Researchers work to save endangered New England cottontail

Scientists with the NH Agricultural Experiment Station are working to restore New Hampshire and Maine’s only native rabbit after new research based on genetic monitoring has found that in the last decade, cottontail populations in northern New England have become more isolated and seen a 50 percent contraction of their range.The endangered New England cottontail is now is at risk of becoming extinct in the region, according to NH Agricultural Experiment Station researchers at the University of New Hampshire College of Life Sciences and Agriculture who believe that restoring habitats is the key to saving the species.”The New England cottontail is a species of great conservation concern in the Northeast. This is our only native rabbit and is an integral component of the native New England wildlife. Maintaining biodiversity gives resilience to our landscape and ecosystems,” said NHAES researcher Adrienne Kovach, research associate professor of natural resources at UNH.New England cottontails have been declining for decades. However, NHAES researchers have found that in the last decade, the New England cottontail population in New Hampshire and Maine has contracted by 50 percent; a decade ago, cottontails were found as far north as Cumberland, Maine.The majority of research on New England cottontails has come out of UNH, much of it under the leadership of John Litvaitis, professor of wildlife ecology, who has studied the New England cottontail for three decades. Kovach’s research expands on this knowledge by using DNA analysis to provide new information on the cottontail’s status, distribution, genetic diversity, and dispersal ecology.The greatest threat and cause of the decline of the New England cottontail is the reduction and fragmentation of their habitat, Kovach said. Fragmentation of habitats occurs when the cottontail’s habitat is reduced or eliminated due to the maturing of forests or land development. Habitats also can become fragmented by roads or natural landscape features, such as bodies of water.”Cottontails require thicketed habitats, which progress from old fields to young forests. Once you have a more mature forest, the cottontail habitat is reduced. A lot of other species rely on these thicket habitats, including bobcats, birds, and reptiles. Many thicket-dependent species are on decline, and the New England cottontail is a representative species for this kind of habitat and its conservation,” Kovach said.Kovach explained that for cottontail and most animal populations to be healthy and grow, it is important for adult animals to leave the place where they were born and relocate to a new habitat, which is known as dispersal. …

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Epigenetic changes can drive cancer, study shows

Cancer has long been thought to be primarily a genetic disease, but in recent decades scientists have come to believe that epigenetic changes — which don’t change the DNA sequence but how it is ‘read’ — also play a role in cancer. In particular DNA methylation, the addition of a methyl group (or molecule), is an epigenetic switch that can stably turn off genes, suggesting the potential to cause cancer just as a genetic mutation can. Until now, however, direct evidence that DNA methylation drives cancer formation was lacking.Researchers at the USDA/ARS Children’s Nutrition Research Center at Baylor College of Medicine and Texas Children’s Hospital have now created a mouse model providing the first in vivo evidence that epigenetic alterations alone can cause cancer. Their report appears in the Journal of Clinical Investigation.”We knew that epigenetic changes are associated with cancer, but didn’t know whether these were a cause or consequence of cancer. Developing this new approach for ‘epigenetic engineering’ allowed us to test whether DNA methylation changes alone can drive cancer,” said Dr. Lanlan Shen, associate professor of pediatrics at Baylor and senior author of the study.Shen and colleagues focused on p16, a gene that normally functions to prevent cancer but is commonly methylated in a broad spectrum of human cancers. They devised an approach to engineer DNA methylation specifically to the mouse p16 regulatory region (promoter). As intended, the engineered p16 promoter acted as a ‘methylation magnet’. As the mice reached adulthood, gradually increasing p16 methylation led to a higher incidence of spontaneous cancers, and reduced survival.”This is not only the first in vivo evidence that epigenetic alteration alone can cause cancer,” said Shen. “This also has profound implications for future studies, because epigenetic changes are potentially reversible. …

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Bacteria on the skin: Our invisible companions influence how quickly wounds heel

A new study suggests microbes living on our skin influence how quickly wounds heal. The findings could lead to new treatments for chronic wounds, which affect 1 in 20 elderly people.We spend our lives covered head-to-toe in a thin veneer of bacteria. But despite a growing appreciation for the valuable roles our resident microbes play in the digestive tract, little is known about the bacteria that reside in and on our skin. A new study suggests the interplay between our cells and these skin-dwelling microbes could influence how wounds heal.”This study gives us a much better understanding of the types of bacterial species that are found in skin wounds, how our cells might respond to the bacteria and how that interaction can affect healing,” said Matthew Hardman, Ph.D., a senior research fellow at The University of Manchester Healing Foundation Centre who led the project. “It’s our hope that these insights could help lead to better treatments to promote wound healing that are based on sound biology.”Chronic wounds — cuts or lesions that just never seem to heal — are a significant health problem, particularly among elderly people. An estimated 1 in 20 elderly people live with a chronic wound, which often results from diabetes, poor blood circulation or being confined to bed or a wheelchair.”These wounds can literally persist for years, and we simply have no good treatments to help a chronic wound heal,” said Hardman, who added that doctors currently have no reliable way to tell whether a wound will heal or persist. “There’s a definite need for better ways to both predict how a wound is going to heal and develop new treatments to promote healing.”The trillions of bacteria that live on and in our bodies have attracted a great deal of scientific interest in recent years. Findings from studies of microbes in the gut have made it clear that although some bacteria cause disease, many other bacteria are highly beneficial for our health.In their recent study, Hardman and his colleagues compared the skin bacteria from people with chronic wounds that did or did not heal. The results showed markedly different bacterial communities, suggesting there may be a bacterial “signature” of a wound that refuses to heal.”Our data clearly support the idea that one could swab a wound, profile the bacteria that are there and then be able to tell whether the wound is likely to heal quickly or persist, which could impact treatment decisions,” said Hardman.The team also conducted a series of studies in mice to shed light on the reasons why some wounds heal while others do not. They found that mice lacking a single gene had a different array of skin microbiota — including more harmful bacteria — and healed much more slowly than mice with a normal copy of the gene.The gene, which has been linked to Chrohn’s disease, is known to help cells recognize and respond to bacteria. …

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Function found for mysterious heart disease gene

A new study from researchers at the University of Ottawa Heart Institute (UOHI), published today in Cell Reports, sheds light on a mysterious gene that likely influences cardiovascular health. After five years, UOHI researchers now know how one genetic variant works and suspect that it contributes to the development of heart disease through processes that promote chronic inflammation and cell division.Researchers at the Ruddy Canadian Cardiovascular Genetics Centre had initially identified a variant in a gene called SPG7 as a potential contributor to coronary artery disease several years ago, but its role in multiple health processes made it difficult to tease out how it affects heart disease.The gene holds instructions for producing a protein called SPG7. This protein resides in mitochondria — the small power plants of cells that produce the energy cells need to function. SPG7’s role is to help break down and recycle other damaged proteins within the mitochondria.Normally, SPG7 requires a partner protein to activate itself and start this breakdown process. But, in people who carry the genetic variant in question, SPG7 can activate itself in certain circumstances, leading to increased production of free radicals and more rapid cell division. These factors contribute to inflammation and atherosclerosis.”We think this variant would definitely heighten the state of inflammation, and we know that inflammation affects diabetes and heart disease,” said Dr. Stewart, Principal Investigator in the Ruddy Canadian Cardiovascular Genetics Centre and senior author of the study. “Interestingly, the variant also makes people more resistant to the toxic side effects of some chemotherapy drugs.”From an evolutionary perspective, this resistance could help such a genetic variant gain a stable place in the human genome. Between 13 and 15 per cent of people of European descent possess this variant.”The idea of mitochondria contributing to inflammation isn’t new,” concluded Dr. Stewart. …

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Increasing longevity of seeds with genetic engineering

A study developed by researchers of the Institute for Plant Molecular and Cell Biology (IBMCP), a joint center of the Universitat Politcnica de Valncia and the Spanish National Research Council (CSIC), in collaboration with the Unit for Plant Genomics Research of Evry, France (URGV, in French) has discovered a new way of improving the longevity of plant seeds using genetic engineering. Plant Physiology magazine has published the research results.The key is the overexpression of the ATHB25 gene. This gene encodes a protein that regulates gene expression, producing a new mutant that gives the seed new properties. Researchers have proven that this mutant has more gibberellin -the hormone that promotes plant growth-, which means the seed coat is reinforced as well. “The seed coat is responsible for preventing oxygen from entering the seed; the increase in gibberellin strengthens it and this leads to a more durable and longer lasting seed,” explains Eduardo Bueso, researcher at the IBMCP (UPV-CSIC).This mechanism is new, as tolerance to stresses such as aging has always been associated with another hormone, abscisic acid, which regulates defenses based on proteins and small protective molecules, instead of producing the growth of structures like gibberellin does.The study has been made on the experimental model plant Arabidopsis thaliana, a species that presents great advantages for molecular biology research. Researchers of the IBMCP traced half a million seeds, related to one hundred thousand lines of Arabidopsis mutated by T-DNA insertion, using the natural system of Agrobacterium tumefaciens. “Finally, we analyzed four mutants in the study and we proved the impact on the seed longevity when the overexpression of the ATHB25 gene is introduced,” states Ramn Serrano, researcher at the IBMCP.Researchers compared the longevity of genetically modified Arabidopsis seeds and seeds which were not modified. In order to do this, they preserved them for thirty months under specific conditions of room temperature and humidity. After thirty months, only 20% of the control plants germinated again, whereas almost the all of the modified plants (90%) began the germination process again.Researchers of the IBMCP are now trying to improve the longevity of different species that are of agronomical interest, such as tomatoes or wheat.Biodiversity and benefits for farmersThis discovery is particularly significant for the conservation of biodiversity, preserving seed species and, especially, for farmers.”In the past, a lot of different plant species were cultivated, but many of them are dissapearing because high performance crops have now become a priority. Seed banks were created in order to guarantee the conservation of species, but they require a periodical regeneration of the seeds. …

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Tumor suppressor gene linked to stem cells, cancer biologists report

Just as archeologists try to decipher ancient tablets to discern their meaning, UT Southwestern Medical Center cancer biologists are working to decode the purpose of an ancient gene considered one of the most important in cancer research.The p53 gene appears to be involved in signaling other cells instrumental in stopping tumor development. But the p53 gene predates cancer, so scientists are uncertain what its original function is.In trying to unravel the mystery, Dr. John Abrams, Professor of Cell Biology at UT Southwestern, and his team made a crucial new discovery — tying the p53 gene to stem cells. Specifically, his lab found that when cellular damage is present, the gene is hyperactive in stem cells, but not in other cells. The findings suggest p53’s tumor suppression ability may have evolved from its more ancient ability to regulate stem cell growth.”The discovery was that only the stem cells light up. None of the others do. The exciting implication is that we are able to understand the function of p53 in stem cells,” said Dr. Abrams, Chair of the Genetics and Development program in UT Southwestern’s Graduate School of Biomedical Sciences. “We may, in fact, have some important answers for how p53 suppresses tumors.”The findings appear online in the journal eLife, a joint initiative of the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust.p53 is one of the hardest working and most effective allies in the fight against cancer, said Dr. Abrams. …

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Gene silencing instructions acquired through ‘molecular memory’ tags on chromatin

Scientists at Indiana University have unlocked one of the mysteries of modern genetics: how acquired traits can be passed between generations in a process called epigenetic inheritance. The new work finds that cells don’t know to silence some genes based on information hardwired into their DNA sequences, but recognize heritable chemical marks that are added to the genes. These chemical tags serve as a form of molecular memory, allowing cells to recognize the genes and remember to silence them again in each new generation.The discovery made by a 12-member all-Indiana University team of scientists led by IU biologist and biochemist Craig Pikaard provides important new insight into how plant cells know to silence a genetic locus — that specific place on a chromosome where a gene is located — in every successive generation.Rather than rely on intrinsic, DNA sequence-based information, the cells instead must recall the need to silence specific loci by relying on chemical marks displayed on the complex of DNA and proteins called chromatin. Addition, or removal, of one-carbon (methyl) or two-carbon (acetyl) chemical tags are ways of modifying chromatin that can impart additional, epigenetic (literally, “above genetic”) information to a locus beyond the genetic information encoded in the DNA.The ability to perpetuate chromatin marks serves as a form of epigenetic memory that confers what Pikaard calls silent locus identity, a pre-established state that is needed for the cell to deliver to the loci the machinery that actually accomplishes silencing in a multi-step process known as RNA-directed DNA methylation (RdDM). RdDM involves short-interfering RNAs (siRNA), tiny RNA molecules that are 24 nucleotides long and that guide the addition of methyl groups to matching DNA strands, ultimately rendering the genes inactive.”Importantly, this work shows that silent locus identity is required for, but separable from, actual gene silencing,” Pikaard said. “We’ve found that epigenetic inheritance is a two-step process, with the heritable specification of silent locus identity occurring before actual silencing of the locus can occur.”Scientists are interested in epigenetic inheritance because it’s a process by which heritable modifications occur in gene function without changes in the base sequence of an organism’s DNA being required. Disease states such as cancer, which occur sporadically during an individual’s lifetime, are increasingly recognized as having an epigenetic basis. Pikaard said the new work not only sheds important new light on the mechanisms responsible for epigenetic inheritance, a topic of broad interest in the fields of genetics and chromosome biology, but it also helps explain the basis for the recruitment of two plant-specific gene silencing enzymes — the RNA polymerases Pol IV and Pol V — first identified by Pikaard in 1999.Specifically, the researchers tested and identified the relationship between histone deacetylase 6 (HDA6), an enzyme that removes acetyl groups from histones, and the CG DNA sequence maintenance methyltransferase, MET1, and discovered that their partnership in maintenance methylation can explain the perpetuation of epigenetic memory that accounts for silent locus identity.”Collectively, our results show that silent locus identity is perpetuated from generation to generation through the actions of HDA6 and MET1,” Pikaard said. “These activities are not sufficient to silence the loci but maintain a chromatin state that is required for Pol IV recruitment, siRNA biogenesis and RdDM, which is what ultimately silences the loci.” When the team removed the RdDM pathway in Pol IV and Pol V mutant strains of the model plant Arabidopsis thaliana (rockcress), all gene silencing was lost, but silent locus identity remained. They then removed the HDA6 and MET1-dependent process that specifies silent locus identity and, importantly, the epigenetic memory required for silent locus identity was lost and unable to be regained.Story Source:The above story is based on materials provided by Indiana University. …

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Contagious yawning a mystery: May not be linked to empathy after all

While previous studies have suggested a connection between contagious yawning and empathy, new research from the Duke Center for Human Genome Variation finds that contagious yawning may decrease with age and is not strongly related to variables like empathy, tiredness and energy levels.The study, published March 14 in the journal PLOS ONE, is the most comprehensive look at factors influencing contagious yawning to date.The researchers said a better understanding of the biology involved in contagious yawning could ultimately shed light on illnesses such as schizophrenia or autism.”The lack of association in our study between contagious yawning and empathy suggests that contagious yawning is not simply a product of one’s capacity for empathy,” said study author Elizabeth Cirulli, Ph.D., assistant professor of medicine at the Center for Human Genome Variation at Duke University School of Medicine.Contagious yawning is a well-documented phenomenon that occurs only in humans and chimpanzees in response to hearing, seeing or thinking about yawning. It differs from spontaneous yawning, which occurs when someone is bored or tired. Spontaneous yawning is first observed in the womb, while contagious yawning does not begin until early childhood.Why certain individuals are more susceptible to contagious yawning remains poorly understood. Previous research, including neuroimaging studies, has shown a relationship between contagious yawning and empathy, or the ability to recognize or understand another’s emotions. Other studies have shown correlations between contagious yawning and intelligence or time of day.Interestingly, people with autism or schizophrenia, both of which involve impaired social skills, demonstrate less contagious yawning despite still yawning spontaneously. A deeper understanding of contagious yawning could lead to insights on these diseases and the general biological functioning of humans.The current study aimed to better define how certain factors affect someone’s susceptibility to contagious yawning. The researchers recruited 328 healthy volunteers, who completed cognitive testing, a demographic survey, and a comprehensive questionnaire that included measures of empathy, energy levels and sleepiness.The participants then watched a three-minute video of people yawning, and recorded the number of times they yawned while watching the video.The researchers found that certain individuals were less susceptible to contagious yawns than others, with participants yawning between zero and 15 times during the video. Of the 328 people studied, 222 contagiously yawned at least once. When verified across multiple testing sessions, the number of yawns was consistent, demonstrating that contagious yawning is a very stable trait.In contrast to previous studies, the researchers did not find a strong connection between contagious yawning and empathy, intelligence or time of day. The only independent factor that significantly influenced contagious yawning was age: as age increased, participants were less likely to yawn. …

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Farm salmon pose clear reproductive threat to wild gene pools, researchers say

Findings published today reveal that, while farmed salmon are genetically different to their wild counterparts, they are just as fertile. This is important information because millions of farmed salmon escape into the wild — posing threats to wild gene pools.Lead Researcher Prof Matt Gage from UEA’s school of Biological Sciences said: “Around 95 per cent of all salmon in existence are farmed, and domestication has made them very different to wild populations, each of which is locally adapted to its own river system.”Farmed salmon grow very fast, are aggressive, and not as clever as wild salmon when it comes to dealing with predators. These domestic traits are good for producing fish for the table, but not for the stability of wild populations.”The problem is that farmed salmon can escape each year in their millions, getting into wild spawning populations, where they can then reproduce and erode wild gene pools, introducing these negative traits.”We know that recently-escaped farmed salmon are inferior to wild fish in reproduction, but we do not have detailed information on sperm and egg performance, which could have been affected by domestication. Our work shows that farm fish are as potent at the gamete level as wild fish, and if farm escapes can revive their spawning behaviour by a period in the wild, clearly pose a significant threat of hybridisation with wild populations.”Researchers used a range of in vitro fertilization tests in conditions that mimicked spawning in the natural environment, including tests of sperm competitiveness and egg compatibility. All tests on sperm and egg form and function showed that farmed salmon are as fertile as wild salmon — identifying a clear threat of farmed salmon reproducing with wild fish.”Some Norwegian rivers have recorded big numbers of farmed fish present — as much as 50 per cent. Both anglers and conservationists are worried by farmed fish escapees which could disrupt locally adapted traits like timing of return, adult body size, and disease resistance.”Salmon farming is a huge business in the UK, Norway and beyond, and while it does reduce the pressure on wild fish stocks, it can also create its own environmental pressures through genetic disruption.”A viable solution is to induce ‘triploidy’ by pressure-treating salmon eggs just after fertilisation — where the fish grows as normal, but with both sex chromosomes; this is normal for farming rainbow trout. The resulting adult develops testes and ovaries but both are much reduced and most triploids are sterile. These triploid fish can’t reproduce if they escape, but the aquaculture industry has not embraced this technology yet because of fears that triploids don’t perform as well in farms as normal diploid fish, eroding profits.”Story Source:The above story is based on materials provided by University of East Anglia. Note: Materials may be edited for content and length.

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Mutations in leukemia gene linked to new childhood growth disorder

Mutations in a gene associated with leukemia cause a newly described condition that affects growth and intellectual development in children, new research reports.A study led by scientists at The Institute of Cancer Research, London, identified mutations in the DNA methyltransferase gene, DNMT3A, in 13 children.All the children were taller than usual for their age, shared similar facial features and had intellectual disabilities. The mutations were not present in their parents, nor in 1,000 controls from the UK population.The new condition has been called ‘DNMT3A overgrowth syndrome’.The research is published today in the journal Nature Genetics and is a part of the Childhood Overgrowth Study, which is funded by the Wellcome Trust, and aims to identify causes of developmental disorders that include increased growth in childhood. The DNMT3A gene is crucial for development because it adds the ‘methylation’ marks to DNA that determine where and when genes are active.Intriguingly, DNMT3A mutations are already known to occur in certain types of leukemia. The mutations that occur in leukemia are different from those in DNMT3A overgrowth syndrome and there is no evidence that children with DNMT3A mutations are at increased risk of cancer.Researchers at The Institute of Cancer Research (ICR), with colleagues at St George’s, University of London, The Royal Marsden NHS Foundation Trust, and genetics centres across Europe and the US, identified the mutations after analysing the genomes of 152 children with overgrowth disorders and their parents.Study leader Professor Nazneen Rahman, Head of Genetics and Epidemiology at The Institute of Cancer Research, London, and Head of Cancer Genetics at The Royal Marsden NHS Foundation Trust, said: “Our findings establish DNMT3A mutations as the cause of a novel human developmental disorder and add to the growing list of genes that appear to have dual, but distinct, roles in human growth disorders and leukemias.”The new discovery is of immediate value to the families in providing a reason for why their child has had problems. Moreover, because the mutations have arisen in the child and have not been inherited from either parent, the risk of another child in the family being similarly affected is very low. This is very welcome news for families.Study co-leader Dr Katrina Tatton-Brown, Clinical Researcher at The Institute of Cancer Research, London, and Consultant Geneticist at St George’s, University of London, said: “Having a diagnosis can make a real difference to families — I recently gave the result back to one of the families in which we identified a DNMT3A mutation and they greatly appreciated having a reason for their daughter’s condition after many years of uncertainty.”Story Source:The above story is based on materials provided by Institute of Cancer Research. Note: Materials may be edited for content and length.

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New theory on cause of endometriosis

Changes to two previously unstudied genes are the centerpiece of a new theory regarding the cause and development of endometriosis, a chronic and painful disease affecting 1 in 10 women.The discovery by Northwestern Medicine scientists suggests epigenetic modification, a process that enhances or disrupts how DNA is read, is an integral component of the disease and its progression. Matthew Dyson, research assistant professor of obstetrics and gynecology at Northwestern University Feinberg School of Medicine and and Serdar Bulun, MD, chair of obstetrics and gynecology at Feinberg and Northwestern Memorial Hospital, also identified a novel role for a family of key gene regulators in the uterus.”Until now, the scientific community was looking for a genetic mutation to explain endometriosis,” said Bulun, a member of the Center for Genetic Medicine and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. “This is the first conclusive demonstration that the disease develops as a result of alterations in the epigenetic landscape and not from classical genetic mutations.”The findings were recently published in PLoS Genetics.Women develop endometriosis when cells from the lining of the uterus, usually shed during menstruation, grow in other areas of the body. The persistent survival of these cells results in chronic pelvic pain and infertility. Although the cause of the disease has remained unknown on a cellular level, there have been several different models established to explain its development.Endometriosis only occurs in menstruating primates, suggesting that the unique evolution behind uterine development and menstruation are linked to the disease. Scientists consider retrograde menstruation — cells moving up the fallopian tubes and into the pelvis — as one probable cause. Previous models, however, have been unable to explain why only 10 percent of women develop the disease when most experience retrograde menstruation at some point. Nor do they explain instances of endometriosis that arise independent of menstruation.Bulun and Dyson propose that an epigenetic switch permits the expression of the genetic receptor GATA6 rather than GATA2, resulting in progesterone resistance and disease development.”We believe an overwhelming number of these altered cells reach the lining of the abdominal cavity, survive and grow,” Bulun said. “These findings could someday lead to the first noninvasive test for endometriosis.”Clinicians could then prevent the disease by placing teenagers predisposed to this epigenetic change on a birth control pill regimen, preventing the possibility of retrograde menstruation in the first place, Bulun said.Dyson will also look to use the epigenetic fingerprint resulting from the presence of GATA6 rather than GATA2 as a potential diagnostic tool, since these epigenetic differences are readily detectable.”These findings have the potential to shift how we view and treat the disease moving forward,” Bulun said.Story Source:The above story is based on materials provided by Northwestern University. …

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3-D imaging sheds light on Apert syndrome development

Three dimensional imaging of two different mouse models of Apert Syndrome shows that cranial deformation begins before birth and continues, worsening with time, according to a team of researchers who studied mice to better understand and treat the disorder in humans.Apert Syndrome is caused by mutations in FGFR2 — fibroblast growth factor receptor 2 — a gene, which usually produces a protein that functions in cell division, regulation of cell growth and maturation, formation of blood vessels, wound healing, and embryonic development. With certain mutations, this gene causes the bones in the skull to fuse together early, beginning in the fetus. These mutations also cause mid-facial deformation, a variety of neural, limb and tissue malformations and may lead to cognitive impairment.Understanding the growth pattern of the head in an individual, the ability to anticipate where the bones will fuse and grow next, and using simulations “could contribute to improved patient-centered outcomes either through changes in surgical approach, or through more realistic modeling and expectation of surgical outcome,” the researchers said in today’s (Feb. 28) issue of BMC Developmental Biology.Joan T. Richtsmeier, Distinguished Professor of Anthropology, Penn State, and her team looked at two sets of mice, each having a different mutation that causes Apert Syndrome in humans and causes similar cranial problems in the mice. They checked bone formation and the fusing of sutures, soft tissue that usually exists between bones n the skull, in the mice at 17.5 days after conception and at birth — 19 to 21 days after conception.”It would be difficult, actually impossible, to observe and score the exact processes and timing of abnormal suture closure in humans as the disease is usually diagnosed after suture closure has occurred,” said Richtsmeier. “With these mice, we can do this at the anatomical level by visualizing the sutures prenatally using micro-computed tomography — 3-D X-rays — or at the mechanistic level by using immunohistochemistry, or other approaches to see what the cells are doing as the sutures close.”The researchers found that both sets of mice differed in cranial formation from their littermates that were not carrying the mutation and that they differed from each other. They also found that the changes in suture closure in the head progressed from 17.5 days to birth, so that the heads of newborn mice looked very different at birth than they did when first imaged prenatally.Apert syndrome also causes early closure of the sutures between bones in the face. Early fusion of bones of the skull and of the face makes it impossible for the head to grow in the typical fashion. The researchers found that the changed growth pattern contributes significantly to continuing skull deformation and facial deformation that is initiated prenatally and increases over time.”Currently, the only option for people with Apert syndrome is rather significant reconstructive surgery, sometimes successive planned surgeries that occur throughout infancy and childhood and into adulthood,” said Richtsmeier. …

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Genetically modified spuds beat blight

In a three-year GM research trial, scientists boosted resistance of potatoes to late blight, their most important disease, without deploying fungicides.The findings, funded by the Biotechnology and Biological Sciences Research Council and The Gatsby Foundation, will be published in Philosophical Transactions of the Royal Society B on 17 February.In 2012, the third year of the trial, the potatoes experienced ideal conditions for late blight. The scientists did not inoculate any plants but waited for races circulating in the UK to blow in.Non-transgenic Desiree plants were 100% infected by early August while all GM plants remained fully resistant to the end of the experiment. There was also a difference in yield, with tubers from each block of 16 plants weighing 6-13 kg while the non-GM tubers weighed 1.6-5 kg per block.The trial was conducted with Desiree potatoes to address the challenge of building resistance to blight in potato varieties with popular consumer and processing characteristics.The introduced gene, from a South American wild relative of potato, triggers the plant’s natural defense mechanisms by enabling it to recognize the pathogen. Cultivated potatoes possess around 750 resistance genes but in most varieties, late blight is able to elude them.”Breeding from wild relatives is laborious and slow and by the time a gene is successfully introduced into a cultivated variety, the late blight pathogen may already have evolved the ability to overcome it,” said Professor Jonathan Jones from The Sainsbury Laboratory.”With new insights into both the pathogen and its potato host, we can use GM technology to tip the evolutionary balance in favor of potatoes and against late blight.”In northern Europe, farmers typically spray a potato crop 10-15 times, or up to 25 times in a bad year. Scientists hope to replace chemical control with genetic control, though farmers might be advised to spray even resistant varieties at the end of a season, depending on conditions.The Sainsbury Laboratory is continuing to identify multiple blight resistance genes that will difficult for blight to simultaneously overcome. Their research will allow resistance genes to be prioritized that will be more difficult for the pathogen to evade.In a new BBSRC-funded industrial partnership award with American company Simplot and the James Hutton Institute, the TSL researchers will continue to identify and experiment with multiple resistance genes. By combining understanding of resistance genes with knowledge of the pathogen, they hope to develop Desiree and Maris Piper varieties that can completely thwart attacks from late blight.Story Source:The above story is based on materials provided by Norwich BioScience Institutes. Note: Materials may be edited for content and length.

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New ideas change your brain cells, research shows

A new University of British Columbia study identifies an important molecular change that occurs in the brain when we learn and remember.Published this month in Nature Neuroscience, the research shows that learning stimulates our brain cells in a manner that causes a small fatty acid to attach to delta-catenin, a protein in the brain. This biochemical modification is essential in producing the changes in brain cell connectivity associated with learning, the study finds.In animal models, the scientists found almost twice the amount of modified delta-catenin in the brain after learning about new environments. While delta-catenin has previously been linked to learning, this study is the first to describe the protein’s role in the molecular mechanism behind memory formation.”More work is needed, but this discovery gives us a much better understanding of the tools our brains use to learn and remember, and provides insight into how these processes become disrupted in neurological diseases,” says co-author Shernaz Bamji, an associate professor in UBC’s Life Sciences Institute.It may also provide an explanation for some mental disabilities, the researchers say. People born without the gene have a severe form of mental retardation called Cri-du-chat syndrome, a rare genetic disorder named for the high-pitched cat-like cry of affected infants. Disruption of the delta-catenin gene has also been observed in some patients with schizophrenia.”Brain activity can change both the structure of this protein, as well as its function,” says Stefano Brigidi, first author of the article and a PhD candidate Bamji’s laboratory. “When we introduced a mutation that blocked the biochemical modification that occurs in healthy subjects, we abolished the structural changes in brain’s cells that are known to be important for memory formation.”Story Source:The above story is based on materials provided by University of British Columbia. Note: Materials may be edited for content and length.

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Whole genome analysis speeds up: 240 full genomes in 50 hours

Although the time and cost of sequencing an entire human genome has plummeted, analyzing the resulting three billion base pairs of genetic information from a single genome can take many months.In the journal Bioinformatics, however, a University of Chicago-based team — working with Beagle, one of the world’s fastest supercomputers devoted to life sciences — reports that genome analysis can be radically accelerated. This computer, based at Argonne National Laboratory, is able to analyze 240 full genomes in about two days.”This is a resource that can change patient management and, over time, add depth to our understanding of the genetic causes of risk and disease,” said study author Elizabeth McNally, MD, PhD, the A. J. Carlson Professor of Medicine and Human Genetics and director of the Cardiovascular Genetics Clinic at the University of Chicago Medicine.”The supercomputer can process many genomes simultaneously rather than one at a time,” said first author Megan Puckelwartz, a graduate student in McNally’s laboratory. “It converts whole genome sequencing, which has primarily been used as a research tool, into something that is immediately valuable for patient care.”Because the genome is so vast, those involved in clinical genetics have turned to exome sequencing, which focuses on the two percent or less of the genome that codes for proteins. This approach is often useful. An estimated 85 percent of disease-causing mutations are located in coding regions. But the rest, about 15 percent of clinically significant mutations, come from non-coding regions, once referred to as “junk DNA” but now known to serve important functions. If not for the tremendous data-processing challenges of analysis, whole genome sequencing would be the method of choice.To test the system, McNally’s team used raw sequencing data from 61 human genomes and analyzed that data on Beagle. They used publicly available software packages and one quarter of the computer’s total capacity. …

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Regenerating orthopedic tissues within the human body

By combining a synthetic scaffolding material with gene delivery techniques, researchers at Duke University are getting closer to being able to generate replacement cartilage where it’s needed in the body.Performing tissue repair with stem cells typically requires applying copious amounts of growth factor proteins — a task that is very expensive and becomes challenging once the developing material is implanted within a body. In a new study, however, Duke researchers found a way around this limitation by genetically altering the stem cells to make the necessary growth factors all on their own.They incorporated viruses used to deliver gene therapy to the stem cells into a synthetic material that serves as a template for tissue growth. The resulting material is like a computer; the scaffold provides the hardware and the virus provides the software that programs the stem cells to produce the desired tissue.The study appears online the week of Feb. 17 in the Proceedings of the National Academy of Sciences.Farshid Guilak, director of orthopaedic research at Duke University Medical Center, has spent years developing biodegradable synthetic scaffolding that mimics the mechanical properties of cartilage. One challenge he and all biomedical researchers face is getting stem cells to form cartilage within and around the scaffolding, especially after it is implanted into a living being.The traditional approach has been to introduce growth factor proteins, which signal the stem cells to differentiate into cartilage. Once the process is under way, the growing cartilage can be implanted where needed.”But a major limitation in engineering tissue replacements has been the difficulty in delivering growth factors to the stem cells once they are implanted in the body,” said Guilak, who is also a professor in Duke’s Department of Biomedical Engineering. “There’s a limited amount of growth factor that you can put into the scaffolding, and once it’s released, it’s all gone. We need a method for long-term delivery of growth factors, and that’s where the gene therapy comes in.”For ideas on how to solve this problem, Guilak turned to his colleague Charles Gersbach, an assistant professor of biomedical engineering and an expert in gene therapy. Gersbach proposed introducing new genes into the stem cells so that they produce the necessary growth factors themselves.But the conventional methods for gene therapy are complex and difficult to translate into a strategy that would be feasible as a commercial product.This type of gene therapy generally requires gathering stem cells, modifying them with a virus that transfers the new genes, culturing the resulting genetically altered stem cells until they reach a critical mass, applying them to the synthetic cartilage scaffolding and, finally, implanting it into the body.”There are a few challenges with that process, one of them being that there are way too many extra steps,” said Gersbach. “So we turned to a technique I had previously developed that affixes the viruses that deliver the new genes onto a material’s surface.”The new study uses Gersbach’s technique — dubbed biomaterial-mediated gene delivery — to induce the stem cells placed on Guilak’s synthetic cartilage scaffolding to produce growth factor proteins. …

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Water samples taken from the Upper Ganges River shed light on the spread of potential ‘superbugs’

Experts from Newcastle University, UK, and the Indian Institute of Technology in Delhi (IIT-Delhi), reveal the spread of antibiotic-resistance to one of the most pristine locations in Asia is linked to the annual human pilgrimages to the region. The research team are now calling on governments around the world to recognise the importance of clean drinking water in our fight against antibiotic resistance.The spread of antibiotic-resistance to one of the most pristine locations in Asia is linked to the annual human pilgrimages to the region, new research has shown.Experts from Newcastle University, UK, and the Indian Institute of Technology in Delhi (IIT-Delhi), sampled water and sediments at seven sites along the Upper Ganges River, in the foothills of the Himalayas.They found that in May and June, when hundreds of thousands of visitors travel to Rishikesh and Haridwar to visit sacred sites, levels of resistance genes that lead to “superbugs” were found to be about 60 times greater than other times of the year.Publishing their findings today in the journal Environmental Science and Technology, the team say it is important to protect people visiting and living at these sites while also making sure nothing interferes with these important religious practices.They argue that preventing the spread of resistance genes that promote life-threating bacteria could be achieved by improving waste management at key pilgrimage sites.”This isn’t a local problem — it’s a global one,” explains Professor David Graham, an environmental engineer based at Newcastle University who has spent over ten years studying the environmental transmission of antibiotic resistance around the world.”We studied pilgrimage areas because we suspected such locations would provide new information about resistance transmission via the environment. And it has — temporary visitors from outside the region overload local waste handling systems, which seasonally reduces water quality at the normally pristine sites.”The specific resistance gene we studied, called blaNDM-1, causes extreme multi-resistance in many bacteria, therefore we must understand how this gene spreads in the environment.”If we can stem the spread of such antibiotic resistant genes locally — possibly through improved sanitation and waste treatment — we have a better chance of limiting their spread on larger scales, creating global solutions by solving local problems.”Funded by the Engineering and Physical Sciences Research Council (EPSRC), the aim of the research was to understand how antibiotic resistance was transmitted due to a specific human activity. Local “hot-spots” of antibiotic resistance exist around the world, particularly densely-populated regions with inconsistent sanitation and poor water quality.By comparing water quality of the Upper Ganges in February and again in June, the team showed that levels of blaNDM-1 were 20 times higher per capita during the pilgrimage season than at other times.Monitoring levels of other contaminants in the water, the team showed that overloading of waste treatment facilities was likely to blame and that in many cases, untreated sewage was going straight into the river where the pilgrims bathe.”The bugs and their genes are carried in people’s guts,” explains Professor Graham. “If untreated wastes get into the water supply, resistance potential in the wastes can pass to the next person and spiralling increases in resistance can occur.”Worldwide, concern is growing over the threat from bacteria that are resistant to the so-called “last resort” class of antibiotics known as Carbapenems, especially if resistance is acquired by aggressive pathogens.Of particular concern is NDM-1, which is a protein that confers resistance in a range of bacteria. NDM-1 was first identified in New Delhi and coded by the resistant gene blaNDM-1.Until recently, strains that carry blaNDM-1 were only found in clinical settings, but in 2008, blaNDM-1 positive strains were found in surface waters in Delhi. Since then, blaNDM-1 has been found elsewhere in the world, including new variants.There are currently few antibiotics to combat bacteria that are resistant to Carbapenems and worldwide spread of blaNDM-1 is a growing concern.Professor Graham, who is based in the School of Civil Engineering and Geosciences at Newcastle University, UK, said the team had planned to repeat their experiments last year, but the region was hit by massive floods in June and the experiments were abandoned.The team has since returned to Rishikesh and Haridwar and hope their work will prompt public action to improve local sanitation, protecting these socially important sites. On a global scale, they want policymakers to recognise the importance of clean drinking water in our fight against antibiotic resistance.”What humans have done by excess use of antibiotics is accelerate the rate of evolution, creating a world of resistant strains that never existed before” explains Graham.”Through the overuse of antibiotics, contamination of drinking water and other factors, we have exponentially speeded-up the rate at which superbugs might develop.”For example, when a new drug is developed, natural bacteria can rapidly adapt and become resistant; therefore very few new drugs are in the pipeline because it simply isn’t cost-effective to make them.”The only way we are going to win this fight is to understand all of the pathways that lead to antibiotic resistance. Clearly, improved antibiotic stewardship in medicine and agriculture is crucial, but understanding how resistance transmission occurs through our water supplies is also critical. We contend that improved waste management and water quality on a global scale is a key step.”

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Scientists chip away at mystery of what lives in our mouths

Scientists have pieced together sections of DNA from 12 individual cells to sequence the genome of a bacterium known to live in healthy human mouths.With this new data about a part of the body considered “biological dark matter,” the researchers were able to reinforce a theory that genes in a closely related bacterium could be culprits in its ability to cause severe gum disease.Why the dark matter reference? More than 60 percent of bacteria in the human mouth refuse to grow in a laboratory dish, meaning they have never been classified, named or studied. The newly sequenced bacterium, Tannerella BU063, is among those that to date have not successfully been grown in culture — and its genome is identified as “most wanted” by the Human Microbiome Project.The federal Human Microbiome Project aims to improve research about the microbes that play a role in health and disease. Those 12 cells of BU063 are a good example of the complexity of life in the mouth: They came from a single healthy person but represented eight different strains of the bacterium.BU063 is closely related to the pathogen Tannerella forsythia, a bacterium linked to the gum disease periodontitis. Despite being “cousins,” this research revealed that they have clear differences in their genetic makeup.Those genes lacking in BU063 but present in forsythia — meaning they are a likely secret behind forsythia’s virulence — are now identified as good targets for further study, researchers say.”One of the tantalizing things about this study was the ability to do random searches of other bacteria whose levels are higher in periodontitis,” said Clifford Beall, research assistant professor of oral biology at The Ohio State University and lead author of the study. “We looked for genes that were present in these bacteria and forsythia and not in BU063. There is one particular gene complex in a whole list of these periodontitis-related bacteria that could be involved with virulence.”The research is published in the journal PLOS ONE.Periodontitis results when extensive inflammation or infection of the gums spreads beyond the gums to damage structures that support the teeth, including bone. Pockets that form between the gums and teeth are filled with different kinds of bacteria. Treatment typically involves deep cleaning or surgery to remove these infected pockets. Because multiple bacteria are associated with the disease, antibiotics have not been considered effective for treatment.And though many bacteria in these pockets have been collected and at least partially identified, their characteristics remain a mystery.”We think some of the gene differences we’ve found in this study are important, but it’s still not clear what all these genes do, meaning we still don’t know why certain bacteria in periodontitis are pathogenic in the first place. …

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Better broccoli, enhanced anti-cancer benefits with longer shelf life

While researching methods to increase the already well-recognized anti-cancer properties of broccoli, researchers at the University of Illinois also found a way to prolong the vegetable’s shelf life.And, according to the recently published study, the method is a natural and inexpensive way to produce broccoli that has even more health benefits and won’t spoil so quickly on your refrigerator shelf.Jack Juvik, a U of I crop sciences researcher, explained that the combined application of two compounds, both are natural products extracted from plants, increased the presence of cancer-fighting agents in broccoli while prolonging the post-harvest storage period.”We had figured out ways to increase the anti-cancer activity in broccoli, but the way we figured it out created a situation that would cause the product to deteriorate more rapidly after application,” Juvik said. “For fresh-market broccoli that you harvest, it’s not too big a deal, but many of these products have to be shipped, frozen, cut up, and put into other products. Usually the idea is to get it from the farm to at least the distributor (grocery store) within two to three days.”If we could figure out a way to prolong the appearance, taste, and flavor long after harvest and maintain the improved health-promoting properties, that’s always of great interest to growers,” he added.The researchers first used methyl jasmonate (MeJA), a non-toxic plant-signal compound (produced naturally in plants) to increase the broccoli’s anti-cancer potential, which they sprayed on the broccoli about four days before harvest. When applied, MeJA initiates a process of gene activity affiliated with the biosynthesis of glucosinolates (GS), which are compounds found in the tissue of broccoli and other brassica vegetables (such as cauliflower, cabbage, and kale).Glucosinolates have been identified as potent cancer-preventative agents because of their ability to induce detoxification enzymes, such as quinone reductase (QR), that detoxify and eliminate carcinogens from the human body.However, during this process, MeJA also signals a network of genes that lead to plant decay by inducing the release of ethylene, Juvik explained. “While we can use MeJA to turn on phytochemicals like the glucosinolates and dramatically increase the abundance of those helpful anti-cancer compounds, MeJA also reduces the shelf life after harvest,” he said.So the researchers tried using the recently developed compound 1-methylcyclopropene (1-MCP), which has been shown to interfere with receptor proteins in the plant that are receptor-sensitive to ethylene. They applied the compound after harvesting the same broccoli that had already been treated with MeJA before harvest.”Ethylene will move and bind to ethylene receptors and that binding process initiates decay. What this compound does is that it more competitively lands on the protein and binds to or pushes out ethylene,” Juvik explained. “It basically stops or dramatically slows down the decay associated with ethylene.”The combination is good,” he said.Like MeJA, 1-MCP is also a non-toxic compound naturally produced in plants, although Juvik said synthetic forms can be produced. He stressed that both the MeJA and 1-MCP treatments required very small amounts of the compounds.”It’s very cheap, and it’s about as toxic as salt. It takes very little to elevate all the desirable aspects. …

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Prostate cancer advance could improve treatment options

Findings published today in the British Journal of Cancer, and funded by the Association for International Cancer Research (AICR), show how a genetic mutation in untreated patients is linked to aggressive cancer later in life. It was previously thought that the mutation only occurred in response to therapy.The research highlights why relapses could occur in some men following hormone therapy. And it could help identify those patients that will develop fatal prostate cancer much earlier for life-extending therapy.Prostate cancer is the most common cancer in men in the UK, with more than 40,000 new cases diagnosed every year. Treatment options for patients diagnosed with early stage prostate cancer vary from “watchful waiting” to hormone-withdrawal therapy, radiotherapy or surgery.Additional tests for indicators of aggressive cancer are necessary to help categorise patients so that those with a low-risk of the disease spreading can avoid unnecessary treatment, and those diagnosed with a high-risk can be targeted for more aggressive first line therapy.Hormone-withdrawal therapy often results in a dramatic remission, however the disease invariably relapses with a resistant form of the cancer. A third of these are due to an increase in copy number of a particular gene called the ‘androgen receptor’. The gene is on the X-Chromosome and so there is normally only one copy of this gene present in men. Prostate cancer thrives on male hormones, and one way that they develop to grow better is to increase the number of copies of the androgen receptor gene. This also enables the cancer to resist therapy.Lead researchers Dr Jeremy Clark and Prof Colin Cooper from UEA’s school of Biological Sciences carried out the research at the Institute of Cancer Research, London, and at UEA.Dr Clark said: “By the age of 60, the majority of men will have signs of prostate cancer. However, only a small proportion of men will die of the disease. The question is — which of these cancers are dangerous and which are not? …

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