May 16, 2013
"Human health should now ‘be thought of as a collective property of the human-associated microbiota,’ as one group of researchers recently concluded in a landmark review article on microbial ecology — that is, as a function of the community, not the individual."

— Michael Pollan (via Say Hello to the 100 Trillion Bacteria That Make Up Your Microbiome)

August 25, 2012

globalvoices:

The earliest forms of newspaper were handwritten and now ‘The Musalman‘ probably is the last handwritten newspaper in the world. This Urdu language newspaper was established in 1927 by Chenab Syed Asmadullah Sahi and has been published daily in the Chennai city of India ever since.

August 20, 2012
Yes, Todd Akin, victims of 'legitimate rape' get pregnant - here's scientific proof

by Robert T. Gonzalez:

If you haven’t heard yet, it’s time you did: yesterday afternoon, U.S. Senate nominee Todd Akin said in a televised interview that women rarely get pregnant following instances of “legitimate rape,” because the female body has ways to “shut that whole thing down.”

Akin is wrong. He is wrong on many levels, but most importantly he’s wrong about basic medical facts governing how the female body works. So let’s take a step back and examine Akin’s statement from a scientific angle, with the help of some relevant, peer-reviewed publications.

First things first. Here’s the actual quote that, yesterday afternoon, incited the ire and incredulity of just about anyone with a brain, a pulse, and the misfortune of hearing or reading it. Akin’s assertion comes in response to a question about whether abortion should be legal in cases of rape (a video of the exchange is also featured up top):

It seems to me, from what I understand from doctors, that [pregnancy from rape] is really rare. If it’s a legitimate rape, the female body has ways to try to shut that whole thing down.

Go ahead and read that again. Replay the video if you have to. Try to absorb every iota of what Akin is saying. For the record: your mind should be reeling. Did Akin really just assert that some cases of rape are more “legitimate” than others, WHILE arguing that a woman can depend on her body to stave off pregnancy when her efforts to prevent a man from forcing himself upon her fail? In the same breath? All under the banner of medical and scientific evidence? Did that really just happen?

Yeah. Yeah, it did.

Let’s set aside, for the moment, the fact that rape is rape, and that modifiers like “legitimate” and “forcible” (another term Akin has paired with “rape” in the past) are so fraught with ignorance and dishonesty as to warrant their own well-reasoned, thoroughly researched analyses elsewhere. (Here are three such articles, by The Guardian, Jezebel and New Statesman, to get you started.) For now, let’s just focus on the “medical” claim he’s making.

Rape-Related Pregnancy By The Numbers

Let’s look at the science. After all, Representative Akin (who is a sitting congressman in Missouri, and will run against Democratic incumbent Claire McCaskill for a seat in the U.S. Senate in this year’s election cycle) is a member of the House Committee on Science, Space, and Technology; if anyone in Washington is qualified to speak to the medical and scientific evidence surrounding abortion, rape, and pregnancy, surely it is a member of the House Committee on Science. Right?

Evidently not. “It seems to me,” opines Akin, “from what I understand from doctors, that [pregnancy from rape] is really rare.” We may never know whether the doctors Akin is referring to even exist (outside of the congressman’s ill-advised attempt to legitimize his baseless argument), but a 3-year longitudinal study involving over 4,000 adult American women stands in staunch opposition to their spurious claims. The entire article, which is published in a 1996 issue of the American Journal of Obstetrics & Gynecology is relevant to our analysis, but here’s the bit that Akin and his doctors really need to read:

Rape-related pregnancy occurs with significant frequency. It is a cause of many unwanted pregnancies and is closely linked with family and domestic violence. As we address the epidemic of unintended pregnancies in the United States, greater attention and effort should be aimed at preventing and identifying unwanted pregnancies that result from sexual victimization.

If you’re looking for hard numbers, the study concludes that the national rape-related pregnancy rate is 5.0% per rape among victims of reproductive age (12—45), and that an estimated 32,101 pregnancies result from rape each year. Does 32,000 pregnancies per annum sound “rare” to you? It’s not.

Five percent may not sound like much, but the fact is that couples trying to have kids would be ecstatic over a five percent chance of pregnancy per sexual encounter; what’s more, a study published in 2003 in the journal Human Nature found that a single act of rape was more than twice as likely to result in pregnancy than an act of consensual sex:

"Our analysis suggests that per-incident rape-pregnancy rates exceed per-incident consensual pregnancy rates by a sizable margin," write researchers Jon and Tiffani Gottschall, "even before adjusting for the use of relevant forms of birth control." [emphasis mine]

Again, here are the numbers: the researchers examined data collected from 405 women between the ages of 12 and 45 who had suffered a single incidence of penile-vaginal rape, and found that 6.4 percent of these women became pregnant. This number leapt to almost 8% when the researchers accounted for women who’d been using birth control (according to New Scientist, US government statistics show that 20% of the women in the sample were likely to have been using the pill or an IUD). A separate study, conducted by the US National Institute of Environmental Health Sciences in 2001, found the per-incidence pregnancy rate for a single act of consensual sex to be just 3.1 percent.

In light of these studies and statistics, it’s almost not even worth addressing Akin’s assertion that the female body has ways to “shut that whole thing [i.e. pregnancy] down” in cases of “legitimate rape”; but what the congressman seems to be referring to is post-copulatory sexual selection, a real technique used by some female animals to actively control which males will father their offspring. For example, as this episode of Isabella Rossellini’s award-winning Green Porno series explains, the labyrinthine vaginal canals of female ducks allow them to hide their eggs from undesirable males. The ability to store and select sperm from multiple potential mates (a form of post-copulatory sexual selection thought to have evolved in response to the risk of unsolicited sexual encounters, and ironically named “female choice”) has also been observed in reptiles, spiders and insects.

But humans don’t have labyrinthine vaginal canals. They also don’t actively store and select sperm from multiple males inside their bodies. And if there are any hormonal responses at play in a post-copulatory sexual response — as is hypothesized to occur in some species of monkeys — the studies we referenced earlier clearly demonstrate that they certainly aren’t powerful enough to warrant calling pregnancy among rape victims “rare.”

Congressman Akin has since backed away from his remark, saying that he “misspoke” during the interview, though he has still failed to mention which point (or points) he’s referring to.

"In reviewing my off-the-cuff remarks," Akin said in a statement released yesterday afternoon, "it’s clear that I misspoke in this interview and it does not reflect the deep empathy I hold for the thousands of women who are raped and abused every year."

This is a half-assed explanation, and a sorry excuse for an apology (if you can even call it that). Perhaps more shocking is that Akin sits on the House Committee on Science, Space, and Technology. In that role, he should be required to address the spurious nature of his comments by responding to the hard, scientific evidence that he was not simply wrong, but basing his understanding of reproduction on opinion rather than medical facts.

August 18, 2012
In Dialysis, Life-Saving Care at Great Risk and Cost - ProPublica

"…the United States continues to have one of the industrialized world’s highest mortality rates for dialysis care. Even taking into account differences in patient characteristics, studies suggest that if our system performed as well as Italy’s, or France’s, or Japan’s, thousands fewer kidney patients would die each year."

July 29, 2012
Magnetic field, mantle convection and tectonics

On a time scale of tens to hundreds of millions of years, the geomagnetic field may be influenced by currents in the mantle. The frequent polarity reversals of Earth’s magnetic field can also be connected with processes in the mantle. These are the research results presented by a group of geoscientists in the new advance edition of “Nature Geoscience" on Sunday, July 29th. The results show how the rapid processes in the outer core, which flows at rates of up to about one millimeter per second, are coupled with the processes in the mantle, which occur more in the velocity range of centimeters per year.

The international group of scientists led by A. Biggin of the University of Liverpool included members of the GFZ German Research Centre for Geosciences, the IPGP Paris, the universities of Oslo and Utrecht, and other partners.

It is known that the Earth’s magnetic field is produced by convection currents of an electrically conducting iron-nickel alloyin the liquid core, about 3,000 kilometers below the earth’s surface. The geomagnetic field is highly variable, there are changes in Earth’s magnetic field on a multitude of spatial and temporal scales. Above the liquid outer core is the mantle, the rock in which behaves plastically deformable due to the intense heat and high pressure. At the boundary between Earth’s core and mantle at 2900 km depth there is an intense heat exchange, which is on the one hand directed from the Earth’s core into the mantle. On the other hand, processes within Earth’s mantle in turn also affect the heat flow. The interesting question is how the much slower flow in the solid mantle influences the heat flow and its spatial distribution at the core-mantle boundary, and how this will affect the Earth’s magnetic field which is produced due to the much faster currents in the Earth’s core.

Key variable heat transfer

"The key variable is the heat flow. A cooler mantle accelerates the flow of heat from the hot core of the Earth, and in this way alters the also heat-driven convection in the Earth’s core", said Bernhard Steinberger of the GFZ German Research Centre for Geosciences. "Ocean floor sinking into the mantle due to tectonic processes can lead to cooling in the mantle. They cause at these sites an increased heat flow into the cooler parts, namely until they have been heated to the ambient temperature." That might take several hundred million years, however.

Conversely, the hot core of the Earth leads to the ascent of heated rocks in form of large bubbles, so-called mantle plumes that separate from the core-mantle boundary and make their way up to the surface of the earth. This is how Hawaii came into existence. This increases the local heat flux out of the earth’s core and in turn modifies the generator of the geomagnetic field.

Reversals of the magnetic field

In the Earth’s history, polarity reversals of the geomagnetic field are nothing extraordinary. The most recent took place only 780 000 years ago, geologically speaking a very short period of time. The research team was able to determine that in the period of 200 to 80 million years before present, reversals initially happened more often, namely up to ten times in hundred million years. “Surprisingly, these reversals stopped about 120 million years ago and were absent for nearly 40 million years,” explains GFZ scientist Sachs. Scientists presume that the reason for this is a concurrent reorientation of the whole mantle and crust with a shift in the geographic and magnetic poles of about 30°. Known as “true polar wander”, thisprocess is caused by a change in density distribution in the mantle. If it increases the heat flux in equatorial regions, it would presumably lead to more frequent field reversals, if it decreases it, the field reversal might not occur.

Looking to the future

According to current knowledge, therefore, an influence of plate tectonics and mantle convection on the Earth’s magnetic field seems quite possible. The article also shows, however, that further research is still needed for a better understanding of these relationships. In particular, more episodes of “true polar wander” should be derived from paleomagnetic data, and it should be determined whether these are usually associated with an altered behavior of the magnetic field (e.g. frequency of field reversal). Also, future models for the generation of the geomagnetic field should investigate the influence of the spatial and temporal variation of the heat flux at the core-mantle boundary in more detail.

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J. Biggin et al., “Possible links between long-term geomagnetic variations and whole-mantle convection processes”, Nature Geoscience, Vol. 5, August 2012, doi:10.1038/NGEO1521

Images in printable resolution and an animation can be found at: http://www.gfz-potsdam.de/portal/gfz/Public+Relations/M40-Bildarchiv/Magnetfeld_Waermefluss

contact : Dr. Bernhard Steinberger, +49-331-288 1881

July 26, 2012
Two More Patients HIV-Free After Bone Marrow Transplants - ABC News

By LIZA McCLELLAN, M.D.

Researchers at Brigham and Women’s Hospital in Boston have discovered that, following bone marrow transplants, two men no longer have detectable HIV in their blood cells.

The finding is significant because it suggests that by giving these patients transplants while they were on anti-retroviral therapy, they may have been cured of the AIDS-causing virus.

“We expected HIV to vanish from the patients’ plasma, but it is surprising that we can’t find any traces of HIV in their cells,” said Dr. Timothy Henrich, one of the researchers studying the two men. “It suggests that under the cover of anti-retroviral therapy, the cells that repopulated the patient’s immune system appear to be protected from becoming re-infected with HIV.”

The findings were presented Thursday at the AIDS 2012 conference in Washington, D.C. The story shares similarities with that of Timothy Ray Brown, also known as “the Berlin patient,” but there are important differences. While the cells used in Brown’s transplant procedure were specifically chosen from a donor who had a genetic mutation that resisted HIV, these patients received transplants with normal cells. Also, the two patients whose cases were presented at the meeting are still taking anti-retroviral medications normally used to treat HIV-positive patients, while Brown is no longer taking these medications.

Further study will need to be done to prove that the two patients are truly cured.

“Studies over time including biopsies of lymphatic tissue would be required,” said Dr. Michael Saag, an infectious disease expert from University of Alabama at Birmingham. He said only time will tell if these patients remain HIV-free.

While it appears from these cases, as well as that of the Berlin patient, that altering a patient’s immune system may lead to a “cure” for HIV, bone marrow transplants are currently too costly and dangerous for all HIV patients to be able to undergo them.

Separately, scientists are trying to use gene therapy to alter patients’ immune systems to free them of HIV.  Most of the research in this field is very preliminary, but scientists at the Fred Hutchinson Cancer Research Center are trying to perform stem cell transplants with cells that have been genetically modified to be resistant to HIV, much like the cells that the Berlin patient received.

“We have not yet transplanted any patient as part of our study,” said Dr. Hans-Peter Kiem of the Clinical Research Division at Fred Hutchinson Cancer Research Center and an attending transplant physician at Seattle Cancer Care Alliance. But Kiem and his research team have recently been awarded a research grant to further investigate stem cell transplantation as treatment as a means to find a cure for HIV.

May 23, 2012
Scientists turn patients' skin cells into heart muscle cells to repair their damaged hearts

For the first time scientists have succeeded in taking skin cells from heart failure patients and reprogramming them to transform into healthy, new heart muscle cells that are capable of integrating with existing heart tissue.

The research, which is published online today (Wednesday) in the European Heart Journal [1], opens up the prospect of treating heart failure patients with their own, human-induced pluripotent stem cells (hiPSCs) to repair their damaged hearts. As the reprogrammed cells would be derived from the patients themselves, this could avoid the problem of the patients’ immune systems rejecting the cells as “foreign”. However, the researchers warn that there are a number of obstacles to overcome before it would be possible to use hiPSCs in humans in this way, and it could take at least five to ten years before clinical trials could start.

Recent advances in stem cell biology and tissue engineering have enabled researchers to consider ways of restoring and repairing damaged heart muscle with new cells, but a major problem has been the lack of good sources of human heart muscle cells and the problem of rejection by the immune system. Recent studies have shown that it is possible to derive hiPSCs from young and healthy people and that these are capable of transforming into heart cells. However, it has not been shown that hiPSCs could be obtained from elderly and diseased patients. In addition, until now researchers have not been able to show that heart cells created from hiPSCs could integrate with existing heart tissue.

Professor Lior Gepstein, Professor of Medicine (Cardiology) and Physiology at the Sohnis Research Laboratory for Cardiac Electrophysiology and Regenerative Medicine, Technion-Israel Institute of Technology and Rambam Medical Center in Haifa, Israel, who led the research, said: “What is new and exciting about our research is that we have shown that it’s possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young – the equivalent to the stage of his heart cells when he was just born.”

Ms Limor Zwi-Dantsis, who is a PhD student in the Sohnis Research Laboratory, Prof Gepstein and their colleagues took skin cells from two male heart failure patients (aged 51 and 61) and reprogrammed them by delivering three genes or “transcription factors” (Sox2, Klf4 and Oct4), followed by a small molecule called valproic acid, to the cell nucleus. Crucially, this reprogramming cocktail did not include a transcription factor called c-Myc, which has been used for creating stem cells but which is a known cancer-causing gene.

"One of the obstacles to using hiPSCs clinically in humans is the potential for the cells to develop out of control and become tumours," explained Prof Gepstein. "This potential risk may stem from several reasons, including the oncogenic factor c-Myc, and the random integration into the cell’s DNA of the virus that is used to carry the transcription factors – a process known as insertional oncogenesis."

The researchers also used an alternative strategy that involved a virus that delivered reprogramming information to the cell nucleus but which was capable of being removed afterwards so as to avoid insertional oncogenesis.

The resulting hiPSCs were able to differentiate to become heart muscle cells (cardiomyocytes) just as effectively as hiPSCs that had been developed from healthy, young volunteers who acted as controls for this study. Then the researchers were able to make the cardiomyocytes develop into heart muscle tissue, which they cultured together with pre-existing cardiac tissue. Within 24-48 hours the tissues were beating together. “The tissue was behaving like a tiny microscopic cardiac tissue comprised of approximately 1000 cells in each beating area,” said Prof Gepstein.

Finally, the new tissue was transplanted into healthy rat hearts and the researchers found that the grafted tissue started to establish connections with the cells in the host tissue.

"In this study we have shown for the first time that it’s possible to establish hiPSCs from heart failure patients – who represent the target patient population for future cell therapy strategies using these cells – and coax them to differentiate into heart muscle cells that can integrate with host cardiac tissue," said Prof Gepstein.

"We hope that hiPSCs derived cardiomyocytes will not be rejected following transplantation into the same patients from which they were derived. Whether this will be the case or not is the focus of active investigation. One of the obstacles in dealing with this issue is that, at this stage, we can only transplant human cells into animal models and so we have to treat the animals with immunosuppressive drugs so the cells won’t be rejected."

Much research has to be conducted before these results could be translated into treatment for heart failure patients in the clinic. “There are several obstacles to clinical translation,” said Prof Gepstein. “These include: scaling up to derive a clinically relevant number of cells; developing transplantation strategies that will increase cell graft survival, maturation, integration and regenerative potential; developing safe procedures to eliminate the risks for causing cancer or problems with the heart’s normal rhythm; further tests in animals; and large industry funding since it is likely to be a very expensive endeavour. I assume it will take at least five to ten years to clinical trials if one can overcome these problems.”

Prof Gepstein and his colleagues will be carrying out further research into some of these areas, including evaluating using hiPSCs in cell therapy and tissue engineering strategies for repairing damaged hearts in various animal models, investigating inherited cardiac disorders, and drug development and testing.

Editor-in-Chief of the European Heart Journal, Professor Thomas Lüscher, who is Professor and Chairman of Cardiology at the University Hospital Zurich and Director of Cardiovascular Research at the Institute of Physiology of the University Zurich, Switzerland, commented: “The European Heart journal is proud to publish this exciting study which opens the door for a novel approach in regenerative medicine.”

###

Notes:

[1] “Derivation and cardiomyocyte differentiation of induced pluripotent stem cells from heart failure patients,” by Limor Zwi-Dantsis, Irit Huber, Manhal Habib, Aaron Winterstern, Amira Gepstein, Gil Arbel, and Lior Gepstein. European Heart Journal. doi:10.1093/eurheartj/ehs096

May 14, 2012
Berkeley Lab scientists generate electricity from viruses

New approach is a promising first step toward the development of tiny devices that harvest electrical energy from everyday tasks

Imagine charging your phone as you walk, thanks to a paper-thin generator embedded in the sole of your shoe. This futuristic scenario is now a little closer to reality. Scientists from the U.S. Department of Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) have developed a way to generate power using harmless viruses that convert mechanical energy into electricity.

The scientists tested their approach by creating a generator that produces enough current to operate a small liquid-crystal display. It works by tapping a finger on a postage stamp-sized electrode coated with specially engineered viruses. The viruses convert the force of the tap into an electric charge.

Their generator is the first to produce electricity by harnessing the piezoelectric properties of a biological material. Piezoelectricity is the accumulation of a charge in a solid in response to mechanical stress.

The milestone could lead to tiny devices that harvest electrical energy from the vibrations of everyday tasks such as shutting a door or climbing stairs.

It also points to a simpler way to make microelectronic devices. That’s because the viruses arrange themselves into an orderly film that enables the generator to work. Self-assembly is a much sought after goal in the finicky world of nanotechnology.

The scientists describe their work in a May 13 advance online publication of the journal Nature Nanotechnology.

"More research is needed, but our work is a promising first step toward the development of personal power generators, actuators for use in nano-devices, and other devices based on viral electronics," says Seung-Wuk Lee, a faculty scientist in Berkeley Lab’s Physical Biosciences Division and a UC Berkeley associate professor of bioengineering.

He conducted the research with a team that includes Ramamoorthy Ramesh, a scientist in Berkeley Lab’s Materials Sciences Division and a professor of materials sciences, engineering, and physics at UC Berkeley; and Byung Yang Lee of Berkeley Lab’s Physical Biosciences Division.

The piezoelectric effect was discovered in 1880 and has since been found in crystals, ceramics, bone, proteins, and DNA. It’s also been put to use. Electric cigarette lighters and scanning probe microscopes couldn’t work without it, to name a few applications.

But the materials used to make piezoelectric devices are toxic and very difficult to work with, which limits the widespread use of the technology.

Lee and colleagues wondered if a virus studied in labs worldwide offered a better way. The M13 bacteriophage only attacks bacteria and is benign to people. Being a virus, it replicates itself by the millions within hours, so there’s always a steady supply. It’s easy to genetically engineer. And large numbers of the rod-shaped viruses naturally orient themselves into well-ordered films, much the way that chopsticks align themselves in a box.

These are the traits that scientists look for in a nano building block. But the Berkeley Lab researchers first had to determine if the M13 virus is piezoelectric. Lee turned to Ramesh, an expert in studying the electrical properties of thin films at the nanoscale. They applied an electrical field to a film of M13 viruses and watched what happened using a special microscope. Helical proteins that coat the viruses twisted and turned in response—a sure sign of the piezoelectric effect at work.

Next, the scientists increased the virus’s piezoelectric strength. They used genetic engineering to add four negatively charged amino acid residues to one end of the helical proteins that coat the virus. These residues increase the charge difference between the proteins’ positive and negative ends, which boosts the voltage of the virus.

The scientists further enhanced the system by stacking films composed of single layers of the virus on top of each other. They found that a stack about 20 layers thick exhibited the strongest piezoelectric effect.

The only thing remaining to do was a demonstration test, so the scientists fabricated a virus-based piezoelectric energy generator. They created the conditions for genetically engineered viruses to spontaneously organize into a multilayered film that measures about one square centimeter. This film was then sandwiched between two gold-plated electrodes, which were connected by wires to a liquid-crystal display.

When pressure is applied to the generator, it produces up to six nanoamperes of current and 400 millivolts of potential. That’s enough current to flash the number “1” on the display, and about a quarter the voltage of a triple A battery.

"We’re now working on ways to improve on this proof-of-principle demonstration," says Lee. "Because the tools of biotechnology enable large-scale production of genetically modified viruses, piezoelectric materials based on viruses could offer a simple route to novel microelectronics in the future."

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Berkeley Lab’s Laboratory Directed Research and Development fund and the National Science Foundation supported this work.

Lawrence Berkeley National Laboratory addresses the world’s most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab’s scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy’s Office of Science. For more, visit www.lbl.gov.

June 24, 2011
NIH researchers find new clues about aging

Telomere shortening is probably a defense mechanism against cancer. So lengthening telomeres (assuming we had a treatment that would do this) might not lower the risk of all-cause mortality. However, throw in some great cures for cancer and telomere lengthening will suddenly become a very appealing idea.

Genetic splicing mechanism triggers both premature aging syndrome and normal cellular aging

National Institutes of Health researchers have identified a new pathway that sets the clock for programmed aging in normal cells. The study provides insights about the interaction between a toxic protein called progerin and telomeres, which cap the ends of chromosomes like aglets, the plastic tips that bind the ends of shoelaces.

The study by researchers from the National Human Genome Research Institute (NHGRI) appears in the June 13, 2011 early online edition of the Journal of Clinical Investigation.

Telomeres wear away during cell division. When they degrade sufficiently, the cell stops dividing and dies. The researchers have found that short or dysfunctional telomeres activate production of progerin, which is associated with age-related cell damage. As the telomeres shorten, the cell produces more progerin.

Progerin is a mutated version of a normal cellular protein called lamin A, which is encoded by the normal LMNA gene. Lamin A helps to maintain the normal structure of a cell’s nucleus, the cellular repository of genetic information.

In 2003, NHGRI researchers discovered that a mutation in LMNA causes the rare premature aging condition, progeria, formally known as known as Hutchinson-Gilford progeria syndrome. Progeria is an extremely rare disease in which children experience symptoms normally associated with advanced age, including hair loss, diminished subcutaneous fat, premature atherosclerosis and skeletal abnormalities. These children typically die from cardiovascular complications in their teens.

"Connecting this rare disease phenomenon and normal aging is bearing fruit in an important way," said NIH Director Francis S. Collins, M.D., Ph.D., a senior author of the current paper. "This study highlights that valuable biological insights are gained by studying rare genetic disorders such as progeria. Our sense from the start was that progeria had a lot to teach us about the normal aging process and clues about more general biochemical and molecular mechanisms."

Collins led the earlier discovery of the gene mutation responsible for progeria and subsequent advances at NIH in understanding the biochemical and molecular underpinnings of the disease.

In a 2007 study, NIH researchers showed that normal cells of healthy people can produce a small amount of progerin, the toxic protein, even when they do not carry the mutation. The more cell divisions the cell underwent, the shorter the telomeres and the greater the production of progerin. But a mystery remained: What was triggering the production of the toxic progerin protein?

The current study shows that the mutation that causes progeria strongly activates the splicing of lamin A to produce the toxic progerin protein, leading to all of the features of premature aging suffered by children with this disease. But modifications in the splicing of LMNA are also at play in the presence of the normal gene.

The research suggests that the shortening of telomeres during normal cell division in individuals with normal LMNA genes somehow alters the way a normal cell processes genetic information when turning it into a protein, a process called RNA splicing. To build proteins, RNA is transcribed from genetic instructions embedded in DNA. RNA does not carry all of the linear information embedded in the ribbon of DNA; rather, the cell splices together segments of genetic information called exons that contain the code for building proteins, and removes the intervening letters of unused genetic information called introns. This mechanism appears to be altered by telomere shortening, and affects protein production for multiple proteins that are important for cytoskeleton integrity. Most importantly, this alteration in RNA splicing affects the processing of the LMNA messenger RNA, leading to an accumulation of the toxic progerin protein.

Cells age as part of the normal cell cycle process called senescence, which progressively advances through a limited number of divisions in the cell lifetime. “Telomere shortening during cellular senescence plays a causative role in activating progerin production and leads to extensive change in alternative splicing in multiple other genes,” said lead author Kan Cao, Ph.D., an assistant professor of cell biology and molecular genetics at the University of Maryland, College Park.

Telomerase is an enzyme that can extend the structure of telomeres so that cells continue to maintain the ability to divide. The study supplied support for the telomere-progerin link, showing that cells that have a perpetual supply of telomerase, known as immortalized cells, produce very little progerin RNA. Most cells of this kind are cancer cells, which do not reach a normal cell cycle end point, and instead replicate out of control.

The researchers also conducted laboratory tests on normal cells from healthy individuals using biochemical markers to indicate the occurrence of progerin-generating RNA splicing in cells. The cell donors ranged in age from 10 to 92 years. Regardless of age, cells that passed through many cell cycles had progressively higher progerin production. Normal cells that produce higher concentrations of progerin also displayed shortened and dysfunctional telomeres, the tell-tale indication of many cell divisions.

In addition to their focus on progerin, the researchers conducted the first systematic analysis across the genome of alternative splicing during cellular aging, considering which other protein products are affected by jumbled instructions as RNA molecules assemble proteins through splicing. Using laboratory techniques that analyze the order of chemical units of RNA, called nucleotides, the researchers found that splicing is altered by short telomeres, affecting lamin A and a number of other genes, including those that encode proteins that play a role in the structure of the cell.

The researchers suggest that the combination of telomere fraying and loss with progerin production together induces cell aging. This finding lends insights into how progerin may participate in the normal aging process.

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For more about Hutchinson-Gilford progeria syndrome, go to http://www.genome.gov/11007255.

NHGRI is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at its website, www.genome.gov.

The National Institutes of Health (NIH) - The Nation’s Medical Research Agency - includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

June 20, 2011
Bipartisan bill would end government's warrantless GPS tracking

By Nate Anderson:

   Bipartisan bill would end government's warrantless GPS tracking

IMAGE: Jason Chaffetz

Under a new bill dubbed the “GPS Act,” law enforcement officials would no longer be able to obtain geolocation data from cellphones and GPS tracking devices without a warrant.

"I take the Fourth Amendment very seriously," said Rep. Jason Chaffetz (R-UT) at a press conference announcing the bill. "The law enforcement community is going too far" by using GPS trackers without a warrant, he said. “I happen to think that’s wrong.”

Sen. Ron Wyden (D-OR), the lead Senate sponsor of the legislation, said that the US was trying to “race a technological Indy 500” with laws “out of the horse-and-buggy era.” Providing clear rules and tighter privacy protections on geolocation data should benefit everyone, including law enforcement, he said—even if some investigators don’t immediately see it that way.

Under the new bill, geolocation data obtained from devices like tablets, smartphones, and GPS trackers would be held to the same standard as a wiretap request; police can go to court, show probable cause, and obtain a warrant if they need access to such information. The current mishmash of court rulings about the legality of warrantless location tracking would be brought into uniformity, though the warrant standard would be relaxed in certain exceptional cases such as emergencies and 911 calls, among other situations.

IMAGE: Ron Wyden

In addition to laying down a warrant standard for obtaining location data, the law would also apply both to private companies and to individuals. Without a warrant, companies would need consent in order to share a user’s geolocation data with anyone else. The bill would also criminalize those who stalk other people by inserting stealth apps on their phones or computers.

"This is what we’re supposed to be doing: working in a bipartisan, bicameral way," said Chaffetz.

The GPS Act has already rounded up support from CCIA, a DC trade group that represents major tech players like Microsoft. “CCIA supports this long overdue reform that creates clear rules for a 21st century mobile wireless space marked so far by chaos and misunderstandings,” said CEO Ed Black in a statement.

"It balances Americans’ privacy protections with the legitimate needs of law enforcement, and maintains emergency exceptions. The bill creates a universal warrant standard for all geolocation information, regardless of how or when it is obtained, sending a clear signal to users that this information is protected."