'Longevity Gene' Helps Prevent Memory Decline and Dementia.

Scientists at Albert Einstein College of Medicine of Yeshiva University have found that a "longevity gene" helps to slow age-related decline in brain function in older adults. Drugs that mimic the gene's effect are now under development, the researchers note, and could help protect against Alzheimer's disease. (Credit: iStockphoto/Anne De Haas)

Source: ScienceDaily

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ScienceDaily (Jan. 13, 2010) — Scientists at Albert Einstein College of Medicine of Yeshiva University have found that a "longevity gene" helps to slow age-related decline in brain function in older adults. Drugs that mimic the gene's effect are now under development, the researchers note, and could help protect against Alzheimer's disease.

The paper describing the Einstein study is published in the January 13 edition of the Journal of the American Medical Association.
"Most work on the genetics of Alzheimer's disease has focused on factors that increase the danger," said Richard B. Lipton, M.D., the Lotti and Bernard Benson Faculty Scholar in Alzheimer's Disease and professor and vice chair in the Saul R. Korey Department of Neurology at Einstein and senior author of the paper. As an example, he cites APOE ε4, a gene variant involved in cholesterol metabolism that is known to increase the risk of Alzheimer's among those who carry it.
"We reversed this approach," says Dr. Lipton, "and instead focused on a genetic factor that protects against age-related illnesses, including both memory decline and Alzheimer's disease."
In a 2003 study, Dr. Lipton and his colleagues identified the cholesteryl ester transfer protein (CETP) gene variant as a "longevity gene" in a population of Ashkenazi Jews. The favorable CETP gene variant increases blood levels of high-density lipoprotein (HDL) -- the so-called good cholesterol -- and also results in larger-than-average HDL and low-density lipoprotein (LDL) particles.
The researchers of the current study hypothesized that the CETP longevity gene might also be associated with less cognitive decline as people grow older. To find out, they examined data from 523 participants from the Einstein Aging Study, an ongoing federally funded project that has followed a racially and ethnically diverse population of elderly Bronx residents for 25 years.
At the beginning of the study, the 523 participants -- all of them 70 or over -- were cognitively healthy, and their blood samples were analyzed to determine which CETP gene variant they carried. They were then followed for an average of four years and tested annually to assess their rates of cognitive decline, the incidence of Alzheimer's disease and other changes.
"We found that people with two copies of the longevity variant of CETP had slower memory decline and a lower risk for developing dementia and Alzheimer's disease," says Amy E. Sanders, M.D., assistant professor in the Saul R. Korey Department of Neurology at Einstein and lead author of the paper. "More specifically, those participants who carried two copies of the favorable CETP variant had a 70 percent reduction in their risk for developing Alzheimer's disease compared with participants who carried no copies of this gene variant."
The favorable gene variant alters CETP so that the protein functions less well than usual. Dr. Lipton notes that drugs are now being developed that duplicate this effect on the CETP protein. "These agents should be tested for their ability to promote successful aging and prevent Alzheimer's disease," he recommends.
The research was funded by the National Institute on Aging, one of the 27 institutes and centers of the National Institutes of Health.

Story Source:
Adapted from materials provided by Albert Einstein College of Medicine.

Journal Reference:
1. Sanders et al. Association of a Functional Polymorphism in the Cholesteryl Ester Transfer Protein (CETP) Gene With Memory Decline and Incidence of Dementia. JAMA The Journal of the American Medical Association, 2010; 303 (2): 150 DOI: 10.1001/jama.2009.1988

Scientists discover new protein function.

Source: Physorg.com

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Carnegie Mellon University's Philip R. LeDuc and his collaborators in Massachusetts and Taiwan have discovered a new function of a protein that could ultimately unlock the mystery of how these workhorses of the body play a central role in the mechanics of biological processes in people.

"What we have done is find a new function of a protein that helps control cell behavior from a mechanics perspective," said LeDuc, an associate professor of mechanical engineering with courtesy appointments in the Biomedical Engineering, Biological Sciences and Computational Biology departments.
"For over 15 years, researchers have been mainly focusing on a protein called Integrin to study these cell functions, but our team found that another lesser known protein called Syndecan-4 is extremely important in cell behavior in a field called MechanoBiology (a field linking mechanics and biology). Syndecan-4 is known to play an essential role in a variety of diseases like cancer," LeDuc said.
LeDuc's new findings appear in the Dec. 29 edition of the prestigious journal Proceedings of the National Academy of Sciences along with complementary work that is appearing in another highly respected journal, Nature Protocols.
Essentially what his research does is take a look at how a protein's shape and form determines how it functions in the human body from a mechanics perspective. Proteins are composed of long chains of amino acids than can form bonds with other molecules in a chain, kinking, twisting and folding into complicated, three-dimensional shapes, such as helices or densely furrowed globular structures.
"These folded shapes are immensely important because they can define a protein's function in the cell," said LeDuc, who is also developing novel biologically inspired diagnostic approaches and materials as well as computational methods to understand molecular behavior.
LeDuc said his research finds that some protein shapes fit perfectly into cell receptors, turning chemical processes on and off, like a key in a lock. With mechanics changing the shape of proteins, LeDuc says the key might no longer fit into the lock, and serious consequences in the body can occur when proteins fail to assume their preordained shapes or fail to connect properly.
"Misguided proteins have been linked to disease such as cancer, arthritis and wound healing, among others," LeDuc said. "Our research is looking at how protein shapes affect cells and how cell biomechanics impacts the entire process."
Provided by Carnegie Mellon University

Genome of Woodland Strawberry, a Model System for Rosaceae Plants, Sequenced.

Source: ScienceDaily

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ScienceDaily (Jan. 12, 2010) — The genome of a model plant related to peach, cherry and cultivated strawberry has been sequenced by a consortium of international researchers that includes scientists with the Agricultural Research Service (ARS).

Fragaria vesca, commonly known as the woodland or alpine strawberry, is a member of the Rosaceae family, which consists of more than 100 genera and 3,000 species. This large family includes many economically important and popular fruit, nut, ornamental and woody crops, such as almond, apple, peach, cherry, raspberry, strawberry and rose.
F. vesca has many traits that make it an attractive model system for functional genomics studies. Its small size and rapid life cycle enable researchers to conduct genetic analyses with great efficiency and low cost. To determine the importance of a gene of interest, F. vesca can be transformed in order to modulate the activity of that gene in the plant. Most importantly, F. vesca has a relatively small genome, yet shares most gene sequences with other members of the Rosaceae family, making it an important tool for addressing questions regarding gene function.
ARS molecular biologist Janet Slovin, with the Genetic Improvement of Fruits and Vegetables Laboratory in Beltsville, Md., created the nearly inbred line used in the F. vesca genome sequencing project. Named "Hawaii 4," this line allowed the researchers to more easily program a computer to piece the genome together from the relatively short lengths of sequence data generated by modern sequencing machines.
Although the F. vesca genome is a model genome for the Rosaceae group, critical regulatory gene functions will probably differ, hypothesizes Slovin. Scientists can use the genome sequence to identify these genes, to test their function in F. vesca, and to develop molecular genetic markers for more rapid breeding of crops belonging to the Rosaceae group. Slovin will use the genome to study and improve heat tolerance during fruit production in strawberry.
The scientists announced the sequencing of the genome of woodland strawberry January 9 at the Plant and Animal Genome Conference in San Diego, Ca. The project was funded by Roche Diagnostics.

Story Source:
Adapted from materials provided by United States Department of Agriculture-Research, Education, and Economics.

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Evolutionary Surprise: Eight Percent of Human Genetic Material Comes from a Virus.

Source: ScienceDaily

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ScienceDaily (Jan. 8, 2010) — 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.

Story Source:
Adapted from materials provided by University of Texas at Arlington.

Journal References:
1.Masayuki Horie, Tomoyuki Honda, Yoshiyuki Suzuki, Yuki Kobayashi, Takuji Daito, Tatsuo Oshida, Kazuyoshi Ikuta, Patric Jern, Takashi Gojobori, John M. Coffin & Keizo Tomonaga. Endogenous non-retroviral RNA virus elements in mammalian genomes. Nature, 2010; 463 (7277): 84 DOI: 10.1038/nature08695
2.Cédric Feschotte. Virology: Bornavirus enters the genome. Nature, 2010; 463 (7277): 39 DOI: 10.1038/463039a

Evolution's Footprints in Human Genome Precisely Tracked Using New Approach.

Source: ScienceDaily

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ScienceDaily (Jan. 8, 2010) — Fossils may provide tantalizing clues to human history but they also lack some vital information, such as revealing which pieces of human DNA have been favored by evolution because they confer beneficial traits -- resistance to infection or the ability to digest milk, for example. These signs can only be revealed through genetic studies of modern humans and other related species, though the task has proven difficult.

Now, in a paper appearing in the January 7 edition of Science Express, researchers describe a method for pinpointing these preferred regions within the human genome that offers greater precision and resolution than ever before, and the possibility of deeply understanding both our genetic past and present.
"It's clear that positive natural selection has been a critical force in shaping the human genome, but there are remarkably few examples that have been clearly identified," said senior author Pardis Sabeti, an associate member of the Broad Institute of Harvard and MIT and an assistant professor of organismic and evolutionary biology at Harvard University. "The method we've developed makes it possible to zero in on individual genes as well as the specific changes within them that are driving important evolutionary changes."
Positive natural selection is a process in which advantageous traits become more common in a population. That is because these traits boost an individual's chances of survival and reproduction, so they are readily passed on to future generations. Identifying such traits -- and the genes underlying them -- is a cornerstone of current efforts to dissect the biological history of the human species as well as the diseases that threaten human health today.
"In the human genome, positive natural selection leaves behind very distinctive signals," said co-first author Sharon Grossman, a research assistant at Harvard University and the Broad Institute. Yet earlier methods for detecting these signals are limited, highlighting relatively large chunks of the genome that are hundreds of thousands to millions of genetic letters or "bases" in length, and that can contain many genes.
Of the hundreds of these large genomic regions thought to be under positive natural selection in humans, only a handful have so far been winnowed to a precise genetic change. "Finding the specific genetic changes that are under selection can be like looking for a needle in a haystack," said Grossman.
Sabeti, Grossman and their colleagues wondered if there might be a way to enhance this genomic search. Because existing methods for detecting natural selection each measure distinct genomic features, the researchers predicted that an approach that combines them together could yield even better results.
After some initial simulations to test their new method, the research team applied it to more than 180 regions of the human genome that are thought to be under recent positive selection, yet in most cases, the specific gene or genetic variant under selection is unknown.
The researchers' method, called "Composite of Multiple Signals" or CMS, enabled them to dramatically narrow the size of the candidate regions, reducing them from an average of eight genes per region to one. Moreover the number of candidate genetic changes was reduced from thousands to just a handful, helping the researchers tease out the needles from the haystack.
"The list of genes and genetic loci we identified includes many intriguing candidates to follow up," said co-first author Ilya Shylakhter, a computational biologist at the Broad Institute and Harvard University. "For example, a number of genes identified are involved in metabolism, skin pigmentation and the immune system."
In some cases, the researchers were able to identify a specific genetic change that is the likely focal point of natural selection. For example, a variation in a gene called protocadherin 15, which functions in sensory perception, including hearing and vision, appears to be under selection in some East Asian populations. Several other genes involved in sensory perception also appear to be under selection in Asia. In addition, the team uncovered strong evidence of selection in East Asians at a specific point within the leptin receptor gene, which is linked to blood pressure, body mass index and other important metabolic functions.
Interestingly, the researchers also localized signals to regions outside of genes, suggesting that they function not by altering gene structure per se, but by changing how certain genes are turned on and off.
While the findings in the Science paper offer a deep glimpse of evolution's handiwork, the researchers emphasize that further studies of individual genetic variations, involving experiments that explore how certain genetic changes influence biological function, are necessary to fully dissect the role of natural selection and its impact on human biology.
"This method allows us to trace evolution's footprints with a much finer level of granularity than before, but it's one piece of a much larger puzzle," said Sabeti. "As more data on human genetic variation becomes available in the coming years, an even more detailed evolutionary picture should emerge."

Story Source:
Adapted from materials provided by Broad Institute of MIT and Harvard, via EurekAlert!, a service of AAAS.

Journal Reference:
Grossman et al. A composite of multiple signals distinguishes causal variants in regions of positive selection. Science, 2010 DOI: 10.1126/science.1183863

What Came First in the Origin of Life? New Study Contradicts the 'Metabolism First' Hypothesis.

Source: ScienceDaily

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ScienceDaily (Jan. 9, 2010) — A new study published in Proceedings of National Academy of Sciences rejects the theory that the origin of life stems from a system of self-catalytic molecules capable of experiencing Darwinian evolution without the need of RNA or DNA and their replication.

The research, which was carried out with the participation of Mauro Santos, researcher of the Department of Genetics and Microbiology at Universitat Autònoma de Barcelona (UAB), has demonstrated that, through the analysis of what some researchers name "compound genomes," these chemical networks cannot be considered evolutionary units because they lose properties which are essential for evolution when they reach a critical size and greater level of complexity.
The U.S. National Aeronautics and Space Administration (NASA) defines life as a "self-sustaining chemical system capable of Darwinian evolution." The scientific theories on the origin of life revolve around two main ideas: one focuses on genetics -- with RNA or DNA replication as an essential condition for Darwinian evolution to take place -- and the other focuses on metabolism. It is clear that both situations must have begun with simple organic molecules formed by prebiotic processes, as was demonstrated by the Miller-Urey experiment (in which organic molecules were created from inorganic substances). The point in which these two theories differ is that the replication of RNA or DNA molecules is a far too complex process which requires a correct combination of monomers within the polymers to produce a molecular chain resulting from the replication.
Until now no plausible chemical explanation exists for how these processes occured. In addition, defenders of the second theory argue that the processes needed for evolution to take place depend on primordial metabolism. This metabolism is believed to be a type of chemical network entailing a high degree of mutual catalysis between its components which, in turn, eventually allows for adaptation and evolution without any molecular replication.
In the first half of the 20th century, Alexander Oparin established the "Metabolism First" hypothesis to explain the origin of life, thus strengthening the primary role of cells as small drops of coacervates (evolutionary precursors of the first prokaryote cells). Dr Oparin did not refer to RNA or DNA molecules since at that time it was not clear just how important the role of these molecules was in living organisms. However he did form a solid base for the idea of self-replication as a collective property of molecular compounds.
Science more recently demonstrated that sets of chemical components store information about their composition which can be duplicated and transmitted to their descendents. This has led to their being named "compound genomes" or composomes. In other words, heredity does not require information in order to be stored in RNA or DNA molecules. These "compound genomes" apparently fulfil the conditions required to be considered evolutionary units, which suggests a pathway from pre-Darwinian dynamics to a minimum protocell.
Researchers in this study nevertheless reveal that these systems are incapable of undergoing a Darwinian evolution. For the first time a rigorous analysis was carried out to study the supposed evolution of these molecular networks using a combination of numerical and analytical simulations and network analysis approximations. Their research demonstrated that the dynamics of molecular compound populations which divide after having reached a critical size do not evolve, since during this process the compounds lose properties which are essential for Darwinian evolution.
Researchers concluded that this fundamental limitation of "compound genomes" should lead to caution towards theories that set metabolism first as the origin as life, even though former metabolic systems could have offered a stable habitat in which primitive polymers such as RNA could have evolved.
Researchers state that different prebiotic Earth scenarios can be considered. However, the basic property of life as a system capable of undergoing Darwinian evolution began when genetic information was finally stored and transmitted such as occurs in nucleotide polymers (RNA and DNA).

Story Source:
Adapted from materials provided by Universitat Autonoma de Barcelona.

Journal Reference:
Vera Vasasa, Eörs Szathmáry and Mauro Santosa. Lack of evolvability in self-sustaining autocatalytic networks: A constraint on the metabolism-first path to the origin of life. PNAS, January 4, 2010 DOI: 10.1073/pnas.0912628107