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【计时一】
Most Extensive Pictures Ever of an Organism's DNA Mutation Processes
ScienceDaily (Sep. 17, 2012) — Biologists and informaticists at Indiana University have produced one of the most extensive pictures ever of mutation processes in the DNA sequence of an organism, elucidating important new evolutionary information about the molecular nature of mutations and how fast those heritable changes occur.
[attachimg=512,476]106617[/attachimg]
By analyzing the exact genomic changes in the model prokaryote Escherichia coli that had undergone over 200,000 generations of growth in the absence of natural selective pressures, the team led by IU College of Arts and Sciences Department of Biology professor Patricia L. Foster found that spontaneous mutation rates in E. coli DNA were actually three times lower than previously thought.
The new research, which appeared September 17 in early edition of the journal Proceedings of the National Academy of Sciences, also notes that the mismatch repair proteins that survey newly replicated DNA and detect mistakes not only keep mutation rates low but may also maintain the balance of guanine-cytosine content to adenine-thymine content in the genome. Guanine-cytosine and adenine-thymine are the nitrogenous bases that bond between opposing DNA strands to form the rungs of the double helix ladder of DNA.
"We know that even in the absence of natural selection, evolution will proceed because new mutations get fixed at random in the genome," Foster said. "So, if we want to determine whether specific patterns of evolutionary change are driven by selection, knowledge of the expected pattern in the absence of selection is absolutely essential. Here we are defining the rate and molecular spectrum of spontaneous mutations while minimizing the ability of natural selection to promote or eradicate mutations, which allows us to capture essentially all mutations that do not cause the bacterium to die."
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【计时二】
In a parallel mutation accumulation experiment using a strain defective in mismatch repair, in which the mutation rate was increased over 100-fold, the researchers analyzed nearly 2,000 mutations and found that these were strongly biased toward changing adenine-thymine base pairs to guanine-cytosine base pairs, the opposite of what is seen in the normal bacteria.
E. coli chromosome
"The molecular spectrum of spontaneous base-pair substitutions in almost all organisms is dominated by guanine-cytosine to adenine-thymine changes, which tends to drive genomes toward higher adenine-thymine content," Foster noted. "Because the guanine-cytosine content of genomes varies widely, there must be some selective pressure, or some non-adaptive mechanism, that can drive genomes back toward increased guanine-cytosine content."
The new research, co-authored by IU Bloomington School of Informatics and Computing associate professor Haixu Tang, Informatics predoctoral researcher Heewook Lee and Department of Biology postdoctoral researcher Ellen Popodi, demonstrates that mismatch repair is a major factor in the types of mutations that occur and in determining the base composition of the genome. Because the activity of mismatch repair can be influenced by the environment, another implication of this work is that the pattern of mutations could be used in forensics to help determine where a particular bacterial strain originated.
"By establishing baseline parameters for the molecular nature of spontaneous mutational change unbiased by selection, we can begin to achieve a deeper understanding of the factors that determine mutation rates, the mutational spectra, genomic base composition, how these may differ among organisms and how they may be shaped by environmental conditions," Foster said. "Since mutations are the source of variation upon which natural selection acts, understanding the rate at which mutations occur and the molecular nature of spontaneous mutational changes leads us to a fuller understanding of evolution."
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【计时三】
Higher Levels of BPA in Children and Teens Significantly Associated With Obesity
ScienceDaily (Sep. 18, 2012) — Researchers at NYU School of Medicine have revealed a significant association between obesity and children and adolescents with higher concentrations of urinary bisphenol A (BPA), a synthetic chemical recently banned by the U.S. Food and Drug Administration (FDA) from sippy cups and baby bottles. Still, the chemical continues to be used in aluminum cans, such as those containing soda.
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The study appears in the September 19 issue of JAMA (Journal of the American Medical Association), dedicated to the theme of obesity.
“This is the first association of an environmental chemical in childhood obesity in a large, nationally representative sample,” said lead investigator Leonardo Trasande, MD, MPP, associate professor of pediatrics and environmental medicine. “Our findings further demonstrate the need for a broader paradigm in the way we think about the obesity epidemic. Unhealthy diet and lack of physical activity certainly contribute to increased fat mass, but the story clearly doesn’t end there.”
BPA, a low-grade estrogen, was until recently found in plastic bottles labeled with the number 7 recycling symbol, and is still used as an internal coating for aluminum cans. Manufacturers say it provides an antiseptic function, but studies have shown the chemical disrupts multiple mechanisms of human metabolism that may increase body mass. BPA exposure has also been associated with cardiovascular disease, breast cancer, prostate cancer, neurological disorders, diabetes and infertility.
“In the U.S. population, exposure [to BPA] is nearly ubiquitous, with 92.6 percent of persons 6 years or older identified in the 2003-2004 National Health and Nutrition Examination Survey (NHANES) as having detectable BPA levels in their urine. A comprehensive, cross-sectional study of dust, indoor and outdoor air, and solid and liquid food in preschool-aged children suggested that dietary sources constitute 99 percent of BPA exposure,” the investigators wrote.
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【计时四】
Using a sample of nearly 3,000 children and adolescents, ages 6 through 19 years, randomly selected for measurement of urinary BPA concentration in the 2003-2008 NHANES, Dr. Trasande and his co-authors, Jan Blustein, MD, PhD, and Teresa Attina, MD, PhD, MPH, examined associations between urinary BPA concentrations and body mass.
After controlling for race/ethnicity, age, caregiver education, poverty to income ratio, sex, serum cotinine level, caloric intake, television watching, and urinary creatinine level, the researchers found children with the highest levels of urinary BPA had 2.6 times higher odds of being obese than those with the lowest measures of urinary BPA. Among the participants with the highest levels, 22.3 percent were obese compared with 10.3 percent of the participants with the lowest levels.
Further analyses showed this association to be statistically significant in only one racial subpopulation, white children and adolescents. The researchers also found that obesity was not associated with exposure to other environmental phenols commonly used in other consumer products, such as sunscreens and soaps.
“Most people agree the majority of BPA exposure in the United States comes from aluminum cans,” Dr. Trasande said. “This data adds to already existing concerns about BPA and further supports the call to limit exposure of BPA in this country, especially in children. Removing it from aluminum cans is probably one of the best ways we can limit exposure. There are alternatives that manufacturers can use to line aluminum cans.”
The researchers wrote in their study that advocates and policy makers have long been concerned about BPA exposure. “We note the recent FDA ban of BPA in baby bottles and sippy cups, yet our findings raise questions about exposure to BPA in consumer products used by older children. Last year, the FDA declined to ban BPA in aluminum cans and other food packaging, announcing ‘reasonable steps to reduce human exposure to BPA in the human food supply’ and noting that it will continue to consider evidence on the safety of the chemical. Carefully conducted longitudinal studies that assess the associations identified here will yield evidence many years in the future.”
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【计时五】
'Blue Brain' Project Accurately Predicts Connections Between Neurons
ScienceDaily (Sep. 17, 2012) — One of the greatest challenges in neuroscience is to identify the map of synaptic connections between neurons. Called the "connectome," it is the holy grail that will explain how information flows in the brain. In a landmark paper, published the week of 17th of September in the Proceedings of the National Academy of Sciences, the EPFL's Blue Brain Project (BBP) has identified key principles that determine synapse-scale connectivity by virtually reconstructing a cortical microcircuit and comparing it to a mammalian sample. These principles now make it possible to predict the locations of synapses in the neocortex.
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"This is a major breakthrough, because it would otherwise take decades, if not centuries, to map the location of each synapse in the brain and it also makes it so much easier now to build accurate models," says Henry Markram, head of the BBP.
A longstanding neuroscientific mystery has been whether all the neurons grow independently and just take what they get as their branches bump into each other, or are the branches of each neuron specifically guided by chemical signals to find all its target. To solve the mystery, researchers looked in a virtual reconstruction of a cortical microcircuit to see where the branches bumped into each other. To their great surprise, they found that the locations on the model matched that of synapses found in the equivalent real-brain circuit with an accuracy ranging from 75 percent to 95 percent.
This means that neurons grow as independently of each other as physically possible and mostly form synapses at the locations where they randomly bump into each other. A few exceptions were also discovered pointing out special cases where signals are used by neurons to change the statistical connectivity. By taking these exceptions into account, the Blue Brain team can now make a near perfect prediction of the locations of all the synapses formed inside the circuit.
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Virtual Reconstruction
The goal of the BBP is to integrate knowledge from all the specialized branches of neuroscience, to derive from it the fundamental principles that govern brain structure and function, and ultimately, to reconstruct the brains of different species -- including the human brain -- in silico. The current paper provides yet another proof-of-concept for the approach, by demonstrating for the first time that the distribution of synapses or neuronal connections in the mammalian cortex can, to a large extent, be predicted.
To achieve these results, a team from the Blue Brain Project set about virtually reconstructing a cortical microcircuit based on unparalleled data about the geometrical and electrical properties of neurons -- data from over nearly 20 years of painstaking experimentation on slices of living brain tissue. Each neuron in the circuit was reconstructed into a 3D model on a powerful Blue Gene supercomputer. About 10,000 of virtual neurons were packed into a 3D space in random positions according to the density and ratio of morphological types found in corresponding living tissue. The researchers then compared the model back to an equivalent brain circuit from a real mammalian brain.
A Major Step Towards Accurate Models of the Brain
This discovery also explains why the brain can withstand damage and indicates that the positions of synapses in all brains of the same species are more similar than different. " ositioning synapses in this way is very robust," says computational neuroscientist and first author Sean Hill, "We could vary density, position, orientation, and none of that changed the distribution of positions of the synapses."
They went on to discover that the synapses positions are only robust as long as the morphology of each neuron is slightly different from each other, explaining another mystery in the brain -- why neurons are not all identical in shape. "It's the diversity in the morphology of neurons that makes brain circuits of a particular species basically the same and highly robust," says Hill.
Overall this work represents a major acceleration in the ability to construct detailed models of the nervous system. The results provide important insights into the basic principles that govern the wiring of the nervous system, throwing light on how robust cortical circuits are constructed from highly diverse populations of neurons -- an essential step towards understanding how the brain functions. They also underscore the value of the BBP's constructivist approach. "Although systematically integrating data across a wide range of scales is slow and painstaking, it allows us to derive fundamental principles of brain structure and hence function," explains Hill.
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【越障】
Comet May Have Exploded Over Canada 12,900 Years Ago After All
ScienceDaily (Sep. 18, 2012) — Did a massive comet explode over Canada 12,900 years ago, wiping out both beast and man in North America and propelling Earth back into an ice age?
[attachimg=527,633]106620[/attachimg]
That's a question that has been hotly debated by scientists since 2007, with the University of South Carolina's Topper archaeological site right in the middle of the comet impact controversy. However, a new study published Sept.17 in the Proceedings of the National Academy of Sciences (PNAS) provides further evidence that it may not be such a far-fetched notion.
USC archaeologist Albert Goodyear is a co-author on the study that upholds a 2007 PNAS study by Richard Firestone, a staff scientist at the Department of Energy's Lawrence Berkeley National Laboratory.
Firestone found concentrations of spherules (micro-sized balls) of metals and nano-sized diamonds in a layer of sediment dating 12,900 years ago at 10 of 12 archaeological sites that his team examined. The mix of particles is thought to be the result of an extraterrestrial object, such as a comet or meteorite, exploding in Earth's atmosphere. Among the sites examined was USC's Topper, one of the most pristine U.S. sites for research on Clovis, one of the earliest ancient peoples.
"This independent study is yet another example of how the Topper site with its various interdisciplinary studies has connected ancient human archaeology with significant studies of the Pleistocene," said Goodyear, who began excavating Clovis artifacts in 1984 at the Topper site in Allendale, S.C. "It's both exciting and gratifying."
Younger-Dryas is what scientists refer to as the period of extreme cooling that began around 12,900 years ago and lasted 1,300 years. While that brief ice age has been well-documented -- occurring during a period of progressive solar warming after the last ice age -- the reasons for it have long remained unclear. The extreme rapid cooling that took place can be likened to the 2004 sci-fi blockbuster movie "The Day After Tomorrow."
Firestone's team presented a provocative theory: that a major impact event -- perhaps a comet -- was the catalyst. His copious sampling and detailed analysis of sediments at a layer in the Earth dated to 12,900 years ago, also called the Younger-Dryas Boundary (YDB), provided evidence of micro-particles, such as iron, silica, iridium and nano-diamonds. The particles are believed to be consistent with a massive impact that could have killed off the Clovis people and the large North American animals of the day. Thirty-six species, including the mastodon, mammoth and saber-toothed tiger, went extinct.
The scientific community is rarely quick to accept new theories. Firestone's theory and support for it dominated the annual meeting of the American Geophysical Union and other gatherings of Paleoindian archaeologists in 2007 and 2008.
However, a 2009 study led by University of Wyoming researcher Todd Surovell failed to replicate Firestone's findings at seven Clovis sites, slowing interest and research progress to a glacial pace.
This new PNAS study refutes Surovell's findings with its lack of reported evidence.
"Surovell's work was in vain because he didn't replicate the protocol. We missed it too at first. It seems easy, but unless you follow the protocol rigorously, you will fail to detect these spherules. There are so many factors that can disrupt the process. Where Surovell found no spherules, we found hundreds to thousands," said Malcolm LeCompte, a research associate professor at Elizabeth City State University and lead author of the newly released PNAS article.
LeCompte began his independent study in 2008 using and further refining Firestone's sampling and sorting methods at two sites common to the three studies: Blackwater Draw in New Mexico and Topper. He also took samples at Paw Paw Cove in Maryland, a site common to Surovell's study.
At each site he found the same microscopic spherules, which are the diameter of a human hair and distinct in appearance. He describes their look as tiny black ball bearings with a marred surface pattern that resulted from being crystalized in a molten state and then rapidly cooled. His investigation also confirmed that the spherules were not of cosmic origin but were formed from earth materials due to an extreme impact.
【697】
【剩余部分】
LeCompte said it was Topper and Goodyear's collaboration, however, that yielded the most exciting results.
"What we had at Topper and nowhere else were pieces of manufacturing debris from stone tool making by the Clovis people. Topper was an active and ancient quarry at the time," LeCompte said. "Al Goodyear was instrumental in our approach to getting samples at Topper."
Goodyear showed LeCompte where the Clovis level was in order to accurately guide his sampling of sediments for the Younger Dryas Boundary layer. He advised him to sample around Clovis artifacts and then to carefully lift them to test the sediment directly underneath.
"If debris was raining down from the atmosphere, the artifacts should have acted as a shield preventing spherules from accumulating in the layer underneath. It turns out it really worked!" Goodyear said. "There were up to 30 times more spherules at and just above the Clovis surface than beneath the artifacts."
LeCompte said the finding is "critical and what makes the paper and study so exciting. The other sites didn't have artifacts because they weren't tool-making quarries like Topper."
While the comet hypothesis and its possible impact on Clovis people isn't resolved, Goodyear said this independent study clarifies why the Surovell team couldn't replicate the Firestone findings and lends greater credibility to the claim that a major impact event happened at the Younger Dryas Boundary 12,900 years ago.
"The so-called extra-terrestrial impact hypothesis adds to the mystery of what happened at the YDB with its sudden and unexplained reversion to an ice age climate, the rapid and seemingly simultaneous loss of many Pleistocene animals, such as mammoths and mastodons, as well as the demise of what archaeologists call the Clovis culture," Goodyear said. "There's always more to learn about the past, and Topper continues to function as a portal to these fascinating mysteries."
Goodyear joined USC's College of Arts and Sciences and its South Carolina Institute for Archaeology and Anthropology in 1974 to pursue prehistoric archaeology.
The Topper story
Al Goodyear, who conducts research through the University of South Carolina's S.C. Institute of Anthropology and Archaeology, began excavating Clovis artifacts along the Savannah River in Allendale County in 1984. It quickly became one of the most documented and well-known Clovis sites in the United States. In 1998, with the hope of finding evidence of a pre-Clovis culture earlier than the accepted 13,100 years, Goodyear began focused excavations on a site called Topper, located on the property of the Clariant Corp.
His efforts paid off. Goodyear unearthed small tools such as scrapers and blades made of the local chert that he believed to be tools of an ice age culture back some 16,000 years or more. His findings, as well as similar ones yielded at other pre-Clovis sites in North America, sparked great change and debate in the scientific community.
Goodyear reasoned that if Clovis and later peoples used the chert quarry along the Savannah River, the quarry could have been used by even earlier cultures.
Acting on a hunch in 2004, Goodyear dug even deeper into the Pleistocene terrace and found more artifacts of a pre-Clovis type buried in a layer of sediment stained with charcoal deposits. Radiocarbon dates of the burnt plant remains yielded ages of 50,000 years, which suggested man was in South Carolina long before the last ice age.
Goodyear's findings not only captured international media attention, but it has put the archaeology field in flux, opening scientific minds to the possibility of an even earlier pre-Clovis occupation of the Americas.
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发表于 2012-9-19 04:35:52
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