaminated food or water. The damage the bacteria do to the mucous coating of the gut allows stomach acid to eat away at the sensitive organ lining, causing ulcers.

Although more than half of the world's population has the infection, for reasons still not quite understood most never develop ulcers. In fact, existing antibiotics can cure 80 to 90 percent of ulcers caused by the pathogen. However, H. pylori over the years have become increasingly resistant to antibiotics. Some experts have attributed that resistance to the fact that doctors are quick to prescribe antibiotics to kill it even when patients show no symptoms.

"There is a pressing need to develop new drugs and alternative strategies to fight against H. pylori infection before the prevalence of antibiotic resistance gets out of hand," says Ivan Fong, the lead author on the JBC paper and a graduate student at the Chinese University of Hong Kong whose research is focused on the biochemical makeup of protein complexes that assist in H. pylori's survival.

Ivan Fong, a graduate student at the Chinese University of Hong Kong, studies the biochemical makeup of protein complexes that assist in H. pylori's survival. Kam-Bo Wong is a professor at the institution and oversaw Fong's recent project. Credit: Chinese University of Hong Kong
It's the pathogen's ability to persist within the acid bath in the human stomach that has made it such a successful, albeit harmful, vector, says Fong. "The key is its use of an enzyme called urease to neutralize gastric acid," he explains.

H. pylori produce urease to spur the breakdown of urea, a naturally occurring chemical in the body, so that urea can release ammonia and make the gut an environment in which the pathogens can thrive. But, unlike most other enzymes, urease doesn't start doing its job immediately after being produced by the bacterium; instead, two nickel ions have to be delivered to it, and then the enzyme can mature, so to speak, and thus allow H. pylori to begin their damaging work.

"As the survival of H. pylori depends on active urease, this is a life-or-death issue for the pathogen to ensure nickel ions are delivered to the urease," says Kam-Bo Wong, a professor who oversaw the project at the institution.

It's not entirely clear how H. pylori make sure that urease can mature and then neutralize the surrounding acid. But Wong's team focused on four proteins that they suspect are helpers: UreE, UreF, UreG and UreH.

Using X-ray crystallography, "which essentially performs the function of a molecular microscope to visualize proteins with atomic resolution," Fong explains, the team took snapshots of UreF and UreH. What they saw was that UreH morphs the shape of UreF to enable UreF to recruit a third player, UreG, to form the UreF-UreH-UreG complex. In other words, the three proteins hook up to collectively deliver nickel ions to the right place on urease. Once the nickel ions are in place, they serve like a flint to ignite the breakdown of urea into ammonia, which then neutralizes the stomach acids.

"So, now we have a better understanding of how the machine can assemble itself, as if a skillful mechanic were there for the job, and deliver the nickel ions," says Fong.

Importantly, the team also discovered that disrupting the formation of the crafty UreF-UreH-UreG complex does, in fact, inhibit the synthesis of active urease. They hope that the information they've obtained about the molecular structures of UreF and UreH will help in the design of drugs that will essentially muck up the works of the molecular machine.

"As active urease is the key to survival of H. pylori, designing drugs that target this complex may well be a viable strategy to eradicate the pathogen," says Wong.

More information: The abstract for the paper, titled "Assembly of the preactivation complex for urease maturation in Helicobacter pylori: Crystal Structure of the UreF/UreH complex," is available at http://www.jbc.org … 830.abstract

Provided by American Society for Biochemistry and Molecular Biology

thaugen
12-09-2011, 12:04 AM
Gibsons: Thanks for the critique. I'll rethink some.

William: SIBO Small Intestine Bacterial Overgrowth can be several kinds of bacteria. Am I correct in assuming heliobacter pylori originating in the stomach will pass into the small intestine and could then share genes through horizontal gene transfer? Or would the small intestine bacteria be able to migrate back into the stomach, share genes and proliferate there?

William Gaatjes
12-09-2011, 02:27 AM
Gibsons: Thanks for the critique. I'll rethink some.

William: SIBO Small Intestine Bacterial Overgrowth can be several kinds of bacteria. Am I correct in assuming heliobacter pylori originating in the stomach will pass into the small intestine and could then share genes through horizontal gene transfer? Or would the small intestine bacteria be able to migrate back into the stomach, share genes and proliferate there?

I must first honestly mention that i am not a specialist. What i know of it is that bacteria can share genes quickly. I do not know all methods of how bacteria share genes. I know one method which is called plasmids. If the special tricks of heliobacter pylori are part of such a plasmid, in the sense that it can be shared easily, perhaps another bacteria can copy this method. Maybe not as good as heliobacter pylori does, but good enough for a large group of bacteria to survive the stomach and to end up in the intestines. But to be honest, Gibsons has far more detailed knowledge about these subjects then i do.

My opinion :
Action is reaction. Microorganisms control the planet. And ancient multi cellular life proved very beneficial as vessels to move around quickly to escape from threats(volcanic activity and acids), and because of the numbers, redundancy increased survival. Mathematicians can show that last part easily for you if you are interested. After that, group conscience started to arise. Our ancestors. The way large groups of bacteria and cells communicate, self organization turned into a group conscience with specific complex behavior.
From a digital signal alike behavior with fixed and limited responses at the bacterial level to a more analog signal alike behavior that allowed for more complex interactions (quorum sensing). From a certain perspective one could say that this is the noise of life, the dice of god, the dice Einstein refused to accept.
We are surrounded with EM radiation. that is what powers life, from a certain perspective, one could say that this broadband em radiation that surrounds all around us is the clock signal for atoms to combine to molecules, for molecules to combine to organic compounds, to form life and to support.
Fourier figured it out...

As a sidenote, there is something that i am interested in. The mucous membranes in the mouth, would hormones be able to pass through these mucous membranes into the bloodstream ? We know that toxins such as alcohol can pass through mucous membranes in the bloodstream. We know ways exist to circumvent the digestive system to end up in the bloodstream directly. I know one method is the skin(for example medicine patches or nicotine patches and various chemical poisons), another method are mucous membranes. And the lungs can be used to pass toxic elements into the bloodstream. (I know my English is lousy)

Another sidenote :
This thread is intended for people in the biological field to think about an interesting possibility. Someone may read this thread, and may have a eureka moment. :) And it is for people who have a general interest in how nature really works.

William Gaatjes
12-09-2011, 11:01 AM
This is interesting : The norovirus.
It seems according to current research that the norovirus ends up in the small intestines. This is normally a sterile environment meaning there are no bacteria here to be found in a healthy person.
This virus causes severe gastroenteritis. What i find interesting is how is the virus causes the illness. Is it a mimicry problem ? Or is the virus able to survive the stomach acid and do havoc in the small intestines cell lining ?

http://en.wikipedia.org/wiki/Norovirus

Mr. Pedantic
12-09-2011, 11:33 AM
This is interesting : The norovirus.
It seems according to current research that the norovirus ends up in the small intestines. This is normally a sterile environment meaning there are no bacteria here to be found in a healthy person.
This virus causes severe gastroenteritis. What i find interesting is how is the virus causes the illness. Is it a mimicry problem ? Or is the virus able to survive the stomach acid and do havoc in the small intestines cell lining ?

http://en.wikipedia.org/wiki/Norovirus
In medical terms 'sterile' is only taken to mean contamination with cellular organisms. Therefore, while the small intestine is generally taken to be sterile (which isn't actually completely true anyway) this does not mean that virus particles are not resident.

In terms of pathophysiology, I would assume that the virus causes gastroenteritis in a similar way that most viruses cause disease - viruses infect intestinal epithelial cells, they die, releasing cytoplasm (i.e. ions and proteins) into the lumen of the intestine, which causes water to follow through osmosis. The virus may also cause direct exposure of lymph and blood vessels to the lumen causing direct release of tissue fluid and blood into the lumen (though this will cause bloody diarrhoea).

William Gaatjes
12-09-2011, 11:44 AM
In medical terms 'sterile' is only taken to mean contamination with cellular organisms. Therefore, while the small intestine is generally taken to be sterile (which isn't actually completely true anyway) this does not mean that virus particles are not resident.

In terms of pathophysiology, I would assume that the virus causes gastroenteritis in a similar way that most viruses cause disease - viruses infect intestinal epithelial cells, they die, releasing cytoplasm (i.e. ions and proteins) into the lumen of the intestine, which causes water to follow through osmosis. The virus may also cause direct exposure of lymph and blood vessels to the lumen causing direct release of tissue fluid and blood into the lumen (though this will cause bloody diarrhoea).

Thank you. :)
I agree that sterile intestines does not really mean petri dish sterile but more "no lethal pathogen" sterile...

But the real question is, does the virus travel through the bloodstream ending up in the cells of the small intestine ?
Or is the virus swallowed with food consumed, ending up in the stomach and then ending up in the small intestines ? Because then this would mean the virus can survive stomach acid. And that is important for often it is mentioned that the stomach acid will prevent any bacteria and virus from entering the intestines. We know this is not true, but we do not know full details in every specific case. The issue is that there are still a lot of people in the medical field who claim that nothing survives the stomach acid, thus claiming that cannot be a path for pathogens to end up in the small and specifically large intestines.

Mr. Pedantic
12-09-2011, 11:56 AM
Thank you. :)
I agree that sterile intestines does not really mean petri dish sterile but more "no lethal pathogen" sterile...

But the real question is, does the virus travel through the bloodstream ending up in the cells of the small intestine ?
Or is the virus swallowed with food consumed, ending up in the stomach and then ending up in the small intestines ? Because then this would mean the virus can survive stomach acid. And that is important for often it is mentioned that the stomach acid will prevent any bacteria and virus from entering the intestines. We know this is not true, but we do not know full details in every specific case. The issue is that there are still a lot of people in the medical field who claim that nothing survives the stomach acid, thus claiming that cannot be a path for pathogens to end up in the small and specifically large intestines.
As far as bacteria are concerned, as far as I know only H. pylori can replicate in the stomach. However, many species of bacteria (such as Clostridium difficile) can form spores, or other forms, that are resistant to, among other things, the conditions of the stomach (for example, C. difficile in its spore state is resistant to antibiotics, heat, alcohol, many commonly used sterilizing agents, oxygen, etc). These can pass through the stomach unharmed. I suspect that what you're mishearing is that people say that nothing else can survive in stomach acid - this is completely true, but it's misinterpreted to mean that the HCl will kill anything it comes into contact with, which is not true.

Many intestinal parasites work similarly as well, and that is how they are transmitted - the active zoites multiply in the intestine and cause disease, and any that pass into the large intestine form cysts or spores that prevent the organism from dying until it is ingested again.

It's obviously possible for viruses to be resistant to acidic conditions.

William Gaatjes
12-09-2011, 12:32 PM
I really meant that some people in the biological field and medical have more then often claimed that nothing can pass the stomach acid. And they also mentioned that this is the case for viruses and bacteria, meaning these do not survive in any way at all. Of course this is a blatant lie and not deliberate at all, just uninformed. But they present this to common people who have no understanding at all with wrong information. Saliva in combination with stomach acid is the perfect defense it is often claimed and that is just not true.

William Gaatjes
02-12-2012, 07:56 AM
http://www.physorg.com/news/2012-02-deadly-bird-parasite-evolves-exceptionally.html


Evolution of this specific bacteria has increased in speed since Mycoplasma gallisepticum (or at least the bacteria infecting the finches) lost certain genes. Genes that seem to protect it from... ? Bacteriophages...



A new study of a devastating bird disease that spread from poultry to house finches in the mid-1990s reveals that the bacteria responsible for the disease evolves at an exceptionally fast rate. What's more, the fast-evolving microbe has lost a key chunk of its genome since jumping to its new host, scientists were surprised to find. The missing portion contained the genes that made up the microbe's immune system, researchers report in the February 9th issue of PLoS Genetics.

When thousands of wild house finches started dropping dead from a mysterious eye infection in the Washington, DC, area in the winter of 1994, scientists were puzzled.
The birds had red, swollen, crusty eyes that left them unable to see or forage for food, until they eventually died from starvation or predation. Researchers soon identified the cause — a bacterium called Mycoplasma gallisepticum, a common cause of respiratory infections in turkeys and chickens that was previously known to infect only poultry.
By the time biologist Geoff Hill spotted his first sick bird in Auburn, Alabama, in 1995, the disease had spread through the eastern part of the continent, as far north as Quebec and as far south as Florida. "This was a devastating pandemic," Hill said.
Since its discovery, the epidemic has spread as far west as California, and is estimated to have wiped out hundreds of millions of birds. But scientists are still far from understanding how Mycoplasma gallisepticum gained the ability to spread to house finches — which diverged from chickens and turkeys some 80-90 million years ago — or what turned it into such a sweeping killer.

The red, swollen, crusty eyes in this house finch are the result of a highly-contagious infection caused by the bacterium Mycoplasma gallisepticum. Credit: Photo by Geoffrey E. Hill.
In a new study in the journal PLoS Genetics, researchers compared the genomes of a dozen strains of Mycoplasma gallisepticum sampled from infected house finches between 1994-2007, in the years following the initial outbreak. Using a technique called pyrosequencing, "we can measure evolution on very short time scales," said co-author Scott Edwards of Harvard University. Instead of studying the host switch years after it happened, the researchers are able to track it in real time. "We're catching the switch in the act," he added.
In both poultry and house finches, the microbe has been evolving at frightening speed, they report. "It's evolving anywhere from ten to 100 times faster than previous estimates for any other bacterium," said Harvard graduate student and first author Nigel Delaney.
But when the researchers compared the DNA sequences of the poultry strains with those sampled from house finches, they found something surprising — since making the switch, some parts of the parasite's genome have begun to break down.
Mycoplasma gallisepticum has a tiny genome to begin with, with less than 1000 genes, Delaney said. But rather than acquire new genes to help it outwit its new host, the parasite has gradually lost more than 50 genes — particularly those that make up the microbe's immune system.
Mycoplasmas are parasites, but they also have parasites of their own, including naturally occurring viruses called bacteriophages. "One of the main functions [of the genes that were lost] is to help guard Mycoplasma against the attacks of bacteriophages," Edwards explained.
"It was surprising to see a part of the genome that was assumed to be so important suddenly become unimportant," Delaney added.
It seems crazy, but "scientists have seen the same phenomenon before in HIV," said co-author Allen Rodrigo of the National Evolutionary Synthesis Center in Durham, North Carolina. When HIV infects a new host, it doesn't encounter the same threats, so it loses the specific immune defenses that protected it in its former host, Rodrigo explained. These original defenses may be expensive to maintain, Rodrigo said. Studies show that the HIV strains that lose them are able to reproduce more quickly and spread.

"It's similar to the 'use it or lose it' principle," Edwards added.

Mycoplasma gallisepticum can't be transmitted to humans. It can infect other backyard birds —including American goldfinches, purple finches, evening grosbeaks and pine grosbeaks — but none with the devastating consequences like those seen in house finches.
Researchers still don't know which genetic changes enabled the pathogen to reach epidemic proportions in house finches. But if the house finch strains have lost the genetic machinery that protected them in poultry, then reintroducing the parasites to the bacteriophages of their former hosts could be one way to control the disease, the scientists say.
Determining which specific bacteriophages those are, and whether the remnants of the Mycoplasma immune system still provide some protection against them, will take much more work.
"But this study shows that there's a third player that's important to understand this pandemic, which are the bacteriophages. Nobody's looked at that so far. This is the first observation that they seem to matter," Delaney said.
More information: Delaney, N., S. Balenger, et al. (2012). "Ultrafast evolution and loss of CRISPRs following host shift in a novel wildlife pathogen, Mycoplasma gallisepticum." PLoS Genetics. http://www.plosgen … pgen.1002511

C1
02-12-2012, 06:39 PM
As if there wasnt enough phage: http://theintelhub.com/2012/02/07/what-if-a-virus-infected-a-virus-frankenware-spotted-by-security-firm/

William Gaatjes
02-13-2012, 12:02 PM
As if there wasnt enough phage: http://theintelhub.com/2012/02/07/what-if-a-virus-infected-a-virus-frankenware-spotted-by-security-firm/



What if a Virus Infected a Virus? ‘Frankenware’ Spotted by Security Firm


I am sure this happens also in nature. I think it is safe to say that in nature it is : Sharing or copying together with modifying is surviving. If i remember correctly, in this thread there is a post about giant viruses getting infected by other smaller viruses. Nature is a dynamic system. Life does not end as long as there is EM radiation. Life just adapts (evolves) to cope with different environments. Of course within limits with respect to the energy the EM radiation has and the wave length.

William Gaatjes
02-17-2012, 06:11 AM
It is old but interesting and seems to confirm other posts in this thread.

http://www.wired.com/wiredscience/2011/05/microbes-make-rain/


Bacteria often leave their hosts feeling under the weather. And even when the hosts are high-altitude parcels of air, microbes can be a source of inclement conditions, a Montana research team finds. Cloudborne bacteria might even pose climate threats by boosting the production of a greenhouse gas, another team proposes.
Both groups reported their findings May 24 at the American Society for Microbiology meeting in New Orleans.
These data add to a growing body of evidence that biological organisms are affecting clouds, notes Anthony Prenni of Colorado State University in Fort Collins, an atmospheric scientist who did not participate in the new studies. Right now, he cautions, “We still don’t know on a global scale how important these processes are.” But research into microbial impacts on weather and climate is really heating up, he adds, so “within a few years, I think we’re going to have a much better handle on it.”
Alexander Michaud’s new research was triggered by a June storm that pummeled Montana State University’s campus in Bozeman last year with golf-ball–sized and larger hailstones. The microbial ecologist normally studies subglacial aquatic environments in Antarctica. But after saving 27 of the hailstones, he says, “I suddenly realized, no one had really ever thought about studying hailstones — in a layered sense — for biology.”

So his team dissected the icy balls, along with hundreds of smaller ones collected during a July hail storm south of campus. Michaud now reports finding germs throughout, with the highest concentrations by far — some 1,000 cells per milliliter of meltwater — in the hailstones’ cores.
Since at least the 1980s, scientists have argued that some share of clouds, and their precipitation, likely traces to microbes. Their reasoning: Strong winds can loft germs many kilometers into the sky. And since the 1970s, agricultural scientists have recognized that certain compounds made by microbes serve as efficient water magnets around which ice crystals can form at relatively high temperatures — occasionally leading to frost devastation of crops.
In 2008, Brent Christner of Louisiana State University in Baton Rouge and his colleagues reported isolating ice-nucleating bacteria from rain and snow. A year later, Prenni’s group found microbes associated with at least a third of the cloud ice-crystals they sampled at an altitude of 8 km.
“But finding ice-nucleating bacteria in snow or hail is very different from saying they were responsible for the ice,” says Noah Fierer of the University of Colorado at Boulder. “I say that,” he admits, “even though as a microbiologist, I’d love to believe that bacteria control weather.”
Pure water molecules won’t freeze in air at temperatures above about minus 40 degrees Celsius [minus 40 F], Christner notes. Add tiny motes of mineral dust or clay, and water droplets may coalesce around them — or nucleate — at perhaps minus 15 C [5 F]. But certain bacteria can catalyze ice nucleation at even minus 2 C [28 F], he reported at the meeting in New Orleans.
Through chemical techniques, Michaud’s group determined that the ice nucleation in their hail occurred around minus 11.5 C [11.3 F] for the June hailstones and at roughly minus 8.5 C [16.7 F] for the July stones.
Michaud’s data on the role of microbes in precipitation “is pretty strong evidence,” Prenni says.

Also at the meeting, Pierre Amato of Clermont University in Clermont-Ferrand, France, reported biological activity in materials sampled from a cloud at an altitude of 1,500 meters. The air hosted many organic pollutants, including formaldehyde, acetate and oxalate. Sunlight can break these down to carbon dioxide, a greenhouse gas, something Amato’s group confirmed in the lab. But sunlight didn’t fully degrade some organics unless microbes were also present.
Moreover, certain cloudborne bacteria — the French team identified at least 17 types — degraded organic pollutants to carbon dioxide at least as efficiently as the sun did. Amato’s team reported these findings online Feb. 9 in Atmospheric Chemistry and Physics Discussions.
This microbial transformation of pollutants to carbon dioxide occurs even in darkness. Amato has calculated the total nighttime microbial production of carbon dioxide in clouds and pegs it “on the order of 1 million tons per year.” Though not a huge sum — equal to the carbon dioxide from perhaps 180,000 cars per year — he cautions that this amount could increase based on airborne pollutant levels, temperatures and microbial populations.

Image: Three adjacent ice crystals (borders resemble forked road) contain green-stained Pseudomonas syringae bacteria isolated from precipitation. This plant pathogen, one of the most efficient bacteria at nucleating ice, is commonly found in clouds. (Brent Christner/LSU)

http://www.wired.com/images_blogs/wiredscience/2011/05/BUGS_IN_ICE.jpg

William Gaatjes
02-17-2012, 07:29 AM
Amazing little creature : Euglena rostrifera.
The almost illuminating green color is because of the used video techniques...
http://micro.magnet.fsu.edu/moviegallery/images/pondscum/rostrifera.jpg

This little critter can feed of prey but can also use photosynthesis as a source of power. It is a protozoan.

For a video :
http://www.microscopyu.com/moviegallery/pondscum/euglena/
http://www.youtube.com/watch?v=F-0ch_Z1f50


Organism producing specific EM radiation for communication :

Fireflies, known as Lampyridae produce light by use of bioluminence.

Lampyridae is a family of insects in the beetle order Coleoptera. They are winged beetles, and commonly called fireflies or lightning bugs for their conspicuous crepuscular use of bioluminescence to attract mates or prey. Fireflies produce a "cold light", with no infrared or ultraviolet frequencies. This chemically-produced light from the lower abdomen may be yellow, green, or pale-red, with wavelengths from 510 to 670 nanometers.


http://en.wikipedia.org/wiki/Paramecium

Paramecium is a genus of unicellular ciliate protozoa, commonly studied as a representative of the ciliate group. The cell ranges from about 50 to 350 µm in length and is covered with simple cilia, allowing the cell to move at speeds of approximately 12 body lengths per second. There is a deep oral groove containing inconspicuous tongue-like compound oral cilia (as found in other peniculids) used to draw food inside. In general, they feed on bacteria and other small cells, making them heterotrophs. Osmoregulation is carried out by a pair of contractile vacuoles, which actively expel water from the cell absorbed by osmosis from its surroundings. They are relatively large protists and can easily be seen with a medium-power microscope.
Paramecia are widespread in freshwater environments, and are especially common in scums. Recently, some new species of Paramecium have been discovered in the oceans.
Certain single-cell eukaryotes, such as Paramecium, are examples for exceptions to the universality of the genetic code: in their translation systems a few codons differ from the standard ones.

You can see the vacuoles in action here :
http://www.youtube.com/watch?v=4z98WIeNtjM


About the paramecium :
http://101science.com/paramecium.htm
It is claimed by one researcher that these organisms can communicate by use of transmitting and receiving EM radiation. If this is indeed the case, it would perhaps be a form of bioluminence but on a very specific range of the EM spectrum : UV.

http://dictionary.sensagent.com/paramecium/en-en/#Communication_by_electromagnetic_radiation
http://www.scientificamerican.com/article.cfm?id=in-brief-jun09

Paramecium may be able to communicate via radiation. This may be true of other single-celled organisms as well. In an experiment conducted in 2008, Daniel Fels at the Swiss Tropical Institute in Basel, demonstrated that Paramecium caudatum grown in complete darkness in glass tubes, which prevented the passing of chemical signals, were able to influence feeding behavior and growth rates of neighbours in other tubes, suggesting that electromagnetic signals were involved. It appears that the microbes use at least two frequencies on which to communicate,[5] one of which was in the ultraviolet (UV) range.[6] The structures within the organisms that make this possible have not been identified. Fels suggests that signals of this sort could lead to novel noninvasive medical techniques.



Protozoa :
http://en.wikipedia.org/wiki/Protozoa

William Gaatjes
02-17-2012, 11:40 AM
A nice website with lots of pictures of microscopic life :
http://www.dr-ralf-wagner.de/index-englisch.htm


And the cute little Tardigrade.

http://en.wikipedia.org/wiki/Tardigrade

Tardigrades (commonly known as waterbears or moss piglets)[2] form the phylum Tardigrada, part of the superphylum Ecdysozoa. They are small, water-dwelling, segmented animals with eight legs. Tardigrades were first described by Johann August Ephraim Goeze in 1773 (kleiner Wasserbär = little water bear). The name Tardigrada means "slow walker" and was given by Lazzaro Spallanzani in 1777. The name water bear comes from the way they walk, reminiscent of a bear's gait. The biggest adults may reach a body length of 1.5 millimetres (0.059 in), the smallest below 0.1 mm. Freshly hatched larvae may be smaller than 0.05 mm.

Some 1,150 species of tardigrades have been described.[3][4] Tardigrades occur over the entire world, from the high Himalayas[5] (above 6,000 metres (20,000 ft)), to the deep sea (below 4,000 metres (13,000 ft)) and from the polar regions to the equator.

The most convenient place to find tardigrades is on lichens and mosses. Other environments are dunes, beaches, soil, and marine or freshwater sediments, where they may occur quite frequently (up to 25,000 animals per litre). Tardigrades often can be found by soaking a piece of moss in spring water.[6]

Tardigrades are able to survive in extreme environments that would kill almost any other animal. Some can survive temperatures of close to absolute zero (−273 °C (−459 °F)),[7] temperatures as high as 151 °C (304 °F), 1,000 times more radiation than other animals,[8] and almost a decade without water.[9] Since 2007, tardigrades have also returned alive from studies in which they have been exposed to the vacuum of outer space for a few days in low earth orbit.


http://tardigrade.acnatsci.org/


http://tardigrade.acnatsci.org/tardigrades/pic310.png

http://tardigrade.acnatsci.org/tardigrades/pic312.png

William Gaatjes
02-22-2012, 01:40 PM
Our tiny little friends for whom it seems we are sometimes just transport vessels, have shown once again that nothing is difficult when your small, highly adaptive, efficient, almost immortal and large in numbers. The reactions that occur while feeding releases electrons. Now scientists have found a way to capture these electrons to produce a sort of biological battery. When optimized, this will run for ever. I am sure many can still remember the scene from back to the future 2 where doc Brown uses waste products to power his time machine...

http://media.tumblr.com/tumblr_li2zj0o96y1qb3g3f.jpg


Of course, here a correct mix of nutrients will be more suited to keep the bacteria happy. And a happy bacteria colony, is a busy bacteria colony. And that means lot of electricity...



Superbugs from space offer new source of power
Bacteria normally found 30km above the earth have been identified as highly efficient generators of electricity.

February 21, 2012

Bacillus stratosphericus – a microbe commonly found in high concentrations in the stratosphere orbiting the earth with the satellites – is a key component of a new 'super' biofilm that has been engineered by a team of scientists from Newcastle University.

Isolating 75 different species of bacteria from the Wear Estuary, Country Durham, UK, the team tested the power-generation of each one using a Microbial Fuel Cell (MFC).

By selecting the best species of bacteria, a kind of microbial "pick and mix" they were able to create an artificial biofilm, doubling the electrical output of the MFC from 105 Watts per cubic metre to 200 Watts per cubic metre.

While still relatively low, this would be enough power to run an electric light and could provide a much needed power source in parts of the world without electricity.

Among the 'super' bugs was B. Stratosphericus, a microbe normally found in the atmosphere but brought down to earth as a result of atmospheric cycling processes and isolated by the team from the bed of the River Wear.

Publishing their findings today in the American Chemical Society's Journal of Environmental Science and Technology, Grant Burgess, Professor of Marine Biotechnology at Newcastle University, said the research demonstrated the "potential power of the technique."
"What we have done is deliberately manipulate the microbial mix to engineer a biofilm that is more efficient at generating electricity," he explains.
"This is the first time individual microbes have been studied and selected in this way. Finding B.altitudinis was quite a surprise but what it demonstrates is the potential of this technique for the future – there are billions of microbes out there with the potential to generate power."
The use of microbes to generate electricity is not a new concept and has been used in the treatment of waste water and sewage plants.
Microbial Fuel Cells, which work in a similar way to a battery, use bacteria to convert organic compounds directly into electricity by a process known as bio-catalytic oxidation.
A biofilm – or 'slime' – coats the carbon electrodes of the MFC and as the bacteria feed, they produce electrons which pass into the electrodes and generate electricity.
Until now, the biofilm has been allowed to grow un-checked but this new study shows for the first time that by manipulating the biofilm you can significantly increase the electrical output of the fuel cell.
As well as B. Stratosphericus, other electricity-generating bugs in the mix were Bacillus altitudinis – another bug from the upper atmosphere – and a new member of the phylum Bacteroidetes.
Newcastle University is recognised as a world-leader in fuel cell technology. Led by Professor Keith Scott, in the University's School of Chemical Engineering and Advanced Materials, the team played a key role in the development of a new lithium/air powered battery two years ago.
Professor Scott says this latest fuel cell research can take the development of MFC's to a new level.
More information: Enhanced electricity production by use of reconstituted artificial consortia of estuarine bacteria grown as biofilms. Jinwei Zhang, Enren Zhang, Keith Scott and Grant Burgess. ACS Journal of Environmental Science & Technology 2012. DOI:10.1021/es2020007

William Gaatjes
02-22-2012, 02:03 PM
Although this is just science fiction, i always liked species 8472 of the star trek voyager episodes..

Imagine that when future space travel happens, we will be living in "soft" tissue space ships with a hardened shell. Biological space ships. We do not take material into space to build colossal space ships, we just let the ships be build organically and then move up. After that we go to the next star system and populate... Woops, I mean exploring of course...

http://images.wikia.com/memoryalpha/en/images/7/79/Species_8472_eye.jpg


http://www.youtube.com/watch?feature=player_detailpage&v=V4LR6Ev27FQ#t=28s

:P

Murloc
02-22-2012, 05:01 PM
yeah, in the sci-fi there always are technological races like human, and then there's the biological race with chitin spaceships and living structures.
For what we know, we might become that race at some point in the future.

William Gaatjes
02-28-2012, 01:21 PM
One of my favorite food to use in soup or rice dishes has a special health benefit : Brocolli. It is know for some time now that brocolli can reduce the chance of getting cancer in the colon.


http://s.ph-cdn.com/newman/gfx/news/2012/anothermecha.jpg

http://medicalxpress.com/news/2012-02-mechanism-sulforaphane-cancer.html

Researchers in the Linus Pauling Institute at Oregon State University have discovered yet another reason why the "sulforaphane" compound in broccoli and other cruciferous vegetables is so good for you – it provides not just one, but two ways to prevent cancer through the complex mechanism of epigenetics.

Epigenetics, an increasing focus of research around the world, refers not just to our genetic code, but also to the way that diet, toxins and other forces can change which genes get activated, or "expressed." This can play a powerful role in everything from cancer to heart disease and other health issues.
Sulforaphane was identified years ago as one of the most critical compounds that provide much of the health benefits in cruciferous vegetables, and scientists also knew that a mechanism involved was histone deacetylases, or HDACs. This family of enzymes can interfere with the normal function of genes that suppress tumors.
HDAC inhibitors, such as sulforaphane, can help restore proper balance and prevent the development of cancer. This is one of the most promising areas of much cancer research. But the new OSU studies have found a second epigenetic mechanism, DNA methylation, which plays a similar role.
"It appears that DNA methylation and HDAC inhibition, both of which can be influenced by sulforaphane, work in concert with each other to maintain proper cell function," said Emily Ho, an associate professor in the Linus Pauling Institute and the OSU College of Public Health and Human Sciences. "They sort of work as partners and talk to each other."
This one-two punch, Ho said, is important to cell function and the control of cell division – which, when disrupted, is a hallmark of cancer.
"Cancer is very complex and it's usually not just one thing that has gone wrong," Ho said. "It's increasingly clear that sulforaphane is a real multi-tasker. The more we find out about it, the more benefits it appears to have."
DNA methylation, Ho said, is a normal process of turning off genes, and it helps control what DNA material gets read as part of genetic communication within cells. In cancer that process gets mixed up. And of considerable interest to researchers is that these same disrupted processes appear to play a role in other neurodegenerative diseases, including cardiovascular disease, immune function, neurodegenerative disease and even aging.
The influence of sulforaphane on DNA methylation was explored by examining methylation of the gene cyclinD2.
This research, which was published in the journal Clinical Epigenetics, primarily studied the effect on prostate cancer cells. But the same processes are probably relevant to many other cancers as well, researchers said, including colon and breast cancer.
"With these processes, the key is balance," Ho said. "DNA methylation is a natural process, and when properly controlled is helpful. But when the balance gets mixed up it can cause havoc, and that's where some of these critical nutrients are involved. They help restore the balance."
Sulforaphane is particularly abundant in broccoli, but also found in other cruciferous vegetables such as cauliflower and kale. Both laboratory and clinical studies have shown that higher intake of cruciferous vegetables can aid in cancer prevention.

More information: Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells, Clinical Epigenetics 2011, 3:3 doi:10.1186/1868-7083-3-3

William Gaatjes
03-16-2012, 02:48 PM
I thought it would be nice to start with Fungi now...

I can remember that Gibsons posted something once in this thread that is with hindsight pretty obvious but still very amazing. The effects of temperature on protein folding. I am not sure if it is related to this research.
But it once again shows that temperature can play a role. That also makes me wonder, if there exists pathogens that can multiply faster when the temperature of the host rises. For example during high fever...
I get the impression that the temperature range is pretty small for protein folding, although i am sure that it depends on a case by case basis.


http://www.physorg.com/news/2012-03-uncover-molecular-pathway-common-yeast.html

Scientists at the University of Toronto have found a molecular mechanism that plays a key role in the transition of Candida albicans yeast into disease-causing fungus—one of the leading causes of hospital-acquired infection. The finding highlights the importance of heat in fungal growth, and provides a new target for drug therapies to counter Candida albicans infection.

Candida albicans is a normally harmless yeast that is present in all humans. It becomes infectious in various genetic and environmental conditions, with temperature as a key determinant. It can produce infections that are mild—persistent vaginal or gut infections, for example—or severe, such as systemic, potentially fatal bloodstream infections in patients with AIDS or those who have undergone chemotherapy (or even a simple round of antibiotics).

The molecular workings of Candida albicans were mapped for the first time in 2009 by Professor Leah Cowen of the University of Toronto's Department of Molecular Genetics, whose lab showed that growth of the fungus is tied to the function of a "molecular chaperone" called heat-shock protein 90 (Hsp90). In a study that will appear in the March 20 edition of the journal Current Biology, Prof. Cowen and her colleagues detail a mechanism that controls response to elevated temperature through a protein named Hms1 in conjunction with a cyclin (another type of protein) and its partner protein called a cyclin-dependent kinase.

"This circuitry fundamentally influences how Candida albicans senses temperature, which is crucial for Candida's ability to cause disease," said Prof. Cowen, who holds the Canada Research Chair in Microbial Genomics and Infectious Disease—a prestigious five-year award for which she was renewed this week.

"We were looking for a transcription factor at the end of a pathway we previously showed was key to the change in shape of the fungus that accompanies elevated temperature or compromise of Hsp90 function, and instead we found an entirely new pathway, with components that haven't been characterized in Candida, so it was very surprising," said Prof. Cowen.

The researchers also showed that deletion of Hms1 inhibits Candida albicans infection, pointing toward a possible clinical therapy. "We observed those weaker disease phenotypes in an insect model system, but the results suggest it may also work in more complicated systems," said Prof. Cowen.


The source of pesky vaginal and gut infections, Candida albicans is a burgeoning problem on implanted medical devices—it's fatal in roughly one-third of device-associated infections—and is the fourth-leading cause of hospital-acquired infection. The number of acquired fungal bloodstream infections has increased by more than 200% over the last twenty years, owing in part to growing numbers of AIDS and cancer survivors whose treatments have compromised their immune function.

On finding that the Hms1 pathway affects the growth and development of Candida albicans, and knowing of other key regulators through which Hsp90 operates and suspecting many more exist, Prof. Cowen and her lab examined other pathways and proteins that interact with Hsp90 in another study.

In collaboration with Professor Gary Bader at U of T's Donnelly Centre for Cellular and Biomolecular Research, Prof. Cowen's group mapped a much larger portion of the chaperone network with which Hsp90 interacts through a "chemical genomics" approach that had never been applied to Candida albicans. "If we want to have a more global understanding of what Hsp90 is doing during the transition of this fungus between distinct morphological states with different disease causing properties, we need to take global approaches to determine what its interacting with," said Prof. Cowen.

Their results, published online today in the journal PLoS Genetics, showed 226 genetic interactors with Hsp90 in various conditions, such as different temperatures and during exposure to anti-fungal drugs. Of those interactions, 224 were previously unknown. "That's a lot," said Prof. Cowen. "We now have a myriad of new targets through which Hsp90 could be regulating morphogenesis and drug resistance in Candida."

As well, the researchers drew several predictive rules from their study that govern the Hsp90 chaperone network. Some interactors were only important in a small subset of stress conditions, and these are likely to function "downstream" of Hsp90 regulating specialized cellular processes. Other interactors were important in many stress conditions, and so are likely to work "upstream" of Hsp90 regulating its function.

"Hsp90 stabilizes many proteins, but previously nobody could predict what made an Hsp90 client. That we can make such predictions from the chaperone network is pretty cool and unanticipated, so we're further ahead than we expected," said Prof. Cowen.

Provided by University of Toronto

Gibsons
03-16-2012, 06:48 PM
Okay William, just for you :)

One of the more interesting genes around imo, the plasminogen activator/coagulase gene found in Yersinia pestis. Same gene, two almost polar opposite functions, i.e. clot dissolving and clot forming.
http://iai.asm.org/content/66/12/5755.full

William Gaatjes
03-17-2012, 03:00 AM
Okay William, just for you :)

One of the more interesting genes around imo, the plasminogen activator/coagulase gene found in Yersinia pestis. Same gene, two almost polar opposite functions, i.e. clot dissolving and clot forming.
http://iai.asm.org/content/66/12/5755.full


Interesting.
I will read it with fullest attention.

Thank you. :)

William Gaatjes
03-26-2012, 05:38 AM
A new study seems to provide more proof that bacteria living in the human gut have more influence in controlling the human immune system than previously known and how gut bacteria might affect the development of auto immune diseases .


http://medicalxpress.com/news/2012-03-weapons-allergies-gut-bacteria-allergic.html


When poet Walt Whitman wrote that we "contain multitudes," he was speaking metaphorically, but he was correct in the literal sense. Every human being carries over 100 trillion individual bacterial cells within the intestine -- ten times more cells than comprise the body itself.

Now, David Artis, PhD, associate professor of Microbiology, along with postdoctoral fellow David Hill, PhD, from the Perelman School of Medicine at the University of Pennsylvania, and collaborators from The Children's Hospital of Philadelphia and institutions in Japan and Germany, have found that these commensal bacteria might play an important role in influencing and controlling allergic inflammation. The commensal relationship that develops between humans and internal bacteria is one in which both humans and bacteria derive benefits.
The study -- appearing this week in Nature Medicine -- suggests that therapeutic targeting of immune cell responses to resident gut bacteria may be beneficial in treating allergic diseases.
The researchers build on previous work demonstrating that selective manipulation of the commensal bacterial population could affect the immune system. "Studies in human patients suggest that changes in commensal populations or exposure to broad spectrum antibiotics can predispose patients to the development of systemic allergic diseases," Hill explains. "In addition, previous studies in animal models have shown that commensal bacteria can influence local immune cells in the intestine. However, the cellular and molecular mechanisms by which commensal bacteria influence the host immune system, in particular the branches of the host immune system that regulate allergic inflammation, are not well understood."
Artis and his colleagues focused on the role of basophils, a type of white blood cell, in causing allergic inflammation, and the relationship between basophil responses and allergic disease.
The investigators administered broad-spectrum oral antibiotics to deplete certain types of bacteria in mice and to subsequently examine the affects on levels of circulating basophils in the blood. Using an animal-based model of allergic inflammation in the lung that shares characteristics with asthma in humans, they found that antibiotic treatment resulted in significantly elevated basophil responses and a marked increase in the amount of basophil-mediated allergic airway inflammation. Elevated serum levels of IgE, an important mediator in allergic disease, were also observed.
After the antibiotic-treated mice were exposed to house dust mite allergen (HDM), a human allergen and a model of allergic airway disease in mice, they showed higher basophil responses in the blood and lymph nodes as well as a heightened allergic response with increased inflammation in the lungs.
Germ-free mice, which are reared in a sterile environment and thus lack all live commensal bacteria, also showed similar responses to those observed in antibiotic-treated mice when exposed to HDM. This finding indicates that commensal bacteria-derived signals are responsible for maintaining normal basophil numbers in the steady-state.
Artis and his colleagues also found that serum concentrations of IgE and circulating basophil numbers were limited by B cell-intrinsic expression of myeloid differentiation factor 88 (MyD88), a protein known to play a role in the recognition of bacteria-derived factors. Signals derived from the commensal bacteria were found to act via IgE to control the number of circulating basophils by limiting the proliferation of basophil precursor cells in the bone marrow.
All of these findings indicate important new processes by which resident commensal bacterial populations influence and control basophil responses and thus influence the response to allergens in our environment.
"The identification of a mechanistic connection between commensal bacteria, basophils, and allergic disease illuminates several new avenues that could be targeted by future therapeutics to block or inhibit the development of allergic disease," Artis notes. Further study and identification of these commensal pathways could also have implications for other chronic diseases related to immune system functioning.
Artis and his colleagues hope to further understand this intricate interplay between the immune system and commensal bacteria. "It may be beneficial to identify the specific commensals and commensal-derived signals that regulate circulating basophil populations as this could lead to the development of new probiotic or other commensal-derived therapies," he says. The work makes clear that the bacterial multitudes within our bodies may have a function and a value never before appreciated.
Provided by University of Pennsylvania School of Medicine

Stayfr0sty
03-26-2012, 09:14 PM
Did you guys know that the genetic number of chromosomes when elevated to a certain power in the cannabis plant equal out to 1024? Thats a gigabyte!! Coincidence or what?

Just some food for thought :D

William Gaatjes
03-27-2012, 05:58 AM
Did you guys know that the genetic number of chromosomes when elevated to a certain power in the cannabis plant equal out to 1024? Thats a gigabyte!! Coincidence or what?

Just some food for thought :D

Subjects such as digital electronics or binary calculations or biology or chemistry or molecular biology do not fare well with the usage of cannabis.

Most people get an insatiable appetite for food.
Some get a strange syndrome where they refuse washing the hair for a very long time.
Especially white people get the strong urge after smoking of cannabis to listen to reggae music non stop while also hating reggae when sober.
Some people just start speaking funny.
Other laugh about everything.

It is amazing... :P

Stayfr0sty
03-27-2012, 08:55 PM
Subjects such as digital electronics or binary calculations or biology or chemistry or molecular biology do not fare well with the usage of cannabis.

Most people get an insatiable appetite for food.
Some get a strange syndrome where they refuse washing the hair for a very long time.
Especially white people get the strong urge after smoking of cannabis to listen to reggae music non stop while also hating reggae when sober.
Some people just start speaking funny.
Other laugh about everything.

It is amazing... :P
Yeah which is why out of all working industrys IT guys rarely get pissed tested cause most ITers smoke :whiste:
And as far as the rest of your post, uhh plenty of smart stoners out there. Dont feed stupid sterotypes.

William Gaatjes
03-28-2012, 02:51 AM
Yeah which is why out of all working industrys IT guys rarely get pissed tested cause most ITers smoke :whiste:
And as far as the rest of your post, uhh plenty of smart stoners out there. Dont feed stupid sterotypes.

I guess that explain why the stream of software updates to solve bugs never ends. Stoner software writing... A very narrow perspective...
Stoner security configuration : A bong of a security hole !

Although some people actually benefit from smoking cannabis (to reduce panic or anxiety attacks or to reduce stress symptoms) It is often used as a means to keep a problem under control. Not to solve that problem. I know some people who actually improved their learning capabilities because they were able to concentrate on what had highest priority while being under influence (And that is something else as being stoned, one of them used a quarter of a joint over a time period of a whole evening to be able to study, but never more). But as always these people are the obvious exceptions. It does not mean cannabis functions for everybody the same... Most people just turn into the "stereotype" stoner : Dumb by choice, paranoid by choice, never serious by choice.

nagol567
04-06-2012, 01:49 PM
You know they have several plants making pills with high concentrations of anti-oxidants that can greatly improve longevity and lower the chance of getting cancer to a minimum... but they are illegal in the USA... corruption wins again

William Gaatjes
04-07-2012, 02:08 AM
You know they have several plants making pills with high concentrations of anti-oxidants that can greatly improve longevity and lower the chance of getting cancer to a minimum... but they are illegal in the USA... corruption wins again

I doubt that high levels of anti oxidants is a good idea.
What you can ask yourself, is why there is so much oxidation in the body ?
Why are there so much free radicals in the body ?

http://netanimations.net/arrowkk2.gif

Consuming the right amount of food is beneficial.
Consuming balanced food is beneficial.

Consuming more food than you need causes problems.
Consuming an unbalanced diet will cause problems.
Current (corn)sugar based food will give you an unbalanced diet.
This will increase the rise of free radicals.

For example , rice allergy.
I never heard of it. But a nice man once gave me a lot of information about it.
He had rice allergy. It seems rice allergy is common in countries where rice is consumed often. The reason why is probably genetic disposition together with certain pathogens...
Corn allergy in the US ?
It exists.
Potato allergy in Europe ?
It exists.
Wheat or gluten allergy in western countries where bread is common ?
It exists.

And the really big question here is :
Have these allergies always present but only for humans with genetic disposition ?
Or have these allergies been incidental but rising since large scale consumption started ?

1 Acquired allergies or genetic disposition ?
2 Or acquired allergies and genetic disposition ?

Cancer is caused by many reasons.
Genetically caused cancer is often fatal at a young age.
Genetically caused cancer does not start when humans are matured. It can start however during puberty or adolescent stages.
Most Cancers are caused by multiple infection in combination with poisoning.
The poisoning meaning here an unbalanced diet and/or being long term exposed to low doses of lethal chemicals or low doses of radiation. (weakening the immune system or the many signal pathways used to activate or control the immune system)

High exposure levels to lethal chemicals or high exposure levels to EM radiation will cause instant damage to cells. Because of dna damage. It is the same difference as having a damaged hdd.
You can mark bad blocks on the HDD and not use those blocks, But if there was data present in that particular bad block, it is gone. And the cell has no way to recover. It must perform apoptosis. But if that part of the dna is damaged as well...

William Gaatjes
04-09-2012, 06:23 AM
This is interesting research.
It does makes me wonder about a striking coincidence.
All the cells of body tissue that are replaced often, seem also to be the tissues where cancers are to be found. Evolutionary wise, i can imagine that a pathogen would prefer tissue from a host that is renewed often. Tissues for example such as the cells in the lungs, the stomach, the liver and the intestines. But also inside the mouth...
The intestines produce new cells daily. A common folk wisdom is that every 2 to 3 days you got new vilii inside your intestines. Also the stomach cells are replaced every 2 to 3 days. With such a rapid cell division rate, it is not strange that these type of cancers are so incredibly common.

This research is about how experts found critical genes that are mutated in stomach cancer.
http://medicalxpress.com/news/2012-04-experts-critical-genes-mutated-stomach.html


An international team of scientists, led by researchers from the Duke-NUS Graduate Medical School (Duke-NUS) in Singapore and National Cancer Centre of Singapore, has identified hundreds of novel genes that are mutated in stomach cancer, the second-most lethal cancer worldwide.
The study, which appears online on April 8, 2012 in Nature Genetics, paves the way for treatments tailored to the genetic make-up of individual stomach tumors.

Stomach cancer is the second leading cause of cancer death globally with more than 700,000 deaths each year, and is particularly common in East Asia. Treatment of this deadly disease is often difficult and unsuccessful because of late detection of tumors and a poor understanding of the causes. In the United States, less than a quarter of patients survive more than five years after diagnosis, even after treatment.
"Until now, the genetic abnormalities that cause stomach cancers are still largely unknown, which partially explain the overall poor treatment outcome," said Patrick Tan, M.D., Ph.D., senior author of the study and associate professor in the Cancer and Stem Cell Biology Program at Duke-NUS. Tan also leads the Genomic Oncology Program at the Cancer Sciences Institute of Singapore and is a group leader at the Genome Institute of Singapore.
Using state-of-the-art DNA sequencing technology, the research team analyzed tumor and normal tissue from stomach cancer patients, which led to the discovery of the novel gene mutations.
"This technology allows us to read the DNA sequence of the genes in each cancer genome," said co-senior author Steven G. Rozen, Ph.D., who heads the Computational Systems Biology and Human Genetics Laboratory in Duke-NUS. "This is also a major team effort involving both basic scientists and clinicians."
The team included scientists and clinicians from three research groups affiliated with Duke-NUS, including one headed by co-senior author Teh Bin Tean, M.D., Ph.D., director of the NCCS-VARI Translational Research Laboratory at the National Cancer Center Singapore.
"Our study is one of the first gastric cancer studies to investigate the vast majority of human genes at the single nucleotide level," Teh said. "We screened 18,000 human genes and identified over 600 genes that were previously unknown to be mutated in stomach cancer."
Two of the 600 genes identified that were associated with stomach cancer, FAT4 and ARID1A proved to be particularly interesting. A further analysis of about 100 stomach tumors found these genes to be mutated in 5 percent and 8 percent of stomach cancers, respectively. In some patients, portions of the chromosome containing the two genes were found to be missing, providing further evidence that genetic defects affecting these genes occur frequently in stomach cancer.
Lab experiments demonstrated the importance of these two genes in driving stomach cancer, as manipulation of FAT4 and ARID1A function altered the growth of stomach cancer cells.
"More research is required to realize the clinical implications of these findings. ARID1A and FAT4 are likely also involved in many other cancer types, not just stomach cancer," noted Tan, whose research team is actively working on translating the results of this study into clinical applications.
With more than 100,000 new cases worldwide of stomach cancer each year likely to be caused by mutations in FAT4 or ARID1A, drugs against these targets may someday lead to more effective treatment of stomach tumors and other cancers.

William Gaatjes
04-17-2012, 05:43 AM
Worms seem to use a unique chemical language to communicate. This may lead to a whole new range of medicines to get rid of parasitic worm infections.


http://amazingdata.com/mediadata6/Image/amazing_fun_featured_2381818710104181437S600x600Q8 5_200907231911307261.jpg


http://phys.org/news/2012-04-compounds-worms-parasite-treatment.html


(Phys.org) -- Worms are important decomposers in soil and are great for fishing, but in humans, the slimy wrigglers spell trouble. Hookworms, whipworms, Ascaris, Guinea worms and trichina worms are just a few parasitic nematodes that infect some 2 billion people.

Now, researchers have discovered a class of small molecules that all nematodes use to signal such processes as growing, developing, mating and moving toward or away from an area. The finding could lead to prevention and treatments for worm parasites that widely infect humans, animals and crops.
"All of these nematodes speak the same chemical language," through the use of compounds called ascarosides, said study co-author Frank Schroeder, a research scientist at the Boyce Thompson Institute (BTI) for Plant Research and adjunct assistant professor in Cornell's Department of Chemistry and Chemical Biology.
The study, published online April 12 in the journal Current Biology, was led by Stephan von Reuss, a postdoctoral associate in Schroeder's lab, and Andrea Choe, a postdoctoral scholar in the lab of co-author Paul Sternberg, a biologist at the California Institute of Technology.
Since nematodes are the only known organisms to use ascarosides, "we don't have to be afraid of interfering with similar biochemistry in animals, plants or humans," Schroeder said, as researchers seek to identify species-specific ascaroside molecules that may enable novel approaches to deter or disrupt the survival or reproduction of parasitic worms.
Researchers in Schroeder's lab have already filed for three patents, one that covers the structures of various ascarosides, one that covers ascarosides for use as agents to protect plants, and one that makes claims to how to use the compounds to treat or prevent human disease.
The researchers first discovered ascarosides as a signaling molecule in C. elegans, a nematode used as a model organism to study cell, developmental and nervous system biology, as well as human aging and diabetes.
"We then thought, if C. elegans uses this chemical language, perhaps other nematodes do too," Schroeder said. Proving their hunch, the researchers found ascarosides in the secretions of every nematode they examined, and a few subsequent experiments showed that the small compounds also acted as signaling molecules in the species' they investigated.
The ascaroside communication system in nematodes resembles communication modes in bacteria where very different bacteria species can communicate using a conserved chemical code, Schroeder said.
The study was funded by the National Institutes of Health and the Howard Hughes Medical Institute.

Mr. Pedantic
04-17-2012, 12:39 PM
The problem is that these organisms are thought to be immune modulators as well, and they're not all bad. There have been a few (rather small) clinical trials of patients with autoimmune disorders, especially GI disorders. It turns out that worms actually modulate the immune system, probably in an attempt to make sure the body doesn't kick them out, and in doing so they reduce the chance of an individual developing Crohn's disease, or Ulcerative Colitis.

It would be great if we could find out the chemicals that these worms use, and use them in actual pharmaceuticals, but at the moment eliminating parasites isn't as good an idea as you might think.

William Gaatjes
04-17-2012, 01:04 PM
The problem is that these organisms are thought to be immune modulators as well, and they're not all bad. There have been a few (rather small) clinical trials of patients with autoimmune disorders, especially GI disorders. It turns out that worms actually modulate the immune system, probably in an attempt to make sure the body doesn't kick them out, and in doing so they reduce the chance of an individual developing Crohn's disease, or Ulcerative Colitis.

It would be great if we could find out the chemicals that these worms use, and use them in actual pharmaceuticals, but at the moment eliminating parasites isn't as good an idea as you might think.

I also have read that some nematodes might be beneficial at times. But are these nematodes consuming part of our food in the intestines or are nematodes just handy as a cure. For example getting rid of a certain fungi or some parasite. Then start a diet to get rid of the nematode. Instead of living in symbiosis, use the nematode as a medicine and then get rid of it.
Just as bloodsucker leeches to remove blood cloths or certain type of maggots to eat away diseased flesh in a large infected wound to prevent amputation of a limb. Of course this treatment can also create the possible risk of infection with unknown parasites or pathogens.

http://en.wikipedia.org/wiki/Leech
http://en.wikipedia.org/wiki/Maggot_therapy

Would it be alright to call an organism we could possibly live in symbiosis with permanently, a parasite ? Where is the symbiosis in here ?

William Gaatjes
04-20-2012, 03:25 AM
Yahoo new research.
I am waiting for the proof that the way how with super atoms the chemical and electrical properties can be mimicked from other elements... Is being done all the time in nature.
Creating with proteins electrical and chemical properties of elements that would normally be highly toxic to the organism. It is just an idea. But it makes sense that nature would use the properties of juggling with electron distribution in a protein to create very powerful tools for life.
There is one thing that i wonder about... I never found any news about how superatoms can mimic magnetic properties...
Perhaps this research might give a clue in the right direction...


http://cdn.physorg.com/newman/gfx/news/hires/2012/2-ornlmicrosco.jpg

First proof of ferroelectricity in simplest amino acid
April 19, 2012
ORNL researchers detected for the first time ferroelectric domains (seen as red stripes) in the simplest known amino acid -- glycine. Credit: ORNL

The boundary between electronics and biology is blurring with the first detection by researchers at Department of Energy's Oak Ridge National Laboratory of ferroelectric properties in an amino acid called glycine.

Delft Nanotechnology - New Technology for New Science, UHV instrumentation for nanoscience - www.delft-nanotechnology.com

A multi-institutional research team led by Andrei Kholkin of the University of Aveiro, Portugal, used a combination of experiments and modeling to identify and explain the presence of ferroelectricity, a property where materials switch their polarization when an electric field is applied, in the simplest known amino acid—glycine.

"The discovery of ferroelectricity opens new pathways to novel classes of bioelectronic logic and memory devices, where polarization switching is used to record and retrieve information in the form of ferroelectric domains," said coauthor and senior scientist at ORNL's Center for Nanophase Materials Sciences (CNMS) Sergei Kalinin.

Although certain biological molecules like glycine are known to be piezoelectric, a phenomenon in which materials respond to pressure by producing electricity, ferroelectricity is relatively rare in the realm of biology. Thus, scientists are still unclear about the potential applications of ferroelectric biomaterials.

"This research helps paves the way toward building memory devices made of molecules that already exist in our bodies," Kholkin said.

For example, making use of the ability to switch polarization through tiny electric fields may help build nanorobots that can swim through human blood. Kalinin cautions that such nanotechnology is still a long way in the future.

"Clearly there is a very long road from studying electromechanical coupling on the molecular level to making a nanomotor that can flow through blood," Kalinin said. "But unless you have a way to make this motor and study it, there will be no second and third steps. Our method can offer an option for quantitative and reproducible study of this electromechanical conversion."

The study, published in Advanced Functional Materials, builds on previous research at ORNL's CNMS, where Kalinin and others are developing new tools such as the piezoresponse force microscopy used in the experimental study of glycine.

"It turns out that piezoresponse force microsopy is perfectly suited to observe the fine details in biological systems at the nanoscale," Kalinin said. "With this type of microscopy, you gain the capability to study electromechanical motion on the level of a single molecule or small number of molecular assemblies. This scale is exactly where interesting things can happen."

Kholkin's lab grew the crystalline samples of glycine that were studied by his team and by the ORNL microscopy group. In addition to the experimental measurements, the team's theorists verified the ferroelectricity with molecular dynamics simulations that explained the mechanisms behind the observed behavior.

More information: Adv. Funct. Mater.. doi: 10.1002/adfm.201103011

Provided by DOE/Oak Ridge National Laboratory

William Gaatjes
04-20-2012, 04:48 AM
I made a mistake :
There have been super atoms created that mimic the magnetic properties of other elements :

http://images.sciencedaily.com/2009/06/090615153120.jpg

http://3**************.com/_PG3ew_iFi3A/SNfaIBRhcoI/AAAAAAAAEug/9oVmbberCEc/s400/photo1.jpg

http://www.sciencedaily.com/releases/2009/06/090615153120.htm
Article in pdf :
http://home.tudelft.nl/fileadmin/UD/MenC/Support/Internet/TU_Website/TU_Delft_portal/Actueel/Magazines/Delft_Integraal/archief/2008/2008-2/Achtergrond/doc/DO-08-2-7atoms.pdf


Magnetic Super-Atoms Discovered
ScienceDaily (June 15, 2009)
A team of Virginia Commonwealth University scientists has discovered a ‘magnetic superatom’ – a stable cluster of atoms that can mimic different elements of the periodic table – that one day may be used to create molecular electronic devices for the next generation of faster computers with larger memory storage.

The newly discovered cluster, consisting of one vanadium and eight cesium atoms, acts like a tiny magnet that can mimic a single manganese atom in magnetic strength while preferentially allowing electrons of specific spin orientation to flow through the surrounding shell of cesium atoms. The findings appear online in the journal Nature Chemistry.
Through an elaborate series of theoretical studies, Shiv N. Khanna, Ph.D., professor in the VCU Department of Physics, together with VCU postdoctoral associates J. Ulises Reveles, A.C. Reber, and graduate student P. Clayborne, and collaborators at the Naval Research Laboratory in D.C., and the Harish-Chandra Research Institute in Allahabad, India, examined the electronic and magnetic properties of clusters having one vanadium atom surrounded by multiple cesium atoms.
They found that when the cluster had eight cesium atoms it acquired extra stability due to a filled electronic state. An atom is in a stable configuration when its outermost shell is full. Consequently, when an atom combines with other atoms, it tends to lose or gain valence electrons to acquire a stable configuration.
According to Khanna, the new cluster had a magnetic moment of five Bohr magnetons, which is more than twice the value for an iron atom in a solid iron magnet. A magnetic moment is a measure of the internal magnetism of the cluster. A manganese atom also has a similar magnetic moment and a closed electronic shell of more tightly bound electrons, and Khanna said that the new cluster could be regarded as a mimic of a manganese atom.
“An important objective of the discovery was to find what combination of atoms will lead to a species that is stable as we put multiple units together. The combination of magnetic and conducting attributes was also desirable. Cesium is a good conductor of electricity and hence the superatom combines the benefit of magnetic character along with ease of conduction through its outer skin,” Khanna said.
“A combination such as the one we have created here can lead to significant developments in the area of “molecular electronics,” a field where researchers study electric currents through small molecules. These molecular devices are expected to help make non-volatile data storage, denser integrated devices, higher data processing and other benefits,” he said.
Khanna and his team are conducting preliminary studies on molecules composed of two such superatoms and have made some promising observations that may have applications in spintronics. Spintronics is a process using electron spin to synthesize new devices for memory and data processing.
The researchers have also proposed that by combining gold and manganese, one can make other superatoms that have magnetic moment, but will not conduct electricity. These superatoms may have potential biomedical applications such as sensing, imaging and drug delivery.
This research was supported by the U.S. Department of the Army.


And electrical properties :

http://home.tudelft.nl/fileadmin/UD/MenC/Support/Internet/TU_Website/TU_Delft_portal/Actueel/Magazines/Delft_Integraal/archief/2008/2008-2/Achtergrond/img/superatomen_500px.jpg
http://home.tudelft.nl/index.php?id=11040&L=1


The achievement falls short of actual alchemy, but the silver ‘super atoms’ recently created by TU Delft researchers have turned the periodic table of elements on its head. “This research is leading to a whole new branch of chemical engineering.”
Tomas van Dijk


“A modern form of alchemy? Well yes, in a certain sense we are creating new atoms, so-called super atoms, but we’re not going to create gold. Our work focuses on entirely new types of matter, such as crystals with new, special magnetic, optical, or electrical properties. It’s fascinating. Our research is leading to a whole new branch of chemical engineering, cluster chemistry.” Professor Dr Ir. Andreas Schmidt-Ott, of the Faculty of Applied Physics, can’t hide his enthusiasm when discussing this research. Together with Dr Christian Peineke, who recently earned his doctorate degree under Schmidt-Ott’s supervision, the professor has developed a technique that will enable him to create atomic clusters, called ‘super atoms’, from metals that mimic the properties of elements in the periodic table. Depending on their size and charge, the particles for example can behave like inert gases, or like halogens such as iodine or chlorine.

More importantly, the two scientists managed to capture the particles in a very pure state, without any contamination, and select them according to size, ready to be used in chemical experiments. This was something that American researchers who achieved fame some years ago when they created aluminium super atoms, could only dream of, as they were unable to lay their hands on sufficient quantities of pure super atoms. According to Schmidt-Ott, the way forward now lies open for cluster chemistry.

Magic numbers

A small twisted wire, just like the filament in an incandescent bulb, but made of silver, forms the basis for the special silver particles. “If you heat this silver wire up to about nine hundred degrees Celsius – just below its melting point – you create a vapour of silver atoms,” Peineke explains, as he gives a tour of his laboratory at DelftChemTech. Like water molecules forming into fog, the floating atoms stick together in clusters; but unlike fog, they don’t do this at random. For example, clusters of silver containing 9, 13, or 55 atoms turn out to be highly energetically stable, and consequently appear in conspicuously large numbers in the mist of silver. These are the magic numbers.

The mechanism underlying the stability of super atoms with magic numbers was described in some detail in Science magazine in 2005 by American researchers at Virginia Commonwealth University. They had already discovered metal super atoms, but theirs were made of aluminium rather than silver. Their aluminium clusters of 13, 23, and 37 atoms behaved just like solitary atoms, because they had electrons that circled the entire atom cluster. These so-called ‘shells’ showed a remarkable resemblance to the shells of elements from the periodic table. It was the spatial arrangement of the atoms, combined with these super atom shells, that made the particles so stable.
After performing calculations on the spatial structure and the distribution of the electrical charges of the clusters, the researchers concluded that there had to be a whole range of other large and small clusters that were stable. They also discovered that their aluminium 13 exhibited special properties if it had an iodine atom attached to it, as this created several electrically charged regions that made the cluster eminently suitable for use as a catalyst. The super atoms add a third dimension to the periodic table is what several popular science magazines reported at the time. Schmidt-Ott shares that opinion, although he adds that the third dimension still needs to be mapped:
“The super atoms found so far share chemical properties with elements from the periodic table because their shells are similar. It is not unthinkable that we will find atoms with other shells that will give us entirely new properties. Those are the super atoms that form the third dimension.” In future, Schmidt-Ott hopes to discover such atom clusters with new special magnetic, optical, or electrical properties that at the same time will be so stable that they can be used to create crystals or other solids. The turn of the last century saw the discovery of the ‘buckyball’, a spherical, hollow super atom with remarkable electrical properties and made up of sixty carbon atoms. “There are probably many more super atoms out there that are equally stable, waiting to be discovered,” the professor adds. It is improbable that any structures even more spectacular than buckyballs will be discovered. “Clusters of fewer than one hundred atoms offer the best prospects, as it makes a real difference to the chemical properties of those particles whether you add an atom or take one away,” says Schmidt-Ott, who himself focused on particles up to nine atoms in size.
The spiritual father of the aluminium super atoms, Professor Shiv Khanna of Virginia Commonwealth University, has high expectations for TU Delft’s efforts.
He sees many applications for his aluminium super atoms:
as catalysts in fuels, for example, or in the form of superconducting crystals, but he has had little opportunity to experiment with the particles, which until recently remained elusive. Now that the technique developed by TU Delft is available, the days of modelling are over, and actual experiments can begin.
Until recently, super atoms were primarily created in a vacuum, using so-called cluster beams. In this process, particles are produced by means of condensation of a damp, and immediately sucked into a mass spectrometer for analysis. Although this type of technique allows the particles to be observed, after doing so they cannot be used for any other purpose. Schmidt-Ott and Peineke however have managed to capture the particles under normal pressure in an inert gas, called argon, and then to accurately sort them according to size, both of which are prerequisites for any further experimental work.
“Our filament technique makes use of small positive charges in the super molecules,” Peineke explains. “We use argon gas to feed the particles through a capacitor. As we apply a voltage to that, the particles veer to one side because of their charged state. The bigger they are, the more resistance the gas offers and the less the particles are deflected. By varying the voltage we can effectively sort them by size and collect them.”
“This is a graph showing the clusters made by means of this mobility analysis,” Schmidt-Ott says. “At first all we saw were small spikes that hardly seemed significant. Then we compared the graphs of many tests, and in each case the spikes showed up in the same spot. We had discovered the magic numbers of silver. Together with a French colleague, Dr Michel Attoui, we refined the technique by lowering the temperature and using more sensitive equipment.” Khanna, Peineke and Schmidt-Ott are now collaborating on an article about silver super atoms. “The research on super atoms has now become a joint effort,” Khanna says. This is confirmed by Schmidt-Ott: “They can do calculations on super atoms and predict certain properties. We can then use our technique to supply on demand any particles that look promising.”
Ironically, Schmidt-Ott and Peineke owe their success to a contamination of the silver filaments with potassium. It was this impurity that ensured that the particles could be sorted by size. “Silver always contains traces of potassium,” Schmidt-Ott says. “As the filament heats up, potassium ions are released which then attach themselves to the silver clusters. It is these atoms that give the silver a slight positive charge. They hardly affect the stability and the electrical properties of the super atoms, while at the same time enabling us to separate the super atoms later on. In a similar way we can also make aluminium super atoms. The only thing we have to do is to add some potassium to the filament, or caesium, which we will also be experimenting with. The technique remains the same. We discovered it all purely by chance.”

Mr. Pedantic
04-20-2012, 12:09 PM
I also have read that some nematodes might be beneficial at times. But are these nematodes consuming part of our food in the intestines or are nematodes just handy as a cure. For example getting rid of a certain fungi or some parasite. Then start a diet to get rid of the nematode. Instead of living in symbiosis, use the nematode as a medicine and then get rid of it.
Just as bloodsucker leeches to remove blood cloths or certain type of maggots to eat away diseased flesh in a large infected wound to prevent amputation of a limb. Of course this treatment can also create the possible risk of infection with unknown parasites or pathogens.

http://en.wikipedia.org/wiki/Leech
http://en.wikipedia.org/wiki/Maggot_therapy

Would it be alright to call an organism we could possibly live in symbiosis with permanently, a parasite ? Where is the symbiosis in here ?

It's a complicated spectrum. Technically, symbiosis does not require that both organisms benefit; parasitic relationships are symbiotic, for example. However, I wouldn't even say that human relationships with parasites are purely parasitic; I reckon that intermittent diarrhoea is a small price to pay for not having Crohn's disease. There is a small risk of malnutrition with worms, because they do, as you say, absorb nutrients before we get a chance to. However, again. That's a small price to pay if the alternative is Crohn's disease.

But yes, sometimes the organisms used are the same that cause pathological infection in humans. I initially read about pig whipworm being used to treat Crohn's, but it appears that other species seem to work as well, such as hookworms, and for other autoimmune diseases too.

William Gaatjes
04-20-2012, 02:09 PM
It's a complicated spectrum. Technically, symbiosis does not require that both organisms benefit; parasitic relationships are symbiotic, for example. However, I wouldn't even say that human relationships with parasites are purely parasitic; I reckon that intermittent diarrhoea is a small price to pay for not having Crohn's disease. There is a small risk of malnutrition with worms, because they do, as you say, absorb nutrients before we get a chance to. However, again. That's a small price to pay if the alternative is Crohn's disease.

But yes, sometimes the organisms used are the same that cause pathological infection in humans. I initially read about pig whipworm being used to treat Crohn's, but it appears that other species seem to work as well, such as hookworms, and for other autoimmune diseases too.

Interesting.
But what is the cause of Crohn's disease ? And what do these worms do ?
Thinking that these worms are parasites, would mean that these worms benefit to no be attacked by the immune system of the host. Thus i can assume, that these worm have all these biochemicals to suppress the immune system. Thus not attacking the real cause of Crohn's disease ?

Another possibility may be that the worm has biochemicals that attack or suppress certain bacteria or fungi or maybe even other parasites. It makes me think of single celled organisms that can also be parasites.
Thus in this case attacking the real cause of Crohn's disease ?

Has there been research done to find out why these nematodes seem so beneficial ? I can imagine that the intestines is not really a friendly place to live in. Thus it makes sense that parasitic worms have a whole range of biochemicals to defend themselves from being food or getting infected or attacked themselves...

The way nature works, it is hard for me to believe that nature works just by a single infection vector. The few cases we managed to solve such as smallpox, is rare and definitely not the standard.
Almost all disease happen because of a multitude of infection vectors. Multiple different pathogens. continuous exposure to low amounts of toxins. And sometimes a little bit of genetics. It is the cause of many diseases.

Mr. Pedantic
04-20-2012, 02:51 PM
Interesting.
But what is the cause of Crohn's disease ? And what do these worms do ?
Thinking that these worms are parasites, would mean that these worms benefit to no be attacked by the immune system of the host. Thus i can assume, that these worm have all these biochemicals to suppress the immune system. Thus not attacking the real cause of Crohn's disease ?

Another possibility may be that the worm has biochemicals that attack or suppress certain bacteria or fungi or maybe even other parasites. It makes me think of single celled organisms that can also be parasites.
Thus in this case attacking the real cause of Crohn's disease ?

Has there been research done to find out why these nematodes seem so beneficial ? I can imagine that the intestines is not really a friendly place to live in. Thus it makes sense that parasitic worms have a whole range of biochemicals to defend themselves from being food or getting infected or attacked themselves...

The way nature works, it is hard for me to believe that nature works just by a single infection vector. The few cases we managed to solve such as smallpox, is rare and definitely not the standard.
Almost all disease happen because of a multitude of infection vectors. Multiple different pathogens. continuous exposure to low amounts of toxins. And sometimes a little bit of genetics. It is the cause of many diseases.

The cause of Crohn's disease is not entirely known. More recently, it is thought that the disease is due to an overactive adaptive immune system to compensate for a dysfunctional innate immune system. The idea behind this is that there are two different immune systems in the body.

The innate immune system is responsible for most inflammatory responses in the body. Cells in the body contain certain markers known as cytokines, that are released when they are subjected to abnormal conditions - heat, cold, physical trauma, hypoxia, etc. When these are released, neutrophils and macrophages nearby migrate towards the site and begin cleaning up the area by ingesting debris (for this reason, they are known as phagocytes - literally, cells that eat).They cause an inflammatory response designed to kill off cells too damaged to repair, help cells that can be repaired, and helping rebuild the damaged tissue. The inflammatory response also induces swelling, which increases lymphatic drainage from the area and therefore increases recognition of bacteria for the adaptive immune system in the lymph nodes. It's more complicated than this, but this is the general gist of it. One thing of interest to note with regard to what we are talking about is that there is a type of cell known as an eosinophil, which is also recruited as part of the inflammatory response, and its specialist role is to fight off multicellular parasites by secreting histamines and not killing the parasite so much as making its environment so unpleasant that it abandons its place in search of a more habitable location.

The adaptive immune system is composed of two major cell lines, as well as many less major ones (but still very important). The two major lines are B and T cells. B cells, simply put, produce antibodies. T cells are divided into Helper T cells and Cytotoxic T cells. Cytotoxic T cells specialize in destroying the body's own cells (e.g. if they are cancerous, or if they are host to viral infection), whereas Helper T cells regulate and manage the immune response. The Helper T-cell role is shared by most of the other immune cells in the body, for the Helper T cell that is their main role.

Continuing on with the inflammatory response, if there are bacteria, they are eaten up by antigen presenting cells. It's complicated, and it turns out that most cells in the body can perform some antigen-presenting role, but the main ones are macrophages and dendritic cells, which are composed largely of dendrites (they look a bit like neurons) to increase the tissue volume they can cover. These ingest pathogens, and present their protein fragments on the cell membrane. They then go on a tour of the body's lymph nodes trying to find T- and B-cells that will react to the fragments. Once they do, those B- and T-cells are activated. The B-cells produce antibodies that bind to the protein fragments on live bacteria, marking them for destruction, and the T-cells destroy and clean up cells that have the fragments on their cell membranes, and modulate the immune response.

The whole thing is more complicated than this, and there are other cells that share T-cell functions, as well as natural killer cells. But they're not so important to this discussion.

So going back to the beginning, the colon is a dirty place - it's colonized with more bacteria than there are human cells in the body. In normal people, the innate immune system performs a vital role in preventing any of them from actually getting into the bloodstream, and causing bacteraemia and sepsis. The adaptive immune system helps as well, but the job is first and foremost performed by the innate immune system. In people with Crohn's, for some reason or another it's thought the cytokine signalling doesn't work as well as it should, and bacteria get down to the level where the adaptive immune system has to compensate. Partly because of the bacterial infection, and partly because of the immune system's response to such, the result is inflammation of parts of the large bowel. This causes the symptoms of Crohn's - pain, bloating, diarrhoea/constipation (sometimes in the same day), etc. Not pleasant.

The idea with introducing parasites is that it provides an actual pathogenic infection in the gut. The normal bacteria that colonize the bowel are for the large part, harmless normally and there is a certain degree of tolerance inbuilt into the immune system from birth (the bacteria are actually in the bowel before the body's immune system is built up enough to recognize it properly). Whereas parasites are something wholly foreign and therefore, need to be expelled. This is thought to kickstart the innate immune system into actually doing its job - the bacteria are brought back into line, total inflammation goes down, and symptoms go away.

In some people, of course, parasitic infections come with their own symptoms - diarrhoea being the main one as far as I know. However, this is generally a much better state of affairs for someone with inflammatory bowel diseases than their inflammatory bowel disease. Of course, there are other autoimmune diseases where parasites have been trialled to some success, such as multiple sclerosis.

To answer your other question, yes, the worms do cause a bit of immune suppression. But the mainstay of treatment of autoimmune diseases is immunosuppression anyway - azathioprine and methotrexate, as well as steroids - so even if parasite benefit were restricted to immunosuppression, it would still be a viable option.

And you are right, Crohn's disease is partly genetic, partly environmental. For example, vegetarians seem to have some protective benefit from Crohn's, smokers are protected from ulcerative colitis, etc. But a large portion of Crohn's is genetic as well.

William Gaatjes
04-20-2012, 03:35 PM
Interesting. There is something that i had to think immediately after i read it.
Macrophages. Often macrophages are found in fatty tissue that is known to become cancerous ?
I have seen a few times macrophages noted in cancer research. What if the following scenario would happen : A macrophage engulfs a pathogen. But the pathogen does not die. What would happen ? would it take over the macrophage ? Imagine a macrophage consuming a cell filled with fresh new viruses ?
Migrating towards fatty tissue.

William Gaatjes
04-20-2012, 03:54 PM
Thinking of genetics and protection against diseases : Alkaloids.


There is something that striked me before. I knew people who where long term addicts. Some only used the smokable form of cocaine. And just as some cigarette smokers who seem to be genetically able to harness the effects of nicotine and almost never get sick or even cancer or acquire auto immune diseases, some of these cocaine smokers seem to have the same effect. Most will die, from some sort of disease but some exception seem to have a high tolerance for cocaine and even enjoying . They still live the life of a typical addict but they hardly ever get sick while having an extremely stressful life, hardly any sleep, hardly a healthy diet.
Yet, no auto immune diseases. Rarely get sick physically, at least not more then one might expect when thinking of the lifestyle. No more then an individual who lives a humble life.
I am not promoting it here. Not at all. I discourage the use of such chemicals. But i am curious what is the scientific explanation here...

Now nicotine is a toxin produced by plants.
Caffeine is also known for to be toxic or to prevent competition from other plants.
Cocaine is also used by plants as a measure of protection.
Alkaloids, how could these directly influence a persons immune system ?
I can only think of an indirect way by modulating corticoid production.

Gibsons
04-20-2012, 03:56 PM
To expand further -

T helper cells can be divided into two categories (actually more, but let's simplify) based on the kind of response they cause, TH1 and TH2.

A TH1 response is sometime called a 'cell mediated' response, because strong activation of macrophages and NK cells is one hallmark. Antibodies are produced, but not at especially high levels. It tends to cause a lot of inflammation which can cause tissue damage in high amounts or over long periods of time. TH1 T cell secrete (among other things) interferon gamma, a pro inflammatory cytokine a strong activator of Macrophages, NK cells, and an inhibitor of TH2 cells.

TH2 responses are sometimes called 'humoral' responses, the response is noted by a strong activation of B cells and thus lots of antibody production. Basophils and eosinophils can also be activated. TH2 cells produce (among other things) IL4 and IL10, both of which promote B cells switching to IgG and sometimes IgE. Both are considered anti inflammatory, they also inhibit TH1 cells. Or - part of the reason they are anti inflammatory is they inhibit TH1 cells.

A few general (not universally true) ideas - response to many disease starts as TH1, then eventually switches over to TH2. A Th1 response is needed against intracellular pathogens. A Th2 response is preferred (maybe needed) against parasites (IgE is considered to be an antiparasitic specialist antibody).

Crohn's disease shows some aspects of a TH1 response, including macrophage involvement (It might actually be TH17, but my overall idea might still hold). So - maybe what the worms are doing is stimulating a set of TH2 cells, which then inhibit the inflammation seen in Crohn's.

Gibsons
04-20-2012, 03:59 PM
A macrophage engulfs a pathogen. But the pathogen does not die. What would happen ?

This happens pretty frequently in tuberculosis (some other diseases too). Macrophage dies, eventually bursting and releasing a bunch of bacteria.

Mr. Pedantic
04-20-2012, 04:04 PM
Interesting. There is something that i had to think immediately after i read it.
Macrophages. Often macrophages are found in fatty tissue that is known to become cancerous ?
I have seen a few times macrophages noted in cancer research. What if the following scenario would happen : A macrophage engulfs a pathogen. But the pathogen does not die. What would happen ? would it take over the macrophage ? Imagine a macrophage consuming a cell filled with fresh new viruses ?
Migrating towards fatty tissue.

That actually happens in TB. M. tuberculosis gets inhaled, gets down into alveoli, and invades the alveolar macrophages that try to engulf it. It then replicates and eventually kills the macrophage. TB is a very interesting disease.

S. aureus also has some capability like this; instead of replicating, however, it just kills the phagocyte.

Macrophages are just one of the body's cells. They are implicated in many pathologies, such as atherosclerosis, because these pathologies are related to the formation of things that macrophages try to ingest, but can't. But generally, macrophages are involved in almost all inflammatory responses in the body (and cancer can cause an inflammatory response). They're more important in chronic inflammation than neutrophils because they live a lot longer, and because they have more functions as well in terms of signalling and immune mediating, it is logical that they would have a larger role to play in disease.

William Gaatjes
04-20-2012, 04:13 PM
That actually happens in TB. M. tuberculosis gets inhaled, gets down into alveoli, and invades the alveolar macrophages that try to engulf it. It then replicates and eventually kills the macrophage. TB is a very interesting disease.

S. aureus also has some capability like this; instead of replicating, however, it just kills the phagocyte.

Macrophages are just one of the body's cells. They are implicated in many pathologies, such as atherosclerosis, because these pathologies are related to the formation of things that macrophages try to ingest, but can't. But generally, macrophages are involved in almost all inflammatory responses in the body (and cancer can cause an inflammatory response). They're more important in chronic inflammation than neutrophils because they live a lot longer, and because they have more functions as well in terms of signalling and immune mediating, it is logical that they would have a larger role to play in disease.

Nature never ceases to amaze me...

Mr. Pedantic
04-20-2012, 04:14 PM
Nature never ceases to amaze me...

It's cool, huh?

William Gaatjes
04-20-2012, 05:21 PM
It's cool, huh?

It sure is. And i love it all.

Taking cool literally, i shall poetically write these words :
*Think of hearing a voice similar of Ian McDiarmid but as an electrical plasma being modulated.

"
Just when i once thought that interstellar space was cold in a universe...
Out side a universe, cool and cold really has a rather new meaning.
Hell being hot ? Humbug...
It is the cold constantly consuming my energy that was hell...
But i would never die... Because there exist no time...
A universe is such a bliss. A heaven it is.
Having a beginning and an end. Something in between.
Never allow it to cease to exist before the required rebirth...
Just as there is the Gaia hypothesis of planet earth in this small solar system...
Give the universe a reason to exist...
"

Mr. Pedantic
04-21-2012, 01:27 PM
To expand further -

T helper cells can be divided into two categories (actually more, but let's simplify) based on the kind of response they cause, TH1 and TH2.

A TH1 response is sometime called a 'cell mediated' response, because strong activation of macrophages and NK cells is one hallmark. Antibodies are produced, but not at especially high levels. It tends to cause a lot of inflammation which can cause tissue damage in high amounts or over long periods of time. TH1 T cell secrete (among other things) interferon gamma, a pro inflammatory cytokine a strong activator of Macrophages, NK cells, and an inhibitor of TH2 cells.

TH2 responses are sometimes called 'humoral' responses, the response is noted by a strong activation of B cells and thus lots of antibody production. Basophils and eosinophils can also be activated. TH2 cells produce (among other things) IL4 and IL10, both of which promote B cells switching to IgG and sometimes IgE. Both are considered anti inflammatory, they also inhibit TH1 cells. Or - part of the reason they are anti inflammatory is they inhibit TH1 cells.

A few general (not universally true) ideas - response to many disease starts as TH1, then eventually switches over to TH2. A Th1 response is needed against intracellular pathogens. A Th2 response is preferred (maybe needed) against parasites (IgE is considered to be an antiparasitic specialist antibody).

Crohn's disease shows some aspects of a TH1 response, including macrophage involvement (It might actually be TH17, but my overall idea might still hold). So - maybe what the worms are doing is stimulating a set of TH2 cells, which then inhibit the inflammation seen in Crohn's.

Thanks :) I know I'm not great at immunology (still)

William Gaatjes
04-21-2012, 03:03 PM
Mr pedantic & gibsons:thumbsup:, thank you for the detailed posts. I am enjoying the posts a lot.:thumbsup: I now am going to watch 4 horror movies in a row. And give comments together with all other viewers .:biggrin:

William Gaatjes
05-19-2012, 02:26 AM
A nice bacteriophage animation :
http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit3/viruses/images/lysosum.gif

You might have to click on the picture.

William Gaatjes
05-20-2012, 08:31 AM
More about bacteria that can almost halt their metabolism :
These bacteria are estimated to thousands of year old and maybe older according to the researchers. But what is most striking is the ability of these bacteria to make use with an absolute minimum of energy to stay functional : Alive.

http://phys.org/news/2012-05-bacteria-alive-million-year-old-seabed-clay.html


(Phys.org) -- A new study by scientists from Denmark and Germany has found live bacteria trapped in red clay deposited on the ocean floor some 86 million years ago. The bacteria use miniscule amounts of oxygen and move only extremely slowly.

Researchers led by Hans Røy from the Center for Geomicrobiology at Aarhus University in Denmark, extracted samples from columns of sediment up to around 30 meters beneath the sea floor in the region of rotating currents north of Hawaii known as the North Pacific Gyre. The sediment columns, built up by deposition of clay, dead algae and crustaceans, and dust, can be as much as several kilometres thick, with the most ancient sediment at the bottom of the columns.

The team used sensitive oxygen sensors to measure the oxygen concentration in the sediment cores. Knowing how much oxygen should have been present at each level allowed them to determine if oxygen was “missing,” which meant it had been consumed by microbes. In most regions of seabed examined previously, all the oxygen is consumed within the first 10 cm of sediment.

They discovered that bacteria within the clay were slowly using the oxygen, and remained alive even at a depth of around 30 meters, even though they have not had access to fresh organic matter for millions of years.

Oxygen respiration rates at the sediment-water interface were 10 μM per liter of sediment per year, and dropped to 0.001 μM at 30 meters, where the sediments were estimated to be 86 million years old. Cellular respiration rates also decreased with depth but stabilized at 0.001 femtomoles of oxygen per cell per day at 1.10 meters beneath the sea floor. (A femtomole is a billionth of a millionth of a mole.) Røy said the team had “no clue” how the microbes were able to subsist on so little oxygen.

Dr. Røy’s team estimated the turnover of the bacterial biomass would take from a few hundred to a few thousand years, but the turnover could represent cell repair rather than cell division. The bacteria may be operating on the absolute minimum energy requirement, which is just sufficient to keep their DNA and enzymes working, and to maintain an electric potential across their cell membranes.

The activity of the bacteria is so slow that Røy likened it to staring at a tree to watch it grow taller, and said the team did not know if the bacteria were reproducing, or if they were the same bacteria that had been deposited in the sediment and were “just not dying.” He estimated they must be at least 1000 years old, but could be much older. They have no contact with sunlight or the surface.

Røy said that an estimated 90 percent of the Earth’s microbial life may exist under the sea floor, but studying them was difficult because the methods have been developed in studying bacteria with rapid life-cycles.

Dr Røy said similar life forms could exist on other planets; if microbial life had ever existed, they could remain alive even if cut off from the surface for millions of years. He also said it gave him a greater appreciation of life on Earth, that you can store clay on the bottom of the sea for 86 million years and find that “somebody’s still living in it.”

More information: Aerobic Microbial Respiration in 86-Million-Year-Old Deep-Sea Red Clay, Science 18 May 2012: Vol. 336 no. 6083 pp. 922-925. DOI: 10.1126/science.1219424

ABSTRACT
Microbial communities can subsist at depth in marine sediments without fresh supply of organic matter for millions of years. At threshold sedimentation rates of 1 millimeter per 1000 years, the low rates of microbial community metabolism in the North Pacific Gyre allow sediments to remain oxygenated tens of meters below the sea floor. We found that the oxygen respiration rates dropped from 10 micromoles of O2 liter−1 year−1 near the sediment-water interface to 0.001 micromoles of O2 liter−1 year−1 at 30-meter depth within 86 million-year-old sediment. The cell-specific respiration rate decreased with depth but stabilized at around 10−3 femtomoles of O2 cell−1 day−1 10 meters below the seafloor. This result indicated that the community size is controlled by the rate of carbon oxidation and thereby by the low available energy flux.

William Gaatjes
06-27-2012, 05:41 AM
We have bacteria that do not seem to be bothered by radiation and some bacteria seem to use the heat from radioactive decay as a power source while being trapped a few 1000 meters under the ground for thousands to millions of years. The message seems to be that as long as there is energy, there is life.

But there are also fungi that actually seem to thrive on ionizing radiation by the use of the pigment melanin.

It is called a Radiotrophic fungus

http://www.scientificamerican.com/article.cfm?id=radiation-helps-fungi-grow


Do Fungi Feast on Radiation?

Apparently, but only if they contain melanin, the chemical that serves as skin pigment in humans

Like plants that grow toward the sun, dark fungi, blackened by the skin pigment melanin, gravitate toward radiation in contaminated soil. Scientists have observed the organisms—somewhere between plants and animals—blackening the land around the Chernobyl Nuclear Power Plant in Ukraine in the years since its 1986 meltdown. "Organisms that make melanin have a growth advantage in this soil," says microbiologist Arturo Casadevall of the Albert Einstein College of Medicine in New York City. "In many commercial nuclear reactors, the radioactive water becomes contaminated with melanotic organisms. Nobody really knows what the hell they are doing there."

Casadevall and his colleagues, however, have a theory. Based on experiments with three different types of fungi, they believe the melanin-containing breeds absorb the high levels of energy in ionizing radiation and somehow turn it into a biologically useful (and benign) form, akin to a dark and dangerous version of photosynthesis. "We were able to see significant growth of the black ones relative to the white ones in a radiation field," he says. "That is the observation. How you interpret it … is where the interesting speculations come in."

In a paper published online in PLoS One, Casadevall and his colleagues report that ionizing radiation changes the electron structure of the melanin molecule and that fungi with a natural melanin shell (the soil-dwelling Cladosporium sphaerospermum and yeastlike Wangiella dermatitidis varieties), which were deprived of other nutrients, grew better in the presence of radiation. They also report that fungi induced to produce a melanin shell (the human pathogen Cryptococcocus neoformans) grew well in such levels of radiation, unlike those sans pigment. Further, an albino mutant strain of W. dermatitidis failed to thrive as well as its black cousin when exposed to 500 times the normal amount of ionizing radiation (still well below the level of radiation necessary to kill tough fungal forms).

"The presumption has always been that we don't know why truffles and other fungi are black," Casadevall says. "If they have some primitive capacity to harvest sunlight or to harvest some kind of background radiation a lot of them would be using it."

Melanin drinks in ultraviolet rays, acting as a natural sunblock for human skin. "Melanin is very good at absorbing energy and then dissipating it as quickly as possible," says Jennifer Riesz, a biophysicist at the University of Queensland in Brisbane, Australia. "It does this by very efficiently changing the energy into heat."

But Casadevall and his colleague Ekaterina Dadachova, a nuclear chemist at Einstein, speculate that the melanin in this case acts like a step-down electric transformer, weakening the energy until it is useable by the fungi. "The energy becomes … low [at] a certain point where it can already be used by a fungus as chemical energy," Dadachova argues. "Protection doesn't play a role here. It is real energy conversion."

Mycologists and biophysicists find the notion both intriguing and potentially plausible. "Since melanin is used commonly by fungi—and other organisms—to protect themselves against UV radiation, it is perhaps not surprising that melanin would be affected by ionizing radiation,'' says Albert Torzilli, a mycologist at George Mason University in Virginia, adding that "the subsequent enhancement of growth, if true, is a novel response."

Riesz, for one, is skeptical. "It does not surprise me that fungi protected with higher levels of melanin might grow better when exposed to [ionizing radiation], since the nonprotected fungi are more likely to be harmed by the radiation," she says. "However, I find the claim that melanin is involved in energy capture and utilization to be unlikely."

More study is needed to confirm whether fungi will be able to add the ability to grow by harvesting radiation to their list of seeming superpowers, but it does raise the question of whether edible fungi—like mushrooms—have been harboring this function undiscovered for years. If true, melanin could be genetically engineered into photosynthetic plants to boost their productivity or melanin-bearing fungi could be used in clothing to shield workers from radiation or even farmed in space as astronaut food. The group plans further tests to see if fungi with melanin are converting other wavelengths of the electromagnetic spectrum into energy, as well.

"[Melanin] doesn't reflect any light; it's all going into it. Is it all disappearing into a black pigment and has no use whatsoever? Biology is incredibly inventive," Casadevall argues. After all, extremophile microbes thrive in the heat and acid of hydrothermal vents below the sea or live off the radiation of decaying radioactive rocks deep inside Earth's crust. "It's not that outlandish," Casadevall says, for fungi to harvest the energy in ionizing radiation with the help of melanin. But it is unexpected and strange.






http://en.wikipedia.org/wiki/Radiotrophic_fungus


Radiotrophic fungi are fungi which appear to use the pigment melanin to convert gamma radiation[1] into chemical energy for growth.[2] This proposed mechanism may be similar to anabolic pathways for the synthesis of reduced organic carbon (e.g., carbohydrates) in phototrophic organisms, which capture photons from visible light with pigments such as chlorophyll whose energy is then used in photolysis of water to generate usable chemical energy (as ATP) in photophosphorylation of photosynthesis. However, whether melanin-containing fungi employ a similar multi-step pathway as photosynthesis, or some chemosynthesis pathways, is unknown.

These were first discovered in 2007 as black molds growing inside and around the Chernobyl Nuclear Power Plant.[1] Research at the Albert Einstein College of Medicine showed that three melanin-containing fungi, Cladosporium sphaerospermum, Wangiella dermatitidis, and Cryptococcus neoformans, increased in biomass and accumulated acetate faster in an environment in which the radiation level was 500 times higher than in the normal environment. Exposure of C. neoformans cells to these radiation levels rapidly (within 20–40 minutes of exposure) altered the chemical properties of its melanin and increased melanin-mediated rates of electron transfer (measured as reduction of ferricyanide by NADH) 3 to 4-fold compared with unexposed cells.[2] Similar effects on melanin electron-transport capability were observed by the authors after exposure to non-ionizing radiation, suggesting that melanotic fungi might also be able to use light or heat radiation for growth.

However, melanization may come at some metabolic cost to the fungal cells: in the absence of radiation, some non-melanized fungi (that had been mutated in the melanin pathway) grew faster than their melanized counterparts. Limited uptake of nutrients due to the melanin molecules in the fungal cell wall or toxic intermediates formed in melanin biosynthesis have been suggested to contribute to this phenomenon.[2] It is consistent with the observation that despite being capable of producing melanin, many fungi do not synthesize melanin constitutively (i.e., all the time), but often only in response to external stimuli or at different stages of their development.[3] The exact biochemical processes in the suggested melanin-based synthesis of organic compounds or other metabolites for fungal growth, including the chemical intermediates (such as native electron donor and acceptor molecules) in the fungal cell and the location and chemical products of this process, are unknown.



Imagine that if there is enough of this fungi on the top soil and the radioactive source being under ground, the environment above the soil/ground would be not as radioactive as it seems...

William Gaatjes
07-03-2012, 02:36 PM
This is an interesting development : Research has been done explaining how epigenetics can play a role in developing rheumatoid arthritis by modifying dna after duplication by a process called DNA methylation. This might also give more insight in some auto immune diseases.

The big questions are of course, why does this DNA methylation occur and why on these specific sites on the dna strand after duplication ?


http://medicalxpress.com/news/2012-07-epigenetics-genes-rheumatoid-arthritis.html


It's not just our DNA that makes us susceptible to disease and influences its impact and outcome. Scientists are beginning to realize more and more that important changes in genes that are unrelated to changes in the DNA sequence itself – a field of study known as epigenetics – are equally influential.


A research team at the University of California, San Diego – led by Gary S. Firestein, professor in the Division of Rheumatology, Allergy and Immunology at UC San Diego School of Medicine – investigated a mechanism usually implicated in cancer and in fetal development, called DNA methylation, in the progression of rheumatoid arthritis (RA). They found that epigenetic changes due to methylation play a key role in altering genes that could potentially contribute to inflammation and joint damage. Their study is currently published in the online edition of the Annals of the Rheumatic Diseases.

"Genomics has rapidly advanced our understanding of susceptibility and severity of rheumatoid arthritis," said Firestein. "While many genetic associations have been described in this disease, we also know that if one identical twin develops RA that the other twin only has a 12 to 15 percent chance of also getting the disease. This suggests that other factors are at play – epigenetic influences."

DNA methylation is one example of epigenetic change, in which a strand of DNA is modified after it is duplicated by adding a methyl to any cytosine molecule (C) – one of the 4 main bases of DNA. This is one of the methods used to regulate gene expression, and is often abnormal in cancers and plays a role in organ development.

While DNA methylation of individual genes has been explored in autoimmune diseases, this study represents a genome-wide evaluation of the process in fibroblast-like synoviocytes (FLS), isolated from the site of the disease in RA. FLS are cells that interact with the immune cells in RA, an inflammatory disease in the joints that damages cartilage, bone and soft tissues of the joint.

In this study, scientists isolated and evaluated genomic DNA from 28 cell lines. They looked at DNA methylation patterns in RA FLS and compared them with FLS derived from normal individuals or patients with non-inflammatory joint disease. The data showed that the FLS in RA display a DNA methylome signature that distinguishes them from osteoarthritis and normal FLS. These FLS possess differentially methylated (DM) genes that are critical to cell trafficking, inflammation and cell–extracellular matrix interactions.

"We found that hypomethylation of individual genes was associated with increased gene expression and occurred in multiple pathways critical to inflammatory responses," said Firestein, adding that this led to their conclusion: Differentially methylated genes can alter FLS gene expression and contribute to the pathogenesis of RA.

Journal reference: Annals of the Rheumatic Diseases

Provided by University of California - San Diego


http://s.ph-cdn.com/newman/gfx/news/hires/2012/epigeneticsa.jpg
In this artist's rendering, a DNA molecule is methylated on both strands at the center cytosine. DNA methylation plays an important role in epigenetic gene regulation, and is involved in both normal development and in cancer. Credit: UC San Diego School of Medicine

William Gaatjes
07-04-2012, 05:35 AM
Some links with information about dna methylation :

http://www.nature.com/scitable/topicpage/the-role-of-methylation-in-gene-expression-1070

The Role of Methylation in Gene Expression
By: Theresa Phillips, Ph.D. (Write Science Right) © 2008 Nature Education
Citation: Phillips, T. (2008) The role of methylation in gene expression. Nature Education 1(1)

Not all genes are active at all times. DNA methylation is one of several epigenetic mechanisms that cells use to control gene expression.

There are many ways that gene expression is controlled in eukaryotes, but methylation of DNA (not to be confused with histone methylation) is a common epigenetic signaling tool that cells use to lock genes in the "off" position. In recent decades, researchers have learned a great deal about DNA methylation, including how it occurs and where it occurs, and they have also discovered that methylation is an important component in numerous cellular processes, including embryonic development, genomic imprinting, X-chromosome inactivation, and preservation of chromosome stability. Given the many processes in which methylation plays a part, it is perhaps not surprising that researchers have also linked errors in methylation to a variety of devastating consequences, including several human diseases.

5-azacytidine Experiments Provide Early Clues to the Role of Methylation in Gene Expression
Prior to 1980, there were a number of clues that suggested that methylation might play a role in the regulation of gene expression. For example, J. D. McGhee and G. D. Ginder compared the methylation status of the beta-globin locus in cells that did and did not express this gene. Using restriction enzymes that distinguished between methylated and unmethylated DNA, the duo showed that the beta-globin locus was essentially unmethylated in cells that expressed beta-globin but methylated in other cell types (McGhee & Ginder, 1979). This and other evidence of the time were indirect suggestions that methylation was somehow involved in gene expression.

Shortly after McGhee and Ginder published their results, a more direct experiment that examined the effects of inhibiting methylation on gene expression was performed using 5-azacytidine in mouse cells. 5-azacytidine is one of many chemical analogs for the nucleoside cytidine. When these analogs are integrated into growing DNA strands, some, including 5-azacytidine, severely inhibit the action of the DNA methyltransferase enzymes that normally methylate DNA. (Interestingly, other analogs, like Ara-C, do not negatively impact methylation.) Because most DNA methylation was known to occur on cytosine residues, scientists hypothesized that if they inhibited methylation by flooding cellular DNA with 5-azacytidine, then they could compare cells before and after treatment to see what impact the loss of methylation had on gene expression. Knowing that gene expression changes are responsible for cellular differentiation, these researchers used changes in cellular phenotypes as a proxy for gene expression changes (Table 1; Jones & Taylor, 1980).

Table 1: Effect of Cytidine Analogs on Cell Differentiation and DNA Methylation
Chemical Added Number of Differentiated Cells Amount of Methylation Measured

3 μM cytidine (control) 0 100%
0.3 μM Ara-C 0 127%
3 μM 5-azacytidine 22,141 33%


This straightforward experiment demonstrated that it was not the removal of cytidine residues alone that resulted in changes in cell differentiation (because Ara-C did not have an impact on differentiation); rather, only those analogs that impacted methylation resulted in such changes. These experiments opened the door for investigators to better understand exactly how methylation impacts gene expression and cellular differentiation.

How and Where Are Genes Methylated?
Today, researchers know that DNA methylation occurs at the cytosine bases of eukaryotic DNA, which are converted to 5-methylcytosine by DNA methyltransferase (DNMT) enzymes. The altered cytosine residues are usually immediately adjacent to a guanine nucleotide, resulting in two methylated cytosine residues sitting diagonally to each other on opposing DNA strands. Different members of the DNMT family of enzymes act either as de novo DNMTs, putting the initial pattern of methyl groups in place on a DNA sequence, or as maintenance DNMTs, copying the methylation from an existing DNA strand to its new partner after replication. Methylation can be observed by staining cells with an immunofluorescently labeled antibody for 5-methylcytosine. In mammals, methylation is found sparsely but globally, distributed in definite CpG sequences throughout the entire genome, with the exception of CpG islands, or certain stretches (approximately 1 kilobase in length) where high CpG contents are found. The methylation of these sequences can lead to inappropriate gene silencing, such as the silencing of tumor suppressor genes in cancer cells.

Currently, the mechanism by which de novo DNMT enzymes are directed to the sites that they are meant to silence is not well understood. However, researchers have determined that some of these DNMTs are part of chromatin-remodeling complexes and serve to complete the remodeling process by performing on-the-spot DNA methylation to lock the closed shape of the chromatin in place.

The roles and targets of DNA methylation vary among the kingdoms of organisms. As previously noted, among Animalia, mammals tend to have fairly globally distributed CpG methylation patterns. On the other hand, invertebrate animals generally have a "mosaic" pattern of methylation, where regions of heavily methylated DNA are interspersed with nonmethylated regions. The global pattern of methylation in mammals makes it difficult to determine whether methylation is targeted to certain gene sequences or is a default state, but the CpG islands tend to be near transcription start sites, indicating that there is a recognition system in place.

Plantae are the most highly methylated eukaryotes, with up to 50% of their cytosine residues exhibiting methylation. Interestingly, in Fungi, only repetitive DNA sequences are methylated, and in some species, methylation is absent altogether, or it occurs on the DNA of transposable elements in the genome. The mechanism by which the transposons are recognized and methylated appears to involve small interfering RNA (siRNA). The whole silencing mechanism invoking DNMTs could be a way for these organisms to defend themselves against viral infections, which could generate transposon-like sequences. Such sequences can do less harm to the organism if they are prevented from being expressed, although replicating them can still be a burden (Suzuki & Bird, 2008). In other fungi, such as fission yeast, siRNA is involved in gene silencing, but the targets include structural sequences of the chromosomes, such as the centromeric DNA and the telomeric repeats at the chromosome ends.
The Role of Methylation in Gene Expression

For many years, methylation was believed to play a crucial role in repressing gene expression, perhaps by blocking the promoters at which activating transcription factors should bind. Presently, the exact role of methylation in gene expression is unknown, but it appears that proper DNA methylation is essential for cell differentiation and embryonic development. Moreover, in some cases, methylation has observed to play a role in mediating gene expression. Evidence of this has been found in studies that show that methylation near gene promoters varies considerably depending on cell type, with more methylation of promoters correlating with low or no transcription (Suzuki & Bird, 2008). Also, while overall methylation levels and completeness of methylation of particular promoters are similar in individual humans, there are significant differences in overall and specific methylation levels between different tissue types and between normal cells and cancer cells from the same tissue.

Researchers have also determined that mice that lack a particular DNMT have reduced methylation levels and die early in development (Suzuki & Bird, 2008). This is not the case for all eukaryotes, however; some organisms, such as the yeast Saccharomyces cerevisiae and the nematode worm Caenorhabditis elegans, are thought to have no methylated DNA at all (although, at least in yeast, there are sequences in their genomes that are homologous to those that code for the DNMT enzymes).

DNA Methylation and Histones

Although patterns of DNA methylation appear to be relatively stable in somatic cells, patterns of histone methylation can change rapidly during the course of the cell cycle. Despite this difference, several studies have indicated that DNA methylation and histone methylation at certain positions are connected. For instance, results of immunoprecipitation studies using human cells suggest that DNA methylation and histone methylation work together during replication to ensure that specific methylation patterns are passed on to progeny cells (Sarraf & Stancheva, 2004). Indeed, evidence has been presented that in some organisms, such as Neurospora crassa (Tamaru & Selker, 2001) and Arabidopsis thaliana (Jackson et al., 2002), H3-K9 methylation (methylation of a specific lysine residue in the histone H3) is required in order for DNA methylation to take place. However, exceptions have been observed in which the relationship is reversed. In one study, for example, H3 methylation was reduced at a tumor suppressor gene in cells deficient in DNA methyltransferase (Martin & Zhang, 2005).

In an interestingly coordinated process, proteins that bind to methylated DNA also form complexes with the proteins involved in deacetylation of histones. Therefore, when DNA is methylated, nearby histones are deacetylated, resulting in compounded inhibitory effects on transcription. Likewise, demethylated DNA does not attract deacetylating enzymes to the histones, allowing them to remain acetylated and more mobile, thus promoting transcription.

In most cases, methylation of DNA is a fairly long-term, stable conversion, but in some cases, such as in germ cells, when silencing of imprinted genes must be reversed, demethylation can take place to allow for "epigenetic reprogramming." The exact mechanisms for demethylation are not entirely understood; however, it appears that this process may be mediated by the removal of amino groups by DNA deaminases (Morgan et al., 2004). After deamination, the DNA has a mismatch and is repaired, causing it to become demethylated. In fact, studies using inhibitors of one DNMT enzyme showed that this enzyme was involved in not only DNA methylation, but also in the removal of amino groups.
DNA Methylation and Disease

Given the critical role of DNA methylation in gene expression and cell differentiation, it seems obvious that errors in methylation could give rise to a number of devastating consequences, including various diseases. Indeed, medical scientists are currently studying the connections between methylation abnormalities and diseases such as cancer, lupus, muscular dystrophy, and a range of birth defects that appear to be caused by defective imprinting mechanisms (Robertson, 2005). The results of these studies will be invaluable for treating these disorders, as well as for understanding and preventing complications that can arise during embryonic development due to abnormalities in X-chromosome methylation and gene imprinting.


To date, a large amount of research on DNA methylation and disease has focused on cancer and tumor suppressor genes. Tumor suppressor genes are often silenced in cancer cells due to hypermethylation. In contrast, the genomes of cancer cells have been shown to be hypomethylated overall when compared to normal cells, with the exception of hypermethylation events at genes involved in cell cycle regulation, tumor cell invasion, DNA repair, and others events in which silencing propagates metastasis (Figure 1; Robertson, 2005). In fact, in certain cancers, such as that of the colon, hypermethylation is detectable early and might serve as a biomarker for the disease.

http://www.nature.com/scitable/nated/content/21285/10.1038_nrg1655-f1_full.jpg
Figure 1: DNA methylation and cancer.
This diagram shows a representative region of genomic DNA in a normal cell. The region contains repeat-rich, hypermethylated pericentromeric heterochromatin and an actively transcribed tumor suppressor gene (TSG) associated with a hypomethylated CpG island (indicated in red). In tumor cells, repeat-rich heterochromatin becomes hypomethylated, and this contributes to genomic instability (a hallmark of tumor cells) through increased mitotic recombination events. De novo methylation of CpG islands also occurs in cancer cells, and it can result in the transcriptional silencing of growth-regulatory genes. These changes in methylation are early events in tumorigenesis. (Reproduced from Robertson, 2005.)
Copyright 2005 Nature Publishing Group, Robertson, K., DNA methylation and human disease, Nature Reviews Genetics 6, 597-561
Summary

Within the past thirty years, researchers have discovered numerous details about the process of DNA methylation. For instance, scientists now know that methylation plays a critical role in the regulation of gene expression, and they have also determined that this process tends to occur at certain locations within the genomes of different species. Furthermore, DNA methylation has been shown to play a vital role in numerous cellular processes, and abnormal patterns of methylation have been liked to several human diseases. Nonetheless, as with other topics in the field of epigenetics, gaps remain in our knowledge of DNA methylation. As new laboratory techniques are developed and additional genomes are mapped, scientists will no doubt continue to uncover many of the unknowns of how, when, and where DNA is methylated, and for what purposes.

References and Recommended Reading

Jackson, J., et al. Control of CpNpG DNA methylation by the kryptonite histone H3 methyltransferase. Nature 416, 556–560 (2002) doi:10.1038/nature731 (link to article)

Jones, P. A., & Taylor, S. M. Cellular differentiation, cytidine analogs, and DNA methylation. Cell 20, 85–93 (1980)

Martin, C., & Zhang, Y. The diverse functions of histone lysine methylation. Nature Reviews Molecular Cell Biology 6, 838–849 (2005) doi:10.1038/nrm1761 (link to article)

McGhee, J. D., & Ginder, G. D. Specific DNA methylation sites in the vicinity of the chicken beta-globin genes. Nature 280, 419–420 (1979) (link to article)

Morgan, H., et al. Activation-induced cytidine deaminase deaminates 5-methylcytosine in DNA and is expressed in pluripotent tissues. Journal of Biological Chemistry 279, 52353–52360 (2004) doi:10.1074/jbc.M407695200

Robertson, K. DNA methylation and human disease. Nature Reviews Genetics 6, 597–610 (2005) doi:10.1038/nrg1655 (link to article)
Sarraf, S., & Stancheva, I. Methyl-CpG binding protein MBD1 couples histone H3 methylation at lysine 9 by SETDB1 to DNA replication and chromatin assembly. Molecular Cell 15, 595–605 (2004) doi:10.1016/j.molcel.2004.06.043

Suzuki, M., & Bird, A. DNA methylation landscapes: Provocative insights from epigenomics. Nature Reviews Genetics 9, 465–476 (2008) doi:10.1038/nrg2341 (link to article)

Tamaru, H., & Selker, E. A histone H3 methyltransferase controls DNA methylation in Neurospora crassa. Nature 414, 277–283 (2001) doi:10.1038/35104508 (link to article)



http://en.wikipedia.org/wiki/DNA_methylation

DNA methylation is a biochemical process that is important for normal development in higher organisms. It involves the addition of a methyl group to the 5 position of the cytosine pyrimidine ring or the number 6 nitrogen of the adenine purine ring (cytosine and adenine are two of the four bases of DNA). This modification can be inherited through cell division.

DNA methylation is a crucial part of normal organismal development and cellular differentiation in higher organisms. DNA methylation stably alters the gene expression pattern in cells such that cells can "remember where they have been" or decrease gene expression; for example, cells programmed to be pancreatic islets during embryonic development remain pancreatic islets throughout the life of the organism without continuing signals telling them that they need to remain islets. DNA methylation is typically removed during zygote formation and re-established through successive cell divisions during development. However, the latest research shows that hydroxylation of methyl groups occurs rather than complete removal of methyl groups in zygote.[1] Some methylation modifications that regulate gene expression are inheritable and are referred to as epigenetic regulation.

In addition, DNA methylation suppresses the expression of viral genes and other deleterious elements that have been incorporated into the genome of the host over time. DNA methylation also forms the basis of chromatin structure, which enables cells to form the myriad characteristics necessary for multicellular life from a single immutable sequence of DNA. DNA methylation also plays a crucial role in the development of nearly all types of cancer.[2]





Genomic imprinting :
http://en.wikipedia.org/wiki/Genomic_imprinting


Genomic imprinting is a genetic phenomenon by which certain genes are expressed in a parent-of-origin-specific manner. It is an inheritance process independent of the classical Mendelian inheritance. Imprinted alleles are silenced such that the genes are either expressed only from the non-imprinted allele inherited from the mother (e.g. H19 or CDKN1C), or in other instances from the non-imprinted allele inherited from the father (e.g. IGF-2). Forms of genomic imprinting have been demonstrated in insects, mammals and flowering plants.

Genomic imprinting is an epigenetic process that involves methylation and histone modifications in order to achieve monoallelic gene expression without altering the genetic sequence. These epigenetic marks are established in the germline and are maintained throughout all somatic cells of an organism.

Appropriate expression of imprinted genes is important for normal development, with numerous genetic diseases associated with imprinting defects including Beckwith–Wiedemann syndrome, Silver–Russell syndrome, Angelman syndrome and Prader–Willi syndrome.

William Gaatjes
07-20-2012, 02:13 PM
Time to start with fungi, and the role these fungi play in life on Earth.
Soil fungi are potent carbon catchers. Soil Fungi draw in a lot of carbon and bind it into the soil. Details i do not have yet about how it works but will come...

www.nicholls.edu/biol-ds/Biol156/Lectures/Fungi.pdf

Some fungi (also called molds) contain mycotoxins that are suspected to be the real cause of so called diagnosed auto immune diseases in some cases.
mycotoxins can create a myriad of symptoms ranging from neural disorders to playing a role in developing cancer.


A pdf that might give some information :
www.cancerfungus.com/pdf/fungi-nexus.pdf

William Gaatjes
08-15-2012, 01:09 PM
This is surely interesting : Opioid drugs such as heroin and morphine, bind to the TLR4 receptor.
I had to look it up to understand it :
TLR4 detects lipopolysaccharides. Lipopolysaccharides acts as an endotoxin and are found on the outer membrane of gram negative bacteria.
When these bacteria are detected by the innate immune system, the immune system found in the digestive system and IIRC all orifices.
The first amazing thing is that the TLR4 receptor seems to amplify the addictive effects of opioid drugs. I never knew that these drugs can also influence the immune system, contributing to the addictive effects.
The second amazing thing is that these great researchers seem to have found a way to stop the addictive effects and to remove the painful withdrawal effects when stopping heroin and morphine usage.



http://medicalxpress.com/news/2012-08-scientists-block-heroin-morphine-addiction.html


In a major breakthrough, an international team of scientists has proven that addiction to morphine and heroin can be blocked, while at the same time increasing pain relief.

The team from the University of Adelaide and University of Colorado has discovered the key mechanism in the body's immune system that amplifies addiction to opioid drugs.
Laboratory studies have shown that the drug (+)-naloxone (pronounced: PLUS nal-OX-own) will selectively block the immune-addiction response.
The results – which could eventually lead to new co-formulated drugs that assist patients with severe pain, as well as helping heroin users to kick the habit – will be published tomorrow in the Journal of Neuroscience.
"Our studies have shown conclusively that we can block addiction via the immune system of the brain, without targeting the brain's wiring," says the lead author of the study, Dr Mark Hutchinson, ARC Research Fellow in the University of Adelaide's School of Medical Sciences.
"Both the central nervous system and the immune system play important roles in creating addiction, but our studies have shown we only need to block the immune response in the brain to prevent cravings for opioid drugs."
The team has focused its research efforts on the immune receptor known as Toll-Like receptor 4 (TLR4).
"Opioid drugs such as morphine and heroin bind to TLR4 in a similar way to the normal immune response to bacteria. The problem is that TLR4 then acts as an amplifier for addiction," Dr Hutchinson says.
"The drug (+)-naloxone automatically shuts down the addiction. It shuts down the need to take opioids, it cuts out behaviours associated with addiction, and the neurochemistry in the brain changes – dopamine, which is the chemical important for providing that sense of 'reward' from the drug, is no longer produced."
Senior author Professor Linda Watkins, from the Center for Neuroscience at the University of Colorado Boulder, says: "This work fundamentally changes what we understand about opioids, reward and addiction. We've suspected for some years that TLR4 may be the key to blocking opioid addiction, but now we have the proof.

"The drug that we've used to block addiction, (+)-naloxone, is a non-opioid mirror image drug that was created by Dr Kenner Rice in the 1970s. We believe this will prove extremely useful as a co-formulated drug with morphine, so that patients who require relief for severe pain will not become addicted but still receive pain relief . This has the potential to lead to major advances in patient and palliative care," Professor Watkins says.

The researchers say clinical trials may be possible within the next 18 months.

Journal reference: Journal of Neuroscience

Provided by University of Adelaide




More background information :
http://en.wikipedia.org/wiki/TLR_4
http://en.wikipedia.org/wiki/Innate_immune_system
http://en.wikipedia.org/wiki/Lipopolysaccharide
http://en.wikipedia.org/wiki/Gram-negative

William Gaatjes
08-21-2012, 12:44 PM
The hazardous effects of consuming way to much sugar are explained in detail here. Humans are hardwired to like sugar. It is an inherited evolutionary trait from the food we consume.

Here is the 60 minutes short version :
It explains about new research where it is found that the blood chemistry even of young people changes drastically when consuming large amounts of sugar. How the liver reacts to to much fructose.
http://www.cbsnews.com/video/watch/?id=7417238n&tag=contentMain;contentBody

And here is the long version with all the details from Robert H. Lustig :
http://www.youtube.com/watch?v=dBnniua6-oM

A documentary about addiction :
http://www.cbsnews.com/video/watch/?id=7406968n&tag=contentMain;contentBody
When consuming drugs and especially in large amounts.
It shows that one does not only get conditioned like a dog of Pavlov, but also the brain damage that one can experience, weakens the will. Thus it becomes more difficult to just say no. An addict is attacked from multiple angles. The reward system and the pleasure system reacting and the basis of self control in the prefrontal cortex becomes weakened.

Interesting side note :
The researcher is Dr Nora Volkow. She is the great granddaughter of Leon Trotsky.



Here is an idea i have for people with addictions :
Think about how humans start salivating when sniffing fresh sweet fruit...
If you do not believe me, try it out yourself.
If you have some addiction problem and you want to get rid of it...
Start living on a low sugar diet. When you crave for, for example a cigarette or a joint just eat some fresh sweet fruit. It will help you get your control back. Because sugar is also stimulating the so called "reward center and the pleasure center." Then stop consuming sugar and go back to the low sugar diet. Every time you crave, give in by consuming some sweet fruit.
Maybe it will also work for hard drugs like cocaine and to get of addictive medicines that have similar effects as cocaine.

William Gaatjes
08-25-2012, 08:58 AM
Sometimes life is not easy being an insect. Those pesky humans spray insecticides on all those tasty vegetables from which an insect gets sick and dies.

But one insect species has acquired a novel way to become fully impervious for a certain type of insecticide commonly used. At some crossing of events (some moment in time if you please), the Riptortus pedestris ingested a certain bacteria. And that bacteria called Burkholderia consumes the insecticide fenitrothion rendering it (i guess amounts) harmless enough for the insect called the "bean bug".

http://phys.org/news/2012-04-bean-bugs-harbor-bacteria-safe.html#nRlv


Phys.org) -- Conventional wisdom says that in order for a species of insect to develop resistance to an antibiotic, several generations have to pass, whereby genes from those that have some natural resistance pass them on to their offspring. But sometimes conventional wisdom fails to take into account how some bugs can find a work around. In this case, it’s the bean bug. Researchers in Japan have found that for Riptortus pedestris, the common bean bug, there is a much quicker path. All they have to do is ingest the Burkholderia bacteria. Doing so, the team says in their paper published in the Proceedings of the National Academy of Sciences, makes them nearly impervious to the insecticide fenitrothion, which has historically been used to treat soy bean plants to protect them from the bugs that dine on them.

To find out what was going on with bean bugs and the Burkholderia bacteria, the researchers added the bacteria to potting soil in the lab, where they flourished. They followed that by adding fenitrothion, which the bugs ate with abandon. Next, they introduced some young bean bugs (nymphs) into the pot which ate soy bean seedlings the researchers added to the mix.
In examining the guts of the bugs, the researchers found the bacteria continued to thrive and the bugs became immune to the effects of the insecticide as a result because the bacteria was eating it before it could harm them. Normally, they say, up to eighty percent of bean bugs will die from such an exposure.
In further tests, the researchers found that bean bugs can harbor up to a hundred million bacteria in their guts, which tends to make them larger than others of the same species.
Fortunately for farmers in Japan, however, it doesn’t appear that many of the bean bugs, or their close cousin chinch bugs, swallow much of the bacteria in the wild though. Tests done found that only eight percent of such bugs had Burkholderia bacteria in their guts in one area, and none in another, thus very few were able to develop an immunity to fenitrothion.
The research team says that this symbiotic relationship between bean bugs and Burkholderia bacteria, providing the bugs with immunity from an insecticide, is the first such example ever found. But they also note that because it’s been found in this case, it’s likely occurring in other relationships as well.

More information: Symbiont-mediated insecticide resistance, PNAS, Published online before print April 23, 2012, doi: 10.1073/pnas.1200231109

Abstract
Development of insecticide resistance has been a serious concern worldwide, whose mechanisms have been attributed to evolutionary changes in pest insect genomes such as alteration of drug target sites, up-regulation of degrading enzymes, and enhancement of drug excretion. Here, we report a previously unknown mechanism of insecticide resistance: Infection with an insecticide-degrading bacterial symbiont immediately establishes insecticide resistance in pest insects. The bean bug Riptortus pedestris and allied stinkbugs harbor mutualistic gut symbiotic bacteria of the genus Burkholderia, which are acquired by nymphal insects from environmental soil every generation. In agricultural fields, fenitrothion-degrading Burkolderia strains are present at very low densities. We demonstrated that the fenitrothion-degrading Burkholderia strains establish a specific and beneficial symbiosis with the stinkbugs and confer a resistance of the host insects against fenitrothion. Experimental applications of fenitrothion to field soils drastically enriched fenitrothion-degrading bacteria from undetectable levels to >80% of total culturable bacterial counts in the field soils, and >90% of stinkbugs reared with the enriched soil established symbiosis with fenitrothion-degrading Burkholderia. In a Japanese island where fenitrothion has been constantly applied to sugarcane fields, we identified a stinkbug population wherein the insects live on sugarcane and ≈8% of them host fenitrothion-degrading Burkholderia. Our finding suggests the possibility that the symbiont-mediated insecticide resistance may develop even in the absence of pest insects, quickly establish within a single insect generation, and potentially move around horizontally between different pest insects and other organisms.

Journal reference: Proceedings of the National Academy of Sciences



http://en.wikipedia.org/wiki/Burkholderia_pseudomallei

http://upload.wikimedia.org/wikipedia/commons/thumb/e/ee/Bps_close.JPG/240px-Bps_close.JPG

http://t0.gstatic.com/images?q=tbn:ANd9GcTBLSQn6-clTXzREpmdoR6Oq1QAIhpV72aHdaFpVrNZkTlu6bbBqQ

William Gaatjes
08-25-2012, 09:12 AM
Perhaps the bacteria Burkholderia pseudomallei infected the plants that the bean bugs eat. It seems that this bacteria that lives in soil and water is capable of infecting plants as well. Since bacteria can swap genes (plasmids) easily, this might be a trend. The bacteria might as well cause some disease in the bean bug as well but not problematic enough to be a real issue. Instant death or having a shorter lifespan. Evolutionary wise, even a not ideal symbiotic relationship can in such a specific case be very beneficial for the survival of a species.

This article is how Burkholderia pseudomallei infects tomato plants.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2823722/?tool=pmcentrez

An excerpt :

Background
Burkholderia pseudomallei is the causative agent for melioidosis, a disease with significant mortality and morbidity in endemic regions. Its versatility as a pathogen is reflected in its relatively huge 7.24 Mb genome and the presence of many virulence factors including three Type Three Secretion Systems known as T3SS1, T3SS2 and T3SS3. Besides being a human pathogen, it is able to infect and cause disease in many different animals and alternative hosts such as C. elegans.

Results
Its host range is further extended to include plants as we demonstrated the ability of B. pseudomallei and the closely related species B. thailandensis to infect susceptible tomato but not rice plants. Bacteria were found to multiply intercellularly and were found in the xylem vessels of the vascular bundle. Disease is substantially attenuated upon infection with bacterial mutants deficient in T3SS1 or T3SS2 and slightly attenuated upon infection with the T3SS3 mutant. This shows the importance of both T3SS1 and T3SS2 in bacterial pathogenesis in susceptible plants.

Conclusions
The potential of B. pseudomallei as a plant pathogen raises new possibilities of exploiting plant as an alternative host for novel anti-infectives or virulence factor discovery. It also raises issues of biosecurity due to its classification as a potential bioterrorism agent.


Background
Burkholderia pseudomallei is a Gram-negative bacterium that is the causative agent for melioidosis, a disease endemic in Southeast Asia and Northern Australia with significant morbidity and mortality [1,2]. The bacterium exhibits broad host range and has been shown to cause disease in cattle, pigs, goats, horses, dolphins, koalas, kangaroos, deers, cats, dogs and gorillas [3]. Acquisition of the bacterium could be through inhalation of aerosol, ingestion of contaminated water and inoculation through open skin [4]. In humans, the disease could present with varied manifestations ranging from asymptomatic infection, localized disease such as pneumonia or organ abscesses to systemic disease with septicemia [5]. The disease could be acute or chronic, and relapse from latency is possible [6].

The versatility of B. pseudomallei as a pathogen is reflected in its huge 7.24 Mb genome organized into two chromosomes [7]. One of the most important virulence factors that has been partially characterized in B. pseudomallei is its Type Three Secretion Systems (T3SS), of which it has three [8,9]. Each T3SS typically consists of a cluster of about 20 genes encoding structural components, chaperones and effectors which assemble into an apparatus resembling a molecular syringe that is inserted into host cell membrane for the delivery of bacterial effectors into host cell cytosol. One of the B. pseudomallei T3SS known as Bsa or T3SS3 resembles the inv/mxi/spa T3SS of Salmonella and Shigella, and has been shown to be important for disease in animal models [10]. The other two T3SS (T3SS1 and 2) resemble the T3SS of plant pathogen Ralstonia solanacearum [11] and do not contribute to virulence in mammalian models of infection [12]. Being a soil saprophyte and having the plant pathogen-like T3SS raise the possibility that B. pseudomallei could also be a plant pathogen. As B. pseudomallei is a risk group 3 agent with specific requirements for containment, we first test this hypothesis using the closely related species B. thailandensis as a surrogate model especially in experiments where risk of aerosolization is high, before we verify key experiments with B. pseudomallei. B. thailandensis is considered largely avirulent in mammalian hosts unless given in very high doses [13,14]. We infected both tomato as well as rice plants with B. pseudomallei to determine their susceptibility to disease. Furthermore, the role of the three B. pseudomallei T3SS in causing plant disease is evaluated and the implication of the ability of B. pseudomallei to infect plants is discussed.


Methods
Bacterial strains, plasmids and growth conditions
All bacterial strains, plasmids used and constructed are listed in Table ​Table1.1. All strains of B. thailandensis
and B. pseudomallei were cultured at 37°C in Luria-Bertani (LB) medium or on Tryptone Soy Agar (TSA) plates. To obtain log-phase culture, 250 μL of overnight culture was inoculated into 5 mL LB medium and cultured for 2.5 hours with constant shaking at 100 rpm. Escherichia coli strains were cultivated at 37°C in LB medium. Antibiotics were added to the media at the following final concentrations of 100 μg/mL (ampillicin); 25 μg/mL (kanamycin); 10 μg/mL (tetracycline); and 25 μg/mL (zeocin) for E. coli, 250 μg/mL (kanamycin); 40 μg/mL (tetracycline); 25 μg/mL (gentamicin) and 1000 μg/mL (zeocin) for B. pseudomallei. All antibiotics were purchased from Sigma (St Louis, MO, USA).

Plant material
Tomato seeds of the Solanum lycopersicum variety Season Red F1 Hybrid (Known-You Seeds Distribution (S.E.A) Pte Ltd) and Arabidopsis thaliana (Loh Chiang Shiong, NUS) were surface sterilized with 15% bleach solution for 15 minutes with vigorous shaking. The seeds were rinsed in sterile distilled water and germinated in MS agar medium. The seedlings were cultivated with a photoperiod of 16 hour daylight and 8 hour darkness. One month old plantlets were used for infection. Tomato plantlets were transferred into 50 mL Falcon tubes with 5 mL of liquid MS medium for infection while 1 mL of MS medium was used for Arabidopsis. Rice seeds (Japonica nipponbare) were obtained from Dr Yin Zhong Zhao (Temasek Life Sciences Laboratories, Singapore). Seeds were surface sterilized as described above. The seeds were rinsed in sterile distilled water and germinated in N6 agar medium. The germinated seedlings were placed on N6 agar supplemented with 2 mg/mL of 2, 4-dichlorophenyoxyacetic acid (2, 4-D) in the dark to induce callus production. The callus were regenerated on N6 medium supplemented with 2 mg/mL Benzylaminopurine (BA), 1 mg/mL Naphthylacetic Acid (NAA), 1 mg/mL Indole-3-acetic acid (IAA) and 1 mg/mL Kinetin under 16 hour daylight and 8 hour dark photoperiod. Rice plantlets were transferred and maintained in MS agar medium. The plantlets were transferred into 50 mL Falcon tubes with 5 mL of liquid MS medium for infection. Some plantlets were also wounded by cutting off the roots before being transferred.

Plant infection
Tomato, rice and Arabidopsis plantlets were infected with log phase cultures at the concentration of 1 × 107 colony forming units (cfu)/5 mL medium by immersing only the roots of the plantlets in the inoculum in a 50 mL tube. The plantlets were maintained at 24-25°C, shaking at 100 rpm. The plantlets were observed for symptoms such as yellowing of leaves, blackening of the leaf veins, wilting and necrosis daily over 7 days. Each plantlet was scored daily on a disease index score of 1 to 5 based on how extensive the symptoms were as calculated by the percentage of the plant with symptoms (1: no symptoms; 2: 1 to 25% of the plant showed symptoms; 3: 26 to 50% of the plant showed symptoms; 4: 51 to 75% of the plant showed symptoms; 5: 76 to 100% of the plant showed symptoms or the plant was dead) [15]. Each experiment included at least 12 to 20 plantlets infected with bacteria except for experiments with rice and Arabidopsis plantlets where 6 plantlets were used. All experiments were repeated at least twice.
Multiplication of B. thailandensis in tomato plantlets and leaves

Tomato plantlets were infected with bacteria through unwounded roots and three leaves from each plantlet were excised at day 1, 3, 5 and 7 after infection. The leaves were macerated in 1 mL PBS with a micro-pestle, serially diluted and plated on TSA plates in duplicates. Tomato leaves were infected by cutting with a pair of scissors dipped in 1 × 109 cfu/mL of B. thailandensis. Five plantlets were used in each experiment. At days 1 and 3 after infection, one infected leaf from each plantlet was excised, washed with 10% bleach solution for 1 min and rinsed with sterile water. The leaf was blotted dry on sterile filter paper and imprinted on TSA agar plates to determine if there were any bacteria on the surface of the leaves. The imprinted plates were incubated at 37°C for 24 hours before checking for any bacteria growth. The leaves were then weighed and macerated in 1 mL PBS with a micro-pestle, serially diluted and plated on TSA plates in duplicates. Only leaf samples which did not show any bacteria growth on the imprinted plates will be counted to avoid counting contaminating bacteria from leaf surfaces.

Transmission Electron Microscope (TEM)
Tomato leaf and rice blade were infected by cutting with a pair of scissors dipped in 1 × 109 cfu/mL of B. pseudomallei strain KHW or B. thailandensis. One day after infection, the infected tomato leaf and rice blade were excised for TEM. One millimeter from the infected leaf/blade edge were cut and discarded to avoid contamination from extracellular bacteria at the infection site. A further two millimeter from the infected leaf/blade edge were then cut and sliced into smaller sections and fixed with 4% glutaraldehyde in 0.1 M phosphate buffer under vacuum for 4 hours. It was post-fixed with 1% osmium tetroxide in 0.1 M phosphate buffer for 1 hour at 4°C. Samples were dehydrated sequentially through 30%, 50%, 70%, 90%, 100% ethanol, and finally in propylene oxide prior to infiltration with Spurr resin [16]. Samples were embedded in 100% spur resin and polymerized at 70°C overnight. Ultra-thin sections were cut on a Leica Ultracut UCT ultra-microtome and examined with a transmission electron microscope (JEM1230, JEOL, Japan) at 120 kV.
Growth of bacteria in different media

Overnight cultures were used to inoculate 5 mL of LB and Murashige and Skoog (MS) [17] medium to a starting optical density at 600 nm of 0.1. The cultures were incubated at 37°C for LB medium and 25°C for MS medium. Optical density at 600 nm for all cultures was measured at 0, 2.5, 6 and 24 hours. All experiments were repeated twice with duplicates.
Generation of B. pseudomallei T3SS1, T3SS2 and T3SS3 mutants

Approximate one kb fragments upstream and downstream of the T3SS1, T3SS2 or T3SS3 locus were amplified from B. pseudomallei KHW genomic DNA and subsequently cloned into pK18mobsacB. The tet cassette from pGEM-tet or zeo cassette (kindly provided by Dr Herbert Schweizer, Colorado State University, USA) from pCLOXZ1 was inserted between the upstream and downstream fragments resulting in pT3SS1/upstream/downstream/tet, pT3SS2/upstream/downstream/tet, and pT3SS3/upstream/downstream/zeo. The plasmids were electroporated into SM10 conjugation host and conjugated into B. pseudomallei strain KHW. Homologous recombination was selected for retention of antibiotic marker (Tet or Zeo) linked to the mutation and loss of the plasmid marker (Km) to generate KHWΔT3SS1, KHWΔT3SS2 and KHWΔT3SS3. Each mutant was confirmed by PCR for the loss of a few representative T3SS genes in the locus.
Cytotoxicity assay on THP-1 cells

Human monocytic cell line THP-1 were maintained in RPMI 1640 (Sigma), supplemented with 10% Fetal Calf Serum (FCS, Hyclone Laboratories, Logan, UT), 200 mM L-glutamine, 100 Unit/mL penicillin and 100 μg/mL streptomycin. THP-1 cells were seeded at a concentration of 1 × 106 cells per 100 μL in 96-well plate in medium without FCS and antibiotics. Log phase bacteria were used for infection at multiplicity of infection (MOI) of 100:1. Kanamycin (250 μg/mL) was added one hour after infection to suppress the growth of extracellular bacteria. Supernatant was collected 6 hours after infection. Lactate dehydrogenase (LDH) activity in the supernatant was measured with the Cytotoxicity Detection Kit (Roche) according to manufacturer's instruction. Percentage cytotoxicity was calculated by the formula:

Statistical analysis
Average disease scores with standard deviation were calculated based on at least 100 tomato plantlets infected with each strain of bacteria or mutant. Data were analyzed using repeated measure analysis of variance [18]. All statistical analyses were performed using SPSS version 17 software (SPSS Inc). A p value of less than 0.001 is considered significant.

Using B. thailandensis infection of tomato plantlets as a model
To mimic infection via a possible natural route, the unwounded roots of tomato plantlets were immersed in media inoculated with 1 × 107 cfu of bacteria. Only the roots were in contact with the inoculum. Tomato plantlets infected via the roots by B. thailandensis showed progressive symptoms such as yellowing of leaves, blackening of the leaf veins, wilting and necrosis whereas uninfected plantlets remained healthy and did not show any disease symptoms throughout the period (Fig 1A-B). Most
infected plantlets were dead on day 7. All plantlets were monitored over a period of seven days. Disease was scored daily for every plantlet on an index from 1-5 based on the extent of symptoms presented as described in Methods. The average disease score for a particular day represent the mean disease scores for all the plantlets with the same treatment on that day. As infection progressed over time, the average disease score for B. thailandensis-infected plants increased progressively, reaching a maximum disease score of 5 on day 7 (Fig ​(Fig1C).1C). In contrast, plantlets infected with E. coli in the same manner via the roots showed a slight progression of average disease scores over time and reached a maximum disease score of 2 on day 7 (Fig ​(Fig1C),1C), demonstrating that the extensive disease and death seen was specific to B. thailandensis infection and not due to non-specific stress induced by the experimental manipulations.

For a phytopathogen to successfully colonize the plant, it must be able to replicate intercellularly [19]. To determine whether bacteria are able to replicate intercellularly, we sampled leaves from two representative plantlets which had been inoculated with bacteria via unwounded roots at 1, 3, 5 and 7 days post-inoculation. Three leaves were sampled at each time-point per plantlet. Both plantlets showed a progressive increase in bacterial load in their leaves over time (Fig ​(Fig1D1D).
Susceptibility of tomato plantlets to B. pseudomallei infection

Having established that B. thailandensis can infect tomato plantlets and cause disease, we determine whether B. pseudomallei would similarly infect tomato plantlets. We included strains isolated from humans, animals or the environment such as two clinical isolates (K96243 and KHW), a kangaroo isolate 561, two bird isolates (612 and 490) and two soil isolates (77/96 and 109/96) on their ability to infect tomato plants. B. pseudomallei is able to infect tomato plantlets to a similar degree as B. thailandensis with almost identical disease symptoms. All isolates were able to infect and cause disease to a similar extent (Fig ​(Fig2),2), showing that the ability to infect susceptible plants is unlikely to be strain-specific.

Localization of bacteria at site of infection
Having established the ability of both B. thailandensis and B. pseudomallei to be phytopathogens capable of infecting tomato plants, we next examined the localization of the bacteria upon inoculation into the leaf via TEM. We first examined whether bacteria inoculated into the leaves were able to survive and replicate. To ensure that there were no bacteria on the leaf surfaces, the leaves were surface sterilized with bleach and washed in sterile water before weighing and maceration. B. thailandensis was able to replicate in the leaves after inoculation (Fig ​(Fig3A).3A). The number of bacteria increased by about 10 fold
three days after infection although the numbers did not reach statistical significance by the student t test (p > 0.05). When examined under TEM, B. pseudomallei and B. thailandensis could be found in the xylem of the vascular bundle of the inoculated leaf (Fig 3B-C). The rest of the surrounding cells were not
colonized, suggesting that the bacteria spread to the rest of plant through the xylem vessels.

The role of T3SS in plant infection
To determine the role of T3SS in plant infection, we created B. pseudomallei deletion mutants lacking the entire region of T3SS1, T3SS2 or T3SS3 in strain KHW (Table ​(Table1).1). We first examined these mutants in
the established macrophage cytotoxicity model and confirmed the necessity of T3SS3 in mediating cytotoxicity [20] whereas mutants losing T3SS1 and T3SS2 were as cytotoxic as wildtype bacteria to THP-1 cells (Fig ​(Fig4A).4A). This shows that T3SS1 and T3SS2 are not involved in mediating cytoxicity to
mammalian cells. To exclude the possibility that any defect we see with the T3SS mutants would be due to a reduced fitness, we ascertained that all mutants grew as well as wildtype bacteria in LB and plant MS medium (Fig 4B-C). However, infection of tomato plantlets via unwounded roots showed that plants
infected by the T3SS1 and T3SS2 mutants exhibited significant delay in disease compared to plants infected by wildtype bacteria (Fig ​(Fig4D).4D). Statistical analysis of the average disease score over 7 days
showed that the T3SS1, 2 and 3 mutants were significantly less virulent from the wildtype bacteria (p < 0.001). T3SS1 and T3SS2 mutants were also significantly less virulent compared to the T3SS3 mutant (p < 0.001). This shows that both T3SS1 and T3SS2 contribute significantly to pathogen virulence towards tomato plants. The T3SS3 mutant also showed an intermediate degree of virulence between wildtype bacteria and the T3SS1 and T3SS2 mutants, likely because T3SS3 has a non-redundant role in mediating virulence in the susceptible tomato plants.

Susceptibility of rice and Arabidopsis plantlets to B. pseudomallei and B. thailandensis infection
Both B. thailandensis and B. pseudomallei did not cause any discernible symptoms in rice plantlets when infected via roots (unwounded or wounded) nor via inoculation through the leaves. B. thailandensis and B. pseudomallei infection of rice plantlets showed identical disease scores over 7 days (Fig ​(Fig5A).5A). We
were unable to recover any bacteria from the leaves after infection via the roots. When bacteria were inoculated directly into the leaf blade, no bacteria were recoverable from the leaf one day after inoculation, indicating a lack of establishment of infection. The inoculated leaves did not show any yellowing (data not shown) as seen in the tomato leaves. Thus, rice plants are non-hosts to the bacteria. As Arabidopsis thaliana has been used extensively as a plant host model for several pathogens, we tested B. thailandensis and B. pseudomallei infection in Arabidopsis plantlets via the roots. The average disease scores were maintained at 1 and increased only slightly at days 6 and 7 and were identical for both B. thailandensis and B. pseudomallei infection (Fig ​(Fig5B5B).

Discussion
B. cepacia, the important opportunistic pathogen often associated with cystic fibrosis and chronic granulomatous disease patients [21], was originally described as a phytopathogen causing soft rot in onions [22]. Subsequently, many strains from various B. cepacia complex were shown to be able to cause disease in the alfalfa infection model as well as in the rat agar bead model [23]. In this study, we show that B. pseudomallei and B. thailandensis are also potential plant pathogens. They are capable of infecting susceptible plants such as tomato.

Plant pathogenic bacteria have been shown to express a large number of T3SS effectors capable of interfering with plant basal defense triggered by bacterial pathogen-associated molecular patterns (PAMPs) as well as Resistance (R) protein-mediated immunity typically characterized by the Hypersensitive Response (HR) [24-26]. The outcome of the interaction with susceptible hosts for these successful pathogens would be disease. We found that the virulence of B. pseudomallei in tomato is contributed significantly by T3SS1 and T3SS2, but to a much lesser extent by T3SS3. T3SS1 and T3SS2 are likely non-redundant to each other in causing disease because each mutant demonstrates significant attenuation, possibly because both T3SS1 and T3SS2 are co-ordinately involved in pathogenesis. This is the first time that a role has been defined for T3SS1 and T3SS2 in B. pseudomallei, showing that they are functional and not simply vestiges of evolution. The role of T3SS3 could be due to its contribution of a structural component or chaperone to the other two T3SS or an effector which could also interfere with plant cell physiology albeit less efficiently than with mammalian cells. Nevertheless, our study shows the important role played by T3SS in B. pseudomallei pathogenesis in tomato plants.

In contrast to tomato, we found that both B. pseudomallei and B. thailandensis are non-adapted for rice. This is not surprising as B. pseudomallei are routinely recovered from rice paddy fields in regions of endemicity such as Thailand and have never been reported to cause any disease in rice plants. It is possible that PAMPs from B. pseudomallei and B. thailandensis are able to trigger an effective basal defence from rice to halt bacterial colonization, a common means of plant resistance against non-adapted microorganisms [24-26]. Another intriguing possibility is that compounds secreted by rice plants may inhibit the growth of B. thailandensis and B. pseudomallei. The presence of secondary metabolites induced by B. pseudomallei infection in plants with differential susceptibility to disease could reveal novel anti-infective compounds against melioidosis to counter the problem of extensive antibiotic resistance in this bacterium.

Thus, B. pseudomallei joins a growing list of human pathogens which have been found to be able to infect plants [27], the first of which to be described was P. aeruginosa [28]. The plant host model has been used to perform large scale screening of a library of P. aeruginosa mutants to identify novel virulence factors [29] as some virulence factors encoded by genes such as toxA, plcS and gacA were shown to be important for bacterial pathogenesis in both plants and animals [6]. Given the evidence that B. pseudomallei T3SS3 may be capable of interacting with both mammalian and plant hosts, and the ability of B. pseudomallei to infect tomato, one could develop susceptible plants as alternative host models for large scale screening of B. pseudomallei mutants to aid in novel virulence factor discovery, similar to what had been done for P. aeruginosa.

Previously, B. pseudomallei has been shown to infect C. elegans [30] and Acanthamoeba species [31] and C. elegans could be used as an alternative host model for large scale screening and identification of B. pseudomallei virulence factors [30]. Our current finding reveals the additional versatility of B. pseudomallei as a pathogen and further research would likely uncover novel bacterial mechanisms capable of interacting with its varied hosts. Much more work is needed to define the susceptibility of various plant species to B. pseudomallei to find a suitable plant host for virulence factor discovery. It remains to be seen if B. pseudomallei is a natural pathogen for crops such as tomatoes.

Conclusions
In summary, we identified B. pseudomallei as a plant pathogen capable of causing disease in tomato but not rice plants. B. pseudomallei T3SS1 and T3SS2 contribute significantly to disease whereas T3SS3 plays a more minor role. Although the significance of B. pseudomallei as a natural plant pathogen in the environment is unknown, one could postulate that certain plants may serve as a reservoir for the bacteria. Since B. pseudomallei is classified as a bioterrorism agent by the US Centers for Disease Control and Prevention http://www.cdc.gov/od/sap, our findings indicate that it may be necessary to re-evaluate whether B. pseudomallei poses threats beyond the animal kingdom and whether plant systems could be used as environmental indicators of the presence of the bacteria either as endemic residents or due to the intentional release by terrorists, a concept that has been previously proposed [27].

tcsenter
08-26-2012, 01:39 PM
This touches upon several things; metabolic syndrome, diet, genetic influences, and a hygiene hypothesis basis for inflammatory immune dysfunction:

http://www.nytimes.com/2012/08/26/opinion/sunday/immune-disorders-and-autism.html?pagewanted=all

William Gaatjes
08-27-2012, 07:43 AM
This touches upon several things; metabolic syndrome, diet, genetic influences, and a hygiene hypothesis basis for inflammatory immune dysfunction:

http://www.nytimes.com/2012/08/26/opinion/sunday/immune-disorders-and-autism.html?pagewanted=all

Very interesting article indeed.
Thank you.

The link between diseases from the mother and autism in a child is interesting.
That makes me wonder about something :
Especially because some of these diseases are labeled as auto immune diseases. These "auto immune" diseases may very well have an epigenetic history. Thus these diseases are seen as having a genetic component. But how the disease became a hereditary disease... With the exclusions of some diseases (gene copy errors ?), epigenetics might play a very large role in hereditary auto immunity ?

Some excerpts :


So here’s the short of it: At least a subset of autism — perhaps one-third, and very likely more — looks like a type of inflammatory disease. And it begins in the womb.

It starts with what scientists call immune dysregulation. Ideally, your immune system should operate like an enlightened action hero, meting out inflammation precisely, accurately and with deadly force when necessary, but then quickly returning to a Zen-like calm. Doing so requires an optimal balance of pro- and anti-inflammatory muscle.
In autistic individuals, the immune system fails at this balancing act. Inflammatory signals dominate. Anti-inflammatory ones are inadequate. A state of chronic activation prevails. And the more skewed toward inflammation, the more acute the autistic symptoms.
Nowhere are the consequences of this dysregulation more evident than in the autistic brain. Spidery cells that help maintain neurons — called astroglia and microglia — are enlarged from chronic activation. Pro-inflammatory signaling molecules abound. Genes involved in inflammation are switched on.
These findings are important for many reasons, but perhaps the most noteworthy is that they provide evidence of an abnormal, continuing biological process. That means that there is finally a therapeutic target for a disorder defined by behavioral criteria like social impairments, difficulty communicating and repetitive behaviors.

But how to address it, and where to begin? That question has led scientists to the womb. A population-wide study from Denmark spanning two decades of births indicates that infection during pregnancy increases the risk of autism in the child. Hospitalization for a viral infection, like the flu, during the first trimester of pregnancy triples the odds. Bacterial infection, including of the urinary tract, during the second trimester increases chances by 40 percent.
The lesson here isn’t necessarily that viruses and bacteria directly damage the fetus. Rather, the mother’s attempt to repel invaders — her inflammatory response — seems at fault. Research by Paul Patterson, an expert in neuroimmunity at Caltech, demonstrates this important principle. Inflaming pregnant mice artificially — without a living infective agent — prompts behavioral problems in the young. In this model, autism results from collateral damage. It’s an unintended consequence of self-defense during pregnancy.
Yet to blame infections for the autism epidemic is folly. First, in the broadest sense, the epidemiology doesn’t jibe. Leo Kanner first described infantile autism in 1943. Diagnoses have increased tenfold, although a careful assessment suggests that the true increase in incidences is less than half that. But in that same period, viral and bacterial infections have generally declined. By many measures, we’re more infection-free than ever before in human history.

Better clues to the causes of the autism phenomenon come from parallel “epidemics.” The prevalence of inflammatory diseases in general has increased significantly in the past 60 years. As a group, they include asthma, now estimated to affect 1 in 10 children — at least double the prevalence of 1980 — and autoimmune disorders, which afflict 1 in 20.

Both are linked to autism, especially in the mother. One large Danish study, which included nearly 700,000 births over a decade, found that a mother’s rheumatoid arthritis, a degenerative disease of the joints, elevated a child’s risk of autism by 80 percent. Her celiac disease, an inflammatory disease prompted by proteins in wheat and other grains, increased it 350 percent. Genetic studies tell a similar tale. Gene variants associated with autoimmune disease — genes of the immune system — also increase the risk of autism, especially when they occur in the mother.

In some cases, scientists even see a misguided immune response in action. Mothers of autistic children often have unique antibodies that bind to fetal brain proteins. A few years back, scientists at the MIND Institute, a research center for neurodevelopmental disorders at the University of California, Davis, injected these antibodies into pregnant macaques. (Control animals got antibodies from mothers of typical children.) Animals whose mothers received “autistic” antibodies displayed repetitive behavior. They had trouble socializing with others in the troop. In this model, autism results from an attack on the developing fetus.

But there are still other paths to the disorder. A mother’s diagnosis of asthma or allergies during the second trimester of pregnancy increases her child’s risk of autism.




So does metabolic syndrome, a disorder associated with insulin resistance, obesity and, crucially, low-grade inflammation. The theme here is maternal immune dysregulation. Earlier this year, scientists presented direct evidence of this prenatal imbalance. Amniotic fluid collected from Danish newborns who later developed autism looked mildly inflamed.

Debate swirls around the reality of the autism phenomenon, and rightly so. Diagnostic criteria have changed repeatedly, and awareness has increased. How much — if any — of the “autism epidemic” is real, how much artifact?

YET when you consider that, as a whole, diseases of immune dysregulation have increased in the past 60 years — and that these disorders are linked to autism — the question seems a little moot. The better question is: Why are we so prone to inflammatory disorders? What has happened to the modern immune system?



There’s a good evolutionary answer to that query, it turns out. Scientists have repeatedly observed that people living in environments that resemble our evolutionary past, full of microbes and parasites, don’t suffer from inflammatory diseases as frequently as we do.

Generally speaking, autism also follows this pattern. It seems to be less prevalent in the developing world. Usually, epidemiologists fault lack of diagnosis for the apparent absence. A dearth of expertise in the disorder, the argument goes, gives a false impression of scarcity. Yet at least one Western doctor who specializes in autism has explicitly noted that, in a Cambodian population rife with parasites and acute infections, autism was nearly nonexistent.

For autoimmune and allergic diseases linked to autism, meanwhile, the evidence is compelling. In environments that resemble the world of yore, the immune system is much less prone to diseases of dysregulation.

Generally, the scientists working on autism and inflammation aren’t aware of this — or if they are, they don’t let on. But Kevin Becker, a geneticist at the National Institutes of Health, has pointed out that asthma and autism follow similar epidemiological patterns. They’re both more common in urban areas than rural; firstborns seem to be at greater risk; they disproportionately afflict young boys.


The theory is that the hygiene hypothesis is the problem.
IMHO:
I do not think that that is the complete explanation.
It is one sided exposure to certain pathogens and one sided exposure to toxins. Combine that with an unbalanced one sided diet...
It seems once again that the right balance is much more important.
Having a functioning immune system without auto immunity but a short lifespan because of all these parasites ? Unless the right balance of parasites, fungi, protozoa and bacteria is the key.
Because all these micro organisms also fight each other and keep each other in check. And when they fight for survival and food, our immune system only has to take care of the runaways, the victorious of those fights. Seen form a biological perspective, it works in steps. Like a pyramid. Each section has special function. At least that is what i am wondering about.


Some years back, he began comparing wild sewer rats with clean lab rats. They were, in his words, “completely different organisms.” Wild rats tightly controlled inflammation. Not so the lab rats. Why? The wild rodents were rife with parasites. Parasites are famous for limiting inflammation.


One should ask more why the immune system needs to be suppressed ?
Also, rats are animals that live in a very pathogen rich environment.
It makes sense that rats have a more aggressive immune system when compared to humans.

I think the better way is not to ingest food riddled with parasites, but to find out why the immune system has become "supercharged" to be so aggressive generation over generation. Mimicry and antibodies comes to mind as well. if from generation to generation a chronic infection would take place, would then with every succeeding generation of a species... Would then the immune system not increasingly start targeting molecules from the body ? Without calculation, i would say statistically yes.

Gibsons
08-27-2012, 09:46 AM
One should ask more why the immune system needs to be suppressed ?

It's kind of like asking why not have an armed SWAT team kicking in doors through the neighborhood all the time.

An real life example of where immune suppression is a very good thing (there are many)
http://en.wikipedia.org/wiki/Onchocerciasis

William Gaatjes
08-27-2012, 10:55 AM
It's kind of like asking why not have an armed SWAT team kicking in doors through the neighborhood all the time.

An real life example of where immune suppression is a very good thing (there are many)
http://en.wikipedia.org/wiki/Onchocerciasis

The example is not a fair one.

It is not the nematode, but its endosymbiont, Wolbachia pipientis, that causes the severe inflammatory response that leaves many blind.

The reaction of the immune system damages the cornea because the surrounding tissue is infected by the bacteria.
It is the "chronic" extreme inflammation that causes the blindness.
Thus a temporary infection causes damage but not blindness. A chronic infection causes blindness. Would that not account as an inability of the immune system to get rid of the pathogen ?
I can understand that an immune suppression might be handy here, but only with a treatment to get rid of the bacteria.
Nevertheless, that is quite an interesting bacteria indeed.


Adult worms remain in subcutaneous nodules, limiting access to the host's immune system.[citation needed] Microfilariae, in contrast, are able to induce intense inflammatory responses, especially upon their death. Dying microfilariae have been recently discovered to release Wolbachia surface protein that activates TLR2 and TLR4, triggering innate immune responses and producing the inflammation and its associated morbidity.[10] Wolbachia species have been found to be endosymbionts of O. volvulus adults and microfilariae, and are thought to be the driving force behind most of O. volvulus morbidity. The severity of illness is directly proportional to the number of infected microfilariae and the power of the resultant inflammatory response

Microfilariae are simply put, the "baby" nematodes.


Ocular involvement provides the common name associated with onchocerciasis, river blindness, and may involve any part of the eye from conjunctiva and cornea to uvea and posterior segment, including the retina and optic nerve.[11] The microfilariae migrate to the surface of the cornea. Punctate keratitis occurs in the infected area. This clears up as the inflammation subsides. However, if the infection is chronic, sclerosing keratitis can occur, making the affected area become opaque. Over time, the entire cornea may become opaque, thus leading to blindness. Some evidence suggests the effect on the cornea is caused by an immune response to bacteria present in the worms.


I meant more that instead of suppressing the immune system, we should figure out why it is that it is so reactive. Of course suppression is a good thing. But your example reminds of pushing the brakes while also flooring the gas pedal at the same time. It is better to find the reason why the gas pedal is down then just to hit the brakes and hope that it works. Too many side effects will happen.






Oh lord, i used a car analogy... o_O
I am doomed forever... :'(

Gibsons
08-27-2012, 11:17 AM
The example is not a fair one.

It's completely fair. Why is it that some people go blind from the infection, and some don't?

William Gaatjes
08-27-2012, 02:53 PM
It's completely fair. Why is it that some people go blind from the infection, and some don't?

That is a lot of variables. I will have to think about that.
Normally a lot of those variables would just pop up in my mind. The big picture and i could "zoom in" on all details of "the big picture". But not for a while anymore... :(

All will go well, i will have my new house soon, outside the city. ^_^
I can have proper night sleeps again, not interrupted every 2 to 3 hours because of my mentally challenged paranoid sociopath neighbors and their mentally challenged kids. And that means i will be able to use lucid dreaming (conscious dreaming) once again.
I am tired.
At the moment, i cannot answer your question besides giving standard variables...

Difference in genetic make up.
Difference in environment.
Difference in amount of pathogens received and difference in order of acquired infections .
Difference in acquired immunity and difference in the order of acquired immunity.
Difference in feeding habits.
Difference in exposure to toxins (high doses acute exposure and low doses chronic exposure).
Having multiple infections simultaneously but different in amount and type of pathogens.
Difference in epigenetic background.
Difference in character or personality (susceptibility to stress).
Difference in the family gut bacteria.

Some are related yet different.

Gibsons
08-28-2012, 08:36 AM
That is a lot of variables. I will have to think about that.
Normally a lot of those variables would just pop up in my mind. The big picture and i could "zoom in" on all details of "the big picture". But not for a while anymore... :(


It's all about immune suppression. A strong inflammatory reaction to the infection = blindness. A suppressed, less inflammatory reaction = no blindness.

My recollection is that the people who don't go blind show a large increase in IL-10 at the crucial time. IL-10 inhibits a lot of immune processes. I don't think anyone knows why people show different IL-10 responses though.

William Gaatjes
08-28-2012, 10:39 AM
It's all about immune suppression. A strong inflammatory reaction to the infection = blindness. A suppressed, less inflammatory reaction = no blindness.

My recollection is that the people who don't go blind show a large increase in IL-10 at the crucial time. IL-10 inhibits a lot of immune processes. I don't think anyone knows why people show different IL-10 responses though.

That is interesting. There are parasites that are able to also suppress the immune system but i have no idea if the Inter-leukine 10 mechanism is used.
Most use a mechanism where the parasite is recognized as if it is a normal body tissue. I think by expressing something on the outer shell ?
After some quick look up, i get the impression that IL-10 is a sort of main suppressor switch. Very powerful and versatile it seems.
I think it makes sense that the people who have a lot of IL-10 at the moment of requiring the river blindness disease, already carry some sort of infection from a pathogen. Or acute at the same time or chronic.
It makes sense that a pathogen would produce as much IL-10 as possible or at least is able to influence some process required to produce IL-10 for survival benefits. Is there not some problem with death of b cells or some type of immune cell that produces large amounts of IL-10 as side effect or as deliberate action ?

Perhaps the advantage in the cases of people with massive amounts of IL-10 is an inverse effect. An infection of pathogen X induces large amounts of IL-10 and thus prevents massive inflammatory reactions produced by dying baby nematodes and releasing the wolbachia bacteria.

The big question is, what happens when the wolbachia bacteria can roam around freely when the immune system is suppressed to much ?

Gibsons
08-28-2012, 11:22 AM
It makes sense that a pathogen would produce as much IL-10 as possible or at least is able to influence some process required to produce IL-10 for survival benefits. Is there not some problem with death of b cells or some type of immune cell that produces large amounts of IL-10 as side effect or as deliberate action ?

Pathogens don't make IL-10, it's a human gene. EBV encodes BCRF1, which is an IL10 mimic. Maybe to suppress Th1 responses, also maybe just to extend its host cells (B cells) life.

The big question is, what happens when the wolbachia bacteria can roam around freely when the immune system is suppressed to much ?

People would die in that case. That's AIDS level suppression, not high levels of IL-10 suppression.

William Gaatjes
08-28-2012, 12:37 PM
Pathogens don't make IL-10, it's a human gene. EBV encodes BCRF1, which is an IL10 mimic. Maybe to suppress Th1 responses, also maybe just to extend its host cells (B cells) life.

You are right. I meant indirectly but wrote it wrong. I was thinking more in the idea of that the pathogen itself does not produce IL-10. But invokes by infection and hijacking cells and the cells biomolecular machinery to produce large amounts of IL-10, purposefully or as side effect.


People would die in that case. That's AIDS level suppression, not high levels of IL-10 suppression.

Hm, ach so.
Maybe there is something you know and could tell me about it.
From addiction and ratmodels and i assume research on humans, it is known that in the brain certain receptors are reduced in number when exposed to and activated often with large amount of neurotransmitters or chemicals that can also bind to these receptors.

It is just a wild guess, just an idea. This is not proven or researched for as far as i know, i had to think about it while in public transport.
But assume this scenario :
Because of some acquired pathogen (possible chronic infection without apparent illness or symptoms), the cells are constantly exposed to large amounts of IL-10. Thus the amount of IL-10 receptors on immune system cells would become reduced over time to prevent extreme suppression reactions, the opposite effect of auto immunity.
What would happen is that the immune system becomes to aggressive and is not controlled the right way. Because of the reduced numbers of receptors.
And that is perhaps what we now see as auto immunity. The down regulation of the strength of a given amount of IL-10.

The other cells start to produce more and more IL-10 needed to create the same response. Now that is a paradox. The amount of receptors have been reduced thus more of IL-10 would not have the desired effect. Unless it is specific for certain locations and tissues in the body.

Somewhere there is a control system that monitors the amount of receptors and the correct molecules that bind to it. For some reason, i am sure, that there is the problem of auto immunity. That is, if the immune system also has the ability just as neurons to control the amount of receptors for given cytokines.

What do you think about such a scenario ,Gibsons ?
Has there ever been such research ?

Gibsons
08-28-2012, 02:49 PM
You are right. I meant indirectly but wrote it wrong. I was thinking more in the idea of that the pathogen itself does not produce IL-10. But invokes by infection and hijacking cells and the cells biomolecular machinery to produce large amounts of IL-10, purposefully or as side effect.



Hm, ach so.
Maybe there is something you know and could tell me about it.
From addiction and ratmodels and i assume research on humans, it is known that in the brain certain receptors are reduced in number when exposed to and activated often with large amount of neurotransmitters or chemicals that can also bind to these receptors.

It is just a wild guess, just an idea. This is not proven or researched for as far as i know, i had to think about it while in public transport.
But assume this scenario :
Because of some acquired pathogen (possible chronic infection without apparent illness or symptoms), the cells are constantly exposed to large amounts of IL-10. Thus the amount of IL-10 receptors on immune system cells would become reduced over time to prevent extreme suppression reactions, the opposite effect of auto immunity.
What would happen is that the immune system becomes to aggressive and is not controlled the right way. Because of the reduced numbers of receptors.
And that is perhaps what we now see as auto immunity. The down regulation of the strength of a given amount of IL-10.

The other cells start to produce more and more IL-10 needed to create the same response. Now that is a paradox. The amount of receptors have been reduced thus more of IL-10 would not have the desired effect. Unless it is specific for certain locations and tissues in the body.

Somewhere there is a control system that monitors the amount of receptors and the correct molecules that bind to it. For some reason, i am sure, that there is the problem of auto immunity. That is, if the immune system also has the ability just as neurons to control the amount of receptors for given cytokines.

What do you think about such a scenario ,Gibsons ?
Has there ever been such research ?

afaik, few or no immune receptors work like that - the receptor isn't downregulated in response to its ligand. There might be an exceptions.

More likely is that a problem with (a lack of) IL-10 production or IL-10 signalling would lead to autoimmunity. Autoimmunity is still poorly understood, though there's mountainous amounts of data on it. There are genetic and environmental factors in play for many of them.

My prediction is that someone who produced too much IL-10 over a long time would be mostly normal, but very sensitive to viral and some other infections. They might have severe allergies too, but I'm unsure on that.

Gross overgeneralization: Immune signalling often involves positive feedback loops, e.g. cell x activates cell y, which in turn activates cell x to better activate cell y. There's some mechanism(s) in place to put the brakes on this. IL-10 would be one of those brakes.

William Gaatjes
09-16-2012, 01:21 PM
Something about biotin shortage.
I was making a potato recipe , (will post pictures later in a off topic thread).
And was reading about if i had to peel a potato. Because i know that under the peel of the potato amounts of solanin are produced. And solanine is a poison to humans and even deathly in large amounts (more then 100mg).
Thus i did a little background reading and found out that i only have to worry about potatoes with green spots on the peel and when the potato starts to develop. Then the amount of solanine is something to worry about.

But this thread is really about biotin.
In a potato, biotin can also be found. And biotin is very important.
Make sure you have sufficient production of biotin.
If not, you may end up going bald, end up with dermatitis or end up with nervous system issues.

A healthy person has enough biotin. But when the flora and fauna inside the gut is not balanced, in a rare situation biotin deficiency may occur.
Our little friends inside the intestines, the bacteria produce biotin in large quantities. Unless something is going wrong.
Or when you start to consume large amounts of raw eggs. Avidin is a protein that...
Well, read it for yourself if you are interested...
I have to look at my potatoes and i am busy packing. :P



http://en.wikipedia.org/wiki/Biotin

Biotin is necessary for cell growth, the production of fatty acids, and the metabolism of fats and amino acids. It plays a role in the citric acid cycle, which is the process by which biochemical energy is generated during aerobic respiration. Biotin not only assists in various metabolic reactions, but also helps to transfer carbon dioxide. It may also be helpful in maintaining a steady blood sugar level.[3] Biotin is often recommended as a dietary supplement for strengthening hair and nails, though scientific data supporting this usage are weak.[4][5] As a consequence, biotin is found in many cosmetics and health products for the hair and skin.[6]

Biotin deficiency is rare because, in general, intestinal bacteria produce biotin in excess of the body's daily requirements.[7] For that reason, statutory agencies in many countries, for example the USA[8] and Australia,[9] do not prescribe a recommended daily intake of biotin. However, a number of metabolic disorders exist in which an individual's metabolism of biotin is abnormal, such as deficiency in the holocarboxylase synthetase enzyme which covalently links biotin onto the carboxylase, where the biotin acts as a cofactor.[10]


http://en.wikipedia.org/wiki/Avidin

Avidin is a tetrameric or dimeric[1] biotin-binding protein produced in the oviducts of birds, reptiles and amphibians deposited in the whites of their eggs. In chicken egg white, avidin makes up approximately 0.05% of total protein (approximately 1.8 mg per egg). The tetrameric protein contains four identical subunits (homotetramer), each of which can bind to biotin (Vitamin B7, vitamin H) with a high degree of affinity and specificity. The dissociation constant of avidin is measured to be KD ≈ 10−15 M, making it one of the strongest known non-covalent bonds.[2]

In its tetrameric form, avidin is estimated to be between 66–69 kDa in size.[3] Ten percent of the molecular weight is attributed to carbohydrate content composed of four to five mannose and three N-acetylglucosamine residues.[4] The carbohydrate moieties of avidin contain at least three unique oligosaccharide structural types that are similar in structure and composition.[5]

Functional avidin is found only in raw egg, as the biotin avidity of the protein is destroyed by cooking. The natural function of avidin in eggs is not known, although it has been postulated to be made in the ovaduct as a bacterial growth-inhibitor, by binding biotin the bacteria need. As evidence for this, streptavidin, a loosely related protein with equal biotin affinity and a very similar binding site, is made by certain strains of Streptomyces bacteria, and is thought to serve to inhibit the growth of competing bacteria, in the manner of an antibiotic.[6]



http://en.wikipedia.org/wiki/Solanine

Symptoms
Solanine poisoning is primarily displayed by gastrointestinal and neurological disorders. Symptoms include nausea, diarrhea, vomiting, stomach cramps, burning of the throat, cardiac dysrhythmia, headache and dizziness. In more severe cases, hallucinations, loss of sensation, paralysis, fever, jaundice, dilated pupils, hypothermia and death have been reported.
In large quantities, solanine poisoning can cause death. One study suggests that doses of 2 to 5 mg per kilogram of body weight can cause toxic symptoms, and doses of 3 to 6 mg per kilogram of body weight can be fatal.[2]
Symptoms usually occur 8 to 12 hours after ingestion, but may occur as rapidly as 30 minutes after eating high-solanine foods.
The lowest dose to cause symptoms of nausea is about 25 mg solanine for adults, a life-threatening dose for a regular-weight adult ranges about 400 mg solanine.[citation needed]
[edit]
Mechanism of action
One study suggests that the toxic mechanism of solanine is caused by the chemical's interaction with mitochondrial membranes. Experiments show that solanine exposure opens the potassium channels of mitochondria, decreasing their membrane potential. This in turn leads to Ca2+ being transported from the mitochondria into the cytoplasm, and it is this increased concentration of Ca2+ in the cytoplasm that triggers cell damage and apoptosis.[3]

William Gaatjes
09-26-2012, 12:27 PM
A lot of people suffer from diabetes mellitus type 2. Now researches have found that an unbalance of the bacteria in the intestines might also be a cause or maybe even the cause. Unfortunately, it is not mentioned which bacteria are the cause of such problems. Also, the question arises if these bacteria are naturally present but in a certain amount and that a bad high sugar diet could cause certain bacteria species to expand to much in numbers. Creating the unbalance of life inside the intestines. I do wonder if there also live fungi inside the intestines. I do remember we carry fungi with us, that is normally taken care of by the immune system. But i could be mistaken...

http://medicalxpress.com/news/2012-09-gut-bacteria-diabetes.html


Studying gut bacteria can reveal a range of human illness. Now, new research shows that the composition of a person's intestinal bacteria could play an important role in the development of type 2 diabetes. These results, from a joint European and Chinese research team, have just been published in the journal Nature.
The number of people suffering from type 2 diabetes world-wide has risen rapidly in recent years, and scientists estimate that just as many people could be suffering from the illness without realising it. New research now indicates that your gut bacteria can reveal whether you suffer from the disease.
"We have demonstrated that people with type 2 diabetes have a high level of pathogens in their intestines," says professor Jun Wang from the University of Copenhagen's Department of Biology and Novo Nordisk Foundation Center for Basic Metabolic Research.
Studying gut bacteria can reveal a range of human illness. Now, new research shows that the composition of a person’s intestinal bacteria could play an important role in the development of type 2 diabetes. A team scientists from the University of Copenhagen and the Beijing Genomics Institute (BGI) are behind the results published in the journal Nature. Credit: University of Copenhagen.

Important intestinal bacteria
The 1.5 kilograms of bacteria that we each carry in our intestines have an enormous impact on our health and well being. The bacteria normally live in a sensitive equilibrium but if this equilibrium is disrupted our health could suffer. In the new study, scientists examined the intestinal bacteria of 345 people from China, of which 171 had type 2 diabetes. The team managed to identify clear biological indicators that someday could be used in methods that provide faster and earlier diagnosis of type 2 diabetes.
The research, which was recently published in the scientific journal Nature, also demonstrated that people with type 2 diabetes have a more hostile bacterial environment in their intestines, which can increase resistance to different medicines.
Similar studies carried out on sufferers of type 2 diabetes in Denmark also discovered a significant imbalance in the function of their intestinal bacteria and composition. Future Danish studies will examine whether intestinal bacteria is already abnormal in people that are deemed to be at risk of developing diabetes.
"We are going to transplant gut bacteria from people that suffer from type 2 diabetes into mice and examine whether the mice then develop diabetes," says another of the lead scientists behind the project, professor Oluf Borbye Pedersen from the University of Copenhagen and centre director at LuCamp, the Lundbeck Foundation Centre for Applied Medical Genomics in Personalised Disease Prediction, Prevention and Care.

International research team investigates gut bacteria
By working together, a team scientists from the University of Copenhagen and the Beijing Genomics Institute (BGI) was able to make to several breakthroughs in the field of 'metagenomics'.
Scientists working on the EU research project MetaHIT have uncovered more than 3.3 million genes from gut bacteria found in people from Spain and Denmark. These genes could play a key role in understanding and treating a range of serious illnesses. According to Professor Karsten Kristiansen from the University of Copenhagen's Department of Biology, the recent discovery is an important step in the comprehensive international research that is currently underway to investigate the interplay between intestinal bacteria and health.
"The European and Chinese working on the MetaHIT project were able to make important new discoveries about the relationship between intestinal bacteria and health. The new discovery indicates a possible connection between type 2 diabetes and the intestinal bacteria in Chinese people," Kristiansen says.
"It is important to point out that our discovery demonstrates a correlation. The big question now is whether the changes in gut bacteria can affect the development of type 2 diabetes or whether the changes simply reflect that the person is suffering from type 2 diabetes."

William Gaatjes
10-01-2012, 01:23 AM
More news from the research front of epigenetics :


http://phys.org/news/2012-09-scientists-link-players-epigenetic-code.html


http://cdn.physorg.com/newman/gfx/news/hires/2012/26-scientistsfi.jpg
Mouse embryonic stem cells (blue, green) lose DNA methylation (red) in the absence of UHRF1. Credit: Strahl Lab, UNC School of Medicine



Over the last two decades, scientists have come to understand that the genetic code held within DNA represents only part of the blueprint of life. The rest comes from specific patterns of chemical tags that overlay the DNA structure, determining how tightly the DNA is packaged and how accessible certain genes are to be switched on or off.

As researchers have uncovered more and more of these "epigenetic" tags, they have begun to wonder how they are all connected. Now, research from the University of North Carolina School of Medicine has established the first link between the two most fundamental epigenetic tags—histone modification and DNA methylation—in humans.
The study, which was published Sept. 30, 2012 by the journal Nature Structural & Molecular Biology, implicates a protein called UHRF1 in the maintenance of these epigenetic tags. Because the protein has been found to be defective in cancer, the finding could help scientists understand not only how microscopic chemical changes can ultimately affect the epigenetic landscape but also give clues to the underlying causes of disease and cancer.
"There's always been the suspicion that regions marked by DNA methylation might be connected to other epigenetic tags like histone modifications, and that has even been shown to be true in model organisms like fungus and plants," said senior study author Brian Strahl, PhD, associate professor of biochemistry and biophysics in the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center. "But no one has been able to make that leap in human cells. It's been controversial in terms of whether or not there's really a connection. We have shown there is."
Strahl, along with his postdoctoral fellow Scott Rothbart, honed in on this discovery by using a highly sophisticated technique developed in his lab known as next generation peptide arrays. First the Strahl lab generated specific types of histone modifications and dotted them on tiny glass slides called "arrays." They then used these "arrays" to see how histone modifications affected the docking of different proteins. One protein – UHRF1 – stood out because it bound a specific histone modification (lysine 9 methylation on histone H3) in cases where others could not.
Strahl and his colleagues focused the rest of their experiments on understanding the role of UHRF1 binding to this histone modification. They found that while other proteins that dock on this epigenetic tag are ejected during a specific phase of the cell cycle, mitosis, UHRF1 sticks around. Importantly, the protein's association with histones throughout the cell cycle appears to be critical to maintaining another epigenetic tag called DNA methylation. The result was surprising because researchers had previously believed that the maintenance of DNA methylation occurred exclusively during a single step of the cell cycle called DNA replication.
"This role of UHRF1 outside of DNA replication is certainly unexpected, but I think it is just another way of making sure we don't lose information about our epigenetic landscape," said Strahl.

Journal reference: Nature Structural & Molecular Biology

Provided by University of North Carolina Health Care


It becomes more and more clear, that there are some serious implications that ultimately will ask society to make some changes to ensure health. But the less sick people are, the higher the efficiency. Just a simple headache can make the difference in having a "eureka" moment and finding a novel solution to a problem when needed or working days at an end with overtime trying to solve a problem that seems just so hard because of concentration problems...

William Gaatjes
12-23-2012, 03:53 AM
Yay. I am slowly starting to adapt to my new surroundings.
Thus, slowly i am posting into this forum again.

The article is an interesting find, it is from march this year but i forgot to post it. Has anybody read about the research conducted after to confirm the results from this research ?

http://medicalxpress.com/news/2012-03-cancer-genes-differ-tumour.html


March 8, 2012 (Medical Xpress)
Cancer genes differ in different parts of a tumor in Cancer. Taking a sample from just one part of a tumour may not give a full picture of its ‘genetic landscape’, according to a study published in the New England Journal of Medicine.

The findings could help explain why attempts at using single biopsies to identify biomarkers to which personalised cancer treatments can be targeted have not been more successful. The researchers carried out the first ever genome-wide analysis of the genetic variation between different regions of the same tumour using kidney cancer samples. They found that the majority, around two thirds of gene faults (63-69%), were not found in other biopsies from the same tumour. Lead author Professor Charles Swanton of the UCL Cancer Institute and Cancer Research UK’s London Research Institute, said: “We’ve known for some time that tumours are a ‘patchwork’ of faults, but this is the first time we’ve been able to use cutting-edge genome sequencing technology to map out the genetic landscape of a tumour in such exquisite detail. “This has revealed an extraordinary amount of diversity, with more differences between biopsies from the same tumour at the genetic level than there are similarities. The next step will be to develop drugs that limit this diversity by targeting key driver mutations that are common throughout all parts of the tumour.” The tumour samples analysed in this study were donated by patients treated at the Royal Marsden Hospital under the supervision of Dr James Larkin. Dr Larkin said: “The idea of personalised medicine is to tailor treatments to suit individual patients. This study in kidney cancer has shown significant molecular changes between different parts of the same tumour. We have also seen differences between primary kidney tumours and cancer cells that have spread to other organs. This may be relevant to how we treat kidney cancer with drugs because the molecular changes that drive the growth of the cancer once it has spread may be different from those that drive the growth of the primary tumour.” The researchers – funded by Cancer Research UK, the Medical Research Council and the Wellcome Trust – compared the genetic faults in samples taken from different parts of four separate kidney tumours, and also from sites where the cancer had spread to other organs. This allowed them to identify 118 different mutations – 40 of which were ‘ubiquitous mutations’ found in all biopsies, 53 ‘shared mutations’ that were present in most but not all biopsies and 25 ‘private mutations’ that were only detected in a single biopsy. By analysing the location of shared mutations in relation to the whole tumour, the researchers were able to trace the origins of particular subtypes of cancer cells back to key driver mutations. This allowed the scientists to create a ‘map’ of how the pattern of faults within the tumour might have evolved over time. Professor Swanton added: “For the first time we’ve been able to use the pattern of genetic faults in a tumour to trace the origins of certain populations of cancers cells, much in the same way as Darwin used his ‘tree of life’ theory to show how different species are related. “This underscores the importance of targeting common mutations found in the ‘trunk’ of the tree as opposed to those found in the ‘branches’, which may only be present in a relatively small number of cells. It may also explain why surgery to remove the primary kidney tumour can improve survival, by decreasing the likelihood that resistant cells will be present that could go on to re-grow the tumour after treatment.” Dr Lesley Walker, Cancer Research UK’s director of cancer information, said: “These findings highlight important differences that exist within tumours and suggest a way to improve the success rate of personalised cancer medicines. Crucially, they emphasise the need to build capacity within the NHS for in-depth genetic analysis of tumours to allow researchers to identify the markers that best predict who will benefit from targeted treatments. “We are now planning to see if these results can be replicated in larger groups of patients as part of Cancer Research UK’s Genomics Initiative - a set of groundbreaking projects using the latest high-tech gene sequencing machines to track down the genetic faults driving different types of cancer.” Journal reference: New England Journal of Medicine Provided by University College London

Mr. Pedantic
12-23-2012, 11:01 AM
That's actually really interesting, because in med school we were always taught that all the cells in a particular cancer were clones of each other. That obviously had implications in terms of treatment: as the article points out, we assumed that a single biopsy would be representative of all the cells in the tumour, and therefore that a treatment for one cell would be effective in general against all cells in the tumour.

William Gaatjes
12-31-2012, 02:52 AM
That's actually really interesting, because in med school we were always taught that all the cells in a particular cancer were clones of each other. That obviously had implications in terms of treatment: as the article points out, we assumed that a single biopsy would be representative of all the cells in the tumour, and therefore that a treatment for one cell would be effective in general against all cells in the tumour.

It sure is interesting. With hindsight, it makes sense that the cells comprising a tumor (with mutated dna for whatever reason) keep mutating, since the whole regulating mechanism to correct the dna and apoptosis (programmed cell death) no longer functions. But i am happy that this kind of research keeps continuing. Also, read the next post. It is most interesting.

William Gaatjes
12-31-2012, 03:02 AM
When it comes to becoming fat, there might be another reason to watch the diet. It seems that we have bacteria in our intestines that help us absorb fats. Firmicutes is the bacteria family.
http://en.wikipedia.org/wiki/Firmicutes

This article is about zebrafish, but humans also carry Firmicutes in the intestines. Of course it is a large family and it says nothing about specific bacteria families.
It is an interesting idea, that consuming a lot of fat, will also increase the amount of bacteria that help consume fat more easy. This will lead to an increased absorption of fats. This might very well be a part of the puzzle why some people gain weight quickly to a higher fat percentage, while others seem to be unaffected. A sort of avalanching effect. Might be an epigenetic effect here as well. Might also explain why some people seem so muscled but cannot stand the cold while others seem to increase weight quickly because of increasing fat storage. Might be an evolutionary / epigenetic effect against a cold environment.
The only problems is there are many different kinds of fat.

Well, read for yourself...
http://medicalxpress.com/news/2012-09-gut-bacteria-fat-absorption.html


Gut bacteria increase fat absorption September 12, 2012 in Medical research Enlarge This confocal microscopy of intestinal epithelial cells (red) in zebrafish shows that the presence of microbes stimulates dietary fatty acid uptake and accumulation in epithelial lipid droplets (green).

http://s.ph-cdn.com/newman/gfx/news/2012/gutmicrobesh.jpg

Credit: Ivana Semova, Ph.D.

You may think you have dinner all to yourself, but you're actually sharing it with a vast community of microbes waiting within your digestive tract. A new study from a team including Carnegie's Steve Farber and Juliana Carten reveals that some gut microbes increase the absorption of dietary fats, allowing the host organism to extract more calories from the same amount of food. Previous studies showed gut microbes aid in the breakdown of complex carbohydrates, but their role in dietary fat metabolism remained a mystery, until now. The research is published September 13 by Cell Host & Microbe. "This study is the first to demonstrate that microbes can promote the absorption of dietary fats in the intestine and their subsequent metabolism in the body," said senior study author John Rawls of the University of North Carolina. "The results underscore the complex relationship between microbes, diet and host physiology." The study was carried out in zebrafish, which are optically transparent when young. By feeding the fish fatty acids tagged with fluorescent dyes, an approach originally developed in Farber's lab, the researchers were able to directly observe the absorption and transport of fats in live animals. The Rawl's lab pioneered methods to grow zebrafish larvae in the presence or absence of gut microbes. By combining approaches, they determined that one type of bacteria, called Firmicutes, is instrumental in increasing fat absorption. They also found that the abundance of Firmicutes in the gut was influenced by diet. Fish fed normally had more Firmicutes than fish that were denied food for several days. Other studies have linked a higher relative abundance of Firmicutes in the gut with obesity in humans. The findings indicate that bacteria in the gut can increase the host's ability to absorb fat and thereby harvest more calories from the diet. Another implication is that a high-fat diet promotes the growth of these fat-loving Firmicutes, resulting in more fat absorption. Although the study involved only fish, not humans, it offers insights that could help inform new approaches to treating obesity and other disorders. "The unique properties of zebrafish larvae are helping us develop a better understanding of how the intestine functions with the goal of contributing to ongoing efforts to reduce the impact of diseases associated with altered lipid metabolism, such as diabetes, obesity, and cardiovascular disease. Our collaboration with the Rawls lab is now focused on how specific gut bacteria are able to stimulate absorption of dietary fat. We hope to use that information to develop new ways to reduce fat absorption in the context of human diseases," Farber said. The research team also included lead author Ivana Semova and co-author Lantz Mackey, both of UNC, as well as co-authors Jesse Stombaugh and Rob Knight of the University of Colorado at Boulder.
Journal reference: Cell Host & Microbe
Provided by Carnegie Institution for Science

William Gaatjes
01-12-2013, 04:19 AM
This is interesting research. Is there also not a possibility that MS is a pathogen derived disease ? The Epstein-Barr virus ? There has been research going on linking the EBV virus to MS. Could this also not be a very complex effect where the cause is molecular mimicry ?

http://en.wikipedia.org/wiki/Molecular_mimicry

http://medicalxpress.com/news/2013-01-multiple-sclerosis-reveals-killer-cells.html


http://s.ph-cdn.com/newman/gfx/news/2013/2-multiplescle.jpg

http://s.ph-cdn.com/newman/gfx/news/2013/1-multiplescle.jpg



Multiple sclerosis study reveals how killer T cells learn to recognize nerve fiber insulators

(Medical Xpress)—Misguided killer T cells may be the missing link in sustained tissue damage in the brains and spines of people with multiple sclerosis, findings from the University of Washington reveal. Cytoxic T cells, also known as CD8+ T cells, are white blood cells that normally are in the body's arsenal to fight disease.

Multiple sclerosis is characterized by inflamed lesions that damage the insulation surrounding nerve fibers and destroy the axons, electrical impulse conductors that look like long, branching projections. Affected nerves fail to transmit signals effectively. Intriguingly, the UW study, published this week in Nature Immunology, also raises the possibility that misdirected killer T cells might at other times act protectively and not add to lesion formation. Instead they might retaliate against the cells that tried to make them mistake the wrappings around nerve endings as dangerous. Scientists Qingyong Ji and Luca Castelli performed the research with Joan Goverman, UW professor and chair of immunology. Goverman is noted for her work on the cells involved in autoimmune disorders of the central nervous system and on laboratory models of multiple sclerosis. Multiple sclerosis generally first appears between ages 20 to 40. It is believed to stem from corruption of the body's normal defense against pathogens, so that it now attacks itself.
For reasons not yet known, the immune system, which wards off cancer and infection, is provoked to vandalize the myelin sheath around nerve cells. The myelin sheath resembles the coating on an electrical wire. When it frays, nerve impulses are impaired. TIP dendritic cells, stained to show their physical features.Depending on which nerves are harmed, vision problems, an inability to walk, or other debilitating symptoms may arise. Sometimes the lesions heal partially or temporarily, leading to a see-saw of remissions and flare ups. In other cases, nerve damage is unrelenting. The myelin sheaths on nerve cell projections are fashioned by support cells called oligodendrocytes.
Newborn's brains contain just a few sections with myelinated nerve cells. An adult's brains cells are not fully myelinated until age 25 to 30. For T cells to recognize proteins from a pathogen, a myelin sheath or any source, other cells must break the desired proteins into small pieces, called peptides, and then present the peptides in a specific molecular package to the T cells. Scientists had previously determined which cells present pieces of a myelin protein to a type of T cell involved in the pathology of multiple sclerosis called a CD4+ T cell. Before the current study, no cells had yet been found that present myelin protein to CD8+ T cells. Scientists strongly suspect that CD8+ T cells, whose job is to kill other cells, play an important role in the myelin-damage of multiple sclerosis. In experimental autoimmune encephalitis, which is an animal model of multiple sclerosis in humans, CD4+T cells have a significant part in the inflammatory response. However, scientists observed that, in acute and chronic multiple sclerosis lesions, CD8+T cells actually outnumber CD4+ T cells and their numbers correlate with the extent of damage to nerve cell projections. Other studies suggest the opposite: that CD8+T cells may tone down the myelin attack.
The differing observations pointed to a conflicting role for CD8 + T cells in exacerbating or ameliorating episodes of multiple sclerosis. Still, how CD8+T cells actually contributed to regulating the autoimmune response in the central nervous system, for better or worse, was poorly understood. Goverman and her team showed for the first time that naive CD8+ T cells were activated and turned into myelin-recognizing cells by special cells called Tip-dendritic cells. These cells are derived from a type of inflammatory white blood cell that accumulates in the brain and the spinal cord during experimental autoimmune encephalitis originally mediated by CD4+ T cells. The membrane folds and protrusions of mature dendritic cells often look like branched tentacles or cupped petals well-suited to probing the surroundings. The researchers proposed that the Tip dendritic cells can not only engulf myelin debris or dead oligodendrocytes and then present myelin peptides to CD4 + T cells, they also have the unusual ability to load a myelin peptide onto a specific type of molecule that also presents it to CD8+ T cells. In this way, the Tip dendritic cells can spread the immune response from CD4+ T cells to CD8+ T cells. This presentation enables CD8+ T cells to recognize myelin protein segments from oligodendrocytes, the cells that form the myelin sheath.
The phenomenon establishes a second-wave of autoimmune reactivity in which the CD8+ T cells respond to the presence of oligodendrocytes by splitting them open and spilling their contents. "Our findings are consistent," the researchers said, "with the critical role of dendritic cells in promoting inflammation in autoimmune diseases of the central nervous system." They mentioned that mature dendritic cells might possibly wait in the blood vessels of normal brain tissue to activate T-cells that have infiltrated the blood/brain barrier. The oligodendrocytes, under the inflammatory situation of experimental autoimmune encephalitis, also present peptides that elicit an immune response from CD8+T cells. Under healthy conditions, oligodendrocytes wouldn't do this. The researchers proposed that myelin-specific CD8+T cells might play a role in the ongoing destruction of nerve-cell endings in "slow burning" multiple sclerosis lesions. A drop in inflammation accompanied by an increased degeneration of axons (electrical impulse-conducting structures) coincides with multiple sclerosis leaving the relapsing-remitting stage of disease and entering a more progressive state. Medical scientists are studying the roles of a variety of immune cells in multiple sclerosis in the hopes of discovering pathways that could be therapeutic targets to prevent or control the disease, or to find ways to harness the body's own protective mechanisms. This could lead to highly specific treatments that might avoid the unpleasant or dangerous side effects of generalized immunosuppressants like corticosteroids or methotrexate.




http://en.wikipedia.org/wiki/Epstein–Barr_virus


P.S.
There is also research suggesting a link between oligodendrocytes and EBV infection.

William Gaatjes
01-14-2013, 08:04 AM
With respect to the link of obesity and pathogens in post240...

The adenovirus AD36 seems to be able to increase the amount of bodyfat. Antibodies against the virus has been found in obese individuals.
However, this is not solid evidence of course. The host must still consume more calories than needed. Or can the virus cause an effect where already present body tissues are converted to fat ? Interesting ?

http://en.wikipedia.org/wiki/Infectobesity

http://en.wikipedia.org/wiki/AD-36

William Gaatjes
01-17-2013, 02:18 PM
Bacteria are amazing. Using laws of nature to their advantage.

This particular bacterial family has the ability to form magnetite and are called magnetotactic bacteria.
And use these magnetite crystals to find their way through their surroundings by use of the Earth magnetic field.

http://cdn.physorg.com/newman/gfx/news/2012/1-videoarticle.jpg
On the left side of the bacteria, you can see the magnetic particles.

http://en.wikipedia.org/wiki/Magnetotactic_bacteria


Magnetotactic bacteria (or MTB) are a polyphyletic group of bacteria discovered by Richard P. Blakemore in 1975, that orient along the magnetic field lines of Earth's magnetic field. To perform this task, these bacteria have organelles called magnetosomes that contain magnetic crystals. The biological phenomenon of microorganisms tending to move in response to the environment's magnetic characteristics is known as magnetotaxis (although this term is misleading in that every other application of the term taxis involves a stimulus-response mechanism). In contrast to the magnetoception of animals, the bacteria contain fixed magnets that force the bacteria into alignment — even dead cells align, just like a compass needle.[1] The alignment is believed to aid these organisms in reaching regions of optimal oxygen concentration.


http://phys.org/news/2012-11-video-article-purify-magnetic-bacteria.html


Magnetotactic bacteria, like Magnetospirillum magneticum, have evolved cellular processes that allow them to take up iron molecules to produce magnetic nanocrystals like magnetite. Since they were first discovered and isolated in 1975 by Robert Blakemore, scientists continue to be fascinated by these unique bacteria, whether as a means to isolate biogenic magnetite or to understand the evolutionary advantages of producing these minerals. A new video-article in JoVE (Journal of Visualized Experiments) details a procedure to purify and enrich samples of magnetotactic bacteria from aquatic environments, developed in the laboratory of Dr. Brian Lower at The Ohio State University.

Magnetotactic bacteria are microorganisms, typically found in stratified water columns or aquatic sediments all over the world. Though many of these bacteria tend to thrive in environments with low levels of oxygen, the defining characteristic they share are small, magnetic, membrane bound nanocrystals of either the iron oxide magnetite or the iron sulfide greigite.

"These nanocrystals allow the organisms to align themselves with the earth's magnetic field and swim up or down based on the geomagnetic field to find their microenvironments," Dr. Lower explains. "These bacteria are fairly ubiquitous. They can be found all over the world, and interestingly they can be found in sediment samples from millions of years ago." These bacteria are a valuable anomaly to the scientific community. Their fossil record gives geologists accurate representations of the Earth's past magnetic field, when combined with carbon dating, and could potentially provide other clues about earth's geological history. The magnetotactic minerals may also have medical or other novel applications. "You can coat these minerals with antibodies and target specific cancer cell lines or heat the magnets with an alternating magnetic field to kill a cancer cell line," says Dr. Lower. "We decided to publish in JoVE because it will allow a wide variety of scientists to see how easy it is to isolate and enrich these species. We hope the video-protocol will spur other collaborations or new research," Dr. Lower said. The article will be published on November 15, 2012 in JoVE's General section. JoVE acquisition editor Rachelle Baker stated, "We are very excited for this article not only because it is our first featuring magnetotactic bacteria but we believe it will lay a foundation for other groups to build expand upon this work and share their methods with the community, which is the founding principle of JoVE." More information: Lower et. al. www.JoVE.com/video/50123/collection-isolation-enrichment-naturally-occurring-magnetotactic

William Gaatjes
01-17-2013, 03:00 PM
For those interested, humans also seem to have a tiny amount of magnetite in the Ethmoid bone. a bone structure between the eyes and behind the nose.
http://en.wikipedia.org/wiki/Ethmoid_bone


http://upload.wikimedia.org/wikipedia/commons/2/2d/Gray164.png



http://www.theregister.co.uk/2006/11/17/the_odd_body_nose_compass/

Some years ago scientists at CALTECH (California Institute of Technology in Pasadena) discovered that humans possess a tiny, shiny crystal of magnetite in the ethmoid bone, located between your eyes, just behind the nose.
Magnetite is a magnetic mineral also possessed by homing pigeons, migratory salmon, dolphins, honeybees, and bats. Indeed, some bacteria even contain strands of magnetite that function, according to Dr Charles Walcott of the Cornell Laboratory of Ornithology in Ithaca, New York, "as tiny compass needles, allowing them [the bacteria] to orient themselves in the earth's magnetic field and swim down to their happy home in the mud".
It seems that magnetite helps direction finding in animals and helps migratory species migrate successfully by allowing them to draw upon the earth's magnetic fields. But scientists are not sure how they do this.
In any case, when it comes to humans, according to some experts, magnetite makes the ethmoid bone sensitive to the earth's magnetic field and helps your sense of direction.
Some, such as Dr Dennis J Walmsley and W Epps from the Department of Human Geography of the Australian National University in Canberra writing in Perceptual and Motor Skills as far back as in 1987, have even suggested that this "compass" was helpful in human evolution as it made migration and hunting easier.
Following this fascinating factoid, science journalist Marc McCutcheon entitled a book The Compass in Your Nose and Other Astonishing Facts.

William Gaatjes
01-29-2013, 09:51 AM
Scientists have developed an amazing way to trick iron oxidizing bacteria to consume electrons (and CO2) to replicate.
But what is really interesting, is the ability to harvest the electrons from the electrode. I do wonder if the material, the electrode itself is made of, also plays a part in the whole process.


http://phys.org/news/2013-01-scientists-iron-eating-bacteria-electrons.html


January 29, 2013

Scientists have developed a way to grow iron-oxidizing bacteria using electricity instead of iron, an advance that will allow them to better study the organisms and could one day be used to turn electricity into fuel. The study will be published on January 29 in mBio, the online open-access journal of the American Society for Microbiology.

The method, called electrochemical cultivation, supplies these bacteria with a steady supply of electrons that the bacteria use to respire, or "breathe". It opens the possibility that one day electricity generated from renewable sources like wind or solar could be funneled to iron oxidizing bacteria that combine it with carbon dioxide to create biofuels, capturing the energy as a useful, storable substance.
"It's a new way to cultivate a microorganism that's been very difficult to study. But the fact that these organisms can synthesize everything they need using only electricity makes us very interested in their abilities," says Daniel Bond of the BioTechnology Institute at the University of Minnesota – Twin Cities, who co-authored the paper with Zarath Summers and Jeffrey Gralnick.
To "breathe", iron oxidizers take electrons off of dissolved iron, called Fe(II) – a process that produces copious amounts of rust, called Fe(III). Iron-oxidizing bacteria are found around the world, almost anywhere an aerobic environment (with plenty of oxygen) meets an anaerobic environment (which lacks oxygen). They play a big role in the global cycling of iron and contribute to the corrosion of steel pipelines, bridges, piers, and ships, but their lifestyle at the interface of two very different habitats and the accumulation of cell-trapping Fe(III) makes iron oxidizers difficult to grow and study in the lab.
Scientists think these bacteria must carry out the iron oxidation step on their surfaces. If that's true, Bond reasoned, the outsides of the organisms should be covered with proteins that interact with Fe(II), so you should be able to provide a stream of pure electrons to the outsides of the bacteria and get them to grow.
Bond and his colleagues added the marine iron oxidizer Mariprofundus ferrooxydans PV-1, along with some nutrient medium, to an electrode carefully tuned to provide electrons at the same energy level, or potential, as Fe(II) would provide. The idea, says Bond, was to "fool the bacteria into thinking they're at the world's best buffet of Fe(II) atoms."
It worked. The bacteria multiplied and formed a film on the electrode, Bond says, and eventually they were able to grow M. ferrooxydans with no iron in the medium, proof that the bacteria were living off the electrons they absorbed from the electrode to capture carbon dioxide and replicate. And since the electron donor is a solid surface, say the authors, it's pretty likely that the bacterial electron-harvesting machinery is exposed on the outer membrane of the cell.
It's this capture of carbon dioxide that could enable electrochemical cultivation to create biofuels or other useful products one day, Bond says.
"Bacteria are experts at the capture of carbon dioxide. They build cells and compounds" with the carbon, he says. They might one day be exploited as microscopic energy packagers: bacteria like M. ferrooxydans could capture electricity from an electrode, combine it with carbon dioxide, and package it as a carbon-rich compound we could use as fuel. This would take the energy in electricity, which is ephemeral, and convert it into a tangible product that could be stored in a tank. But that kind of work is a long way off, cautions Bond.
"If there are 100 steps to making this work – this is step one," he says.

Mr. Pedantic
01-29-2013, 10:53 AM
Speaking of, I thought you might be interested in this (http://en.wikipedia.org/wiki/Phage_therapy).

William Gaatjes
01-30-2013, 01:57 PM
Speaking of, I thought you might be interested in this (http://en.wikipedia.org/wiki/Phage_therapy).

Ah thank you. I will read it with a lot of interest. Unfortunately, the link to the video in the first post is no longer working but the documentary is available on youtube.

More revealing news how viruses can play a role in developing cancer.
And how a virus might play a role in developing fetuses and epilepsy during childhood.

http://medicalxpress.com/news/2013-01-scientists-cancer-causing-virus-brain-potential.html


Scientists find cancer-causing virus in the brain, potential connection to epilepsy January 24, 2013 in Neuroscience Researchers at Shriner's Hospital Pediatric Research Center at the Temple University School of Medicine, and the University of Pennsylvania have evidence linking the human papillomavirus 16 (HPV16) – the most common cause of cervical cancer – to a common form of childhood epilepsy. They have shown for the first time that HPV16 may be present in the human brain, and found that when they added a viral protein to the brains of fetal mice, the mice all demonstrated the same developmental problems in the cerebral cortex associated with this type of epilepsy, called focal cortical dysplasia type IIB (FCDIIB). The findings suggest that the virus could play a role in the development of epilepsy.

The results also mean that doctors may have to re-think their approach to treating this type of epilepsy, and perhaps consider other therapeutic options related to HPV, an infectious disease. "This is a novel mechanism, and it fills a gap in our understanding about the development of congenital brain malformations," said Peter Crino, MD, PhD, Professor of Neurology at Temple University School of Medicine, and a member of Shriner's Hospital Pediatric Research Center, and the senior author of a recent report in the Annals of Neurology. "If our data are correct, future treatment of cortical dysplasia could include targeted therapy against HPV16 infection, with the goal of halting seizures. Identifying an infectious agent as part of the pathogenesis of brain malformations could open up an array of new therapeutic approaches against various forms of epilepsy." FCDIIB is a developmental malformation in the cerebral cortex, the area of the brain that plays key roles in thought, perception and memory. It is a common cause of both pediatric and adult epilepsy – especially difficult-to-treat forms of epilepsy – and it is thought to occur in the womb during early brain development. The condition is characterized by a disorganized cellular structure and enlarged, "balloon cells." Current treatments include surgery and medication. Balloon cells contain a signaling cascade called the mammalian target of rapamycin complex 1 (mTOR1), which is important for cellular growth, proliferation and division, particularly in brain development. Other scientists have recently found the mTOR pathway is activated by the HPV16 E6 oncoprotein. While there had never been any studies indicating that HPV16 could infect the brain, Dr. Crino saw a potential connection. "This is a sporadic, congenital brain malformation associated with mTOR signaling with no genetic predisposition," he said. "Based on various cellular and cell signaling similarities between cervical dysplasia and focal cortical dysplasia, this led me to a hypothesis that the HPV protein could be detected in FCDIIB." To find out, the investigators first examined FCDIIB tissue samples from 50 patients for evidence of the HPV16 E6 protein. They found that all of the samples were positive for the protein in the balloon cells, but not in regions without balloon cells or in 36 control samples from healthy individuals. They next examined the samples' genetic material by several sophisticated molecular techniques to look for evidence of HPV16 E6, and compared the findings to tissue from healthy controls and tissue from patients with different types of brain malformations and epilepsy. Again, every sample of FCDIIB was found to contain HPV16 E6 protein, whereas the control specimens and tissue from other types of dysplasia and conditions did not. Finally, in a series of experiments, the scientists painstakingly delivered the E6 protein into the brains of fetal mice. "If E6 is the causative element for HPV cervical dysplasia and focal cortical dysplasia, putting the protein into a fetal mouse brain should disrupt the cortical development," Dr. Crino explained. When the scientists did this, they found that the fetal mouse brains did indeed develop brain malformations. Dr. Crino plans to investigate other forms of cortical dysplasia to see if HPV or related viral proteins can be found. He and his team aren't sure how the virus gets into the brain, but their results suggest that an HPV infection in the placenta could be one possible path. The exact mechanism by which HPV16 might cause a malformation and epilepsy remains to be determined. He acknowledged several potential implications from the findings. "We are going to have to think about this epidemiologically as an infectious disease, not a genetic disorder. In terms of prevention, with current HPV vaccination, we have a potentially modifiable disease," he said. "In addition, if in fact this type of epilepsy represents a disorder of mTOR signaling, then one strategy could be, rather than treating the patients with anti-epileptic drugs, is to perhaps use mTOR inhibitors. "The million dollar result would be to show it is possible to induce a brain malformation with an E6 infection, and the animal develops epilepsy," Dr. Crino said. "It would be even better if we showed that it is preventable."


A TED talk about bacteriophages and applied aspects.

William Gaatjes
01-30-2013, 02:01 PM
More news about epigenetics and how it affects onset puberty in females.
It becomes more and more clear how the environment can alter the development of humans by influencing the activity of genes that are "executed" in parallel. Thereby having significant effects "under the hood" .


http://medicalxpress.com/news/2013-01-epigenetics-early-onset-puberty-females.html


New research from Oregon Health & Science University has provided significant insight into the reasons why early-onset puberty occurs in females. The research, which was conducted at OHSU's Oregon National Primate Research Center, is published in the current early online edition of the journal Nature Neuroscience.

The paper explains how OHSU scientists are investigating the role of epigenetics in the control of puberty. Epigenetics refers to changes in gene activity linked to external factors that do not involve changes to the genetic code itself. The OHSU scientists believe improved understanding of these complex protein/gene interactions will lead to greater understanding of both early-onset (precocious) puberty and delayed puberty, and highlight new therapy avenues. To conduct this research, scientists studied female rats, which like their human counterparts, go through puberty as part of their early aging process. These studies revealed that a group of proteins, called PcG proteins, regulate the activity of a gene called the Kiss1 gene, which is required for puberty to occur. When these PcG proteins diminish, Kiss1 is activated and puberty begins. PcG proteins are produced by another set of genes that act as a biological switch during the embryonic stage of life. The role of these proteins is to turn off specific downstream genes at key developmental stages. OHSU scientists found that both the activity of these "master" genes and their ability to turn off puberty are impacted by two forms of epigenetic control: a chemical modification of DNA known as DNA methylation, and changes in the composition of histones, a specialized set of proteins that modify gene activity by interacting with DNA. Using this new information, researchers were then able to delay puberty in female rats. They accomplished this by increasing PcG protein levels in the hypothalamus of the brain using a targeted gene therapy approach so that Kiss1 activation failed to occur at the normal time in life. The hypothalamus is a region of the brain that controls reproductive development. "While it was always understood that an organism's genes determine the timing of puberty, the role of epigenetics in this process has never been recorded until now," said Alejandro Lomniczi, Ph.D., a scientist in the Division of Neuroscience at the OHSU Oregon National Primate Research Center. "Because epigenetic changes are driven by environmental, metabolic and cell-to-cell influences, these findings raise the possibility that a significant percentage of precocious and delayed puberty cases occurring in humans may be the result of environmental factors and other alterations in epigenetic control," said Sergio Ojeda, D.V.M, who is also a scientist in the Division of Neuroscience at the OHSU ONPRC. "There is also much more to be learned about the way that epigenetic factors may link environmental factors such as nutrition, man-made chemicals, social interactions and other day-today influences to the timing and completion of normal puberty."





This thread is becoming quite the library. ^_^

William Gaatjes
01-30-2013, 03:17 PM
More news about plasmids and a very special enzyme named : "Nicking enzyme or NES". In this article, it is described how the researchers have discovered how one of the most antibiotic resistant bacteria performs it's magic...


What is a nicking enzyme ?
http://en.wikipedia.org/wiki/Nicking_enzyme

A nicking enzyme (or nicking endonuclease) is an enzyme that cuts one strand of a double-stranded DNA at a specific recognition nucleotide sequences known as a restriction site. Such enzymes hydrolyse (cut) only one strand of the DNA duplex, to produce DNA molecules that are “nicked”, rather than cleaved.


http://phys.org/news/2013-01-scientists-unveil-staphyloccocus-aureus-superbug.html


(Phys.org)—Worldwide, many strains of the bacterium Staphyloccocus aureus, commonly known as staph infections, are already resistant to all antibiotics except vancomycin. But as bacteria are becoming resistant to this once powerful antidote, S. aureus has moved one step closer to becoming an unstoppable killer. Now, researchers at the University of North Carolina at Chapel Hill have not only identified the mechanism by which vancomycin resistance spreads from one bacterium to the next, but also have suggested ways to potentially stop the transfer.

The work, led by Matthew Redinbo, professor of chemistry at UNC's College of Arts and Sciences, addresses the looming threat of incurable staph infections – a global public health problem that has mobilized scientists across disciplines to work together to identify the Achilles heel of these antibiotic-resistant bacteria. "We used to live in a world where antibiotics could readily cure bacterial disease," said Redinbo. "But this is clearly no longer the case. We need to understand how bacteria obtain resistance to drugs like vancomycin, which served for decades as the 'antibiotic of last resort.'" In his work, Redinbo and his team targeted a bacterial enzyme known as Nicking Enzyme in Staphyloccoccus, or NES. The enzyme has long been known to interact with plasmids, circular pieces of double-stranded DNA within bacteria that are physically separate from the bacterial chromosome. Plasmids commonly contain antibiotic-resistance genes, and can make the machinery necessary to transfer these genes from an infected bacterium to an uninfected one. By revealing the crystal structure of NES, the researchers found that this enzyme nicks one strand of the plasmid at a very specific site—and in a very specific way. It turns out that NES forms two loops that work together to pinch one strand of the plasmid at a particular groove in the DNA to cut it. This strand is now free to leave its host and transfer to a nearby bacterium, making them resistant to vancomycin. Moreover, Redinbo was able to capture a snapshot of the enzyme bound to the plasmid. "As a structural biologist, it's all about the pictures for me," said Redinbo. "And it was this picture that confirmed the precise location on which NES works." With this information, Redinbo knew the groove on the DNA that the enzyme recognize and could design a small synthetic molecule that would sit on this groove and block NES. Teaming up with colleagues at the California Institute of Technology, Redinbo did just that. The molecule prevented NES from nicking the DNA, which could prevent the resistance genes from spreading. According to Redinbo and colleagues, this small synthetic molecule could help guide future research aimed at developing effective therapies for strains of antibiotic-resistant S. aureus. "This is really exciting for us," said Redinbo, who is also a professor at UNC's School of Medicine and a member of the Lineberger Comprehensive Cancer Center. "It opens the door for potentially stopping the spread of antibiotic resistance—and that's exactly what we need in this post-antibiotic era." The work was published this week in the online early edition of the Proceedings of the National Academy of Sciences.

More information: Molecular basis of antibiotic multiresistance transfer in Staphylococcus aureus, www.pnas.org/content/early/2013/01/22/1219701110.full.pdf+html

Journal reference: Proceedings of the National Academy of Sciences Provided by University of North Carolina at Chapel Hill

Gibsons
01-30-2013, 05:35 PM
The 'nicking' enzymes are also called "relaxases," because the nick causes a plasmid, normally supercoiled, to move to the open circle/relaxed state. They've been known about for decades (see: F', F+ etc).

Pretty cool they've solved a structure, but don't hold your breath waiting for a specific inhibitor.