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July 20, 2016
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https://www.sciencedaily.com/releases/2016/07/160720135647.htm
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Synthetic biology used to limit bacterial growth and coordinate drug release
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Researchers at the University of California San Diego and the Massachusetts Institute of Technology (MIT) have come up with a strategy for using synthetic biology in therapeutics. The approach enables continual production and release of drugs at disease sites in mice while simultaneously limiting the size, over time, of the populations of bacteria engineered to produce the drugs. The findings are published in the July 20 online issue of
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UC San Diego researchers led by Jeff Hasty, a professor of bioengineering and biology, engineered a clinically relevant bacterium to produce cancer drugs and then self-destruct and release the drugs at the site of tumors. The team then transferred the bacterial therapy to their MIT collaborators for testing in an animal model of colorectal metastasis. The design of the therapy represents a culmination of four previous The new study offers a therapeutic approach that minimizes damage to surrounding cells."In synthetic biology, one goal of therapeutics is to target disease sites and minimize damage," said UC San Diego bioengineering and biology professor Jeff Hasty. He wondered if a genetic "kill" circuit could be engineered to control a population of bacteria In order to achieve this, he and his team synchronized the bacteria to release bursts of known cancer drugs when a bacterial colony self-destructs within the tumor environment. The use of bacteria to deliver cancer drugs "The new work by Jeff Hasty and team is a brilliant demonstration of how theory in synthetic biology can lead to clinically meaningful advances," said Jim Collins, a professor at MIT who is known as a founder of the field of synthetic biology. "Over a decade ago during the early days of the field, Jeff developed a theoretical framework for synchronizing cellular processes across a community of cells. Now his team has shown experimentally how one can harness such effects to create a novel, clinically viable therapeutic approach."In order to observe the bacterial population dynamics, the researchers designed custom microfluidic devices for careful testing before investigations in animal disease models. Consistent with the engineering design, they observed cycling of the bacterial population that successfully limits overall growth while simultaneously enabling production and release of encoded cargo. When the bacteria were equipped with a gene that drives production of a therapeutic, the synchronized lysis of the bacterial colony was shown to kill human cancer cells. It is the first engineered gene circuit in synthetic biology to achieve these objectives."In this paper, we describe a circuit that contains a gene that codes for a small molecule that can diffuse between cells and can turn on genes," said Omar Din, the paper's lead author and a UC San Diego Jacobs School of Engineering bioengineering Ph.D. student in Hasty's research group. "Once the population grows to a critical size -- a few thousand cells -- there's a high-enough concentration of that molecule present in the cells to cause mass transcription of the genes behind the promoter."The molecule, AHL, is known to coordinate gene expression across a colony of bacterial cells. Once on, the genes driven by the promoter are also activated, including the AHL-producing gene itself. Thanks to this positive feedback loop, the more AHL accumulates, the more it is produced. Because AHL is small enough to diffuse between cells and turn on the promoter in neighboring cells, the genes activated by it would also be produced in high amounts, leading to a phenomenon known as quorum sensing. Bacteria use quorum sensing to communicate with each other about the size of their population, and regulate gene expression accordingly. Scientists have used this natural ability of bacteria extensively as a tool.Din used quorum sensing as an engineering tool to synchronize the cells and then added a kill gene that causes cells to break open (lyse) when a bacterial colony grows to a threshold. After the mass self-destruction event, a few cells remain to repopulate the colony and the resulting population dynamics are cyclical."The lysis circuit was originally conceived for use as an aquatic biosensor, but it subsequently became clear that an exciting application could be the coordinated release of drugs when bacteria lyse Watch a video showing the Next, the researchers needed to find the right drug for delivery by the bacteria. They tested three different therapeutic proteins that had been shown to shrink tumors. The tests showed that the proteins were most effective when combined. They placed the genes responsible for these proteins in the circuit along with the lysis gene. They then conducted experiments with HeLa cells that showed enough protein was produced to kill cancer cells.The testing of the therapy in mice was carried out by UC San Diego bioengineering alumnus Tal Danino while he was a postdoctoral researcher in Sangeeta Bhatia's research group at MIT. Danino is now a professor at Columbia University.The bacteria were first injected into mice with a grafted subcutaneous tumor. This mouse model was used to visualize the bacterial population in vivo and observe their dynamics. The result was a decrease in tumor size. Danino then used a more advanced mouse model with liver metastases, where bacteria were fed to the mice. After testing a combination of the engineered bacteria and chemotherapy with this model, the researchers found that the combined therapy prolonged survival of the mice over either therapy administered alone. The researchers note that this new approach has not yet cured any mice. They did find that the therapy led to around a 50 percent increase in life expectancy, but it's difficult to anticipate how this would translate to humans. Taken together, the experiments in mice establish a proof-of-principle for using the tools of synthetic biology to engineer 'tumor-targeting' bacteria to deliver therapeutic proteins in vivo.The new "This paper describes a highly innovative strategy employing synthetic biology to weaponize bacteria," said Bert Vogelstein, Director of the Ludwig Center at Johns Hopkins University and pioneer in the field of cancer genomics. "The authors show that these bacteria can be used to slow the growth of tumors growing in mice. Though much further work will be required to make this therapy applicable to humans, it's just the kind of new, forward-thinking approach that we desperately need if we are to more effectively combat cancer."Next possible steps include investigating the natural presence of bacteria in tumors and then engineering these bacteria for use in vivo and using multiple strains of bacteria to form a therapeutic community."Additionally, we are currently investigating methods for maintaining the circuit inside bacteria," said Din. "Since the proteins produced by the circuit put a burden on the bacteria, the bacteria are prone to mutate these genes. Additionally, there is a selection pressure to get rid of the plasmids which harbor the genes comprising the circuit. Thus, one of our future research aims is to identify strategies for stabilizing the circuit components in bacteria and decreasing their susceptibility to mutations."
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July 18, 2016
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https://www.sciencedaily.com/releases/2016/07/160718133340.htm
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Malaria: A genetically attenuated parasite induces an immune response
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With nearly 3.2 billion people currently at risk of contracting malaria, scientists from the Institut Pasteur, the CNRS and Inserm have experimentally developed a live, genetically attenuated vaccine for
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Despite increased prevention and eradication efforts over the past fifteen years, especially targeting mosquito vectors, malaria remains the parasitic disease that poses the biggest threat for the world's population. Approximately 214 million cases and 438,000 deaths from malaria were recorded in 2015, mostly children under the age of five and pregnant women. An effective vaccine is needed to combat this disease, but the complex biological make-up of The team led by Salaheddine Mécheri in the Biology of Host-Parasite Interactions Unit (a CNRS / Inserm unit at the Institut Pasteur), working in cooperation with Robert Ménard from the Institut Pasteur's Malaria Infection & Immunity Unit, decided to take an original approach to attenuate parasite virulence for effective vaccine development. The scientists genetically modified strains of the The resulting mutants, which no longer expressed HRF, proved to be highly effective in triggering a potent immune response. The absence of HRF boosted the production of the IL-6 cytokine, known for its ability to stimulate the immune response, in the liver and the spleen. This conferred mice with protection from any potential reintroduction of the The HRF mutants obtained in this study are the first genetically modified parasites whose mutation has a direct impact on the host's immune response. Use of this target gene, or a similar strategy to stimulate immunity, could lead to the development of effective, long-lasting live vaccines for malaria."In recent years, the vaccine strategy of choice using live, genetically attenuated parasites to combat malaria has received renewed interest. The HRF mutant is a promising prototype in this respect, offering a rapid, long-lasting and wide-ranging protective effect," commented Salaheddine Mécheri.
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July 18, 2016
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https://www.sciencedaily.com/releases/2016/07/160718133216.htm
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Gas sensors 'see' through soil to analyze microbial interactions
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Rice University researchers have developed gas biosensors to "see" into soil and allow them to follow the behavior of the microbial communities within.
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In a study in the American Chemical Society's journal The bacteria are programmed using synthetic biology to release gas to report when they exchange DNA through horizontal gene transfer, the process by which organisms share genetic traits without a parent-to-child relationship. The biosensors allow researchers to monitor such processes in real time without having to actually see into or disturb a lab soil sample.The Rice researchers expect their technique will serve the same purpose for environmental scientists that fluorescent reporter proteins serve for biochemists who track protein expression and other processes in biological systems.The work by the Rice labs of biogeochemist Caroline Masiello, biochemist Jonathan Silberg, microbiologist George Bennett and lead author Hsiao-Ying (Shelly) Cheng, a Rice graduate student, is the first product of a $1 million grant by the W.M. Keck Foundation to develop gas-releasing microbial sensors."This paper describes a new tool to study how microbes trade genetic material in the environment," said Masiello, a professor of Earth science."We care about this because the process of horizontal gene transfer controls a lot of things that are important to humans either because they're good -- it's how rhizobia trade the genes they need to fix nitrogen and support plant growth -- or they're bad -- it's how bacteria trade antibiotic resistance in soils," she said. "It's been much more challenging in the past to construct models of this dynamic process in real soils and to study how horizontal gene exchange varies across soil types. We've created a new set of tools that makes that possible."The researchers expect scientists will use gas biosensors in the lab to study nitrogen fixing in agriculture, antibiotic exchange in wastewater treatment, gene transfer in conditions where nutrients are scarce and the relationship between gene expression in soil and the release of greenhouse gases."There are other technologies that will build on this," said Silberg, an associate professor of biochemistry and cell biology. "The idea of using gases opens up most anything that's genetically encoded. However, we do need to improve technologies for some of the subtler kinds of questions."He said releasing and sensing methyl halide gas represented an easy proof of concept. "Now we want higher-resolution information about other types of biological events by creating more sophisticated genetic programs using synthetic biology," Silberg said.They expect they will soon be able to test agricultural soil samples to help fine-tune crop growth through more efficient watering and fertilizer use. "How can agriculture get this extra level of efficiency without the waste? Lots of people are coming to that, and there are lots of ways to do it," he said. "We're trying to build high-tech tools that allow us to understand mechanisms to make reliable predictions. That's the long game with these tools."The researchers emphasized that these are tools for soil studies within lab environments. The synthetic microbes are destroyed once the results are obtained.The Rice lab tested soil samples from the National Science Foundation's Kellogg Biological Station Long-Term Ecological Research Site in Michigan after adding Escherichia coli bacteria programmed to release gas upon transfer of their DNA to another microbe. Signals from the gas were up to 10,000 times the lab's detection limit.The gas sensors were effective in anoxic -- or oxygen-depleted -- conditions, unlike green fluorescent protein, which requires oxygen to work. It is anticipated the reporter proteins can be used in many kinds of soil microbes, and some are currently being tested, Bennett said.
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Genetically Modified
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July 18, 2016
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https://www.sciencedaily.com/releases/2016/07/160718133011.htm
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Genome of 6,000-year-old barley grains sequenced for first time
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An international team of researchers has succeeded for the first time in sequencing the genome of Chalcolithic barley grains. This is the oldest plant genome to be reconstructed to date. The 6,000-year-old seeds were retrieved from Yoram Cave in the southern cliff of Masada fortress in the Judean Desert in Israel, close to the Dead Sea. Genetically, the prehistoric barley is very similar to present-day barley grown in the Southern Levant, supporting the existing hypothesis of barley domestication having occurred in the Upper Jordan Valley.
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Members of the research team are from the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK) in Gatersleben, Germany; Bar-Ilan University in Ramat Gan, Israel; Hebrew University, Jerusalem, Israel; the Max Planck Institute for the Science of Human History in Jena, Germany; and the University of Haifa, Israel; The James Hutton Institute, UK; University of California, Santa Cruz, USA; University of Minnesota St. Paul, USA; University of Tübingen, Germany.The analyzed grains, together with tens of thousands of other plant remains, were retrieved during a systematic archaeological excavation headed by Uri Davidovich, from the Institute of Archaeology, The Hebrew University of Jerusalem, and Nimrod Marom, from Zinman Institute of Archaeology, University of Haifa, Israel. The archaeobotanical analysis was led by Ehud Weiss, of Bar-Ilan University. The cave is very difficult to access and was used only for a short time by humans, some 6,000 years ago, probably as ephemeral refuge.Most examination of archaeobotanical findings has been limited to the comparison of ancient and present-day specimens based on their morphology. Up to now, only prehistoric corn has been genetically reconstructed. In this research, the team succeeded in sequencing the complete genome of the 6,000-year-old barley grains. The results are now published in the online version of the journal "These archaeological remains provided a unique opportunity for us to finally sequence a Chalcolithic plant genome. The genetic material has been well-preserved for several millennia due to the extreme dryness of the region," explains Ehud Weiss, of Bar-Ilan University. In order to determine the age of the ancient seeds, the researchers split the grains and subjected half of them to radiocarbon dating while the other half was used to extract the ancient DNA. "For us, ancient DNA works like a time capsule that allows us to travel back in history and look into the domestication of crop plants at distinct time points in the past," explains Johannes Krause, Director of the Department of Archaeogenetics at the Max Planck Institute for the Science of Human History in Jena. The genome of Chalcolithic barley grains is the oldest plant genome to be reconstructed to date.Wheat and barley were already grown 10,000 years ago in the Fertile Crescent, a sickle-shaped region stretching from present-day Iraq and Iran through Turkey and Syria into Lebanon, Jordan and Israel. Up to this day, the wild forms of these two crops persist in the region and are among the major model species studied at the Institute of Evolution in the University of Haifa. "It was from there that grain farming originated and later spread to Europe, Asia and North Africa," explains Tzion Fahima, of the University of Haifa."Our analyses show that the seeds cultivated 6,000 years ago greatly differ genetically from the wild forms we find today in the region. However, they show considerable genetic overlap with present-day domesticated lines from the region," explains Nils Stein, who directed the comparison of the ancient genome with modern genomes at the Leibniz Institute of Plant Genetics and Crop Plant Research (IPK), Gatersleben, with the support of Robbie Waugh and colleagues at the James Hutton Institute, Dundee, Scotland, and Gary Muehlbauer, University of Minnesota, USA. "This demonstrates that the domestication of barley in the Fertile Crescent was already well advanced very early."The comparison of the ancient seeds with wild forms from the region and with so-called 'landraces' (i.e., local barley lines grown by farmers in the Near East) enabled to geographically suggest, according to Tzion Fahima and his colleagues at the University of Haifa and Israel's Tel-Hai College, "the origin of the domestication of barley within the Upper Jordan Valley -- a hypothesis that is also supported by two archaeological sites in the surrounding area where the hitherto earliest remains of barley cultivation have been found.Also the genetic overlap with present-day domesticated lines from the region is revealing to the researchers. "This similarity is an amazing finding considering to what extent the climate, but also the local flora and fauna, as well as the agricultural methods, have changed over this long period of time," says Martin Mascher, from the Leibniz Institute of Plant Genetics and Crop Plant Research, the lead author of the study. The researchers therefore assume that conquerors and immigrants coming to the region did not bring their own crop seeds from their former homelands, but continued cultivating the locally adapted extant landraces.Combining archaeology, archaeobotany, genetics and computational genomics in an interdisciplinary study has produced novel insights into the origins of our crop plants. "This is just the beginning of a new and exciting line of research," predicts Verena Schuenemann, from Tuebingen University, the second lead author of the study. "DNA-analysis of archaeological remains of prehistoric plants will provide us with novel insights into the origin, domestication and spread of crop plants."
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July 15, 2016
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https://www.sciencedaily.com/releases/2016/07/160715181915.htm
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Proteins team up to turn on T cells
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The fates of various cells in our bodies -- whether they become skin or another type of tissue, for example -- are controlled by genetic switches. In a new study, Caltech scientists investigate the switch for T cells, which are immune cells produced in the thymus that destroy virus-infected cells and cancers. The researchers wanted to know how cells make the choice to become T cells.
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"We already know which genetic switch directs cells to commit to becoming T cells, but we wanted to figure out what enables that switch to be turned on," says Hao Yuan Kueh, a postdoctoral scholar at Caltech and lead author of a The study found that a group of four proteins, specifically DNA-binding proteins known as transcription factors, work in a multi-tiered fashion to control the T-cell genetic switch in a series of steps. This was a surprise because transcription factors are widely assumed to work in a simultaneous, all-at-once fashion when collaborating to regulate genes.The results may ultimately allow doctors to boost a person's T-cell population. This has potential applications in fighting various diseases, including AIDS, which infects mature T cells."In the past, combinatorial gene regulation was thought to involve all the transcription factors being required at the same time," says Kueh, who works in the lab of Ellen Rothenberg, Caltech's Albert Billings Ruddock Professor of Biology. "This was particularly true in the case of the genetic switch for T-cell commitment, where it was thought that a quorum of the factors working simultaneously was needed to ensure that the gene would only be expressed in the right cell type."The authors report that a key to their finding was the ability to image live cells in real-time. They genetically engineered mouse cells so that a gene called Bcl11b -- the key switch for T cells -- would express a fluorescent protein in addition to its own Bcl11b protein. This caused the mouse cells to glow when the Bcl11b gene was turn on. By monitoring how different transcription factors, or proteins, affected the activation of this genetic switch in individual cells, the researchers were able to isolate the distinct roles of the proteins.The results showed that four proteins work together in three distinct steps to flip the switch for T cells. Kueh says to think of the process as a team of people working together to get a light turned on. He says first two proteins in the chain (TCF1 and GATA3) open a door where the main light switch is housed, while the next protein (Notch) essentially switches the light on. A fourth protein (Runx1) controls the amplitude of the signal, like sliding a light dimmer."We identify the contributions of four regulators of Bcl11b, which are all needed for its activation but carry out surprisingly different functions in enabling the gene to be turned on," says Rothenberg. "It's interesting -- the gene still needs the full quorum of transcription factors, but we now find that it also needs them to work in the right order. This makes the gene respond not only to the cell's current state, but also to the cell's recent developmental history."Team member Kenneth Ng, a visiting student from California Polytechnic State University, says he was surprised by how much detail they could learn about gene regulation using live imaging of cells."I had read about this process in textbooks, but here in this study we could pinpoint what the proteins are really doing," he says.The next step in the research is to get a closer look at precisely how the T cell genetic switch itself works. Kueh says he wants to "unscrew the panels" of the switch and understand what is physically going on in the chromosomal material around the Bcl11b gene.
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Genetically Modified
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July 14, 2016
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https://www.sciencedaily.com/releases/2016/07/160714120748.htm
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It's all in the genes: New research reveals why some chickens are resistant to bird flu
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The genes of some chickens make them almost completely resistant to a serious strain of bird flu, new research has revealed.
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The findings, which are published in the journal Led by Dr Colin Butter from the School of Life Sciences at the University of Lincoln, UK, this new research, which was carried out at The Pirbright Institute, could prove valuable in developing our understanding of the mechanisms of influenza transmission within and between birds. Dr Butter is one of the UK's leading authorities on avian flu with expertise in animal science, virology and immunology.Influenza virus is the cause of influenza, or 'flu' -- the contagious respiratory viral disease common in many birds and mammals. The viruses circulating in wild birds and domesticated poultry are of particular interest to scientists because they may mutate into forms that are capable of infecting humans, and represent an emerging threat to human health as potential sources of the next flu pandemic.This danger has led the World Health Organisation to highlight effective control measures, as well as an in-depth assessment of factors surrounding the infection of host animals, as part of their research priorities. Dr Butter's study takes an important step towards meeting these needs.Dr Butter, Reader in Bioveterinary Science at the University of Lincoln, said: "It is important for us to understand how different genetic lines of bird react to influenza viruses, so that we can begin to understand the spread of the disease. Until now we knew relatively little about how a bird's genetics can affect its reaction to flu virus but this new research, which for the first time shows that some poultry lines are genetically resistant to avian flu, represents a significant step forwards."Our results are valuable in emphasising the important role a 'host' plays in the spread of avian flu, and also in highlighting a number factors relating to the chain of infection and control mechanisms which are affected by the route of infection."The research team, based at The Pirbright Institute (an international research centre working to improve the health of farm animals worldwide), also included specialists from the University of Oxford and The Francis Crick Institute in London and was funded by the Biotechnology and Biological Sciences Research Council (BBSRC). The researchers examined two different lines of chickens to determine whether genetics played a part in the susceptibility or resistance to infection.They found that birds that carried the virus but were genetically resistant to the disease only shed the virus through their respiratory tract and for a limited period of time, whereas birds which were susceptible to the disease also shed virus in faeces and over a longer time. The researchers discovered that this was the only relevant means of spreading the virus and that resistant birds were therefore completely unable to initiate or sustain a chain of infection. Further results in the study suggest that this could be due to a genetic restriction within the animal which stops the virus spreading when inside the body.Professor Venugopal Nair, the Head of the Avian Viral Diseases programme at The Pirbright Institute, said: "The findings of this study emphasise the importance of examining the intricate nature of the virus-host interactions and the potential role of the host genetic factors influencing the transmission dynamics and outcomes of important diseases such as avian flu."These findings now lead the way for further investigation and work is being planned to discover and examine the precise biological mechanisms behind genetic resistance. This could have major implications for poultry breeding, as well as human flu treatments, in the future.Dr Butter added: "The prospect of breeding birds with natural immunity to influenza virus would certainly widen the scope of existing control measures and perhaps limit the risk to the human population of the emergence of pandemic viruses. Furthermore, as human genetic determinants for catching flu are comparatively unknown, research such as ours which is developing a better understanding of the genes and mechanisms involved could also lead to improved therapeutic options in humans."
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July 13, 2016
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https://www.sciencedaily.com/releases/2016/07/160713100901.htm
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Rat study shows gut microbes play a role in colon cancer susceptibility
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The microscopic organisms that live in our gut do more than help us digest food. A new study in rats bolsters a growing body of evidence that the complex mix of microorganisms found in the gut, known as gut microbiota, could influence a person's likelihood of developing colon cancer.
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Previous studies in humans have shown that cancer is associated with changes in gut microbiota. In the new study, researchers from the University of Missouri in Columbia used rats to further explore the possible relationship between cancer and bacteria in the gut. They implanted embryos from a strain of rats genetically engineered to develop colon cancer into the wombs of three other strains of rats, each with distinct gut microbiota: F344/NHsd (F344), LEW/SsNHsd (LEW), and Crl:SD (SD).By 1.5 months, the microbiota of the pups, which typically develop tumors by 2 to 4 months of age, resembled that of their surrogate mothers. The researchers looked for tumors when the pups had reached 6 months of age and found that rats with the LEW microbiota developed significantly fewer tumors than the other strains. In fact, two of the rats with the LEW strain gut microbiota did not develop colon tumors at all. The researchers also found more tumors in the rats with the F344 gut microbiota that had higher levels of Peptococcaceae and Akkermansia muciniphila bacteria in their guts. Overall, findings from this study provide new insight into the role of gut microbiota as a modulator and a predictor of cancer in this rat model.Susheel Busi will present this research from 2:30-2:45 p.m. during the Cancer and Immunology Symposium in Crystal Ballroom G1 as part of The Allied Genetics Conference, Orlando World Center Marriott, Orlando, Florida.
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Genetically Modified
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July 13, 2016
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https://www.sciencedaily.com/releases/2016/07/160713100851.htm
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Genetically improving sorghum for production of biofuel
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The bioenergy crop sorghum holds great promise as a raw material for making environmentally friendly fuels and chemicals that offer alternatives to petroleum-based products. Sorghum can potentially yield more energy per area of land than other crops while requiring much less input in terms of fertilizer or chemicals. New research examines how genetic improvement of specific sorghum traits, with an eye toward sustainability, could help maximize the usefulness of sorghum as a bioenergy crop.
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The work was conducted by researchers from the University of Florida in Gainesville, Washington State University in Pullman, the USDA-ARS in Lincoln, Nebraska, and the University of Missouri, Columbia. They highlight disease resistance, flooding tolerance and cell wall composition as key targets for genetically improving sorghum for sustainable production of renewable fuels and chemicals.Improving disease resistance, especially to the fungal disease anthracnose, would help expand sorghum to low-productivity land in the southeastern United States. By making the crop more flood resistant, it could be grown on land prone to seasonal flooding that is not typically used for food crops. Finally, making changes in sorghum's cell wall composition could greatly increase the yield of fermentable sugars that can then be converted to fuels such as ethanol. The researchers are using multidisciplinary approaches to make genetic modifications linked with all three traits, with the aim of improving sorghum for renewable energy and chemical production.Wilfred Vermerris will present this research from 9:00-9:15 p.m. during the PEQG Keynote 2 in Crystal Ballroom J1, K-L as part of The Allied Genetics Conference, Orlando World Center Marriott, Orlando, Florida.
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July 12, 2016
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https://www.sciencedaily.com/releases/2016/07/160712130223.htm
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Disentangling the plant microbiome
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With the human population expected to climb from 7.4 billion to more than 11 billion people by 2100, some scientists hope that manipulating the plant microbiome could open up new ways to meet the growing demand for food.
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But breeding more beneficial communities of microbes in and on crop plants may be easier in some plant tissues and growing conditions than others, finds a study led by researchers at Duke University.The results appear July 12 in Mention the microbiome, and most people think of the vast army of microscopic bacteria and fungi that thrive inside the human body, helping us digest our food and fight infection.But plants are also home to millions of microbes that have a huge impact on plant health and growth. Beneficial bacteria that live in and on roots and leaves can help plants take up minerals and nutrients from the soil, fend off pathogens and withstand salt, heat and drought.Previous studies have shown that a plant's genes can shape its microbiome in the lab, but far fewer studies have measured the extent to which the plant microbiome is under genetic control in the field."There can be thousands of different kinds of bacteria within a single leaf," said first author Maggie Wagner, who was a graduate student at Duke at the time of the study. "The question is: what factors influence the microbes that end up living inside the plant?"To disentangle the relative effects of a plant's genes, environment and other factors, Wagner and colleagues used DNA sequencing to analyze the microbiome of a spindly wildflower called Boechera stricta where it grows wild in the Rocky Mountains.Genetically identical lines of the plant were germinated from seed in greenhouses at Duke and then transplanted as seedlings into three experimental gardens in central Idaho.Two to four years later, the researchers returned to harvest the plants. They sequenced the bacterial DNA in the roots and leaves of 440 individuals.When they compared the bacterial sequences they found to databases of known microbes, the researchers detected nearly 4,000 types of bacteria living inside the plants.Proteobacteria and Actinobacteria were the most common bacterial groups. Roots harbored two to ten times more types of bacteria than leaves.Environmental differences among sites and between years -- such as soil pH, moisture and temperature -- had the biggest influence on the plants' bacterial makeup.On average, 5 percent or less of the variation in microbial diversity was controlled by plant genetics. The influence of plant genes was stronger in the leaves than in the roots, and varied significantly from one site to another."There's a lot of interest in harnessing the power of microbiomes for plant health, especially for crop plants," said Wagner, now a postdoctoral researcher in the Department of Plant Pathology at North Carolina State University.Agricultural companies are already coating seeds with beneficial microbes or adding them to the soil to boost the production of crops like soybean and corn and reduce our reliance on fertilizers and pesticides.These results support the idea that it is also possible to use traditional plant breeding to shape the plant microbiome. But at least for crops in the same plant family as Boechera, such as cabbage and broccoli, breeding a better microbiome may be easier in leaves than roots, and a microbial community that breeds true in one location or set of growing conditions may not be reliably inherited in others."Microbiomes could be a very useful tool for improving agricultural productivity in the face of population growth and climate change," Wagner said, "but designing an effective breeding program could be a lot harder than some people think it is."
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Genetically Modified
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July 11, 2016
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https://www.sciencedaily.com/releases/2016/07/160711092303.htm
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Diabetes reversal after bypass surgery linked to changes in gut microorganisms
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Studies have shown that bariatric surgery can lead to remission of type 2 diabetes mellitus (T2DM) in rodents and humans, but this beneficial effect cannot be explained solely by weight loss. In a new study published in
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"Our research showed that duodenum-jejunum gastric bypass (DJB) surgery may be applied to cure diabetes of both genetic (mutation) and environmental (diet-induced) origin," explained lead investigator Xiang Gao, PhD, of State Key Laboratory of Pharmaceutical Biotechnology and MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute and the Collaborative Innovation Center of Genetics and Development, Nanjing University. "We found that DJB surgery induced gut microbiota alterations, which may be the key reason for diabetes remission after bariatric surgery. Our data indicate that suppressed inflammation is the result, not the cause, of diabetes reversal in these genetically modified mice."The research was performed in the T2DM mouse model that mimics key symptoms including insulin resistance, high blood levels of lipids, metabolic inflammation, and obesity. These mice harbor genetic mutation in brain-derived neurotrophic factor (Bdnf) leading to Bdnf deficiency. Bdnf is a member of the neurotrophic family of growth factors and is a key regulator of both brain function and metabolic balance."Our findings suggest that Bdnf deficiency-induced diabetes can be reversed by DJB surgery in mice, which has potential for the treatment of diabetes in humans," stated Dr. Gao. He and his team found that bypass surgery reversed the metabolic abnormalities indicative of diabetes without changing Bdnf expression directly. Glucose tolerance and insulin sensitivity were greatly improved and there was less fat accumulation in liver and white adipose tissue. Insulin sensitivity reached normal levels within two weeks following surgery and lasted for at least eight weeks. Six weeks after bypass surgery, oral glucose tolerance in the treated mice was significantly lower than in the diabetic mice that had undergone a sham operation and was similar to levels observed in untreated controls.Examination of the composition of bacteria and other microorganisms in the gut of mutated mice before and after bypass surgery and in the control group, showed a decrease in pathogenic bacteria and an increase in beneficial microflora that coincided with the onset of better glycemic control. "More mechanistic studies of gut microbiota alterations after bypass surgery are needed to explain how different families of microbiota may regulate nutrient metabolism in the host," noted Dr. Gao.Inflammation, especially in white fat tissue and liver, is thought to play an important role in obesity and T2DM. Eight weeks after bypass surgery, significant reductions in inflammatory indicators occurred in the liver and fat tissue, although the post-surgical anti-inflammatory effects occurred after insulin sensitivity improved. "These results indicate that the alleviation of inflammation was not the direct cause of the improvement in insulin sensitivity that resulted from bypass surgery," commented Dr. Gao.
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July 7, 2016
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https://www.sciencedaily.com/releases/2016/07/160707151011.htm
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The debut of a robotic stingray, powered by light-activated rat cells
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Researchers have created a robotic mimic of a stingray that's powered and guided by light-sensitive rat heart cells.
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The work exhibits a new method for building bio-inspired robots by means of tissue engineering. Batoid fish, which include stingrays, are distinguished by their flat bodies and long, wing-like fins that extend from their heads. These fins move in energy-efficient waves that emanate from the front of the fin to the back, allowing batoids to glide gracefully through water. Inspired by this design, Sung-Jin Park et al. endeavored to build a miniature, soft tissue robot with similar qualities and efficiency.They created neutrally charged gold skeletons that mimic the stingray's shape, which were overlaid with a thin layer of stretchy polymer. Along the top of the robotic ray, the researchers strategically aligned rat cardiomyocytes (muscle cells). The cardiomyocytes, when stimulated, contract the fins downward.Since stimulating the fins to turn in an upward motion would require a second layer of cardiomyocytes, the researchers instead designed the gold skeleton in a shape that stores some downward energy, which is later released as the cells relax, allowing the fins to rise. So that the researchers can control the robot's movement using pulses of light, the cardiomyoctyes were genetically engineered to respond to light cues.Asymmetrical pulses of light can be used to turn the robot to the left or right, the researchers showed, and different frequencies of light can be used to control its speed, as demonstrated in a series of videos. The method works well enough to guide the robot through a basic obstacle course. The robotic stingray, containing roughly 200,000 cardiomyocytes, is 16 millimeters long and weighs just 10 grams.
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Genetically Modified
| 2,016 |
June 27, 2016
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https://www.sciencedaily.com/releases/2016/06/160627124430.htm
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Global, evolving, and historic make-up of malaria species uncovered
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A team of scientists has uncovered the global, evolving, and historic make-up of
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""The DNA data show that In their study, which appears in the journal The researchers collected patient samples through the International Centers of Excellence for Malaria Research, a global network of independent research centers in malaria-endemic settings that provide knowledge, tools, and evidence-based strategies to support in-country researchers working in a variety of settings, especially within governments and healthcare institutions.The sequencing of the parasite's genome offered an array of new insights into the nature of The research was conducted through the National Institute of Allergy and Infectious Diseases (NIAID)/National Institutes of Health (NIH) International Centers of Excellence for Malaria Research (U19AI089676, U19AI089681, U19AI089686, U19AI089672, U19AI089702) and Contract No. HHSN272200900018C, as well as supported by the National Council for Science and Technology Mexico (29005-M SALUD-2004-119), and the Victorian State Government Operational Infrastructure Support and the Australian Government (NHMRC IRIISS), among others.
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Genetically Modified
| 2,016 |
June 23, 2016
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https://www.sciencedaily.com/releases/2016/06/160623150109.htm
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Fix for 3-billion-year-old genetic error could dramatically improve genetic sequencing
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For 3 billion years, one of the major carriers of information needed for life, RNA, has had a glitch that creates errors when making copies of genetic information. Researchers at The University of Texas at Austin have developed a fix that allows RNA to accurately proofread for the first time. The new discovery, published June 23 in the journal
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Certain viruses called retroviruses can cause RNA to make copies of DNA, a process called reverse transcription. This process is notoriously prone to errors because an evolutionary ancestor of all viruses never had the ability to accurately copy genetic material.The new innovation engineered at UT Austin is an enzyme that performs reverse transcription but can also "proofread," or check its work while copying genetic code. The enzyme allows, for the first time, for large amounts of RNA information to be copied with near perfect accuracy."We created a new group of enzymes that can read the genetic information inside living cells with unprecedented accuracy," says Jared Ellefson, a postdoctoral fellow in UT Austin's Center for Systems and Synthetic Biology. "Overlooked by evolution, our enzyme can correct errors while copying RNA."Reverse transcription is mainly associated with retroviruses such as HIV. In nature, these viruses' inability to copy DNA accurately may have helped create variety in species over time, contributing to the complexity of life as we know it.Since discovering reverse transcription, scientists have used it to better understand genetic information related to inheritable diseases and other aspects of human health. Still, the error-prone nature of existing RNA sequencing is a problem for scientists."With proofreading, our new enzyme increases precision and fidelity of RNA sequencing," says Ellefson. "Without the ability to faithfully read RNA, we cannot accurately determine the inner workings of cells. These errors can lead to misleading data in the research lab and potential misdiagnosis in the clinical lab."Ellefson and the team of researchers engineered the new enzyme using directed evolution to train a high-fidelity (proofreading) DNA polymerase to use RNA templates. The new enzyme, called RTX, retains the highly accurate and efficient proofreading function, while copying RNA. Accuracy is improved at least threefold, and it may be up to 10 times as accurate. This new enzyme could enhance the methods used to read RNA from cells."As we move towards an age of personalized medicine where everyone's transcripts will be read out almost as easily as taking a pulse, the accuracy of the sequence information will become increasingly important," said Andy Ellington, a professor of molecular biosciences. "The significance of this is that we can now also copy large amounts of RNA information found in modern genomes, in the form of the RNA transcripts that encode almost every aspect of our physiology. This means that diagnoses made based on genomic information are far more likely to be accurate. "In addition to Ellefson and Ellington, authors include Jimmy Gollihar, Raghav Shroff, Haridha Shivram and Vishwanath Iyer. All are affiliated with the Department of Molecular Biosciences at The University of Texas at Austin.This research was supported by grants from the Defense Advanced Research Projects Agency, National Security Science and Engineering Faculty Fellows, NASA and the Welch Foundation. A provisional patent was filed on the new sequence of the enzyme.
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Genetically Modified
| 2,016 |
June 23, 2016
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https://www.sciencedaily.com/releases/2016/06/160623122936.htm
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Smell tells intruder mice how to behave
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Male mice appear to be precisely wired to know when they are intruders in another male's territory, according to a study published June 23 in
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"There seems to be a specific part of the brain that says, yeah, this is someone's house, and you need to act accordingly," says lead investigator Larry Zweifel, assistant professor of pharmacology at the University of Washington.The hypothalamus, which is known to be the seat of social behavior in the brain, may contain additional sets of distinct cells wired to respond to other specific social contexts. Together, these signals tell an animal how to behave. The study, one of the first to look at what drives the behavior of subordinate mice rather than aggressors, could help researchers better understand disorders in social behavior in humans. For instance, individuals with autism, schizophrenia, depression, and social anxiety all experience disruptions in social behavior."The basic circuitry that regulates social function in a mouse is essentially the same as it is in humans," says Zweifel. "We're studying these discrete cells in the parts of the brain that regulate social behavior in mice to get some insight into where things go wrong to cause social behavioral deficits."Zweifel's team came across the cells--neurons in the ventral premammillary nucleus of the hypothalamus--because they are genetically programmed to release dopamine, a neurotransmitter his team studies. It turns out that they don't release dopamine. But the team couldn't help but be intrigued when they saw that these cells were strongly activated only to male smells.The team followed up by exposing male mice to a set of social contexts. A control group experienced no encounter. Others were either intruders into a cage occupied by either a male or female or were intruded upon in their own residence by either a male or female. The cells were activated in intruders only upon entering the cage of a male resident. Odors from both the resident animal and the cage, which contained bedding marked by the resident's urine, drove the cellular activity.Most studies have focused on aggressive behavior because of its relevance to human social struggles, but in this social context, an intruder into another's cage is by definition a subordinate. "The parts of the brain that control aggression have been fairly well established," says Zweifel. "But what's it like if you're the animal that's encroaching into another's territory?"Zweifel's team found that the intruder mouse's immediate impulse is to get more information. "They sniff and explore, like dogs in a park," says Zweifel. "Who are you, and are you fun to play with?"Animals sniff and explore in other social situations, too, but these specific cells have nothing to do with it. "If you introduce a male into a female's cage, social investigation goes through the roof," says Zweifel. "But these cells aren't activated in this context."To pin down the exact role of these cells, Zweifel's team inhibited them so that they would not be activated. This reduced exploration in male intruders. They also activated these cells artificially using optogenetics, the genetic engineering of cells to respond to light input. Activation increased exploration in males, causing them to sniff and explore mice they'd known since birth as if they were strangers.In females, however, the cells were not activated by same-sex odorants, suggesting that these cells are not wired to control social exploration in females. "We don't know what they're doing in females yet," says Zweifel.While sensory input induces these hypothalamic neurons to fire, the social control happens downstream in the medial amygdala and other regions of the hypothalamus. Zweifel's team intends to look there next to learn more about how social behavior is wired in the brain.
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Genetically Modified
| 2,016 |
June 16, 2016
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https://www.sciencedaily.com/releases/2016/06/160616140715.htm
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Genetic mutation causes ataxia in humans, dogs
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Cerebellar ataxia is a condition of the cerebellum that causes an inability to coordinate muscle movements. A study publishing June 16 in
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"There are a number of genes linked to motor function that can be involved in ataxia when mutated," says Michel Baudry, a neurobiologist at Western University of Health Sciences. "Not only have we identified another, but we've also refined our understanding of the calpain enzymes, which is important because several companies have been talking about using calpain inhibitors to treat neurodegenerative diseases."Calpain is an enzyme involved with learning, memory, and neurodegeneration in the brain, but it comes in two major forms--calpain-1 and calpain-2. "Nobody could make much progress on figuring out what each form of calpain was doing, because most of the pharmacological studies used molecules that inhibit both types at once" says Baudry. But about eight years ago, Baudry's team obtained a line of mice genetically engineered to lack only calpain-1 to examine the differences.Baudry's mouse studies caught the attention of Henry Houlden, a neurologist at University College London, who was leading a team investigating ataxia. "Around two years ago, we identified two families with CAPN1 mutations with ataxia and spasticity," Houlden explains. Once the researchers determined that the mutation affected calpain-1's function, they looked up Baudry's work on the calpain-1 knockout mice. "Together, we started to investigate the function of this gene," says Houlden. The current study includes four families with members that have CAPN1 mutations and display symptoms of ataxia.Baudry's team started testing whether the knockout mice had ataxia by tracking their balance when placed on a rotating rod. "We had never looked at the cerebellum in our mice before," says Baudry. "But sure enough, we found that they had mild cerebellar ataxia."The researchers demonstrated that during the first week after birth, the mice lacking calpain-1 had a much higher rate of neuronal death in their cerebellum, as compared to normal mice, and many of their synapses failed to mature."Calpain-1 is neuroprotective," explains Baudry. "When the brain matures, excess neurons are supposed to be pruned--but calpain-1 prevents that process from getting out of control." The team further determined that calpain-1 works normally by degrading an enzyme called PHLPP1, a protein phosphatase involved in programmed cell death. Injecting another compound involved in the pathway during the first postnatal week caused the newborn mice with CAPN1 mutations to develop normally.Pharmacologically, the attempts to use calpain inhibitors in the clinic may not be working because they don't discriminate between calpain-1 and calpain-2, says Baudry: "If you want to try to address neurodegeneration, you have to use a calpain-2 inhibitor." Baudry is currently working with a team to develop calpain-2 inhibitors as neuroprotective drugs, under the umbrella of a new company called NeurAegis.
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Genetically Modified
| 2,016 |
June 15, 2016
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https://www.sciencedaily.com/releases/2016/06/160615100352.htm
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Scientists discover protective strategy against pesticide-linked Parkinson's disease
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Exposure to a group of common pesticides, called dithiocarbamates, has long been associated with an increased risk of Parkinson's disease, although the mechanism by which the compounds exert their toxicity on the brain has not been completely understood. A new UCLA study sheds light on the toxicity of the compounds while also suggesting a strategy that may help protect against the disease.
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The research focused on the fungicide ziram, which is used extensively in heavily agricultural areas such as California's Central Valley and which causes the loss of the main source of dopamine in the central nervous system. Loss of this source, called dopaminergic neurons, is associated with Parkinson's disease.The pesticide-linked damage starts with ziram's ability to increase concentrations of a protein, called α-synuclein, which is abundant in the human brain. The α-synuclein proteins then aggregate, or clump together, harming neighboring neurons. This phenomenon also occurs in Parkinson's disease that is not due to pesticide exposures, making it a target for researchers searching for a broad treatment.In the new study, conducted in zebrafish, researchers found that elimination of the α-synuclein protein protected the zebrafish against the ziram-induced loss of dopamine neurons. Because most cases of Parkinson's disease appear to be at least partially caused by environmental factors such as pesticide exposure, these findings support the approach that targeting α-synuclein could slow or stop the progression of Parkinson's in most people with the disease, said study lead author Jeff Bronstein, a professor of neurology and director of movement disorders at the David Geffen School of Medicine at UCLA."These findings add to the growing literature linking pesticide exposure and the development of Parkinson's disease and offers important insights into the mechanisms of ziram toxicity," Bronstein said. "A better understanding of the pathogenesis of Parkinson's disease will ultimately lead to new treatments and eventually a cure."The study was published June 15 in the peer-reviewed journal First, the researchers developed a model of Parkinson's in zebrafish -- the first such animal model of the disease -- and exposed them to ziram so that they lost dopamine. They found that the fish exposed to the ziram did not swim properly, evidence of a Parkinson's-like condition.Then the researchers genetically knocked out the α-synuclein protein in the zebrafish and exposed them to ziram again. The ziram failed to make the fish sick, and the animals continued to swim properly.Next, the researchers gave the non-protected zebrafish an investigational drug, CLRO1, being developed by UCLA scientists that breaks up the protein aggregates, or clumps, in Parkinson's patients. They found that the drug provided protection from the Parkinson's-like condition in the fish."Getting rid of the protein genetically or breaking up the aggregates with this drug protected against ziram toxicity," Bronstein said. "This is important -- it establishes that environmental toxins work on same pathway that is in play in those genetically disposed to Parkinson's. Most important, we can use drugs being developed now on patients who get Parkinson's because of ziram exposure."Going forward, Bronstein and his team will determine if other environmental substances are using the same mechanism to cause Parkinson's. They will also conduct further research on CLRO1 in preparation for clinical trials in human subjects.About 70 percent of Parkinson's cases cannot be explained by genetics, Bronstein said, so the new finding could be vital to a large percentage of patients whose disease is not genetically caused.
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Genetically Modified
| 2,016 |
June 9, 2016
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https://www.sciencedaily.com/releases/2016/06/160609151203.htm
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New insights into mechanism of metabolic disorders: Proteome of an entire family
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Scientists have won new knowledge on the molecular background of fat and energy metabolism disorders through a large-scale proteomic study with mice. The proteome is the entire set of proteins -- in this case, proteins from the livers of mice. A research group specialising in proteomics, led by ETH Zurich Professor Ruedi Aebersold, and a group specialising in mitochondrial physiology and liver diseases, led by EPFL Professor Johan Auwerx, worked together on this ground-breaking project.
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"As with humans, there are individual differences in mice; for example, in cholesterol metabolism or susceptibility to metabolic disorders such as fatty liver," says Evan Williams, one of the two lead authors of the study, which has been published in the latest edition of the scientific journal The scientists compiled comprehensive protein data from a large group of mice to help them explain additional metabolic differences. They used a mass spectrometry measuring technique, known as SWATH-MS, developed in recent years by Aebersold's group at ETH Zurich. It allowed the researchers to measure the concentrations of a broad spectrum of liver proteins in the laboratory animals."It's much more complex to measure the set of proteins than to sequence the entire genome," explains Yibo Wu, postdoc in Aebersold's group and co-lead author of the study. "Using the SWATH-MS technique, it's possible to measure thousands of different proteins in hundreds of samples." In this case, the researchers measured 2,600 different proteins in the tissue samples. In order to conduct these proteome measurements, an extensive protein database is required; Wu has played a leading role in recent years in building up such a database for mouse proteins.The examined cohort consisted of 40 mice strains that date back to the same two ancestors and are therefore closely related to each other. Identical groups of mice, each consisting of representatives from these 40 strains, were fed either a high-fat diet, junk food in human terms, or a healthy low-fat diet. Over a period of weeks, the scientists charted the conventional medical (physiological) data of the mice and tested, inter alia, their performance and how quickly they reduced their weight through physical activity. As the scientists expected, the animals responded in different ways to the high-fat foods. Some of the animals developed metabolic disorders, such as fatty liver, others did not.For the evaluation, the researchers combined the physiological data with data for genome (DNA), transcriptome (RNA) and proteome. From this combined data they were able to characterise the role of several specific proteins in fat and energy metabolism more precisely. One of these is COX7A2L. In mice this protein is responsible for the formation of supercomplexes found in mitochondria (the cell's internal 'power plants'), as the researchers found out. These supercomplexes consist of more than 100 different proteins and are responsible for providing cells with the required energy in the appropriate form. Mice with too little COX7A2L protein can't provide sufficient amounts of available energy, which impacts adversely on the whole organism.This study is the most comprehensive proteomic study to date using SWATH-MS in mammals. The technique developed by ETH Zurich scientists is also ready for use in cohort studies in humans: the researchers in Aebersold's group have generated a corresponding database for thousands of human proteins. "Like the mouse strains in this study, each patient with a disease is genetically different," says ETH Professor Aebersold. "The approach we used in the mouse cohort can now be applied one-for-one in research on human diseases, and particularly for personalized medicine."
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Genetically Modified
| 2,016 |
June 9, 2016
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https://www.sciencedaily.com/releases/2016/06/160609134528.htm
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Rapid retrieval of live, infectious pathogens from clinical samples
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Pinpointing the type of bacteria that are at the root of an infection in clinical samples removed from living tissues, such as blood, urine or joint fluids, to quickly identify the best anti-microbial therapy still poses a formidable challenge. The standard method of culturing can take days to reveal pathogens, and they often fail to bring them to light altogether.
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A team lead by Donald Ingber, M.D., Ph.D., at the Wyss Institute for Biologically Inspired Engineering at Harvard University now reports a method in "We leveraged FcMBL -- the genetically engineered pathogen-binding protein we developed for our sepsis therapeutic device program -- to develop a fast and simple technology to help overcome this diagnostic roadblock," said Ingber, who is the Wyss Institute's Founding Director, the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. "Using clinical samples of joint fluids, we were able to show that this method can be used to quickly and efficiently isolate bacterial pathogens for various kinds of subsequent analysis, including PCR, which is commonly used for molecular diagnostics in clinical laboratories."FcMBL is a recombinant form of the human blood protein, Mannose Binding Lectin (MBL), fused to a portion of the antibody Fc domain. The engineered protein can bind to more than 90 different microbial pathogens and toxins, ranging from fungi to bacteria, viruses and parasites and it even binds antibiotic-resistant organisms.Earlier studies [Hyperlink] by Ingber's team have used FcMBL as the key component of a dialysis-like blood cleansing device for sepsis therapy. The Wyss Institute's efforts focusing on pathogen capture in different applications are funded by the Defense Advanced Research Project Agency (DARPA)."Given our exciting results pulling pathogens out of flowing blood using FcMBL, we asked whether we could also capture live bacteria from clinical samples for detailed molecular analysis," said Michael Super, Ph.D., a Wyss Senior Staff Scientist who helped lead this research effort.As a starting point, the team investigated samples obtained from patients with infections of joints or joint replacements, where the pathogen "We showed that FcMBL-coated magnetic beads bound to 12 clinical The team remedied both problems with a cocktail of enzymes. When joint samples are pre-treated with this cocktail, protease enzymes eliminated the interfering immune factors to expose bacterial surface sugars for FcMBL binding, while another enzyme in the mix, hyaluronidase, breaks down a class of large polymers that are responsible for the high viscosity of joint fluids."Using this approach, we were able to isolate and concentrate pathogenic S. aureus cells in only 2 hours, which could make a tremendous difference in clinical settings, especially in cases where pathogens can not be cultured straight out of the sample. This could let us fast-track the best antimicrobial treatment option in often critical situations," said Alain Bicart-See, M.D. the study's first author who as a Wyss Institute Visiting Scholar collected the samples at Hospital Joseph-Ducuing in Toulouse, France where he specializes in infectious diseases.After their isolation, pathogenic bacteria can be molecularly identified with methods that either look for the presence of DNA snippets specific for candidate pathogens or identified by mass spectrometry, a technique that can survey all pathogenic proteins present in a sample. The Wyss researchers also think that the method will facilitate antibiotic susceptibility testing since bacteria retrieved with the method are alive."This isolation technique should be able to be used to rapidly identify pathogens in other clinical samples including blood, urine, sputum, and cerebral spinal fluid, and thus, it will hopefully shorten the time required for physicians to select the optimal therapy. In addition to saving more lives, this new method also should reduce the use of broad-spectrum antibiotic therapies, or suboptimal regimens, and thereby, decrease development of antibiotic-resistant organisms that become a more general threat in the long run," said Ingber.
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Genetically Modified
| 2,016 |
June 8, 2016
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https://www.sciencedaily.com/releases/2016/06/160608120623.htm
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Gene-drive modified organisms are not ready to be released into environment, experts say
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The emerging science of gene drives has the potential to address environmental and public health challenges, but gene-drive modified organisms are not ready to be released into the environment and require more research in laboratories and highly controlled field trials, says a new report from the National Academies of Sciences, Engineering, and Medicine. To navigate the uncertainty posed by this fast-moving field of study and make informed decisions about the development and potential application of gene-drive modified organisms, the committee that conducted the study and wrote the report recommended a collaborative, multidisciplinary, and cautionary approach to research on and governance of gene drive technologies.
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Gene drives are systems of biased inheritance that enhance a genetic element's ability to pass from parent organism to offspring. With the advent of new, more efficient, and targeted gene-editing techniques such as CRISPR/Cas9, gene modifications can, in principle, be spread throughout a population of living organisms intentionally and quickly via a gene drive, circumventing traditional rules of inheritance and greatly increasing the odds that an altered gene spreads throughout a population. Preliminary evidence suggests that gene drives developed in the laboratory could spread a targeted gene through nearly 100 percent of a population of yeast, fruit flies, or mosquitoes.Gene drives have the potential to address public health threats, conservation-related issues, agricultural pests, and other challenges. For example, gene drives might be developed to modify organisms that carry infectious diseases such as dengue, malaria, and Zika. In agriculture, a gene drive might be used to control or alter organisms that damage crops or carry crop disease. On the other hand, some gene-drive modified organisms might lead to unintended consequences, such as the unintentional disruption of a non-target species or the establishment of a second, more resilient invasive species."The science and technology associated with gene drives is developing very quickly," said committee co-chair James P. Collins, Virginia M. Ullman Professor of Natural History and the Environment in the School of Life Sciences, Arizona State University. "But before gene-drive modified organisms are put into the environment, our committee urges caution -- a lot more research is needed to understand the scientific, ethical, regulatory, and social consequences of releasing such organisms."The remaining gaps in our understanding of the biology of gene drives and the potential effects of gene-drive modified organisms on the environment are fundamental considerations in the development and release of gene-drive modified organisms, the report says. Laboratory and field research is needed to refine gene drive mechanisms and better understand how gene drives work, from the molecular level through species and ecosystem levels. Meeting this need will require collaboration among multiple fields of study including molecular biology, population genetics, evolutionary biology, and ecology. In addition, open-access, online data banks and standard operating procedures should be established to share information and guide research design."Responsible research on gene drives and gene drive technology requires consideration of values and public engagement throughout the process," said committee co-chair Elizabeth Heitman, associate professor of medical ethics, Vanderbilt University Medical Center's Center for Biomedical Ethics and Society. "From conducting basic research, to choosing a problem to address and an organism to modify, to devising strategies to pursue field testing safely, it is essential to examine each gene drive on a case-by-case basis and to engage stakeholders and the public in assessing their potential development."The committee recommended a phased testing approach to gene drive research to guide research from the laboratory to the field. Because the goal of using a gene drive is to spread genetic information throughout a population rapidly, it is difficult to anticipate its impact and important to minimize the potential for unintended consequences. Phased testing can facilitate evidence-based decision making, with every step promoting careful study and evaluation.Each proposed field test or environmental release of a gene-drive modified organism should be subject to robust ecological risk assessment before being approved, the report says. These assessments, which take into account the gene drive's characteristics, effects on humans and the environment, and local values and governance, are a key tool for determining a gene drive's impacts. As of May 2016, no ecological risk assessment has been conducted for a gene-drive modified organism.Public engagement can help frame and define the potential harms and potential benefits of using a gene-drive modified organism, and must be built into risk assessment and practical decision making. The outcomes of public engagement may be as crucial as scientific outcomes in making decisions about whether or not to release a gene-drive modified organism into the environment. The report recommends that the governing authorities, including research institutions, funders, and regulators, develop and maintain clear policies and mechanisms for how public engagement will factor into research, ecological risk assessments, and public policy decisions about gene drives.The report finds that the current regulatory practices for assessing risks or potential environmental effects of field experiments or planned releases are inadequate for gene drives. At present, the regulation of gene drive research does not fit within the purview of any of the U.S. agencies involved in the Coordinated Framework for the Regulation of Biotechnology, which includes the Food and Drug Administration, U.S. Department of Agriculture, and the U.S. Environmental Protection Agency. Gene drive research also raises regulatory concerns about biosafety, biosecurity, and the potential for this technology intended for human benefit to be intentionally misused for harmful purposes.The report calls for flexible and rapidly adaptable governance policies, such as the World Health Organization's Guidance Framework for Testing of Genetically Modified Mosquitoes, to facilitate international coordination and collaboration. In selecting sites for potential field testing and environmental releases, the committee recommended that preference be given to locations in countries with existing scientific capacity and governance frameworks to conduct and oversee the safe investigation of gene drives and the development of gene-drive modified organisms. The scientific community -- including researchers, institutions, and those who fund the research -- must engage with policymakers on best practices to prevent misuse of gene-drive modified organisms.
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Genetically Modified
| 2,016 |
June 6, 2016
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https://www.sciencedaily.com/releases/2016/06/160606100844.htm
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Residents concerned about use of genetically modified mosquitoes to curb insect population
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A small survey of residents of a Florida Keys neighborhood where officials hope to release genetically modified mosquitos to potentially reduce the threat of mosquito-borne illnesses such as Zika finds a lack of support for the control method, according to new research from former and current students at the Johns Hopkins Bloomberg School of Public Health.
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The findings, published last month in The novel mosquito control method has been tried in Brazil and Panama with some success, and the U.S. Food and Drug Administration is considering a trial in Key Haven, a community in the Florida Keys. The scientists, current students and recent graduates of the Bloomberg School, say the research could help public health and community leaders address head-on the objections of residents where such control measures are being contemplated, as the fight against mosquito-borne illnesses heats up. The survey was conducted in the second half of 2015, after locally transmitted dengue and chikungunya cases had been discovered in Florida, but before the Zika epidemic in South and Central America became big news. There is concern that Zika could spread north into the continental U.S. The band from southern Florida, including the Keys, to southern Texas, as well as Hawaii, are believed to be part of the region of the U.S. most at risk.A British company, Oxitec, has been trying for years to get approval to test their genetically modified mosquitoes in the Keys. Some local residents have tried to kill the field trial, concerned about unanticipated consequences of introducing these lab-grown insects into the wild."With the start of mosquito season here and all of the media coverage of Zika, public health officials are going to be faced with important decisions about mosquitoes and how to best protect citizens," says Meghan McGinty, MPH, MBA, a recent PhD recipient from the Bloomberg School and one of the researchers. "People will have objections and it is critical for them to be heard. Our research provides a starting point to understand how the community feels and to begin a dialogue about how to address mosquito-borne diseases."For the study, the researchers mailed a survey in July 2015 to all 456 households in the Key Haven community outside Key West; they received 89 responses. Residents were evenly split over whether they consider mosquitoes a nuisance, but two-thirds agreed there was a need to reduce the mosquito population. Women were more opposed to the genetically modified mosquitoes than men.The most popular mosquito control method was draining standing water to reduce breeding, followed by treating standing water with larvicides designed to kill new mosquitoes before they hatch and spraying insecticides. The least popular was using genetically modified mosquitoes to reduce the population.Fifty-eight percent of respondents said they either "oppose" or "strongly oppose" the use of genetically modified mosquitoes to combat the risk of disease. The most common objection was a concern over disturbing the local ecosystem by eliminating mosquitoes from the food chain. Respondents were also concerned that using genetically modified mosquitoes could lead to an increase in the use of other genetically modified products.Since the survey was conducted before the extent of the Zika epidemic was widely known, respondents were only asked about their concerns about dengue and chikungunya (the area was hit by a dengue outbreak several years ago). Sixty-three percent said they were "a little worried" or "very worried" about becoming sick from one of those mosquito-borne illnesses, and most said they or someone they knew would contract one of the diseases.Researcher Crystal Boddie, MPH, a DrPH candidate in the Bloomberg School's Department of Health Policy and Management, who is also employed at the University of Pittsburgh Medical Center's Center for Health Security in Baltimore, says that those who were most concerned about the risk of contracting one of the mosquito-borne illnesses were more likely to support the release of the new mosquitoes.The researchers recognize that their sample size is small and that with the rising threat of Zika, opinions may have changed about the use of these genetically modified mosquitoes.Still, Boddie says, "the survey provides a baseline of information about residents' attitudes and concerns and can help health officials better educate the public about the risks and benefits of these genetically modified mosquitoes. Then we need to have an honest conversation about where this control method does -- or does not -- fit in."
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Genetically Modified
| 2,016 |
June 2, 2016
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https://www.sciencedaily.com/releases/2016/06/160602220711.htm
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Genetically modified golden rice falls short on lifesaving promises
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Heralded on the cover of Time magazine in 2000 as a genetically modified (GMO) crop with the potential to save millions of lives in the Third World, Golden Rice is still years away from field introduction and even then, may fall short of lofty health benefits still cited regularly by GMO advocates, suggests a new study from Washington University in St. Louis.
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"Golden Rice is still not ready for the market, but we find little support for the common claim that environmental activists are responsible for stalling its introduction. GMO opponents have not been the problem," said lead author Glenn Stone, professor of anthropology and environmental studies in Arts & Sciences.First conceived in the 1980s and a focus of research since 1992, Golden Rice has been a lightning rod in the battle over genetically modified crops.GMO advocates have long touted the innovation as a practical way to provide poor farmers in remote areas with a subsistence crop capable of adding much-needed Vitamin A to local diets. A problem in many poor countries in the Global South, Vitamin A deficiencies leave millions at high risk for infection, diseases and other maladies, such as blindness.Some anti-GMO groups view Golden Rice as an over-hyped Trojan Horse that biotechnology corporations and their allies hope will pave the way for the global approval of other more profitable GMO crops.GMO proponents often claim that environmental groups such as Greenpeace should be blamed for slowing the introduction of Golden Rice and thus, prolonging the misery of poor people who suffer from Vitamin A deficiencies.In a recent article in the journal "The rice simply has not been successful in test plots of the rice breeding institutes in the Philippines, where the leading research is being done," Stone said. "It has not even been submitted for approval to the regulatory agency, the Philippine Bureau of Plant Industry (BPI).""A few months ago, the Philippine Supreme Court did issue a temporary suspension of GMO crop trials," Stone said. "Depending on how long it lasts, the suspension could definitely impact GMO crop development. But it's hard to blame the lack of success with Golden Rice on this recent action."While activists did destroy one Golden Rice test plot in a 2013 protest, it is unlikely that this action had any significant impact on the approval of Golden Rice."Destroying test plots is a dubious way to express opposition, but this was only one small plot out of many plots in multiple locations over many years," he said. "Moreover, they have been calling Golden Rice critics 'murderers' for over a decade."Stone, an internationally recognized expert on the human side of global agricultural trends, was an early advocate for keeping an open mind about "humanitarian" GMO crops, such as Golden Rice.He has also supported the development of a genetically modified strain of cassava, a starchy root crop eaten by subsistence farmers across much of Africa. Unfortunately, efforts to develop a genetically improved, more productive and disease-resistant strain of cassava also appear to be a long way from practical field introduction, he notes."Golden Rice was a promising idea backed by good intentions," Stone said. "In contrast to anti-GMO activists, I argued that it deserved a chance to succeed. But if we are actually interested in the welfare of poor children -- instead of just fighting over GMOs -- then we have to make unbiased assessments of possible solutions. The simple fact is that after 24 years of research and breeding, Golden Rice is still years away from being ready for release."Since 2013, Stone has directed a major Templeton Foundation-funded research project on rice in the Philippines. His research compares Golden Rice to other types of rice developed and cultivated in the Philippines. These include high-yield "Green Revolution" rice strains developed in the 1960s in an effort to industrialize rice farming, and ''heirloom'' landrace varieties long cultivated on the spectacular terraces of the Cordillera mountains of northern Luzon.As part of the Golden Rice initiative, researchers introduce genes into existing rice strains to coax these GMO plants into producing the micronutrient beta carotene in the edible part of the grain. The presence of beta carotene gives the genetically modified rice a yellow hue, which explains the "golden" in its name.As Stone and Glover note in the article, researchers continue to have problems developing beta carotene-enriched strains that yield as well as non-GMO strains already being grown by farmers.Researchers in Bangladesh also are in the early stages of confined field trials of Golden Rice, but it is doubtful that these efforts will progress any quicker than in the Philippines.Even if genetic modification succeeds in creating a strain of rice productive enough for poor farmers to grow successfully, it's unclear how much impact the rice will have on children's health.As Stone and Glover point out, it is still unknown if the beta carotene in Golden Rice can even be converted to Vitamin A in the bodies of badly undernourished children. There also has been little research on how well the beta carotene in Golden Rice will hold up when stored for long periods between harvest seasons, or when cooked using traditional methods common in remote rural locations, they argue.Meanwhile, as the development of Golden Rice creeps along, the Philippines has managed to slash the incidence of Vitamin A deficiency by non-GMO methods, Stone said.
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Genetically Modified
| 2,016 |
May 26, 2016
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https://www.sciencedaily.com/releases/2016/05/160526151738.htm
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How prions kill neurons: New culture system shows early toxicity to dendritic spines
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Prion diseases are fatal and incurable neurodegenerative conditions of humans and animals. Yet, how prions kill nerve cells (or neurons) remains unclear. A study published on May 26, 2016 in
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Some of the earliest and potentially most critical changes in prion-infected brains occur at the connections (synapses) between neurons, and specifically at so-called dendritic spines. Dendritic spines are protrusions on the post-synaptic branches of a neuron that receive signals from other neurons. However, to date there has been no experimentally tractable model system in which the early degenerative changes caused by prions can be studied in cell culture.David Harris, from Boston University School of Medicine, USA, and colleagues have argued that the availability of a neuronal culture system susceptible to the toxic effects of prions is crucial for understanding the underlying mechanisms and for potentially identifying drugs that block neurodegeneration. In this study, they report such a system, which reproduces acute prion neurotoxicity through degeneration of dendritic spines on cultured hippocampal neurons.The researchers started by culturing neurons isolated from the hippocampus (a brain region involved in learning and memory) of mice. These neurons can be maintained in culture for three weeks, during which time they develop mature dendrites studded with spines, which contain chemical receptors that receive signals from neighboring neurons.When the cultured neurons were exposed to brain extracts from mice with prion disease (which are known to contain large amounts of infectious prions), they showed rapid and dramatic changes: Within hours, there was severe retraction of spines, reducing their overall density and the size of the remaining ones. These changes in spines occurred without large-scale destruction of the neurons, suggesting that they represented very early events that would affect the functioning of the neurons prior to their actual death. When the researchers used three different kinds of purified prion preparations, they saw similar dendritic spine retraction in the cultures.It is known that the development of prion disease involves an alteration of the normal cellular prion protein (designated PrPC), such that it assumes an abnormal shape (designated PrPSc). The resulting PrPSc is toxic to neurons, and it can propagate an infection by corrupting the shape of additional molecules of PrPC in a kind of chain-reaction.To test whether the effects of PrPSc in their cell cultures depended on the neurons' normal PrPC, the researchers generated cultures of hippocampal neurons from mice that were genetically engineered to lack PrPC. These cultures, they found, were resistant to toxic prion exposure, i.e., they did not show any of the changes in dendritic spines seen in neurons from normal mice containing PrPC.Finally, the researchers tested neurons from transgenic mice expressing mutant PrPC molecules that were missing a specific region that is thought to interact with toxic prions. And indeed, the researchers found that these neurons--just like neurons without any PrPC--were immune to prion toxicity.The researchers summarize their results as follows: "We describe a new system that is capable of reproducing acute prion neurotoxicity, based on PrPSc-induced degeneration of dendritic spines on cultured hippocampal neurons." The system, they state, "provides new insights into the mechanisms responsible for prion neurotoxicity, and it provides a platform for testing potential therapeutic agents."Because "dendritic spine loss is a common theme in many neurodegenerative conditions, including Alzheimer's, Huntington's, and Parkinson's diseases, and has been suggested to contribute to clinical symptoms in patients," the researchers also suggest that their system allows for "direct comparisons between pathogenic mechanisms involved in prion diseases and other neurodegenerative disorders."
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Genetically Modified
| 2,016 |
May 25, 2016
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https://www.sciencedaily.com/releases/2016/05/160525102150.htm
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Consumer knowledge gap on genetically modified food
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While consumers are aware of genetically modified crops and food, their knowledge level is limited and often at odds with the facts, according to a newly published study by a University of Florida researcher.
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Last year, Brandon McFadden, an assistant professor of food and resource economics at the UF Institute of Food and Agricultural Sciences, published a study that showed scientific facts scarcely change consumers’ impressions of genetically modified food and other organisms.Consumer polls are often cited in policy debates about genetically modified food labeling. This is especially true when discussing whether food that is genetically modified should carry mandatory labels, McFadden said. In conducting their current study, McFadden and his colleague, Jayson Lusk, an agricultural economics professor at Oklahoma State University, wanted to know what data supported consumers’ beliefs about genetically modified food and gain a better understanding of preferences for a mandatory label.So he conducted the survey to better understand what consumers know about biotechnology, breeding techniques and label preferences for GM foods.Researchers used an online survey of 1,004 participants that asked questions to measure consumers’ knowledge of genetically modified food and organisms. Some of those questions tried to determine objective knowledge of genetically modified organisms, while others aimed to find out consumers’ beliefs about genetically modified foods and crops.The results led McFadden to conclude that consumers do not know as much about the facts of genetically modified food and crops as they think they do.Of those sampled, 84 percent supported a mandatory label for food containing genetically modified ingredients. However, 80 percent also supported a mandatory label for food containing DNA, which would result in labeling almost all food. The study is published in the
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Genetically Modified
| 2,016 |
May 20, 2016
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https://www.sciencedaily.com/releases/2016/05/160520110406.htm
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Modified microalgae converts sunlight into valuable medicine
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Researchers from Copenhagen Plant Science Centre at University of Copenhagen have succeeded in manipulating a strain of microalgae to form complex molecules to an unprecedented extent. This may pave the way for an efficient, inexpensive and environmentally friendly method of producing a variety of chemicals, such as pharmaceutical compounds.
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"So basically, the idea is that we hijack a portion of the energy produced by the microalgae from their photosynthetic systems. By redirecting that energy to a genetically modified part of the cell capable of producing various complex chemical materials, we induce the light driven biosynthesis of these compounds," says Post Doc Agnieszka Janina Zygadlo Nielsen, who along with colleagues Post Doc Thiyagarajan Gnanasekaran and PhD student Artur Jacek Wlodarczyk has been the main researcher behind the study.The researchers have as such modified microalgae genetically to become small chemical factories with a build in power supply. According to the research team's study, this basically allows sunlight being transformed into everything ranging from chemotherapy or bioplastics to valuable flavor and fragrance compounds.As Agnieszka Janina Zygadlo Nielsen describes, the problem with many of these substances today is namely that they are extremely expensive and difficult to make, and therefore produced only in small quantities in the medicinal plants."A cancer drug like Taxol for instance is made from old yew trees, which naturally produce the substance in their bark. It is a cumbersome process which results in expensive treatments. If we let the microalgae run the production this problem could be obsolete," she explains.Thiyagarajan Gnanasekaran clarifies that the method can be run sustainably and continuously, and that this is what makes it even more spectacular compared to present methods."Our study shows that it is possible to optimize the enzymatic processes in the cells using only sunlight, water and CO2 by growing them in transparent plastic bags in a greenhouse. Theoretically, the water could be replaced with sewage water, which could make the process run on entirely renewable energy and nutrient sources. Recycling wastewater from industry and cities to produce valuable substances would surely be positive," he points out."If we can create a closed system that produces the valued chemicals from water, sunlight and CO2, it would be a fully competitive method compared to the ones used today, where it is primarily extracted from plants or yeast and However, the research team emphasizes that the method using genetically modified microalgae has its limitations at present time. As Thiyagarajan Gnanasekaran points out, the microalgae use much of the harnessed sunlight to keep their own metabolic processes running:"It is difficult to produce large quantities of the desired compounds in microalgae because they have to use a large amount of the produced energy for themselves, since they are fully photosynthetic organisms. Exactly for this reason, it makes good sense to have them produce the particularly valuable substances which are cost effective to produce in relatively small quantities at a time, as for instance medicine."However, according to the team the expanding methods and genetic tools for microalgae are likely to overcome these limitations within near future.
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Genetically Modified
| 2,016 |
May 19, 2016
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https://www.sciencedaily.com/releases/2016/05/160519130240.htm
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Study identifies unexpected mutation in commonly used research mice
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A strain of inbred mice commonly used for the creation of so-called knockout animals has been found to carry a previously undetected mutation that could affect the results of immune system research studies. In paper receiving online publication in
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"We found an unexpected mutations with potentially important consequences in strains of mice that had been separately engineered in labs in California and Japan, and after some detailed detective work, we traced the problem to a subline of B6 mice from one specific company that have been sold in Asia, North America, Europe and Israel," says Shiv Pillai, MD, PhD, a member of the Ragon Institute and program director of the Autoimmune Center of Excellence at Massachusetts General Hospital. "We have notified this company -- Harlan Laboratories, which is now part of Envigo -- of our findings, and they have been very responsive and will use approaches we have provided to check all of their colonies."Individual inbred mouse strains used for research differ from each other at many gene sites, which can result in differences in their immune responses. In immunological studies conducted across the world, mutant mice are "backcrossed" for many generations into B6 mice so that all genes other than the mutant gene are derived from the B6 strain. This allows the comparison of data from laboratories in different parts of the world and simplifies creating mice with mutations in several genes.A 2009 study out of Pillai's lab had found that two strains of mice engineered to lack the genes Siae or Cmah -- both of which code for enzymes involved with a family of proteins called sialic acids -- also had significant defects in the development of B cells, which were assumed to be the result of the knockout genes. But when Siae-deficient mice were further backcrossed with a different group of C57BL/6 mice, the result was a strain of Siae-knockout mice that did not have the B cell development defects. A newly engineered strain of mice with a different Siae mutation also was found to have normal B cell development.Detailed genetic sequencing of the first knockout line identified a previously unsuspected mutation in a gene called Dock2, located on a chromosome 11 instead of chromosone 9 where Siae is located. The same mutation had been previously reported in two colonies of a different knockout mouse developed in Japan. Pillai's team also found the Dock2 mutation in a completely different group of mice from the University of California, San Diego -- where their Siae-mutant strain had been developed -- and realized that three different engineered strains with the same unwanted mutation had probably acquired it from a common source, eventually traced back to a subline of C57BL/6 mice from Harlan/Envigo.Since most research papers using C57BL/6 mice or other such "background" strains do not indicate the specific subline, of which there are many, the Ragon Institute researchers have no way of knowing how many studies might be affected by their findings. But they hope the publication of these results will alert other research teams to the potential need to review their results. Several commercial laboratories have instituted measures to prevent the occurrence of random mutation in inbred mouse strains, and Pillai notes, all commercial vendors should establish such programs."While embryonic stem cells from C57BL/6 mice have recently become available, which allows the generation of knockout strains with less backcrossing, B6 mice are used for many different kinds of experiments, including as controls," says Pillai, who is a professor of Medicine and of Health Sciences and Technology at Harvard Medical School. "Researchers who have used them need to re-genotype the mice to look for the Dock2 mutation, and if they find it, check to see whether their results are preserved if the Dock2 mutation is bred out."
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Genetically Modified
| 2,016 |
May 19, 2016
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https://www.sciencedaily.com/releases/2016/05/160519140828.htm
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A path away from reliance on oil, with the help of bacteria
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Adding genes to bacteria offers sustainable routes to make compounds currently obtained from petrochemicals.
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The dream of replacing petrochemicals with renewable resources in the manufacture of synthetic fibers and plastics has moved a step closer. Researchers at Agency for Science, Technology and Research (A*STAR), Singapore, have genetically modified the bacterium Escherichia coli to produce a compound that can be converted into a base material for manufacturing nylon and other synthetic products."We need to reduce consumption of oil and gas and move toward more sustainable technologies," explains Sudhakar Jonnalagadda who carried out the work with colleagues at the A*STAR Institute of Chemical and Engineering Sciences.Production of most synthetic fibers and plastics begins with crude oil; a finite resource whose extraction and processing has significant environmental impact. The alternative sustainable route uses bacteria to make the precious starting materials from simple substances such as glucose. The glucose can be extracted from biomass which includes crops and other biological materials that can be grown to meet demand.Bacteria do not naturally produce the required products in significant quantities, so the trick is to persuade these microorganisms to become mini manufacturing plants for chemicals required by industry. One such chemical is muconic acid, which can be readily converted into adipic acid, a chemical used in huge quantities to manufacture nylon.The A*STAR team inserted three genes into E. coli to establish the metabolic pathway that produces muconic acid. Adding these new genes, however, was the first step in a complex genetic engineering task. "A major challenge was to modify the normal E. coli pathways to divert more glucose toward our desired product," says Jonnalagadda.He explains that the combined activity of the foreign and the native genes must be controlled to prevent the accumulation of metabolic intermediates as well as to maximize the efficiency of muconic acid production. This was achieved by using computer simulation to analyze the metabolism of the modified bacteria which helped to pinpoint the required genetic changes.The researchers are now investigating other ways to make the production of muconic acid more efficient. Already, though, this new process produces the compound more efficiently with use of inexpensive and less complex raw materials compared with alternative options."We are at the early stage," says Jonnalagadda, assessing the path from the current achievement into commercial applications. The same research route is also leading the A*STAR researchers and others worldwide to make a wide range of compounds to free the chemical manufacturing industry from its reliance on oil.
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Genetically Modified
| 2,016 |
May 17, 2016
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https://www.sciencedaily.com/releases/2016/05/160517131632.htm
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Genetically engineered crops: Experiences and prospects
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An extensive study by the National Academies of Sciences, Engineering, and Medicine has found that new technologies in genetic engineering and conventional breeding are blurring the once clear distinctions between these two crop-improvement approaches. In addition, while recognizing the inherent difficulty of detecting subtle or long-term effects on health or the environment, the study committee found no substantiated evidence of a difference in risks to human health between current commercially available genetically engineered (GE) crops and conventionally bred crops, nor did it find conclusive cause-and-effect evidence of environmental problems from the GE crops. However, evolved resistance to current GE characteristics in crops is a major agricultural problem.
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A tiered process for regulating new crop varieties should focus on a plant's characteristics rather than the process by which it was developed, the committee recommends in its report. New plant varieties that have intended or unintended novel characteristics that may present potential hazards should undergo safety testing -- regardless of whether they were developed using genetic engineering or conventional breeding techniques. New "-omics" technologies, which dramatically increase the ability to detect even small changes in plant characteristics, will be critical to detecting unintended changes in new crop varieties.The committee used evidence accumulated over the past two decades to assess purported negative effects and purported benefits of current commercial GE crops. Since the 1980s, biologists have used genetic engineering to produce particular characteristics in plants such as longer shelf life for fruit, higher vitamin content, and resistance to diseases. However, the only genetically engineered characteristics that have been put into widespread commercial use are those that allow a crop to withstand the application of a herbicide or to be toxic to insect pests.The fact that only two characteristics have been widely used is one of the reasons the committee avoided sweeping, generalized statements about the benefits and risks of GE crops. Claims about the effects of existing GE crops often assume that those effects would apply to the genetic engineering process generally, but different characteristics are likely to have different effects. A genetically engineered characteristic that alters the nutritional content of a crop, for example, is unlikely to have the same environmental or economic effects as a characteristic for herbicide resistance.The committee examined almost 900 research and other publications on the development, use, and effects of genetically engineered characteristics in maize (corn), soybean, and cotton, which account for almost all commercial GE crops to date. "We dug deeply into the literature to take a fresh look at the data on GE and conventionally bred crops," said committee chair Fred Gould, University Distinguished Professor of Entomology and co-director of the Genetic Engineering and Society Center at North Carolina State University. In addition, the committee heard from 80 diverse speakers at three public meetings and 15 public webinars, and read more than 700 comments from members of the public to broaden its understanding of issues surrounding GE crops.In releasing its report, the committee established a website that enables users to look up the places in the report that address comments received by the committee from the public, and also find the reasoning behind the report's main findings and recommendations. "The committee focused on listening carefully and responding thoughtfully to members of the public who have concerns about GE crops and foods, as well as those who feel that there are great benefits to be had from GE crops," said Gould.There is some evidence that GE insect-resistant crops have had benefits to human health by reducing insecticide poisonings. In addition, several GE crops are in development that are designed to benefit human health, such as rice with increased beta-carotene content to help prevent blindness and death caused by vitamin A deficiencies in some developing nations.Evidence shows that in locations where insect-resistant crops were planted but resistance-management strategies were not followed, damaging levels of resistance evolved in some target insects. If GE crops are to be used sustainably, regulations and incentives are needed so that more integrated and sustainable pest-management approaches become economically feasible. The committee also found that in many locations some weeds had evolved resistance to glyphosate, the herbicide to which most GE crops were engineered to be resistant. Resistance evolution in weeds could be delayed by the use of integrated weed-management approaches, says the report, which also recommends further research to determine better approaches for weed resistance management.Insect-resistant GE crops have decreased crop loss due to plant pests. However, the committee examined data on overall rates of increase in yields of soybean, cotton, and maize in the U.S. for the decades preceding introduction of GE crops and after their introduction, and there was no evidence that GE crops had changed the rate of increase in yields. It is feasible that emerging genetic-engineering technologies will speed the rate of increase in yield, but this is not certain, so the committee recommended funding of diverse approaches for increasing and stabilizing crop yield.All technologies for improving plant genetics -- whether GE or conventional -- can change foods in ways that could raise safety issues, the committee's report notes. It is the product and not the process that should be regulated, the new report says, a point that has also been made in previous Academies reports.In determining whether a new plant variety should be subject to safety testing, regulators should focus on the extent to which the novel characteristics of the plant variety (both intended and unintended) are likely to pose a risk to human health or the environment, the extent of uncertainty about the severity of potential harm, and the potential for human exposure -- regardless of whether the plant was developed using genetic-engineering or conventional-breeding processes. " -omics" technologies will be critical in enabling these regulatory approaches.The United States' current policy on new plant varieties is in theory a "product" based policy, but USDA and EPA determine which plants to regulate at least partially based on the process by which they are developed. But a process-based approach is becoming less and less technically defensible as the old approaches to genetic engineering become less novel and as emerging processes -- such as genome editing and synthetic biology -- fail to fit current regulatory categories of genetic engineering, the report says.The distinction between conventional breeding and genetic engineering is becoming less obvious, says the report, which also reviews emerging technologies. For example, genome editing technologies such as CRISPR/Cas9 can now be used to make a genetic change by substituting a single nucleotide in a specific gene; the same change can be made by a method that uses radiation or chemicals to induce mutations and then uses genomic screening to identify plants with the desired mutation -- an approach that is considered to be conventional breeding by most national regulatory systems. Some emerging genetic engineering technologies have the potential to create novel plant varieties that are hard to distinguish genetically from plants produced through conventional breeding or processes that occur in nature. A plant variety that is conventionally bred to be resistant to a herbicide and one that is genetically engineered to be resistant to the same herbicide can be expected to have similar associated benefits and risks.Regulating authorities should be proactive in communicating information to the public about how emerging genetic-engineering technologies or their products might be regulated and how new regulatory methods may be used. They should also proactively seek input from the public on these issues. Not all issues can be answered by science alone, the report says. Policy regarding GE crops has scientific, legal, and social dimensions.For example, on the basis of its review of the evidence on health effects, the committee does not believe that mandatory labeling of foods with GE content is justified to protect public health, but it noted that the issue involves social and economic choices that go beyond technical assessments of health or environmental safety; ultimately, it involves value choices that technical assessments alone cannot answer.Report:
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Genetically Modified
| 2,016 |
May 17, 2016
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https://www.sciencedaily.com/releases/2016/05/160517122311.htm
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Chance finding could transform plant production
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An almost entirely accidental discovery by University of Guelph researchers could transform food and biofuel production and increase carbon capture on farmland.
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By tweaking a plant's genetic profile, the researchers doubled the plant's growth and increased seed production by more than 400 per cent.The findings were published in the March 2016 issue of The team studied Arabidopsis, a small flowering plant often used in lab studies because of its ease of use and its similarity to some common farm crops. They found that inserting a particular corn enzyme caused the plant's growth rate to skyrocket."Even if the effects in a field-grown crop were less, such as only a tenth of what we've seen in the lab, that would still represent an increase in yield of 40 to 50 per cent, compared with the average one to two per cent a year that most breeding programs deliver," said Prof. Michael Emes, Department of Molecular and Cellular Biology (MCB).He said the team's finding could boost yields of important oilseed crops such as canola and soybean, as well as crops such as camelina, increasingly grown for biofuels.Larger plants would capture more atmospheric carbon dioxide without increasing the amount of farmland, said Emes. "Farmers and consumers would benefit significantly in terms of food production, green energy and the environment. The ramifications are enormous."The finding came almost by chance.Studying the enzyme's effect on starch, the researchers noticed that their genetically engineered plants looked different and much larger in photos taken by lead author Fushan Liu, a former post-doctoral MCB researcher."That's when we realized that we were looking at something potentially much more important," said Ian Tetlow, an MCB professor and study co-author.Although genetic engineering led to more flowers and pods containing seeds, it left the seed composition unchanged."The seeds are where we would get the oil from, and consistent composition is important so that the function and use of the oil isn't changed," said Tetlow.The researchers plan to test canola and other crops. Field tests and analysis with industry and government will likely take several years."This could have enormous implications for agriculture, carbon capture, food production, animal feedstocks and biodiesel," said Emes."These findings are without parallel, and we came to them almost by accident. The reason we started the work was to test some ideas in basic science. It just goes to show that you never know where that science will take you."
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Genetically Modified
| 2,016 |
May 13, 2016
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https://www.sciencedaily.com/releases/2016/05/160513111830.htm
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Using precision-genetics in pigs to beat cancer
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The numbers are staggering: more than 40 % is the lifetime risk of developing cancer in the U.S., with only 66 % survival-rates 5 years after diagnosis, for all types of cancer. Trends suggest that in 2015, over 1.6 million new cases were diagnosed in the U.S., with over 580,000 deaths in consequence.
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These numbers emphasize the need to better understand and treat the various forms of the disease, but mouse models usually used in cancer research have given us limited answers. However, Senior Scientist Adrienne Watson and colleagues at Recombinetics and the University of Minnesota, say that pigs may turn out to be the best alternative models."Many organ systems vary so greatly between rodents and humans that certain types of cancer cannot be accurately modelled," says Watson, despite the major role mouse models have played in our understanding of the disease. The authors conclude that the five deadliest cancers in the U.S. cannot be modeled in rodents, or have ineffective models for identification of treatments that translate to the clinic.Cancer is a genetic disease where cells acquire or inherit genetic mutations, which result in malfunctioning proteins that cause uncontrolled growth of cells in the blood or solid organs. "The anatomical, physiological, and genetic similarities between swine and humans are striking, suggesting that disease modeling in this large animal may better represent the development and progression of cancer seen in people."The authors explain, in their article that was published recently in Using genetically modified pigs would allow overcoming one of the main drawbacks of rodent models, which is their inability so far to identify safe and effective drugs to treat cancer. For example, the size and ease in handling pigs allows for drugs to be administered in the same way as in patients, and for follow up blood-work over time.The authors caution that, as for any novel animal model to be useful in cancer research, it must be adopted and fully tested in many laboratories and under many circumstances. But the higher costs involved in handling these animals in the laboratory setting may be well worth the gains in our understanding of this deadly disease.
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Genetically Modified
| 2,016 |
May 12, 2016
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https://www.sciencedaily.com/releases/2016/05/160512145330.htm
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Fatal attachment: How pathogenic bacteria hang on to mucosa and avoid exfoliation
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Mucous surfaces in the nose, throat, lungs, intestine, and genital tract are points of first contact for many pathogens. As a defensive strategy, most animals (and humans) can rapidly exfoliate these surfaces (i.e., shed the surface layer) to get rid of any attached attackers. A study published on May 12th in
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Christof Hauck, from the University of Konstanz, Germany, and colleagues had recently shown that one type of bacteria, Most pathogen-host interactions are quite complex and involve several bacterial proteins--often referred to as "virulence factors" because they enable the microbes to cause disease. In this study, the researchers examined whether engaging CEACAM is not only necessary but also sufficient to inhibit exfoliation, or whether other factors and processes are also required.They started by genetically engineering bacteria from a normally harmless strain of The researchers also worked with tissue culture cells that don't have any members of the CEACAM family. If these cells are infected with Opa-containing Taken together, these results show that it is the Opa-CEACAM interaction that triggers the increased 'stickiness' of the infected cells. The experiments described so far were done in human cells cultured together with bacteria in plastic dishes, and stickiness was measured by how well the host cells stuck to the plastic surface.To look at the interaction between bacteria and real mucosal surfaces, the researchers studied transgenic mice engineered to express high levels of human CEACAM on their mucosal surfaces. When such mice were infected intra-vaginally with Opa-expressing bacteria, the researchers found that many bacteria were sticking to the mucosal surface. They also recovered large numbers of bacteria 24 hours later, indicating that the initial ability to stick translates into subsequent successful 'colonization' of the mucosa.In contrast, when control mice that expressed only mouse CEACAM on their mucosa were infected with Opa-containing bacteria, very few bacteria were found stuck to the vaginal mucosa. Similarly, when the mice expressing human CEACAM were infected with harmless Several other disease-causing bacterial strains have proteins that can also bind CAECAM but are unrelated to Opa. To see whether those proteins work like Opa, the researchers tested one of the strains in the CEACAM-expressing mice. They found that large numbers of bacteria expressing Afa/Dr (the unrelated CEACAM-binding protein in question) were stuck to the vaginal wall following infection, and these bacteria were also successful in colonizing the vagina subsequently.Based these results, the researchers propose that "CEACAM-binding adhesins have independently evolved in multiple gram-negative bacterial pathogens [...] as a means to facilitate the initial, species-specific contact with the mucosa of an appropriate host organism and to counteract the detachment of superficial cells." They conclude that "detailed mechanistic insight into this process and the ability to manipulate exfoliation might help to prevent or treat bacterial infections."
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Genetically Modified
| 2,016 |
May 11, 2016
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https://www.sciencedaily.com/releases/2016/05/160511131718.htm
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Mouse models of Zika in pregnancy show how fetuses become infected
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Two mouse models of Zika virus infection in pregnancy have been developed by a team of researchers at Washington University School of Medicine in St. Louis. In them, the virus migrated from the pregnant mouse's bloodstream into the placenta, where it multiplied, then spread into the fetal circulation and infected the brains of the developing pups.
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The models provide a basis to develop vaccines and treatments, and to study the biology of Zika virus infection in pregnancy.The research is published May 11 in "This is the first demonstration in an animal model of in utero transmission of Zika virus, and it shows some of the same outcomes we've been seeing in women and infants," said co-senior author Michael Diamond, MD, PhD, a professor of medicine, molecular microbiology and pathology and immunology. "This could be used in vaccine trials, to find out whether vaccinating the mother can protect against uterine infection. You also could test therapeutics, once the mother got infected, to see if they could arrest the transmission to the fetus or prevent damage to the fetus."Since mice with normal immune systems are able to fight off Zika infection, Diamond and colleagues weakened the mice's immune systems before infecting them with the virus.In one model, the researchers genetically modified mice to lack a molecule called interferon alpha receptor that plays a key role in the immune response to viral infections. In the other model, they injected mice with antibodies against the molecule.The scientists infected pregnant mice with Zika virus about a week after conception and examined their placentas and fetuses six to nine days later. Both mouse models reflected some of the key aspects of human Zika infection. In the mice, as in humans, the virus crossed from the mother's bloodstream into the fetus's and infected the developing brain, where damage to neurons was observed.Microcephaly -- which is marked by abnormally small heads, the most striking result of human infection -- was not observed in either model. This may be due to differences in how mouse and human brains develop."Unlike in humans, a significant amount of neurodevelopment in mice actually occurs after birth, especially in the cerebral cortex, which is the part of the brain damaged in microcephaly," Diamond said.Indira Mysorekar, PhD, co-senior author of the study and postdoctoral fellow Bin Cao, PhD, co-first author, found the virus in the placenta at 1,000 times the concentration in the maternal blood, suggesting that it had not just migrated to the placenta, but multiplied there.In the genetically-modified mice, Zika infection caused the death of most of the fetuses, and the remaining fetuses were much smaller than normal. The placentas showed damage: They were shrunken, with a reduced number of blood vessels. Such placentas would be unable to supply enough oxygen and nutrients to a developing fetus, a condition known as placental insufficiency, which causes abnormally slow fetal growth and, in severe cases, fetal death.Placental insufficiency, abnormally small fetuses and miscarriages have been reported in pregnant women infected with Zika virus, as well.In both models, the virus also was detected in the fetal brain. The researchers observed cell death in the brains of infected fetuses, but there were no obvious abnormalities in the overall structure of the brain.In the model in which mice were injected with antibodies, the effect of Zika infection was less severe. The fetuses survived, although some were smaller than normal. Diamond and colleagues plan to use this model to study whether prenatal Zika virus infection causes long-term neurological problems in pups born without obvious brain damage.Not all babies born to women infected with Zika during pregnancy develop microcephaly; some seem healthy at birth. But it is unknown whether such babies will face developmental or intellectual challenges as they grow up.Diamond and Mysorekar, an associate professor of obstetrics and gynecology, and of pathology and immunology, also want to identify the molecules the virus latches onto to get into and through the placenta, so they can block them. Zika's greatest health threat is to developing fetuses; if that threat can be eliminated, the public health emergency would be significantly lessened."For years, we've been studying transplacental infections and what prevents them," Mysorekar said. "It's gratifying to be able to apply all that expertise to something that's suddenly become very important around the world."
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Genetically Modified
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May 9, 2016
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https://www.sciencedaily.com/releases/2016/05/160509132925.htm
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Bacterial individualism: Survival strategy for hard times
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Whether you are a human or a bacterium, your environment determines how you can develop. In particular, there are two fundamental problems. First: what resources can you draw on to survive and grow? And second: how do you respond if your environment suddenly changes?
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A group of researchers from Eawag, ETH Zurich, EPFL Lausanne, and the Max Planck Institute for Marine Microbiology in Bremen recently discovered that the number of individualists in a bacterial colony goes up when its food source is restricted. Their finding goes against the prevailing wisdom that bacterial populations merely respond, in hindsight, to the environmental conditions they experience. Individualists, the study finds, are able to prepare themselves for such changes well in advance.In a recent paper in the journal Schreiber and his colleagues were only able to reveal the astonishing differences between the bacteria by studying them very closely. "We had to measure nutrient uptake by individual bacterial cells -- even though these are only 2 μm large," explains Schreiber. "Usually, microbiologists study the collective properties of millions or even billions of bacteria. It was only thanks to the close collaboration between the research groups, and by pooling our expertise and technical equipment, that we were able to study the bacteria in such detail."The present study shows to what extent individuality -- in bacteria and in general -- can be essential in a changing environment. Differences between individuals give the group new properties, enabling it to deal with tough environmental conditions. "This indicates that biological diversity does not only matter in terms of the diversity of plant and animal species but also at the level of individuals within a species," says Schreiber.Next, Schreiber and his colleagues plan to study whether the individualistic behavior of specific individuals is of equal importance in natural environments.
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Genetically Modified
| 2,016 |
April 27, 2016
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https://www.sciencedaily.com/releases/2016/04/160427151208.htm
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Engineers produce biodiesel from microalgae in three hours
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Microalgae developed in wastewater retain large amounts of lipids, carbohydrates and proteins suitable for energy production, without a biomass limit or transformation. Scientists at the National University of Mexico (UNAM) tell us that they can produce biofuel in three hours.
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A research conducted using academic exchanges with students of the Engineering Institute at UNAM and the University of Newcastle was developed from the sampling of mixed microalgae: Chlorella, Scenedesmus and Desmodesmus native to the Lake of Texcoco.In the generation of biodiesel, about 45 percent of the energy is used in harvesting microalgae, therefore, researchers focus on improving processing operations involved in the transformation to biodiesel. Dr. Sharon Velazquez, expert from the University of Newcastle in the UK, said that "we want to avoid changing the natural environment of microalgae and not introduce genetically modified species.Depending on the biofuel will be the fraction of the microalgae nutrient we use. In our case we use fats, we extract them and transform them into biodiesel, meaning we improve the properties of lipids, its viscosity to use as a liquid fuel. "The graduate of the UNAM also emphasized that for biomass other developments use corn or palm oil and get a very slow growth, lasting weeks. Microalgae, being a cell, grows in less than 24 hours, so its transformation into biodiesel is very fast, takes only about three hours, due to that the algae are harvested daily and biofuel could be produced every day.With more than six years of research, the academic stressed that "it is estimated that the global energy for wastewater treatment will increase up to 44 percent by 2030." Thus it has been determined that the use of this biodiesel has great benefits from environmental contributions to reduce emissions of greenhouse gases, it also boosts the local economy with the creation of new jobs and presents a viable alternative to fossil fuels."Geotechnical studies have described our country as ideal for the growth of microalgae. For example, countries such as Peru and the United States have already opened the spectrum of fuels used in automobiles, we hope that Mexico also star offering this to consumers," concluded the researcher of the Department of Chemical Engineering and Advanced Materials at Newcastle University.
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Genetically Modified
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April 21, 2016
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https://www.sciencedaily.com/releases/2016/04/160421133649.htm
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Temporal cues help keep humans looking human
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Researchers believe that genetically modified bacteria can help explain how a developing animal keeps all of its parts and organs in the same general proportions as every other member of its species.
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In 1952, Alan Turing mathematically demonstrated how the nearly endless variety of patterns seen in nature -- spots on cheetahs or the distinctive coats of leopards, for example -- could be explained by chemicals spreading and interacting by simple rules. Many scientists, however, remained unconvinced, and believed there must be more to the story.Now, Duke University researchers have discovered another way that patterns can form -- through the use of a ticking clock. By combining two chemical signals with a few variables, timing cues emerge. And these timing cues can not only create patterns -- they can also make sure these patterns have roughly the same proportions from one colony to the next.In a study published on April 21 in the journal As the bacterial colony grows and produces more T7RNAP, it also produces a chemical that triggers the production of a protein called T7 lysozyme (tagged fluorescent red), which inhibits the production of T7RNAP. Wherever the two molecules interact, purple patterns appear in the colony.Because bacteria toward the outer edge of the colony are more active than those in the interior, this system causes a purple ring to appear like a bullseye. You and his colleagues discovered that they could control its thickness and how long it took for the bullseye to appear by varying the size of the growing environment and amount of nutrients provided.These variables act as a time cue for the pattern's development. A bigger growth environment or more nutrients causes a delay in the formation of the ring. You speculates that similar timing circuits can operate in other organisms, including animals."In our experiment, we get a spatial cue from an unsuspected source. We sort of get it for free from the timing of the genetic circuit," said You. "These two diffusible molecules aren't dictating at what positions cells are going to stop or start producing proteins. Instead, they're telling the cells when to start or stop producing proteins. That's enough to both produce a pattern and to control its scaling, and it's a fundamentally new mechanism."
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Genetically Modified
| 2,016 |
April 20, 2016
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https://www.sciencedaily.com/releases/2016/04/160420104209.htm
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Transfer of gut bacteria affects brain function, nerve fiber insulation
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Specific combinations of gut bacteria produce substances that affect myelin content and cause social avoidance behaviors in mice, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published today in the medical journal
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Multiple sclerosis is an autoimmune disorder characterized by damage to myelin, the insulating sheath around the axons of nerve cells that allows for faster electrical impulse conduction. Myelination is critical for everyday brain function. Damaged myelin results in altered synaptic transmission and clinical symptoms. Previous research from the Center of Excellence for Myelin Repair at The Friedman Brain Institute at the Icahn School of Medicine reported a thinning of myelin and a reduction of myelinated fibers in preclinical models of depression, thereby providing a biological insight for the high rate of depression in MS patients.This current study led by Patrizia Casaccia, MD, PhD, Professor of Neuroscience, Genetics and Genomics, and Neurology, and Chief of the Center of Excellence for Myelin Repair, and post-doctoral fellow Mar Gacias, PhD, identifies bacteria-derived gut metabolites that can affect myelin content in the brains of mice and induce depression-like symptoms.Researchers transferred fecal bacteria from the gut of depressed mice to genetically distinct mice exhibiting non-depressed behavior. The study showed that the transfer of microbiota was sufficient to induce social withdrawal behaviors and change the expression of myelin genes and myelin content in the brains of the recipient mice."Our findings will help in the understanding of microbiota in modulating multiple sclerosis," says Dr. Casaccia. "The study provides a proof of principle that gut metabolites have the ability to affect myelin content irrespective of the genetic makeup of mice. We are hopeful these metabolites can be targeted for potential future therapies."In an effort to define the mechanism of gut-brain communication, researchers identified bacterial communities associated with increased levels of cresol, a substance that has the ability to pass the blood-brain barrier. When the precursors of myelin-forming cells were cultured in a dish and exposed to cresol, they lost their ability to form myelin, thereby suggesting that a gut-derived metabolite impacted myelin formation in the brain.Further study is needed to translate these findings to humans and to identify bacterial populations with the potential to boost myelin production.
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Genetically Modified
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April 14, 2016
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https://www.sciencedaily.com/releases/2016/04/160414144217.htm
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Improved brain mapping tool 20 times more powerful than previous version
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Salk Institute scientists have developed a new reagent to map the brain's complex network of connections that is 20 times more efficient than their previous version. This tool improves upon a technique called rabies virus tracing, which was originally developed in the Callaway lab at Salk and is commonly used to map neural connections.
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Rabies viral tracing uses a modified version of the rabies virus that jumps between neurons, lighting up connections along the way. The illuminated map allows researchers to precisely trace which neurons connect to each other. Visualizing this neural circuitry can help scientists learn more about conditions ranging from motor diseases to neurodevelopmental disorders."To truly understand brain function, we have to understand how different types of neurons are connected to each other across many distant brain areas. The rabies tracing methods we have developed made that possible, but we were only labeling a fraction of all of the connections," says Edward Callaway, a Salk professor and senior author of the new paper, published April 14, 2016 in the journal He adds that such a dramatic improvement in a critical tool for neuroscience will help researchers illuminate aspects of brain disorders where connectivity and global processing goes awry, such as in autism and schizophrenia.Long distance connections between neurons are key to what is called global processing in the brain. Imagine a ball sailing toward a catcher. The catcher's visual circuits will process the information about the ball and send that information over to the brain's motor circuits. The motor circuits then direct nerves in the catcher's arm and hand to grab the ball. That global processing relies on long-distance neural circuits forming precise connections to specific neuron types; these circuits can be revealed with rabies viral tracers."With this new rabies tracer, we can visualize connectivity neuron by neuron, and across long distance input neurons better than with previous rabies tracers," says Euiseok Kim, a Salk research associate and first author of the paper.There are billions of neurons in the brain, and only a handful of technologies that can map the communication going on between them. Some imaging techniques such as functional MRIs can visualize broad scale communication across the brain, but do not focus on the cellular level. Electrophysiology and electron microscopy can track cell-to-cell connectivity, but aren't suited to mapping neural circuits across the whole brain.Tracing methods using neurotropic viruses, like rabies, have long been utilized to trace connections across neural pathways. But these viruses spread widely throughout the brain across multiple circuits, making it difficult to determine which neurons are directly connected. In 2007, Callaway's lab pioneered a new approach based on genetically modified rabies virus. This approach allowed the viral infection to be targeted to specific types of neurons and also allowed the spread of the virus to be controlled. The result is that this system illuminates neurons across the entire brain, but labels only those that are directly connected to neurons of interest.To control how far the virus travels, scientists ensure the rabies virus can only infect a select group of neurons. First scientists remove and replace the crucial outer-coat of the rabies virus, called glycoproteins. The virus needs this coat of glycoproteins to enter and infect cells, but the replacement glycoprotein prevents the virus from infecting normal neurons. Scientists then alter a group of neurons in mice to become so-called "starter cells" that are uniquely susceptible to infection with the modified glycoprotein. Starter cells are also programmed to provide the rabies glycoproteins so that once a starter cell is infected, new copies of the rabies tracer can spread across the starter cell's synapses into connected neurons. However, once the rabies viral tracer is in the next set of neurons, it won't find the glycoprotein it needs to continue to spread, and so the trail of infection across neural circuits ends.Although the original rabies viral tracer accurately traces circuits, it was only crossing a fraction of the starter cell's synapses. The Salk research team went about engineering a more efficient rabies viral tracer. First, the researchers took pieces from various rabies strains to create new chimeric glycoproteins and then tested the versions in by counting labeled cells in known circuits.The winning chimeric glycoprotein was further genetically modified with a technique called codon optimization to increase levels of the glycoprotein produced in starter cells. Compared to the original rabies tracer, the new codon-optimized tracer increased the tracing efficiency for long distance input neurons by up to 20 fold."Although this improved version is much better, there are still opportunities to improve the rabies tracer further as we continue to examine other rabies strains," says Kim.Other co-authors of the study were Matthew Jacobs and Tony Ito-Cole of the Salk Institute's Systems Neurobiology Laboratory.This work was funded in part by the National Institutes of Health, Gatsby Charitable Foundation and the Howard Hughes Medical Institute Collaborative Innovation Award.
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Genetically Modified
| 2,016 |
April 13, 2016
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https://www.sciencedaily.com/releases/2016/04/160413180332.htm
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Spreading seeds by human migration
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Using DNA collected from corn grown by immigrant farmers in Los Angeles and Riverside, researchers at the University of California, Riverside have found the genetic diversity of corn in some home and community gardens in Southern California far exceeds levels found in commercially available seeds.
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The researchers cautioned that this is a preliminary study with a small sample size. Future research would expand to include a greater number of gardens, and focus on characteristics of the corn, such as tolerance to drought, difference in cob size and flowering time.The research addresses the importance of maintaining a diverse range of genetic resources for future crop improvement. A broad mix of genetic material is useful for breeding modern improved lines, minimizing the vulnerability of inbred crops to pathogens and pests, improving performance and incorporating unique traits.Yet, crop genetic diversity is threatened in developing and developed countries as policies and program encourage the use of relatively homogeneousmodern cultivars and as people migrate from farms to cities, often abandoning farming altogether."As genetic diversity erodes, we stand on a chair with shaky legs," said Norman C. Ellstrand, a professor of genetics at UC Riverside and co-author of the paper, "Maize Germplasm Conservation in Southern California's Urban Gardens: Introduced Diversity Beyond Ellstrand, who is also a member of UC Riverside's Institute for Integrative Genome Biology and interim director of the university's new "broad-sense" agriculture institute, CAFÉ (California Agriculture and Food Enterprise), co-authored the paper with Joanne Heraty, a former UC Davis graduate student who Ellstrand supervised. She is now a project manager for the Yolo County Resource Conservation District.In 2008, the researchers collected corn samples from home gardens and community gardens in Los Angeles and Riverside. They genetically compared the garden populations to five commercially available varieties of corn that included two horticultural varieties, two industrial varieties used in large scale agricultural crop plantings and one bulk bin variety purchased from Big Saver Foods supermarket in Riverside. They included the supermarket variety because farmers indicated that local ethnic markets were sometimes a source of seed for their gardens.Southern California is an ideal location to study joint human and plant migration because immigrants from Mexico and Central America frequently maintain plots of crops from their homelands in home gardens and community gardens.Past research has shown that corn genetic diversity is being eroded, particularly in Mexico and conservation strategies tend to fall into two categories: Ellstrand and Heraty describe home and community gardens in Southern California as providing a third method, which combines "People collect baseball cards and people collect plant seeds," Ellstrand said. "In reality, it is not all that surprising that as people move around they help preserve the genetic diversity of plants."
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Genetically Modified
| 2,016 |
April 8, 2016
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https://www.sciencedaily.com/releases/2016/04/160408102401.htm
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Viruses work together to attack their hosts
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Research at the Cavanilles Institute of Biodiversity and Evolutionary Biology of the University of Valencia, led by professor Rafael Sanjuán, reveals that viruses work in groups to attack host cells more effectively. The results of this study were published in the journal
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A virus that is genetically diverse is better able to colonise new a host, evade immunity and evolve drug resistance. Diversity is typically assessed at the population level. However, the existence of cell-to-cell variations in their genetic makeup means that studying viruses at the level of the individual cell is vital to understanding how they work.To this end, researchers at the Universitat de València (UV) combined cell isolation with other ultra-deep sequencing techniques to define the genetic structure and diversity of an RNA virus at the cellular level. What they found was that individual infectious units are made up of genetically diverse viral genomes, with viral particles that "interact functionally" (Sanjuán).Rafael Sanjuán emphasises that the rate of spontaneous viral mutation varies from cell to cell, and early production of diversity depends on the viral yield of the very first infected cell.The results of this study also show that natural selection "facilitates the teamwork of viruses in relation to their position in the same cell" (Sanjuán).Traditionally, virologists have tried to expunge viruses by isolating single cells. However, in the words of UV researcher Rafael Sanjuán, these research results show that this approach "is not necessarily valid, since it ignores the social dimension of viruses."Social interactions between viruses were first discovered some years ago and have changed our view of these viral microbes. This study, together with others published recently, provides evidence that viruses establish connections, an understanding of which could help us to fight off the infections they cause.Rafael Sanjuán is an associate professor at the Department of Genetics of Universitat de València, and a researcher in the Evolution and Health research group at the Cavanilles Institute of Biodiversity and Evolutionary Biology of the same university. The group's research focuses on the study of the mechanisms behind the creation and maintenance of genetic variation in virus like HIV or hepatitis A. Sanjuán is currently the principal investigator of three national and international research projects, and he has published more than 60 studies on evolution and viruses over the past 10 years.
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Genetically Modified
| 2,016 |
April 7, 2016
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https://www.sciencedaily.com/releases/2016/04/160407150259.htm
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Typhoid toxin increases host survival and promotes asymptomatic infection
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Genotoxins damage the genetic material in cells and can cause mutations and cancer. Some bacteria code for and produce genotoxins. A study published on April 7th in
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DNA damage caused by bacterial genotoxins has been linked to cancer, but what, if any, function genotoxins have in the context of a natural infection is not clear. Teresa Frisan, from the Karolinska Institute in Stockholm, Sweden, and colleagues focused on the typhoid toxin from The researchers infected mice orally with the two bacterial strains and--to their surprise--found that mice infected with the strain carrying the intact typhoid toxin had higher survival rates within the first 10 days post infection. None of the surviving mice from either group fell ill at later stages, but the mice infected with the toxigenic strain were more likely to develop chronic infection without disease signs.When looking more closely at the early stages of infection, the researchers found that the mice infected with the intact toxin strain mounted a weaker inflammatory immune response in the intestines than mice infected with the strain lacking the functional genotoxin. At other sites of infection throughout the body, however, the situation was consistently different: outside the intestine, the immune response in mice infected with the toxigenic strain was stronger than the response against the control strain.Since the intestinal microbiota (the community of microorganisms living in the gut) can contribute to the host immune response, the researchers analyzed a total of 35 mouse stool samples collected from uninfected mice and mice infected with the two Salmonella strains. Analyzing bacterial DNA from the stool samples, they found that the presence of typhoid toxin is associated with a different timing and pattern of the changes in the gut microbiome compared with either no infection or infection with the Salmonella strain that lacks the genotoxin.The researchers conclude that their data "collectively highlight a novel aspect of typhoid toxin as an immune modulator, which reduces the intestinal inflammatory response and the clearance of the bacteria." Commenting on the potential link between genotoxins and cancer, they say "in our experimental conditions, chronic infection was not associated with induction of dysplasia or pre-carcinogenic lesions within the study period."
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Genetically Modified
| 2,016 |
April 1, 2016
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https://www.sciencedaily.com/releases/2016/04/160401092125.htm
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Pros and cons of mandatory GMO labeling
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Malaysian researchers have concluded that mandatory labelling of genetically modified foods is justified, based on an extensive review of international scientific and legal frameworks related to genetically modified organisms (GMOs).
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Genetically modified organisms may offer arguable societal and economic benefits, but some fear they may also pose hazards to humans, animals, plants and the environment.So when Malaysia introduced mandatory labelling laws for GM foods, researchers at University Kebangsaan Malaysia (UKM) began to study whether such laws were justified, using scientific, legal and policy documents in North America, the European Union and Asia. The study became an in-depth review of literature, legislation and labelling regimes worldwide.Genetic modification -- the ability to take genes from one species and splice them into another to create organisms with new properties -- could be one of the biggest advances in recent science. Yet when debating whether GMOs are desirable, pro and con sides often speak past each other such that economic points "for" do little to address environmental points "against" and vice versa.Under a concept known as "substantial equivalence," GM food proponents say they are functionally the same and thus as safe as their natural counterparts, with no need for special labelling.The UKM study found that not everyone is persuaded. Opponents worry that, with the potentially huge amounts of money at play, national scientific and legal frameworks may have been somehow tilted to be industry-friendly.The research team argues that the "substantial equivalence" concept currently lacks adequate scientific backing. As long as safety remains incompletely proven, legislation should acknowledge potential hazards as well as perceived pluses, and set up ways to manage them.While not writing off biotechnology or GM foods, the researchers say that, until more is known, it's prudent to acknowledge and address uncertainties about their effects on people, animals and plants. Mandatory labelling fits within that approach, even if it adds costs. In the long-term, they say, it could prevent unexpected harm. In the meantime, it can educate consumers and allow those with religious, medical or social objections to avoid GMOs.In that context, the team says Malaysia's mandatory labelling legislation for GMOs is justified. As long as some producers or manufacturers fear negative consumer reactions to labelled GM products, voluntary labelling would be inconsistent at best. People have a right to know what kind of food they eat, concludes the team, and that justifies Malaysia's GMO labelling laws.
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Genetically Modified
| 2,016 |
March 31, 2016
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https://www.sciencedaily.com/releases/2016/03/160331134413.htm
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Proving the genetic code's flexibility
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Four letters -- A, C, G and T -- stand in for the four chemical bases that store information in DNA. A sequence of these same four letters, repeating in a particular order, genetically defines an organism. Within the genome sequence are shorter, three-letter codons that represent one of the 20 regularly used amino acids, with three of the possible 64 three-letter codons reserved for stop signals. These amino acids are the building blocks of proteins that carry out a myriad of functions. For example, the amino acid alanine can be represented by the three-letter codon GCU and the amino acid cysteine by the three-letter codon UGU. In some organisms, the three-letter codon UGA, which normally signals the end of a protein-coding gene, is hijacked to code for a rare genetically encoded amino acid called selenocysteine.
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Published ahead online March 16, 2016 in the journal The work is a follow-up to two 2014 publications; a "Access to the tremendous resources at the JGI allowed us to quickly test challenging hypotheses generated from my research projects that have been supported over the long-term by DOE Basic Energy Sicences and the National Institutes of Health," said Dieter Soll, Sterling Professor of Molecular Biophysics and Biochemistry Professor of Chemistry at Yale, the lead author of the paper. Thus a fruitful collaboration resulted; the combined team scanned trillions of base pairs of public microbial genomes and unassembled metagenome data in the National Center for Biotechnology Information and the DOE JGI's Integrated Microbial Genomes (IMG) data management system to find stop codon reassignments in bacteria and bacteriophages. Delving into genomic data from uncultured microbes afforded researchers the opportunity to learn more about how microbes behave in their natural environments, which in turn provides information on their management of the various biogeochemical cycles that help maintain the Earth.From approximately 6.4 trillion bases of metagenomic sequence and 25,000 microbial genomes, the team identified several species that recognize the stop codons UAG and UAA, in addition to 10 sense codons, as acceptable variants for the selenocysteine codon UGA.The findings, the team reported, "opens our minds to the possible existence of other coding schemes... Overall our approach provides new evidence of a limited but unequivocal plasticity of the genetic code whose secrets still lie hidden in the majority of unsequenced organisms."This finding also illustrates the context-dependency of the genetic code, that accurately "reading" the code (and interpreting DNA sequences) and ultimately "writing" DNA (synthesizing sequences to carry out defined functions in bioenergy or environmental sciences) will require study of the language of DNA past the introductory course level.
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Genetically Modified
| 2,016 |
March 31, 2016
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https://www.sciencedaily.com/releases/2016/03/160331082647.htm
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Cyanobacteria used for the production of chemicals
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In order to manufacture chemical products in the industry, a high energy input is required, which consumes mainly our fossil resources. At RUB, two scientists are researching into a resource-efficient and, consequently, sustainable approach.
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Prof Dr Robert Kourist from the junior research group Microbial Biotechnology and Dr Marc Nowaczyk from the Chair for Plant Biochemistry have succeeded in genetically modifying cyanobacteria, thus creating cells that produce enzymes for the manufacture of basic and fine chemicals. The bacteria also supply the energy required by the enzymes -- by performing photosynthesis.To fulfil their function as biocatalysts, enzymes require chemical energy, which is typically supplied in form of sugar or other high-energy bonds. The researchers from Bochum, on the other hand, take advantage of the fact that, like plants, cyanobacteria perform photosynthesis. "During photosynthesis, light energy is initially converted into chemical energy. In the second step, that energy is mainly used for binding of carbon dioxide. However, a small percentage of the energy remains and can be directly utilised," says Marc Nowaczyk. The approach adopted by the researchers is to decouple the supplied chemical energy from carbon fixation and to use it directly for chemical reactions.Using genetically modified living cyanobacteria as catalysts for photosynthesis driven biotransformations is a new approach. As the researchers point out, they have observed that cyanobacteria catalyse only the synthesis of the desired chemical product in their experiments and, consequently, that they function selectively. Many catalytic processes produce not just one product, but also a mirrored one, which has to be painstakingly filtered out. "The outstanding selectivity is crucial for deployment in industrial applications," says Robert Kourist.The experiments have, moreover, demonstrated that enzymes from other organisms can be successfully introduced into cyanobacteria. This means that the process can be used in a number of reactions. "The chemical industry has to become cleaner," as Robert Kourist sums up the researchers' ambitious objective. Utilising photosynthesis to catalyse chemical reactions is a promising step towards this aim.
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Genetically Modified
| 2,016 |
March 29, 2016
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https://www.sciencedaily.com/releases/2016/03/160329112425.htm
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Psychotherapy for depressed rats shows genes aren't destiny
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Genes are not destiny in determining whether a person will suffer from depression, reports a new Northwestern Medicine study. Environment is a major factor, and nurture can override nature.
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When rats genetically bred for depression received the equivalent of rat "psychotherapy," their depressed behavior was alleviated. And, after the depressed rats had the therapy, some of their blood biomarkers for depression changed to non-depressed levels."The environment can modify a genetic predisposition to depression," said lead study investigator Eva Redei, a professor of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine. "If someone has a strong history of depression in her family and is afraid she or her future children will develop depression, our study is reassuring. It suggests that even with a high predisposition for depression, psychotherapy or behavioral activation therapy can alleviate it."The study also found genetic influences and environmental influences on depression likely work through different molecular pathways. Rats bred for depression and rats that were depressed due to their environment showed changes in the levels of entirely different blood markers for depression. Being able to differentiate between the two types of depression eventually could lead to more precise treatment with medication or psychotherapy.The study will be published March 29 in The rats in the Northwestern study had been bred for depression-like behavior for 33 generations and showed extreme despair."You don't have people who are completely genetically predisposed to depression the way the rats were," Redei said. "If you can modify depression in these rats, you most certainly should be able to do it in humans."The genetic rat model of depression is biologically similar to human depression, which Redei reported in previous research on blood biomarkers for depression.In the Northwestern study, Redei and colleagues wanted to see if they could alter the rats' genetically caused depression by changing their environment. They took the depressed rats and put them in large cages with lots of toys to chew on and places for them to hide and climb -- sort of a Disneyland for rats. The rats were kept in the playground for one month."We called it rat psychotherapy," Redei said, "because the enrichment allows them to engage with the environment and each other more." The results of a month in the playground: the rats' depressive behavior was dramatically reduced.After the playground psychotherapy, the rats were placed in a tank of water. Their behavior in the tank is a measure for depression. The control rats will swim around, looking for a way to escape. Depressed rats will simply float, showing despair behavior. After the month in the playground, the genetically depressed rats energetically paddled around the tank, looking for an exit."They did not show despair," Redei said.Northwestern scientists also wanted to see if environmental stress could trigger depression in rats bred to be the non-depressed control group of the experiment. These rates did not show despair behavior originally. The control rats underwent a psychologically stressful situation, which involved being restrained two hours a day for two weeks. After the two weeks, the stressed, control rats displayed depressed behavior when placed in a tank of water. They simply floated -- despair behavior -- and didn't try to escape. After the environmental stress, some of the blood biomarkers for depression changed from non-depressed levels to levels seen in genetically depressed rats.The next step is to find out if the biomarkers actually cause behavioral changes in response to the environment. "If so, then perhaps we can find novel drugs to change the level of biomarkers in depressed rats to those of the non-depressed controls and, thus, discover new antidepressant medications," Redei said.Other Northwestern authors on the study are Neha S. Mehta-Raghavan, Stephanie L. Wert, Claire Morley and Evan N. Graf.The study was funded in part by the Davee Foundation.
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Genetically Modified
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March 24, 2016
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https://www.sciencedaily.com/releases/2016/03/160324083019.htm
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New methods of enhancing efficiency of genetic engineering in mice, rats
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A group of researchers led by Tomoji Mashimo, Associate Professor, Institute of Experimental Animal Sciences, Graduate School of Medicine, Osaka University and Kazuto Yoshitomi, Assistant Professor, Mouse Genomics Resource Laboratory, National Institute of Genetics, Research Organization of Information and Systems developed two new gene modification methods: lsODN (long single-stranded oligodeoxynucleotide) and 2H2OP (two-hit two-oligo with plasmid). These methods use CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) -Cas systems and ssODN (single-stranded oligodeoxynucleotide).
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CRISPR-Cas systems have made gene modification in mice and rats easy. By introducing Cas9 messenger RNA and gRNA, gRNA recognizes targeting DNA and Cas9 cuts the targeting site. DNA breaks are repaired by non-homologous end joining, which causes DNA mutations, resulting in gene knock-out.Likewise, when ssODN is introduced with Cas9-gRNA, DNA breaks are repaired through homology-directed repair using donor DNA, resulting in knock-in of DNA sequences with one to dozens of bases (bp). However, ssODN allowed the synthesis of oligos up to 200 bp, therefore, which made it difficult to knock in large DNA sequences such as GFP (green fluorescent protein).With these two gene modification methods, this group succeeded in achieving efficient and precise knock-in of GFP genes, the introduction of large genomic regions (approx. 200kbp), which was conventionally impossible, as well as replacing rat genes with human-derived genes, or generating gene humanized animals.These two knock-in methods will increase the efficiency of genetic engineering in mice and rats, as well as other various species of organisms, and will become very useful techniques for producing new genetically engineered organisms. It is highly anticipated that these genetically engineered organisms will be used in a wide field of studies such as drug development, translational research, and regenerative medicine.
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Genetically Modified
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March 23, 2016
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https://www.sciencedaily.com/releases/2016/03/160323185649.htm
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Modified maggots could help human wound healing
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In a proof-of-concept study, NC State University researchers show that genetically engineered green bottle fly (
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Sterile, lab-raised green bottle fly larvae are used for maggot debridement therapy (MDT), in which maggots are applied to non-healing wounds, especially diabetic foot ulcers, to promote healing. Maggots clean the wound, remove dead tissue and secrete anti-microbial factors. The treatment is cost-effective and approved by the Food and Drug Administration. However, there is no evidence from randomized clinical trials that MDT shortens wound healing times.With the goal of making a strain of maggots with enhanced wound-healing activity, NC State researchers genetically engineered maggots to produce and then secrete human platelet derived growth factor-BB (PDGF-BB), which is known to aid the healing process by stimulating cell growth and survival.Max Scott, an NC State professor of entomology, and colleagues from NC State and Massey University in New Zealand used two different techniques to elicit PDGF-BB from green bottle fly larvae.One technique utilized heat to trigger the production of PDGF-BB in transgenic green bottle flies. The technique worked -- to a point. The human growth factor was detectable in certain structures within the larvae after the larvae were shocked with high heat -- a level of 37 degrees Celsius -- but PDGF-BB was not detectable in maggot excretions or secretions, making it unworthy of clinical use."It is helpful to know that a heat-inducible system can work for certain proteins in the green bottle fly, but the fact that maggots did not secrete the human growth factor makes this technique a non-starter for clinical applications like MDT," Scott said.The second technique was more successful. Scott and colleagues engineered the flies such that they only made PDGF-BB if raised on a diet that lacked the antibiotic tetracycline. PDGF-BB was made at high levels in the larvae and was found in the excretions and secretions of maggots, making the technique a potential candidate for clinical use."A vast majority of people with diabetes live in low- or middle-income countries, with less access to expensive treatment options," Scott said. "We see this as a proof-of-principle study for the future development of engineered
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Genetically Modified
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March 21, 2016
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https://www.sciencedaily.com/releases/2016/03/160321123533.htm
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Skin regeneration in technicolor
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Skin regeneration, either after injury or normally to replace dead skin, is difficult to observe at the cellular level. A new system--based on the Brainbow technology that labels individual neurons--genetically color-codes skin cells in zebrafish, allowing researchers to track cell populations in real time. The system, which they call Skinbow, is described March 21 in
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"One of the barriers to studying regeneration has been to visualize it at high resolution, examining what individual cells are doing and what a large number of individual cells are doing collectively," says senior author Kenneth Poss, a cell biologist at Duke University. "We can catch all of that with this kind of imaging."Many methods to observe the fate of individual skin cells rely on samples that are "snapshots" of cell growth and movement, which don't tell the whole story. Live imaging of cells is possible but on a small scale. Poss and cell biologist Stefano Di Talia, also at Duke University, wanted to create a system that would allow for real-time imaging of large groups of cells.The research team, with Duke postdoc Chen-Hui Chen and Alberto Puliafito of the Candiolo Cancer Institute, genetically engineered a line of zebrafish that expressed red, green, and blue fluorescent proteins in different combinations on the uppermost layer of skin cells--even in the epithelium covering the eye.This skinbow line results in hundreds of potential colors for any given cell to display. At least 70-80 of these colors can be reliably distinguished from one another, says Di Talia, meaning that each cell is unlikely to share a color with its neighbors. The cellular color-coding shows up when the zebrafish are imaged with a microscope under red, green, and blue channels and the images are combined, though the animals have a reddish tint to the naked eye."In a very non-invasive manner, we can study single-cell dynamics over a timescale of several weeks," says Di Talia.The researchers examined the zebrafish under normal conditions, then subjected the study animals to a variety of injuries--ranging from mild alterations like skin exfoliation with a dry tissue to more severe injuries such as fin amputation--to watch how the cells responded. For example, after a zebrafish's fin was amputated, the team observed the following sequence during fin regeneration: first, skin cells rapidly migrated from nearby areas to cover the injury site; second, new epithelial cells were produced to supplement the recruited cells; and third, the cells expanded in size to cover more space at the wound."We didn't expect any of this, but with this type of imaging, you don't need to have pre-set ideas or hypotheses," says Poss. "You just need to be able to image and track cells and quantify the data."The Skinbow system could also be used to study skin cell behavior in different disease models or after drug treatments. "What we have developed in this study is a way to think about, and tools for analyzing, the behavior of individual cells," says Di Talia.
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Genetically Modified
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March 17, 2016
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https://www.sciencedaily.com/releases/2016/03/160317150002.htm
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Mom's microbes influence her offspring's immune system, mice study shows
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During gestation, a mother's microbiome shapes the immune system of her offspring, a new study in mice suggests. While it's known that a newborn's gut microbiota can affect its own immune system, the impact of a mother's microbiota on her offspring has largely been unexplored.
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Here, Mercedes Gomez de Agüero et al. infected the guts of pregnant mice with E.coli engineered to dwindle over time, allowing the mothers to become germ-free again around the time they gave birth.This temporary colonization of E.coli in the mother affected the immune system of her offspring; after birth, the offspring harbored more innate lymphoid and mononuclear cells in their intestines compared to mice born to microbe-free pregnant mothers. Similar results were seen when pregnant mothers were temporarily colonized with a cocktail of eight other microbes.An RNA analysis of offspring born to gestation-only colonized mothers compared with controls revealed greater expression of numerous genes, including those that influence cell division and differentiation, mucus and ion channels, and metabolism and immune function.By transferring serum from bacteria-colonized pregnant mice to non-colonized pregnant mice, the researchers found that maternal antibodies likely facilitate the transmission and retention of microbial molecules from a mother to her offspring.The results of this study add another surprising chapter to the growing body of literature surrounding the effects of the gut microbiota on immune functioning.
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Genetically Modified
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March 16, 2016
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https://www.sciencedaily.com/releases/2016/03/160316113355.htm
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Surface-going cave crickets actually more isolated than cave-dwelling cousins
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People sometimes rely on the stereotype of a kid living in their parents' basement to illustrate poor socialization and isolation.
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But the basement-dwellers may be connected with others in ways that those who are "out in the world" might not. And that seems to be the case for a group of cave crickets.Recently published research by a team of scientists found that a sub-genus (a group of species) of crickets, "The main issue is that Weckstein is the lead author on the recent publication of the study's findings in the The crickets in the study live in a variety of caves in central Texas, from which the team collected specimens and then analyzed their DNA.Geottetix, meanwhile, are troglobites, which means that they spend all of their lives deep in caves. The team wrote that Going into the study, the scientists believed that since the On the other hand, a lack of dispersal allows individual populations to evolve genetic differences in isolation. Previous studies of other cave-dwelling organisms pointed toward the belief that Ceuthophulus would be less genetically distinct, but the study's data conflicted with that hypothesis."The fact that we see deep genetic structure in the Although the The isolation of In the course of the study, the team discovered a plethora of genetically distinct cricket lineages that likely correspond to undescribed species. They agreed that taxonomic work, describing new species, is critically needed for understanding and conserving this group of organisms."Considering these results and that most of the species in this genus were described more than 75 years ago, the taxonomy for this group is desperately out of date," said Krejca. "If the best management practices for endangered cave invertebrates are to include protection of cave cricket foraging ranges, further work is needed to describe which species occur in different areas and what the differences are in their foraging behavior, migration and habitat use."Ultimately, more research will be needed to fully understand why "Given that we found this distinct pattern of structure between caves, other cave-dwellers that haven't been studied also likely show these patterns," Weckstein said. "So this is a good proxy for studying them."Additionally, discovering that the crickets may not be moving distances outside of the cave has implications for conservation."Cave crickets that go outside the cave and then return to the caves during the day are sources of nutrients for these cave communities," Weckstein explained. "If these
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Genetically Modified
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March 7, 2016
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https://www.sciencedaily.com/releases/2016/03/160307113251.htm
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Non-natural biomedical polymers produced from microorganisms
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Renewable non-food biomass could potentially replace petrochemical raw materials to produce energy sources, useful chemicals, or a vast array of petroleum-based end products such as plastics, lubricants, paints, fertilizers, and vitamin capsules. In recent years, biorefineries which transform non-edible biomass into fuel, heat, power, chemicals, and materials have received a great deal of attention as a sustainable alternative to decreasing the reliance on fossil fuels.
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A Korean research team headed by Distinguished Professor Sang Yup Lee of the Chemical and Biomolecular Engineering Department at the Korea Advanced Institute of Science and Technology (KAIST) established a biorefinery system to create non-natural polymers from natural sources, allowing various plastics to be made in an environmentally-friendly and sustainable manner. The research results were published online in The research team adopted a systems metabolic engineering approach to develop a microorganism that can produce diverse non-natural, biomedically important polymers and succeeded in synthesizing poly(lactate-co-glycolate) (PLGA), a copolymer of two different polymer monomers, lactic and glycolic acid. PLGA is biodegradable, biocompatible, and non-toxic, and has been widely used in biomedical and therapeutic applications such as surgical sutures, prosthetic devices, drug delivery, and tissue engineering.Inspired by the biosynthesis process for polyhydroxyalkanoates (PHAs), biologically-derived polyesters produced in nature by the bacterial fermentation of sugar or lipids, the research team designed a metabolic pathway for the biosynthesis of PLGA through microbial fermentation directly from carbohydrates in The team had previously reported a recombinant In order to produce PLGA by microbial fermentation directly from carbohydrates, the team incorporated external and engineered enzymes as catalysts to co-polymerize PLGA while establishing a few additional metabolic pathways for the biosynthesis to produce a range of different non-natural polymers, some for the first time. This bio-based synthetic process for PLGA and other polymers could substitute for the existing complicated chemical production that involves the preparation and purification of precursors, chemical polymerization processes, and the elimination of metal catalysts.Professor Lee and his team performed in silico genome-scale metabolic simulations of the The team utilized the structural basis of broad substrate specificity of the key synthesizing enzyme, PHA synthase, to incorporate various co-monomers with main and side chains of different lengths. These monomers were produced inside the cell by metabolic engineering, and then copolymerized to improve the material properties of PLGA. As a result, a variety of PLGA copolymers with different monomer compositions such as the US Food and Drug Administration (FDA)-approved monomers, 3-hydroxyburate, 4-hydroxyburate, and 6-hydroxyhexanoate, were produced. Newly applied bioplastics such as 5-hydroxyvalerate and 2-hydroxyisovalerate were also made.The team employed a systems metabolic engineering application which, according to the researchers, is the first successful example of biological production of PGLA and several novel copolymers from renewable biomass by one-step direct fermentation of metabolically engineered E.coli.Professor Lee said, "We presented important findings that non-natural polymers, such as PLGA which is commonly used for drug delivery or biomedical devices, were produced by a metabolically engineered gut bacterium. Our research is meaningful in that it proposes a platform strategy in metabolic engineering, which can be further utilized in the development of numerous non-natural, useful polymers."Director Ilsub Baek at the Platform Technology Division of the Ministry of Science, ICT and Future Planning of Korea, who oversees the Technology Development Program to Solve Climate Change, said,"Professor Lee has led one of our research projects, the Systems Metabolic Engineering for Biorefineries, which began as part of the Ministry's Technology Development Program to Solve Climate Change. He and his team have been continuously achieving promising results and attracting greater interest from the global scientific community. As climate change technology becomes more important, this research on the biological production of non-natural, high value polymers has a great impact on science and industry."
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Genetically Modified
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March 3, 2016
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https://www.sciencedaily.com/releases/2016/03/160303145916.htm
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A synthetic biology approach for a new antidote to coral snake venom
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Coral snake venom carries significant neurotoxicity and human injuries can be severe or even lethal. Despite this, antivenom treatments are scarce due to challenges collecting adequate amounts of venom needed to produce anti-elapidic serum.
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Currently, coral snake antivenom is produced by immunizing horses with the venom and collecting the anti-elapidic serum produced. Despite its high toxicity, venom yield from coral snakes is very low, and the snakes are difficult to keep in captivity. Since 2003, the only FDA-approved coral snake antivenom has been discontinued, leading to patients being hospitalized for treatment while the effects of the venom wear off. A new approach is therefore urgently needed to produce antivenom more efficiently and cheaply.The researchers identified 5 toxins within the snake venom and used a technique called SPOT-synthesis to identify the sections of the toxin (epitopes) that are recognized by coral snake antivenom antibodies. They then designed two DNA strings that coded for these epitopes and used them to genetically immunize different groups of mice.The serum collected from the animals, which contained antibodies to the five toxins, was then tested for antivenom capabilities -- by mixing with coral snake venom before being administered to healthy mice -- and was found to neutralize venom by 40%. To improve on this result, the researchers used recombinant DNA techniques to generate purified recombinant proteins from the designed multiepitope DNA strings, and gave the mice a series of protein booster shots to increase their immune response. This approach resulted in a final serum with 60% neutralization against coral snake venom.Although the ideal of 100% neutralization was not met, this approach is a fascinating new response to the challenge of reducing stocks of coral snake antivenom. The use of synthetic DNA bypasses the need to capture and keep snakes, a difficult and expensive process. "The fact that a neutralization of 100% could not be observed does not disqualify this approach as a promising alternative method for the development of an anti-elapidic antiserum," explains Dr Ramos, former postdoctoral fellow at Butantan Institute. "It is worth noting that all the neutralization capabilities observed in this work were, as expected, intimately related to the antibody titres." Techniques to increase the yield of antibodies are likely to lead to even higher neutralization rates, producing a much-needed readily available source of coral snake antivenom.
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Genetically Modified
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March 1, 2016
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https://www.sciencedaily.com/releases/2016/03/160301131531.htm
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Eliminating GMOs would take toll on environment, economies
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Higher food prices, a significant boost in greenhouse gas emissions due to land use change and major loss of forest and pasture land would be some results if genetically modified organisms in the United States were banned, according to a Purdue University study.
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Wally Tyner, James and Lois Ackerman Professor of Agricultural Economics; Farzad Taheripour, a research associate professor of agricultural economics; and Harry Mahaffey, an agricultural economics graduate student, wanted to know the significance of crop yield loss if genetically modified crops were banned from U.S. farm fields, as well as how that decision would trickle down to other parts of the economy. They presented their findings at the International Consortium on Applied Bioeconomy Research in Ravello, Italy, last year. The findings of the study, funded by the California Grain & Feed Association, will be published in the journal "This is not an argument to keep or lose GMOs," Tyner said. "It's just a simple question: What happens if they go away?"The economists gathered data and found that 18 million farmers in 28 countries planted about 181 million hectares of GMO crops in 2014, with about 40 percent of that in the United States.They fed that data into the Purduedeveloped GTAPBIO model, which has been used to examine economic consequences of changes to agricultural, energy, trade and environmental policies.Eliminating all GMOs in the United States, the model shows corn yield declines of 11.2 percent on average. Soybeans lose 5.2 percent of their yields and cotton 18.6 percent. To make up for that loss, about 102,000 hectares of U.S. forest and pasture would have to be converted to cropland and 1.1 million hectares globally for the average case.Greenhouse gas emissions increase significantly because with lower crop yields, more land is needed for agricultural production, and it must be converted from pasture and forest."In general, the landuse change, the pasture and forest you need to convert to cropland to produce the amount of food that you need is greater than all of the landuse change that we have previously estimated for the U.S. ethanol program," Tyner said.In other words, the increase in greenhouse gas emissions that would come from banning GMOs in the United States would be greater than the amount needed to create enough land to meet federal mandates of about 15 billion gallons of biofuels."Some of the same groups that oppose GMOs want to reduce greenhouse gas emissions to reduce the potential for global warming," Tyner said. "The result we get is that you can't have it both ways. If you want to reduce greenhouse gas emissions in agriculture, an important tool to do that is with GMO traits."With lower crop yields without GMO traits, commodity prices rise. Corn prices would increase as much as 28 percent and soybeans as much as 22 percent, according to the study. Consumers could expect food prices to rise 1-2 percent, or $14 billion to $24 billion per year.In the United States, GMOs make up almost all the corn (89 percent), soybeans (94 percent) and cotton (91 percent) planted each year. Some countries have already banned GMOs, have not adopted them as widely or are considering bans. Tyner and Taheripour said they will continue their research to understand how expansion of and reductions of GMO crops worldwide could affect economies and the environment."If in the future we ban GMOs at the global scale, we lose lots of potential yield," Taheripour said. "If more countries adopt GMOs, their yields will be much higher."
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Genetically Modified
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March 1, 2016
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https://www.sciencedaily.com/releases/2016/03/160301114545.htm
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Improving biorefineries with bubbles
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A team of researchers from Japan's Tohoku University has developed a new method for the pretreatment of organic material, or "biomass," which could lead to more efficient production of biofuels and biochemicals.
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Pretreating biomass improves the formation of sugars that are then used to develop biofuels and biochemicals. But current pretreatment processes leave much to be desired.The new method involves crushing the leaves and stalks of maize plants and placing the resulting powder in a solution of sodium percarbonate (SP). The product is then passed through a "hydrodynamic (HD) cavitation system." When it passes through a constriction in the system, bubbles form and then collapse due to a pressure change after the constriction. This "cavitation" -- the formation, growth and subsequent collapse of microbubbles -- produces high, localized energy that disintegrates the cellulose fibres in the biomass.The team previously developed a pretreatment system that involves applying ultrasonic (US) energy to an SP-treated biomass solution. This also results in cavitation and improved disintegration of cellulose fibres. In their study, published in Industrial & Engineering Chemistry Research, they compared the efficiency of pretreating biomass with HD-SP and US-SP systems.Biorefining -- a technique for producing fuels and chemicals from biomass -- involves the hydrolysis of the cellulose in plant materials to form fermentable sugars, which are then treated with genetically engineered microbes and chemical catalysts to produce biofuels.The team found that the HD-SP system was even more efficient than the US-SP system in producing fermentable sugars. They also found that having a smaller constriction in the HD-SP system was more effective in biomass treatment.Because an HD cavitation reactor can be scaled up easily for high production capacities and requires much lower energy input than a US cavitation reactor, the team believes the HD-SP system shows promise for the pre-treatment of plant biomass.They recommend further study of other factors -- such as the SP concentration and pre-treatment temperature and time -- in order to further improve the system.
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Genetically Modified
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March 1, 2016
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https://www.sciencedaily.com/releases/2016/03/160301074240.htm
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DNA as a weapon of immune defense
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Our innate immune system, made up mainly of phagocytes, protects our body by exterminating bacteria. To do this, it uses two mechanisms. The first kills foreign bodies within the phagocyte itself. The second kills them outside the cell. These two strategies were already known to researchers, but only in humans and other higher animals. Microbiologists from the University of Geneva (UNIGE), Switzerland, have just discovered that a social amoeba, a unicellular microorganism living in the soils of temperate forests, also uses both these mechanisms, and has done so for over a billion years. Since this amoeba possesses an innate defense system similar to that of humans, while being genetically modifiable, the researchers can therefore carry out experiments on it in order to understand and fight genetic diseases of the immune system. This discovery can be read in the journal
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To defend themselves, our immune cells have two mechanisms. The first, called phagocytosis, kills bacteria within the phagocytic cell itself. The cell envelops the foreign body and exterminates it specifically by using reactive oxygen species (ozone, hydrogen peroxide, bleach), generated thanks to the enzyme NOX2. However, when the invader is too large to be taken up, cells use a second defense mechanism which consists of expelling their genetic material, that is to say their DNA. This DNA transforms into sticky and poisoned nets called "neutrophil extracellular traps" (NETs). These DNA nets then capture bacteria outside of the cell and kill them.In collaboration with researchers from Baylor College of Medicine in Huston (USA), Professor Thierry Soldati's team from the Department of Biochemistry of the Faculty of Science at UNIGE studies the social amoeba Dictyostelium discoideum. These microorganisms are bacteria predators. But when food is short, they come together and form a "mini animal" of more than 100,000 cells, called a slug. This will then turn into a "fruiting body" made up of a mass of spores on top of a stalk. Dormant spores will survive without food until the wind or other elements disperse them to new areas where they can germinate and find something to eat.To make up the slug, approximately 20% of cells sacrifice themselves to create the stalk and 80% will become spores. However, there is a small remaining 1% that keeps its phagocytic functions. "This last percentage is made up of cells called "sentinel" cells. They make up the primitive innate immune system of the slug and play the same role as immune cells in animals. Indeed, they also use phagocytosis and DNA nets to exterminate bacteria that would jeopardize the survival of the slug. We have thus discovered that what we believed to be an invention of higher animals is actually a strategy that was already active in unicellular organisms one billion years ago," explains Thierry Soldati, last author of the study.This discovery plays a primordial role in understanding immune system diseases in humans. Patients with chronic granulomatous disease (CGD) are for example incapable of expressing the functional NOX2 enzyme. Therefore, they suffer recurrent infections, since their immune system lacks the reactive oxygene species that kill bacteria inside the phagosome or via DNA nets. By genetically modifying the social amoeba Dictyostelium discoideum, the microbiologists from UNIGE are able to conduct all sorts of experiments on the mechanisms of the innate immune system. This microorganism can therefore serve as a scientific model for the research on defects in these defense processes, opening the way to possible treatments.
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Genetically Modified
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February 29, 2016
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https://www.sciencedaily.com/releases/2016/02/160229152922.htm
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Engineered swarmbots rely on peers for survival
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Duke University researchers have engineered microbes that can't run away from home; those that do will quickly die without protective proteins produced by their peers.
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Dubbed "swarmbots" for their ability to survive in a crowd, the system could be used as a safeguard to stop genetically modified organisms from escaping into the surrounding environment. The approach could also be used to reliably program colonies of bacteria to respond to changes in their surrounding environment, such as releasing specific molecules on cue.The system is described online February 29, 2016, in "Safety has always been a concern when modifying bacteria for medical applications because of the danger of uncontrolled proliferation," said Lingchong You, the Paul Ruffin Scarborough Associate Professor of Engineering at Duke University."Other labs have addressed this issue by making cells rely on unnatural amino acids for survival or by introducing a 'kill switch' that is activated by some chemical," You said. "Ours is the first example that uses collective survival as a way of intrinsically realizing this safeguard."In the experiment, You and his colleagues engineered a non-pathogenic strain of The researchers then confined a sufficiently large number of the bacteria to a capsule and bathed it in antibiotics. As long as the While this specific example would not work in general environments without the antibiotic present, You says that the experiments are a proof of concept. The concept can be applied to other circuits that can implement collective survival in one or multiple populations."In general, this concept does not depend on the use of antibiotics," said You. "There are multiple directions we are hoping to follow with this platform. We're using non-pathogenic "We can imagine programming probiotics that can respond to changes in their environmental conditions," said Shuqiang Huang, a postdoctoral associate in You's lab. "That response could include delivering proteins or chemicals to modulate the microbiome."Another way to take advantage of the technology would be to insert a contained population of bacteria that could help the body respond to intruders."We want to program cells to respond to signals produced by pathogenic bacteria," said Anna Lee, a graduate student in You's lab, who plans to pursue this line of research for her doctoral thesis. "We could inhibit their virulence and attack them at the same time.""This is the foundation," said You. "Once we've established the platform, then we have the freedom to introduce whatever proteins we choose and allow these cells to engage in many different applications."Video --
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Genetically Modified
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February 25, 2016
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https://www.sciencedaily.com/releases/2016/02/160225153423.htm
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Bacteria take 'RNA mug shots' of threatening viruses
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Scientists from The University of Texas at Austin, the Stanford University School of Medicine and two other institutions have discovered that bacteria have a system that can recognize and disrupt dangerous viruses using a newly identified mechanism involving ribonucleic acid (RNA). It is similar to the CRISPR/Cas system that captures foreign DNA. The discovery might lead to better ways to thwart viruses that kill agricultural crops and interfere with the production of dairy products such as cheese and yogurt.
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The research appears online Feb. 25 in the journal Both RNA and DNA are critical for life. In humans and many other organisms, DNA molecules act as the body's blueprints, while RNA molecules act as the construction crew--reading the blueprints, building the body and maintaining the functions of life.The research team found for the first time that bacteria can snatch bits of RNA from invaders such as viruses and incorporate the RNA into their own genomes, using this information as something akin to mug shots. They then help the bacteria recognize and disrupt dangerous viruses in the future."This mechanism serves a defensive purpose in bacteria," says Alan Lambowitz, director of the Institute for Cellular and Molecular Biology at UT Austin and co-senior author of the paper. "You could imagine transplanting it into other organisms and using it as a kind of virus detector."The newly discovered mechanism stores both DNA and RNA mug shots from viruses in a bacterium's genome. That makes sense from an evolutionary standpoint, the researchers say, given that some viruses are DNA-based and some are RNA-based.Lambowitz says that as a next step, researchers can examine how to genetically engineer a crop such as tomatoes so that each of their cells would carry this virus detector. Then the researchers could do controlled laboratory experiments in which they alter environmental conditions to see what effects the changes have on the transmission of pathogens."Combining these plants with the environment that they face, be it natural or involving the application of herbicides, insecticides or fungicides, could lead to the discovery of how pathogens are getting to these plants and what potential vectors could be," says Georg Mohr, a research associate at UT Austin and co-first author of the paper.Another application might be in the dairy industry, where viruses routinely infect the bacteria that produce cheese and yogurt, causing the production process to slow down or even preventing it from going to completion. Currently, preventing infections is complicated and costly. Lambowitz and Mohr say dairy bacteria could be engineered to record their virus interactions and defend against subsequent infections.This RNA-based defense mechanism is closely related to a previously discovered mechanism, called CRISPR/Cas, in which bacteria snatch bits of DNA and store them as mug shots. That method has inspired a new way of editing the genomes of virtually any living organism, launching a revolution in biological research and sparking a patent war, but the researchers say they do not anticipate this new discovery will play a role in that sort of gene-editing. However, the enzymatic mechanism used to incorporate RNA segments into the genome is novel and has potential biotechnological applications.Researchers discovered this novel defense mechanism in a type of bacteria commonly found in the ocean called
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Genetically Modified
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February 25, 2016
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https://www.sciencedaily.com/releases/2016/02/160225101103.htm
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Genetically modified E. coli pump out morphine precursor
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A common gut microbe could soon be offering us pain relief. Japanese bioengineers have tweaked
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"Morphine has a complex molecular structure; because of this, the production of morphine and similar painkillers is expensive and time-consuming," said study author Fumihiko Sato of Kyoto University. "But with our Morphine is extracted from poppy sap in a process that results in opiates such as thebaine and codeine. Other synthetic biologists have recently engineered the yeast genome so that it produces opiate alkaloids from sugar. There were ethical concerns, however, including a risk that the pain-killing molecules could be produced easily and unregulated, provided that one has access to the necessary yeast strain.With "Four strains of genetically modified In 2011, Sato and colleagues engineered "By adding another two genes, our
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Genetically Modified
| 2,016 |
February 24, 2016
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https://www.sciencedaily.com/releases/2016/02/160224100552.htm
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EU decision process hinders use of genetically modified trees
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Just like other crops, trees can also be genetically modified in order to introduce new, useful characteristics. Although such trees offer many socio-economic and environmental benefits, complex and unpredictable EU procedures are hindering their introduction to the market. This is the conclusion reached by researchers in a joint text drawn up as part of a European Cooperation in Science and Technology (COST) project about genetically modified trees. The researchers state that Europe is lagging behind in worldwide GM developments and call for a more scientifically substantiated decision process. René Custers, Regulatory & Responsible Research Manager at VIB and Prof. Wout Boerjan (VIB/UGent) contributed to the text.
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Genetically modified trees can be used as an efficient raw material for renewable products or bioenergy, which could in turn promote the transition to a sustainable, CO2-neutral economy. However, Europe imposes a comprehensive risk assessment and authorization procedure on the development and use of genetically modified crops.René Custers, Regulatory & Responsible Research Manager (VIB): "The European Food Safety Authority (EFSA) has drawn up written guidelines on this. Many of the criteria also apply to GM trees. These mainly relate to environmental issues, such as the question of whether modified trees could spread into the natural environment and what the possible consequences of this might be for other crops, people or animals."Trees have a huge number of interactions with their environment, so an enormous amount of data needs to be collected to draw up a risk analysis. Trees also have a long growth cycle, so study of the long-term consequences through field tests takes a very long time.Prof. Wout Boerjan (VIB/UGent): "It's also difficult to predict exactly how detailed the risk analyses need to be. This all means that the risk-analysis process for GM trees in Europe demands a huge amount of time and money. More clarity on the data required and the use of predictive models is needed."The European decision process is not only complex, but also unpredictable. After the risk analysis and a scientific conclusion from EFSA, it is still by no means certain that a European approval will follow. The fact that individual EU Member States can restrict or prohibit the cultivation of GMOs on their territory for reasons having nothing to do with substantiated risks further increases this uncertainty.Prof. Wout Boerjan (VIB/UGent): "This is in sharp contrast to the introduction of conventionally cultivated, non-European trees and other cultivated crops. Although these also interact differently with their environment, a prior risk analysis is not required for this."Genetically modified poplars are already being planted in China and it looks like the green light will also be given in North and South America.René Custers: "Just like with other GM crops, the commercial developments in the field of GM trees are taking place outside Europe. The question is whether that can be scientifically substantiated. After all, more than twenty years of experiments and commercial application have shown that genetic modification poses no inherent risks. There is no reason to assume trees would be different. Europe should learn from the experience we have built up with GM technology and base its decisions more on scientific facts. Today the decision process is politicized and dogmatic and the environment itself could end up being the biggest victim of this."
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Genetically Modified
| 2,016 |
February 19, 2016
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https://www.sciencedaily.com/releases/2016/02/160219092209.htm
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New device may speed up DNA insertion into bacteria
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Genetically engineering any organism requires first getting its cells to take in foreign DNA. To do this, scientists often perform a process called electroporation, in which they expose cells to an electric field.
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If that field is at just the right magnitude, it will open up pores within the cell membrane, through which DNA can flow. But it can take scientists months or even years to figure out the exact electric field conditions to reversibly unlock a membrane's pores.A new microfluidic device developed by MIT engineers may help scientists quickly home in on the electric field "sweet spot" -- the range of electric potentials that will harmlessly and temporarily open up membrane pores to let DNA in. In principle, the simple device could be used on any microorganism or cell, significantly speeding up the first step in genetic engineering."We're trying to reduce the amount of experimentation that's needed," says Cullen Buie, the Esther and Harold E. Edgerton Associate Professor of mechanical engineering at MIT. "Our big vision for this device and future iterations is to be able to take a process that usually takes months or years, and do it in a day or two."Buie and his colleagues, including postdoc Paulo Garcia, graduate student Zhifei Ge, and lecturer Jeffrey Moran, have published their results this week in the journal Currently, scientists can order various electroporation systems -- simple instruments that come with a set of instructions for penetrating an organism's cell membranes. Each system may include instructions for roughly 100 different organisms, such as strains of bacteria and yeast, each of which requires a unique electric field and set of experimental conditions for permeation. However, Buie says the number of organisms for which these instructions are known is but a fraction of what actually exists in nature."There's a tremendous amount of biodiversity we're unable to access," Buie says. "Part of the problem is, we can't even get the DNA in, much less get it expressed by the organism. And for electroporation, the search for the conditions that might work is like a shot in the dark."For electroporation to work, the applied electric field must be strong enough to puncture the membrane temporarily, but not so strong as to do so permanently, which would cause a cell to die."It's like surgery -- this is pretty invasive," Buie says. "There's a sweet spot between killing them and not affecting them at all, that you need to find to be able to open them reversibly, just enough so that DNA gets in and they reseal on their own."Whether an electric field penetrates a membrane also depends on a cell's surrounding conditions. Scientists have also had to experiment with parameters such as the composition of a cell's solution and the way in which the electric field is applied."For a novel organism, it could take you months or years to develop new conditions so that the cell is happy and will survive the poration process, and it will uptake the DNA," Buie says.The group's new microfluidic device may significantly shorten the time it takes to identify these ideal conditions. The device consists of a channel created using soft lithography. The channel narrows in the middle. When an electric field is applied to the device, the channel's geometry causes the field to exhibit a range of electric potentials, the highest being at the channel's narrowest region.The researchers flowed several strains of bacterial cells through the device and exposed the cells to an electric field. They then added a fluorescent marker that lights up in the presence of DNA. If cells were successfully permeated by the electric field, they would let in the fluorescent marker, which would then light up in response to the cell's own genetic material. To identify the magnitude of the electric potential that was able to open a cell membrane, the researchers simply marked the location of each fluorescent cell along the channel."In one experiment, you can test a range of electric fields and get some information almost instantly, in terms of whether there's been something successful in opening pores," Buie says. "So now, in your searching process, you don't need to run a bunch of different experiments and test different electric fields separately. You can do it in one go, and it literally lights up. "The researchers successfully permeated strains of E. coli and Mycobacterium smegmatis, a bacterium in the same family as the organism that causes tuberculosis -- a family whose membranes, Buie says, are "notoriously difficult" to penetrate.The group's first set of experiments involved opening up pores to take in the fluorescent marker -- a molecule that is slightly smaller than DNA. The researchers also ran experiments in which they applied an electric field to bacterial cells in the presence of DNA encoded for antibiotic resistance. The team checked that the cells took up the DNA by removing them from the device and growing them on a separate plate with antibiotics -- a standard procedure known as a streak test. They found that the cells were able to reproduce -- a sign that the DNA was successfully incorporated, and the membranes closed back up."At present, only a limited number of cell types can be genetically modified due to limitations in the technologies available for introducing DNA into cells," says Garcia. "We have developed a microfluidic device that will facilitate genetic engineering of many different cell types. By mediating genetic engineering of novel cell types, this technology will contribute to the areas of drug discovery, regenerative medicine, cancer therapy, and DNA vaccination."
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Genetically Modified
| 2,016 |
February 18, 2016
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https://www.sciencedaily.com/releases/2016/02/160218145141.htm
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Genetically modified technology a safe tool to help meet food supply demands, plant scientists say
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More than 1,000 scientists from nonprofit, corporate, academic, and private institutions say public doubts about genetically modified food crops are hindering the next Green Revolution. In a letter published in the journal
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The petition, which is the first organized by individual scientists in support of GM technology, yielded more than 1,400 signatures from plant science experts supporting the American Society of Plant Biologists' (ASPB) position statement on genetically modified (GM) crops, which states that they are "an effective tool for advancing food security and reducing the negative environmental impacts of agriculture." The ASPB is the world's largest organization of plant biologists.Although there is broad support in the scientific community for genetically modified crops, the petition organizers feel that too much confusion about the issue is hindering effective deployment of these technologies."To meet our current and future food supply demands, without destroying our planet, we need every efficacious tool available," they write. The letter's authors are Carnegie's Jose Dinneny; Noah Fahlgren, Rebecca Bart, and Daniel Chitwood of the Donald Danforth Plant Science Center in St. Louis, MO; and Luis Herrera Estrella and Rubén Rellán Álvarez of the National Laboratory of Genomics for Biodiversity in Mexico.The signatories of the petition represent a knowledgeable consortium of scientists, who have published more than 17,600 scientific papers on subjects including plant breeding, the molecular and genetic mechanisms underlying plant growth and development, and plant responses to environmental stresses. The petitioners' goal is to demonstrate to the public that there is consensus within their scientific community about the safety and efficacy of using genetic modification technology in agriculture."Our petition gives voice to the individual scientist," Chitwood explains.Carnegie President Matthew Scott, one of the petitioners, says: "GM crops, deployed appropriately in light of scientific knowledge and societal and environmental imperatives, can improve food and health substantially without detriment to the environment. In fact there is considerable potential for preserving the environment through use of GMOs to reduce excessive use of pesticides and fertilizers."The document adds voices to the already existing position statements in support of genetically modified organisms from other scientific organizations including the American Medical Association, the U.S. National Academy of Sciences, the American Association for the Advancement of Science, and the World Health Organization."We hope that the consensus among plant scientists presented here is heard by policymakers, the business community, and, more importantly, the general public and initiates a new conversation on how best to implement GM tools to improve crops for sustainable agriculture. We invite advocates of the responsible use of such tools to read the ASPB position statement, sign our petition, and make your voice heard to encourage the use of the best-available scientific information in setting GMO policy and evaluating individual agricultural products," says Dinneny.The ASPB position statement and the petition can be found at
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Genetically Modified
| 2,016 |
February 18, 2016
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https://www.sciencedaily.com/releases/2016/02/160218132245.htm
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Engineered mini-stomachs produce insulin in mice
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Researchers have spent decades trying to replace the insulin-producing pancreatic cells, called beta cells, that are lost in diabetes. Now a team of researchers, reporting Feb. 18, 2016 in
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To find the body tissue most amenable to reprogramming for insulin production, the researchers genetically engineered mice to express three genes that can turn other cell types into beta cells. "We looked all over, from the nose to the tail of the mouse," says senior author Qiao Zhou, of the Harvard University Department of Stem Cell and Regenerative Biology. "We discovered, surprisingly, that some of the cells in the pylorus region of the stomach are most amenable to conversion to beta cells. This tissue appears to be the best starting material."The pylorus region connects the stomach to the small intestine. When reprogrammed, cells in this area were the most responsive to high glucose levels, producing insulin to normalize the mouse's blood sugar. To test the cells' effectiveness, the researchers destroyed the mice's pancreatic beta cells, forcing their bodies to rely only on the altered stomach cells. Control animals, without tissue reprogramming, died within eight weeks. But the experimental mice's reprogrammed cells maintained insulin and glucose levels in their blood for as long as the animals were tracked, up to six months.The pyloric stomach has another advantage: stem cells naturally renew the gut tissue on a regular basis. When cells in the pyloric stomach expressed the conversion genes, and the first set of reprogrammed cells were experimentally destroyed, the region's stem cells refreshed the insulin-producing cell population. "In various disease states, you have a constant loss of beta cells," Zhou says. "We provide, in principle, an advantage to replenish those."But to get closer to a potential therapy, Zhou and his colleagues had to take a different approach. "When the mouse grew into an adult, we turned on the three genes. But in terms of a clinical future, you can't do a transgenic human being," he says. So the researchers took stomach tissue from the mice, engineered it to express the beta-cell reprogramming factors in the lab, and coaxed the cells to grow into a tiny ball of a mini-stomach that would both produce insulin and refresh itself with stem cells. The team then placed these mini-organs in the membrane that covers the inside of the mouse's abdominal cavity.When the research team destroyed the mice's pancreatic cells to see if the mini-organs would compensate, they found that glucose levels stayed normal in five of the 22 experimental animals, which was the team's expected success rate. "When you put this together, you are basically asking the harvested stem cells to self-organize into an organ on a matrix," Zhou says. "The limitation is all about whether the tissue you transplanted can successfully reorganize with the right layers."The insulin-producing potential of the pyloric stomach cells likely comes from their natural similarity to pancreatic beta cells. The researchers found that many genes critical for beta cell function are also normally expressed in the pylorus's hormone-producing cells. "What is potentially really great about this approach is that one can biopsy from an individual person, grow the cells in vitro and reprogram them to beta cells, and then transplant them to create a patient-specific therapy," Zhou says. "That's what we're working on now. We're very excited."
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Genetically Modified
| 2,016 |
February 17, 2016
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https://www.sciencedaily.com/releases/2016/02/160217112849.htm
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Fluorescent biosensors light up high-throughput metabolic engineering
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Synthetic biologists are learning to turn microbes and unicellular organisms into highly productive factories by re-engineering their metabolism to produce valued commodities such as fine chemicals, therapeutics and biofuels. To speed up identification of the most efficient producers, researchers at Harvard's Wyss Institute for Biologically Inspired Engineering describe new approaches to this process and demonstrate how genetically encoded fluorescent biosensors can enable the generation and testing of billions of individual variants of a metabolic pathway in record time. The discussion and findings are reported in
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Biotechnologists that tinker with the metabolism of microorganisms to produce valued products look at the engineering process through the lens of the so-called 'design-build-test cycle.' The idea is that multiple iterations of this cycle ultimately allow the identification of combinations of genetic and metabolic elements that produce the highest levels of a desired drug or chemical. Key to the cycle's efficiency, however, is the ability to construct and test the largest number of variants possible; in the end, only a few of these variants will produce the product in industrially attractive amounts.In the Bioengineers thoroughly understand how metabolic pathways work on the biochemical level and have a plethora of DNA sequences encoding variants of all of the necessary enzymes at their disposal. Deploying these sequences with the help of computational tools and regulating their expression with an ever-growing number of genetic elements, gives them access to an almost infinite pool of design possibilities. Similarly, revolutionary advances in technologies enabling DNA synthesis and manipulation have made the construction of billions of microorganisms, each containing a distinct design variant, a routine process."The real bottleneck in achieving high-throughput engineering cycles lies in the testing step. Current technology limits the number of designs scientists can evaluate to hundreds, or maybe even a thousand, different designs per day. Often the assays necessary are painstaking and prone to user error," said Rogers.Church and Rogers discuss how genetically encoded biosensors can help bioengineers overcome this hurdle. Such biosensors work by coupling the amount of a desired product produced within a microorganism to the expression of an antibiotic resistance gene such that only high producers survive. Alternatively, the expression of a fluorescent protein can be used for high-speed sorting of rare but highly productive candidates from large populations of less productive microbes."Now, by having developed both types of genetically encoded biosensors we can close the loop of a fully multiplexed engineering cycle. This enables exploration of design spaces for specific metabolic pathways in much greater breadth and depth. Fluorescent biosensors, in particular, enable a brand new type of pipeline engineering in which we can observe metabolic product levels at all times during the process with extraordinary sensitivity and ability to further manipulate the engineering cycle," said Church.Earlier work by Church's team at the Wyss Institute already demonstrated that the levels of commercially valuable chemicals produced by bacteria could be raised through several rounds of a design-build-test cycle that employed an antibiotic selection-based biosensor. Now, Church and Rogers report in PNAS the unique advantages that fluorescent biosensors provide to bioengineers."Our fluorescent biosensors are built around specialized proteins that directly sense commercially valuable metabolites. These sensor proteins switch on the expression of a fluorescent reporter protein, resulting in cellular brightness that is proportional to the amount of chemical produced within the engineered cells. We can literally watch the biological production of valuable chemicals in real-time as the synthesis occurs and isolate the highest producers out of cultures with billions of candidates," said Rogers, who was named one of Forbes' "30 Under 30" in Science for opening new perspectives in bioengineering.Using this strategy, the Wyss researchers have established fluorescent biosensors for the production of super-absorbent polymers and plastics like the coveted acrylate from which a range of products is made. In fact, the study established the first engineered pathway able to biologically produce acrylate from common sugar, rather than the previously required petroleum compounds."This newly emerging biosensor technology has the potential to transform metabolic engineering in areas ranging from industrial manufacturing to medicine, and it can have a positive impact on our environment by making the production of drugs and chemicals independent from fossil fuels," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is the Judah Folkman Professor of Vascular Biology at HMS and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
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Genetically Modified
| 2,016 |
February 17, 2016
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https://www.sciencedaily.com/releases/2016/02/160217090806.htm
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DNA evidence shows that salmon hatcheries cause substantial, rapid genetic changes
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A new study on steelhead trout in Oregon offers genetic evidence that wild and hatchery fish are different at the DNA level, and that they can become different with surprising speed.
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The research, published today in A single generation of adaptation to the hatchery resulted in observable changes at the DNA level that were passed on to offspring, scientists reported.This research was conducted at Oregon State University in collaboration with the Oregon Department of Fisheries and Wildlife. Scientists say the findings essentially close the case on whether or not wild and hatchery fish can be genetically different.Differences in survival and reproductive success between hatchery and wild fish have long offered evidence of rapid adaptation to the hatchery environment. This new DNA evidence directly measured the activity of all genes in the offspring of hatchery and wild fish. It conclusively demonstrates that the genetic differences between hatchery and wild fish are large in scale and fully heritable."A fish hatchery is a very artificial environment that causes strong natural selection pressures," said Michael Blouin, a professor of integrative biology in the OSU College of Science. "A concrete box with 50,000 other fish all crowded together and fed pellet food is clearly a lot different than an open stream."It's not clear exactly what traits are being selected for, but the study was able to identify some genetic changes that may explain how the fish are responding to the novel environment in the hatchery."We observed that a large number of genes were involved in pathways related to wound healing, immunity, and metabolism, and this is consistent with the idea that the earliest stages of domestication may involve adapting to highly crowded conditions," said Mark Christie, lead author of the study.Aside from crowding, which is common in the hatchery, injuries also happen more often and disease can be more prevalent.The genetic changes are substantial and rapid, the study found. It's literally a process of evolution at work, but in this case it does not take multiple generations or long periods of time."We expected hatcheries to have a genetic impact," Blouin said. "However, the large amount of change we observed at the DNA level was really amazing. This was a surprising result."With the question put to rest of whether hatchery fish are different, Blouin said, it may now be possible to determine exactly how they are different, and work to address that problem. When the genetic changes that occur in a hatchery environment are better understood, it could be possible to change the way fish are raised in order to produce hatchery fish that are more like wild fish. This research is a first step in that direction.
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Genetically Modified
| 2,016 |
February 15, 2016
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https://www.sciencedaily.com/releases/2016/02/160215123751.htm
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Using light to control protein transport from cell nucleus
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Light can be used to control the transport of proteins from the cell nucleus with the aid of a light-sensitive, genetically modified plant protein. Biologists from Heidelberg University and the German Cancer Research Center (DKFZ) working in the field of optogenetics have now developed such a tool. The researchers, under the direction of Dr. Barbara Di Ventura and Prof. Dr. Roland Eils, employed methods from synthetic biology and combined a light sensor from the oat plant with a transport signal. This makes it possible to use external light to precisely control the location and hence the activity of proteins in mammalian cells. The results of this research were published in the journal
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Eukaryotic cells are characterised by the spatial separation between the cell nucleus and the rest of the cell. "This subdivision protects the mechanisms involved in copying and reading genetic information from disruptions caused by other cellular processes such as protein synthesis or energy production," explains Prof. Eils, Director of Heidelberg University's BioQuant Centre and head of the Bioinformatics Department at Ruperto Carola and the DKFZ. Proteins and other macromolecules pass through the nuclear pore complex into and out of the cell nucleus in order to control a number of biological processes.While smaller proteins passively diffuse through the nuclear pores, larger particles must latch onto so-called carrier proteins to make the trip. Usually short peptides on the protein surface signal the carriers that the protein is ready for transport. This signal is known as the nuclear localization signal (NLS) for transport into the nucleus, and the nuclear export sequence (NES) for transport out of the nucleus. "Artificially inducing the import or export of selected proteins would allow us to control their activities in the living cell," says Dr. Di Ventura, group leader in Prof. Eils' department.The Di Ventura lab has specialised in optogenetics, a relatively new field of research in synthetic biology. Optogenetics combines the methods of optics and genetics with the goal of using light to turn certain functions in living cells on and off. To this end, light-sensitive proteins are genetically modified and then introduced into specific target cells, making it possible to control their behaviour using light.The recently published work reporting an optogenetic export system builds upon previous studies by other working groups investigating the LOV2 domain, which originally comes from the oat plant. In nature, this domain acts as a light sensor and, among other things, assists the plant in orienting to sunlight. The LOV2 domain fundamentally changes its three-dimensional structure as soon as it comes into contact with blue light, explains Dominik Niopek, primary author of the study.The property of light-induced structure change can now be used specifically to synthetically control cellular signal sequences -- like the nuclear export signal (NES). Dominik Niopek first developed a hybrid LOV2-NES protein made up of the LOV2 domain of the oat and a synthetic nuclear export signal. In the dark state, the signal is hidden in the LOV2 domain and not visible to the cell. Light causes the structure of the LOV2 to change, which renders the NES visible and triggers the export of the LOV2 domain from the nucleus."In principle, the hybrid LOV2-NES protein can be attached to any cellular protein and used to control its export from the nucleus using light," says Prof. Eils. The researcher and his team demonstrated this using the p53 protein, a member of the family of cancer-suppressing proteins that monitor cell growth and prevent genetic defects during cell division. According to Roland Eils, p53 is switched off in a number of aggressive tumours by harmful genetic mutations that allow the tumour cells to reproduce uncontrollably.Using the LOV2-NES protein, the Heidelberg researchers were able to control the export of p53 from the nucleus using light to control its gene regulatory functions. "This new ability to directly control p53 in living mammalian cells has far-reaching potential to explain its complex function in depth. We hope to uncover new clues about the role of possible defects in p53 regulation related to the development of cancer," says Dr. Di Ventura.The researchers are convinced that their new optogenetic tool can also be used to make important discoveries on the dynamics of protein transport and its influence on cell behaviour. "Our research is only as good as our tools," says Prof. Eils. "The development of innovative molecular tools is therefore the key to understanding basic cellular functions as well as the mechanisms that cause illness."
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Genetically Modified
| 2,016 |
February 12, 2016
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https://www.sciencedaily.com/releases/2016/02/160212163909.htm
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Gene technology to help healthy skin in Aboriginal Australians
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Australian researchers have used cutting-edge genome technologies to reveal the genetic makeup of a widespread skin parasite causing serious health problems in Aboriginal communities.
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The research team identified the genetic 'map' of the human parasitic scabies mite, accelerating research that could lead to new ways of preventing and treating scabies infestations and prevent lifelong complications for people in remote Aboriginal communities.Scabies is a contagious and extremely itchy skin infestation caused by scabies mites. Scabies is rife in many remote Aboriginal communities in Australia, affecting one in two children and one in four adults each year.Scabies infestations often become infected, causing serious -- even lifelong or fatal -- complications, such as bacterial blood infections (sepsis), and are associated with serious kidney and heart diseases.The research was led by Associate Professor Tony Papenfuss from the Walter and Eliza Hall Institute and Dr Katja Fischer from the QIMR Berghofer Medical Research Institute, Queensland, and was published today in Genomic technologies are critical for finding ways to prevent and control scabies, Associate Professor Papenfuss said. "A shocking seven out of ten children in remote Aboriginal communities will contract scabies before they reach one year of age," he said.Scabies wounds often become infected by Group A streptococcus bacteria, which can cause rheumatic fever, acute kidney disease and rheumatic heart disease. These infections have dramatic effects on life quality and expectancy."Genomic technologies have revolutionised how we treat many diseases, such as cancer," Associate Professor Papenfuss said. "We are excited that we can now apply these technologies to tackle a major, yet neglected, health problem in Indigenous Australians."To get the first insight into the genetic makeup of scabies mites, the team analysed DNA from the cellular 'energy factories' called mitochondria. Mitochondrial DNA evolves slowly compared with other types of DNA, making it useful for examining the relatedness of different parasite strains.Dr Fischer said the team compared DNA sequences from human scabies mites with those from domestic pigs, which commonly have scabies. "One of the unexpected things we found was that one patient was infected with mites that were genetically more similar to pig mites than to human mites," she said. "This suggests it may be possible for certain animal strains of mites to infect humans, which we did not previously know was possible. If subsequent studies confirm this finding, it could have major implications for disease control programs."Prior to this study, little was known about the genetic makeup of the scabies mite. Understanding the genetic makeup of the scabies mite would help identify how it becomes resistant to certain drugs and could suggest new strategies for development of novel therapeutics.Associate Professor Papenfuss said that analysing the scabies mite was a challenge due to their tiny size. "We analysed thousands of mites to get sufficient DNA for sequencing and developed bespoke analysis methods to overcome DNA contamination from the host animal and bacteria in the wound."
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Genetically Modified
| 2,016 |
February 10, 2016
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https://www.sciencedaily.com/releases/2016/02/160210134950.htm
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Study of Asian common toad reveals three divergent groups
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Most species are negatively affected when humans transform natural habitats into urban areas and agricultural lands, but a few species actually benefit from these activities. These species -- called human commensals -- thrive in human-modified environments. One example, the Asian common toad (
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A research project by Bryan L. Stuart, Research Curator of Herpetology at the North Carolina Museum of Natural Sciences, and colleagues at the University of California, Berkeley, and Institut Teknologi in Indonesia, tested the hypothesis that Asian common toad populations across Southeast Asia are genetically similar owing to their commensal nature and high dispersive ability. To the researchers' surprise, three genetically divergent groups of toads were found, each in a different geographic area (mainland Southeast Asia, coastal Myanmar and the islands of Java and Sumatra). The ranges of these three groups of toads were also found to have statistically different climates. This suggests that the toads may be adapting to local climatic conditions and evolving into separate species. Thus, toads of one group may not be able to disperse and persist within the range of another group because of climatic differences.This research changes the view on the conservation value of these toads. One common toad may not be the same as another. What is thought to be a single, common species having a large range may actually be three distinct species, each having smaller ranges with specific climatic needs. Asian common toads have recently invaded the Southeast Asian islands of Borneo, Sulawesi and Seram and the African island of Madagascar, presumably via shipping containers. The discovery that there are three genetically and ecologically divergent groups of Asian common toads may explain why some islands have been successfully colonized and others not -- and what the future range of these toads will be as humans continue to modify habitats and transport cargo around the world.
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Genetically Modified
| 2,016 |
February 3, 2016
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https://www.sciencedaily.com/releases/2016/02/160203145710.htm
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Parasitic ants alter how captive ants recognize nest mates
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Enslaved Formica worker ants are more genetically and chemically diverse and less aggressive towards non-nest mates than free-living Formica ant colonies, according to a study published February 3, 2016 in the open-access journal
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Highly social ants, bees and wasps employ sophisticated recognition systems to identify colony members and deny foreign individuals access to their nest. Ants use chemical signals, called cuticular hydrocarbons, to determine nest membership, but some parasitic ants can break the recognition code and live unopposed within a host colony. In this study, the authors examine the influence of the socially parasitic slave-making ant, The authors found that enslaved Formica colonies were more genetically and chemically diverse than their free-living counterparts. The researchers think these differences are likely caused by seasonal raids to steal pupa from several adjacent host colonies."When free-living Formica ants are kidnapped into the Polyergus colony, they enter a society that [comprises] kidnapped ants from many other Formica colonies. Here, we show that this rich social environment alters the behaviors displayed by the enslaved ants," said Neil Tsutsui.The different social environments of enslaved and free-living Formica also appear to affect their recognition behaviors: enslaved Formica workers were less aggressive towards non-nest mates than were free-living Formica. Future studies are needed to understand the underlying mechanisms, but the authors suggest their findings indicate that parasitism by P. breviceps alters both the chemical and genetic context in which their hosts develop, leading to changes in how they recognize nest mates.
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Genetically Modified
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February 2, 2016
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https://www.sciencedaily.com/releases/2016/02/160202090536.htm
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Monsanto's glyphosate now most heavily used weed-killer in history
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Monsanto's signature herbicide glyphosate, first marketed as "Roundup," is now the most widely and heavily applied weed-killer in the history of chemical agriculture in both the U.S. and globally, according to a landmark report published in the journal,
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A paper published Feb. 2, 2016 in the peer-reviewed journal Enough glyphosate was applied in 2014 to spray over three-quarters of a pound of glyphosate active ingredient on every harvested acre of cropland in the U.S., and remarkably, almost one-half pound per acre on all cropland worldwide (0.53 kilogram/hectare).The paper by Charles Benbrook, PhD, titled "Trends in glyphosate herbicide use in the United States and globally," and is available free, online at ["The dramatic and rapid growth in overall use of glyphosate will likely contribute to a host of adverse environmental and public health consequences," noted Dr. Benbrook in his paper.Last year, 17 of the world's top cancer researchers unanimously voted to elevate the cancer profile of glyphosate on behalf of the World Health Organization. The WHO's International Agency for Research on Cancer (IARC) now classifies the weed-killer as "probably carcinogenic to humans" after the panel of experts reviewed all of the publicly available research. Following up on the action by the WHO, the state of California is currently in the process of listing glyphosate as a known human carcinogen under its Prop 65 law.As the paper notes, recent studies have made the connection between glyphosate exposure and a number of serious health effects beyond cancer, including the degeneration of the liver and kidney, as well as non-Hodgkin lymphoma, among others.Remarkably, 74 percent of all the glyphosate sprayed on crops since the mid-1970s has been applied in just the last 10 years as the amount of genetically engineered corn and soybean crops have exploded on both U.S. and global croplands.First sold commercially in 1974, the use of glyphosate by farmers was limited since this active ingredient kills both weeds and agronomic crops. The development and approval of genetically engineered (GE), herbicide-tolerant (HT) crops dramatically changed how farmers could apply glyphosate. Starting in 1996, GE-HT versions of three major crops -- cotton, corn, and soybeans -- were marketed by Monsanto and other seed companies, making it possible for farmers to apply glyphosate for months after crops had started growing.The use and efficacy of HT technology, particularly in its first decade, led to rapid and near-universal adoption in the U.S., Canada, Argentina, Brazil, and a half-dozen other countries. As a result, glyphosate use by farmers in the U.S. rose from 12.5 million pounds in 1995 to 250 million pounds in 2014, a 20-fold increase. Globally, total use rose from 112.6 million pounds in 1995 to 1.65 billion in 2014, a 14.6-fold jump."My hope is that this paper will stimulate more research on glyphosate use, and human and environmental exposure patterns, to increase the chance that scientists will quickly detect any problems that might be triggered, or made worse by glyphosate exposure," Benbrook added."This report makes it clear that the use of glyphosate combined with the dominance of genetically engineered crops has produced an looming public health threat both in the U.S. and around the world," said Mary Ellen Kustin, a senior policy analyst at EWG. "Farmers have sprayed billions of pounds of a chemical now considered a probable human carcinogen over the past decade. Spraying has increased to multiple times a year recently on the majority of U.S. cropland. The sheer volume of use of this toxic weed-killer is a clear indication that this chemical dependency is a case of farming gone wrong."This is Benbrook's second paper published in
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January 25, 2016
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https://www.sciencedaily.com/releases/2016/01/160125114237.htm
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A behemoth in Leviathan's crypt: Second Cryptomaster daddy longlegs species
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Suggestively called
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The Curiously, both Having its localities further increased as a result of the present study, Bearing the name of the huge notorious Hebrew monster Leviathan, the first member of the harvestman genus has won its name because of its excessive size when compared to its relatives within the family of travunioid daddy longlegs. Following the already established trend, the new species is called "This research highlights the importance of short-range endemic arachnids for understanding biodiversity and further reveals mountainous southern Oregon as a hotspot for endemic animal species," point out the authors in conclusion.
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Genetically Modified
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January 21, 2016
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https://www.sciencedaily.com/releases/2016/01/160121130704.htm
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Exact pol(e) position -- precisely where the polymerase is changed
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Scientists at the Helmholtz Zentrum München, working with colleagues from the Ludwig-Maximilians-Universität München, have developed a method for the thorough analysis of protein modifications. They mapped the phosphorylation sites of the RNA polymerase II enzyme, which is responsible for expressing our genes. The results have now been published in the
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The contents in our genetic information are actually silent (meaning inactive) and first have to be made to "speak." Like the read head in a tape recorder, RNA polymerase II, Pol II for short, runs over the DNA (tape) and transcribes the genetic and epigenetic information into RNA. In order to keep the enzyme from working randomly, however, it is dynamically modified at many different points in order to control its activity depending on the situation."Phosphorylation makes it possible to influence the activity of the enzyme at 240 different sites," explains Prof. Dirk Eick, the study's last author and head of the Research Unit Molecular Epigenetics at Helmholtz Zentrum München. Together with colleagues from the Biomedical Center and Gene Center of the Ludwig-Maximilians-Universität München and the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, he and his team have developed a method for simultaneously examining all 240 sites in Pol II."The trick is a combination of genetic and mass spectrometric methods," reveals first author Dr. Roland Schüller. "By producing genetically modified variants of the regions in question, we can examine each individual phosphorylation site with a mass spectrometer." This allows the researchers to determine exactly how and precisely where certain enzymes that influence phosphorylation act. The scientists also successfully compared the Pol II modification patterns in humans and in yeast."The regulation of the transcription of genes by Pol II is an elementary process in life and gene regulation deviations are the basis for many human disorders," study leader Eick explains the work's background. "Research into the phosphorylation pattern at certain times during the transcription cycle is therefore necessary in order to be able to gain an understanding of the underlying mechanisms of gene regulation at the transcription level sometime in the future."
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Genetically Modified
| 2,016 |
January 20, 2016
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https://www.sciencedaily.com/releases/2016/01/160120201207.htm
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Fatty acids from genetically modified oilseed crops could replace fish oil
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Oil from genetically modified (GM) oil seed crops could replace fish oil as a primary source of the beneficial Omega 3 fatty acid EPA -- according to new research from the University of East Anglia (UEA).
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Researchers studied the effect in mice of consuming feed enriched with oil from glasshouse-grown genetically engineered The goal of the research was to discover whether mammals (using mice as a model) can absorb and accumulate EPA from this novel source of omega-3s.The team examined levels of EPA in various organs in the body such as the liver, as well as its effect on the expression of genes key for regulating the way the body processes fats. The results show that the benefits were similar to those derived from fish oils.Lead researcher Prof Anne-Marie Minihane, from UEA's Norwich Medical School, said: "The long chain omega-3 polyunsaturated fatty acid EPA is beneficial for cardiovascular and cognitive health, as well as for foetal development in pregnancy."The recommended minimum dietary intake can be achieved by eating one to two portions of oily fish per week."But for everyone in the world to achieve their minimum dietary intake, you would need around 1.3 million metric tonnes of EPA per year. Fish currently provide around 40 per cent of the required amount -- so there is a large deficit between supply and demand."There is a great need to identify alternative and sustainable sources of these beneficial fatty acids."We wanted to test whether oil from genetically modified plants could be used as a substitute. This first study indicates that mammals can efficiently accumulate the key health-beneficial omega-3 fatty acid EPA."The research team studied mice which had been fed with EPA oil from genetically engineered The researchers looked to see whether consuming oil from the engineered plants was as beneficial as EPA rich -- fish oil. They did this by testing tissue concentrations of fatty acids in liver, muscle and brain tissue, along with the expression of genes involved in regulating EPA status and its physiological benefits.Prof Minihane said: "The mice were fed with a control diet similar to a Westernised human diet, along with supplements of EPA from genetically engineered "We found that the genetically engineered oil is a bioavailable source of EPA, with comparable benefits for the liver to eating oily fish."
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Genetically Modified
| 2,016 |
January 13, 2016
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https://www.sciencedaily.com/releases/2016/01/160113103322.htm
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Environmental changes can elicit fast changes in pathogens
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Changes in environmental conditions may affect epidemics not only by altering the number of free-living pathogens but also by directly increasing pathogen virulence with immediate changes in the physiological status of infecting bacteria.
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Pathogens' abilities to cause infections is often considered to be consequence of long term selection pressures with their hosts. However, changes in environmental conditions could affect epidemics by altering the number of free-living pathogens but also by directly increasing pathogen virulence with immediate changes in the physiological status of infecting bacteria.Researchers tested if short-term exposure to different outside host resource types and concentrations affect Serratia marcescens -bacterium's virulence in Galleria mellonella -moth. S. marcescens is an environmentally growing opportunistic pathogen that can infect a wide range of host, including immunocompromised humans. As expected, severity of the infection was mostly dictated by the bacterial dose, but researchers also found a clear increase in virulence when the bacterium had inhabited a low (vs. high) resource concentration, or animal based (vs. plant based) resources 48 hours prior to infection.The findings suggest that depending on the exposure to different food sources prior infection, even genetically similar bacteria can differ in their virulence."Based on these results one could say that depending on if a single genetically similar bacterial cell originates from a piece of meat, instead of a plant, the virulence is higher. Such changes in virulence could stem from commonly observed resource dependent upregulation of genes that are known to regulate important virulence factors," academy Research Fellow, Tarmo Ketola, clarifies.The research was conducted in Academy of Finland´s Centre of Excellence in Biological Interactions, in colaboration between Finnish Universities of Jyväskylä and Helsinki. Article was published in
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Genetically Modified
| 2,016 |
January 7, 2016
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https://www.sciencedaily.com/releases/2016/01/160107140413.htm
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Tweak in gene expression may have helped humans walk upright
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Consider the engineering marvel that is your foot. Be it hairy or homely, without its solid support you'd be hard-pressed to walk or jump normally.
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Now, researchers at the Stanford University School of Medicine and the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama, have identified a change in gene expression between humans and primates that may have helped give us this edge when it comes to walking upright. And they did it by studying a tiny fish called the threespine stickleback that has evolved radically different skeletal structures to match environments around the world."It's somewhat unusual to have a research project that spans from fish all the way to humans, but it's clear that tweaking the expression levels of molecules called bone morphogenetic proteins can result in significant changes not just in the skeletal armor of the stickleback, but also in the hind-limb development of humans and primates," said David Kingsley, PhD, professor of developmental biology at Stanford. "This change is likely part of the reason why we've evolved from having a grasping hind foot like a chimp to a weight-bearing structure that allows us to walk on two legs."Kingsley, who is also a Howard Hughes Medical Institute investigator, is the senior author of a paper describing the work that will be published online Jan. 7 in The threespine stickleback is remarkable in that it has evolved to have many different body structures to equip it for life in different parts of the world. It sports an exterior of bony plates and spines that act as armor to protect it from predators. In marine environments, the plates are large and thick; in freshwater, the fish have evolved to have smaller, lighter-weight plates, perhaps to enhance buoyancy, increase body flexibility and better slip out of the grasp of large, hungry insects. Kingsley and his colleagues wanted to identify the regions of the fish's genome responsible for the skeletal differences that have evolved in natural populations.The researchers identified the area of the genome responsible for controlling armor plate size, and then looked for differences there in 11 pairs of marine and freshwater fish with varying armor-plate sizes. They homed in on a region that includes the gene for a bone morphogenetic protein family member called GDF6. Due to changes in the regulatory DNA sequence near this gene, freshwater sticklebacks express higher levels of GDF6, while their saltwater cousins express less. Strikingly, marine fish genetically engineered to contain the regulatory sequence of freshwater fish expressed higher levels of GDF6 and developed smaller armor plates, the researchers found.Kingsley and his colleagues wondered whether changes in GDF6 expression levels might also have contributed to critical skeletal modifications during human evolution. The possibility was not as far-fetched as it might seem. Other studies by evolutionary biologists, including Kingsley, have shown that small changes in the regulatory regions of key developmental genes can have profound effects in many vertebrates.They began by working with colleagues in the laboratory of Gill Bejerano, PhD, Stanford associate professor of developmental biology, of computer science and of pediatrics, to compare differences in the genomes of chimps and humans. In previous surveys, they found over 500 places in which humans have lost regulatory regions that are conserved from chimps and many other mammals. Two of these occur near the GDF6 gene. They homed in on one in particular."This regulatory information was shared through about 100 million years of evolution," said Kingsley. "And yet, surprisingly, this region is missing in humans."To learn more about what the GDF6 regulatory region might be controlling, the researchers used the chimp regulatory DNA to control the production of a protein that is easy to visualize in mice. Laboratory mice with the chimp regulatory DNA coupled to the reporter protein strongly and specifically expressed the protein in their hind limbs, but not their forelimbs, and in their lateral toes, but not the big toes of the hind limbs. Mice genetically engineered to lack the ability to produce GDF6 in any part of their bodies had skull bones that were smaller than normal and their toes were shorter than those of their peers. Together, these findings gave the researchers a clue that GDF6 might play a critical role in limb development and evolution.The fact that humans are missing the hind-limb-regulatory region probably means that we express less of the gene in our legs and feet during development, but comparable amounts in our nascent arms, hands and skulls. Loss of this particular regulatory sequence would also shorten lateral toes but not the first toe of feet. This may help explain why the big toe is aligned with other short, lateral toes in humans. Such a modification would create a more sturdy foot with which to walk upright."These bone morphogenetic proteins are strong signals for bone and cartilage growth in all types of animals," said Kingsley."You can evolve new skeletal structures by changing where and when the signals are expressed, and it's very satisfying to see similar regulatory principles in action whether you are changing the armor of a stickleback, or changing specific hind-limb structures during human evolution."
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Genetically Modified
| 2,016 |
January 6, 2016
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https://www.sciencedaily.com/releases/2016/01/160106125042.htm
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Generous mothers are nagged less
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If a mother is already a generous provider, her offspring will nag her less, according to new research in mice by University of Manchester scientists.
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The study, published in Though the study was conducted on mice, the findings are applicable to any social species, including humans."Our aim was to unpick the genetic conflict between the care a parent provides and the amount that offspring want," says evolutionary biologist Reinmar Hager from The University of Manchester."If offspring are too demanding it can be costly to parents and to themselves. But if parents don't invest enough, their genes may not survive the next generation," he says.The level of maternal care was measured as the sum of nursing, suckling and nest-building behaviour. One of the most important roles of a mouse parent is to keep offspring warm. Hypothermia is the leading cause of death in pups.A key part of the study looked at how genes expressed in offspring influence their mother's behaviour. For the first time, the researchers were able to show that genes expressed in offspring affect maternal behaviour.During their analysis, the researchers identified genetic variation in pups that influences nest-building by mothers. If a pup carries a specific variation of a gene on chromosome 7, from its sixth day of life its mother or adoptive mother will spend more time gathering nesting material and using it to construct and repair a nest.Similarly, if a pup carries a specific variation on chromosome 5, from day 14 mothers show increased levels of maternal behaviour. This is a crucial time for pups as it is around the time when 'weaning conflict' is expected to be at its height -- the battle between a developing pup's desire to continue to nurse and a mother's desire to stop is waged until pups are fully weaned at three weeks."For the first time we have identified specific genetic variations in offspring that lead to preferential maternal treatment, which in turn improves offspring fitness," says first author David Ashbrook, a PhD student from Manchester."There will therefore be a strong selection pressure on genes expressed in offspring that influence parental behaviour," he says.However, all genotypes benefited from the extra investment by mothers genetically predisposed to give better quality care, known as the B6 maternal phenotype.
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Genetically Modified
| 2,016 |
January 6, 2016
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https://www.sciencedaily.com/releases/2016/01/160106114837.htm
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Purple limes, blood oranges could be next for Florida citrus
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University of Florida horticulture scientist Manjul Dutt is hoping to turn your next margarita on its head by making it a lovely lavender instead of passé pale green.
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Dutt and Jude Grosser from the UF Citrus Research and Education Center are developing genetically engineered limes containing some similar genetic factors that are expressed in grape skin and blood orange pulp. These modified Mexican limes have a protein that induces anthocyanin biosynthesis, the process that creates the "red" in red wine, and causes the limes to develop a range of colors in the pulp from dark purple to fuchsia."Anthocyanins are beneficial bioflavonoids that have numerous roles in human well-being," Dutt explained. "Numerous pharmacological studies have implicated their intake to the prevention of a number of human health issues, such as obesity and diabetes."Anthocyanins also naturally occur in a variety of oranges called blood oranges, which has a red to maroon colored flesh and, some say, a better taste than Florida's "blond" oranges. But blood oranges need cold temperatures to develop their trademark vibrant color. They grow and color well in the cooler climates of Spain and Italy, but do not exhibit the characteristic blood red color when grown in the subtropical climate of the Florida citrus belt.These new limes were developed using genes isolated from the red grape "Ruby Seedless" and the Blood Orange "Moro." Research on the utilization of these genes was conducted initially to develop a more consumer-friendly, alternative, plant-derived, system. They are the first step toward Florida farmers producing blood oranges and, possibly, a new grapefruit cultivar.In addition to changing the color of the fruit, the introduction of anthocyanins also change the color of leaves stems and flowers, and could lead to the creation of ornamental citrus plants."Novel fruit, leaf, and flower colors could be produced by regulating anthocyanin biosynthesis," Dutt said. "Flower color ranged from light pink to fuchsia."Dutt and Grosser's study is being published in the January edition of the
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Genetically Modified
| 2,016 |
January 4, 2016
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https://www.sciencedaily.com/releases/2016/01/160104080037.htm
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Creating safer polio vaccine strains for the post-eradication era
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While the goal of polio virus eradication is in sight, there are concerns about post-eradication manufacturing and stockpiling vaccine stores containing live virus that could escape and repopulate the environment. A study published on December 31st in
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Different types of polio vaccines currently exist, but none are optimal from a safety point of view. Live attenuated (weakened) vaccine strains carry genetic mutations that prevent them from causing disease, but they can--in rare cases--revert to more dangerous (or virulent) virus. There are also examples in which live attenuated virus can survive in the gut of immune-compromised individuals and can be shed into the environment through their feces. Inactivated vaccines are themselves safe, but their production at present involves growing large amounts of wild-type (i.e., active virulent) virus that is then killed with a chemical called formalin.After eradication, WHO plans to stop the use of live-attenuated polio vaccines. In addition, to improve safety, WHO has strongly encouraged new manufacturers to switch the source of inactivated virus from virulent wild-type strains to an attenuated strain, named after the polio vaccine pioneer Sabin. Arguing that the attenuated Sabin strain is unstable and therefore potentially problematic, Philip Minor, from the National Institute for Biological Standards and Control in Potters Bar, UK, and colleagues present data on alternative attenuated strains which they propose as a safer alternative source for inactivated vaccine.The researchers started with a Sabin vaccine strain whose attenuation and reversion has been extensively studied and is well understood. Based on this knowledge, they modified a particular region of the viral RNA in ways that they predicted would make the resulting strains genetically stable (i.e. they would not revert to wild-type or other virulent forms). They then compared these new strains with both the original Sabin vaccine strain and the wild-type strain currently used in the production of inactivated vaccine.Besides testing the genetic stability of the new strains, the researchers examined their ability to grow in tissue culture (necessary for vaccine production), their risk for causing paralysis in mice engineered to carry a human polio-virus receptor, and whether--after inactivation--they effectively immunized rats. Finally it was shown that these new strains were unable to infect primates by mouth. In all these tests, the new strains behaved as predicted, that is, they are effective, suitable to mass production, and safer than the alternatives."We have developed new strains for IPV production with negligible risk to the human population should they escape," the researchers conclude, and add that the attributes of the new strains "allow for safe vaccine production in the post-eradication world."To address whether the use of new vaccine strains is compatible with WHO's stated post-polio eradication strategy, the researchers state that the current WHO action plan "leaves open the option of assessing new derivatives by an expert panel that will compare the novel strains to the Sabin strains with respect to degree and stability of attenuation, potential for person to person transmission and neurovirulence in animal models to define the containment required which is not specified." The researchers would like their strains assessed in this way. At the very least, they say, this will establish a system for assessment, which they think is necessary.
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Genetically Modified
| 2,016 |
December 18, 2015
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https://www.sciencedaily.com/releases/2015/12/151218161234.htm
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Bacterium carrying a cloned Bt-gene could help millions infected with roundworms
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Intestinal nematodes and roundworms infect more than one billion people worldwide. These parasites lead to malnutrition and developmental problems, especially in children. Unfortunately, resistance to the existing drug treatment is increasing. Now a team of researchers has successfully inserted the gene for a naturally-occurring, insecticidal protein called Bt into a harmless bacterium. This could then be incorporated into dairy products, or used as a probiotic to deliver the protein to the intestines of people afflicted with roundworms.
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The research is published in The Bt crystal protein is used in organic insecticidal sprays and has been produced in genetically modified plants as a safe pesticide to kill insects that eat those plants. Bt can also kill some nematodes. In the study, the investigators used the gene for one type of the insecticidal protein, which is naturally produced by the soil bacterium, Bacillus thuringiensis.The investigators spliced the gene into a plasmid, a short, circular piece of DNA which can replicate independently of the genome in most bacteria. The investigators then inserted the plasmid into An important property of this bacterium has to do with an odd discovery these researchers made nearly 15 years ago. Normally, molecules of substantial size can only escape from a cell either if cellular machinery in the cell membrane actively exports them, or if the microbe breaks open in a process called lysis. "We observed that large proteins could be released from this particular bacterium without cell lysis or an active export system," said Todd Klaenhammer, PhD, Distinguished University Professor in the Department of Food, Bioprocessing and Nutrition Sciences, at North Carolina State University, Raleigh. He said the mechanism for this "leaky In the next step, the investigators found that this genetically modified microbe could inhibit the common laboratory roundworm, C. elegans, via the cloned and expressed Bt protein.This method of treating roundworm infections orally with food grade bacteria could be very inexpensive, said Klaenhammer. This would be a huge advantage, because roundworms infect millions of people in impoverished nations."What if someday children who are infected with parasitic round worms could simply eat a dish of locally made fermented milk or yogurt and be cured," said lead author Evelyn Durmaz, MS, a research associate at North Carolina State University. Klaenhammer also noted that "Our laboratories are currently investigating the possibilities of using probiotic bacteria and food safe bacteria to orally deliver vaccines and other biotherapeutics directly to the GI tract."
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Genetically Modified
| 2,015 |
December 17, 2015
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https://www.sciencedaily.com/releases/2015/12/151217130456.htm
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An alternative TALEN/CRISPR-mediated gene insertion technique described in detail
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A streamlined protocol for an alternative gene insertion method using genome editing technologies, the PITCh (Precise Integration into Target Chromosome) system, has been reported in
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The PITCh system is more convenient and effective than existing methods for inserting foreign DNA into targeted genomic loci by using genome-editing tools. This new versatile technique can aid the rapid progression of research in fields such as screening of new drug candidates and creating cell or animal models of human diseases.Genome editing is an innovative technique used in genetic engineering that enables researchers to modify the genome not at random but at a particular target. In this technique, researchers employ engineered nucleases as "molecular scissors," which create DNA breaks at desired locations in the genome. When DNA breaks are repaired by repair pathways, genetic modifications including insertion of foreign DNA into the genome (knock-in) and replacement or removal of a targeted genomic locus are induced."The PITCh system is an alternative knock-in method that is independent of homologous recombination (HR), one of DNA-break repair pathways, unlike existing knock-in techniques that use genome editing tools like TALEN or CRISPR-Cas9, which mainly utilize HR," said Dr. Sakuma. "The existing knock-in techniques cannot be applied to every cell type and organism owing to variable HR frequencies. Therefore, we aimed at another repair pathway, microhomology-mediated end-joining (MMEJ), and developed the PITCh system."In this article, we describe detailed procedures for constructing a desired vector, transfecting it into cells, selecting knocked-in cells, and checking after insertion together with an actual successful example. Furthermore, a simplified method of gene insertion in frog embryos is also described. This article will allow researchers to use this powerful tool easily, and will contribute to the progress of not only basic but also applied research in the life science.
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Genetically Modified
| 2,015 |
December 11, 2015
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https://www.sciencedaily.com/releases/2015/12/151211130113.htm
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Urban swans' genes make them plucky
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Researchers have discovered that swans' wariness is partly determined by their genes. The research, which is published in the open access journal
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It is often assumed that animals that live in urban areas become less wary of humans through habituation, but until now, no research has been conducted which tests whether animals' preference for an urban or non-urban environment might be genetically determined.A team of researchers from Victoria University, Deakin University and The University of Melbourne, Australia, conducted a series of tests to establish the wariness of two separate populations of black swans (The researchers quantified the birds' wariness by walking slowly towards them, and then measuring the distance at which the bird flew away, called the Flight Initiation Distance (FID). Separately, they also took blood samples from the two populations of birds so that they could look for variations in two sets of genes -- DRD4 and SERT -- typically associated with behaviours related to anxiety and harm avoidance in animals.As expected, the swans living in an urban setting were much bolder than their rural counterparts, with an average FID of 13 meters, compared to 96 meters for the non-urban swans. The genetic tests revealed no significant differences between the two populations in SERT genotypes, but they found five different variants of DRD4 which were associated with different levels of wariness.The vast majority (88.8%) of the urban swans shared the most common genotype for DRD4, whereas only 60% of the rural swans exhibited this genotype. Of all the swans, 83% with the most common DRD4 genotype had a shorter average FID, suggesting that the birds' wariness is at least partly determined by their genes.As swans are typically highly mobile, and have the ability to migrate between different habitats, the researchers conclude that wary swans may be more likely to choose to inhabit a non-urban site, with bolder swans colonising urban areas.Lead researcher, Wouter van Dongen, says: "Growing global urbanisation means that wild animals are increasingly settling near to humans. Although we often assume that animals become less wary of humans by simply getting used to them, our results suggest that at least part of this response might be genetically determined. This has important implications for conservation, particularly for the introduction of animals bred in captivity, which could in future be screened for genotypes that are associated with wariness, allowing them to be released to a location commensurate with their expected wariness."
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Genetically Modified
| 2,015 |
December 10, 2015
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https://www.sciencedaily.com/releases/2015/12/151210124546.htm
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Bacteria engineered with synthetic circadian clocks
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Many of the body's processes follow a natural daily rhythm or so-called circadian clock, so there are certain times of the day when a person is most alert, when the heart is most efficient, and when the body prefers sleep. Even bacteria have a circadian clock, and in a December 10
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"The answer seems to be especially simple: the clock proteins sense the metabolic activity in the cell," says senior author Michael Rust, of the University of Chicago's Institute for Genomics and Systems Biology."This is probably because cyanobacteria are naturally photosynthetic--they're actually responsible for a large fraction of the photosynthesis in the ocean--and so whether the cell is energized or not is a good indication of whether it's day or night," he says. For photosynthetic bacteria, every night is a period of starvation, and it is likely that the circadian clock helps them grow during the day in order to prepare for nightfall.To make their discovery, Rust and his colleagues had to separate metabolism from light exposure, and they did this by using a synthetic biology approach to make photosynthetic bacteria capable of living on sugar rather than sunlight."I was surprised that this actually worked--by genetically engineering just one sugar transporter, it was possible to give these bacteria a completely different lifestyle than the one they have had for hundreds of millions of years," Rust says. The findings indicate that the cyanobacteria's clock can synchronize to metabolism outside of the context of photosynthesis. "This suggests that in the future this system could be installed in microbes of our own design to carry out scheduled tasks," he says.In a related analogy, engineers who developed electrical circuits found that synchronizing each step of a computation to an internal clock made increasingly complicated tasks possible, ultimately leading to the computers we have today. "Perhaps in the future we'll be able to use synthetic clocks in engineered microbes in a similar way," Rust says.Other researchers have shown that molecules involved in the mammalian circadian clock are also sensitive to metabolism, but our metabolism is not so closely tied to daylight as the cyanobacteria's. Therefore, our bodies' clocks evolved to also sense light and dark."This is presumably why, in mammals, there are specialized networks of neurons that receive light input from the retina and send timing signals to the rest of the body," Rust explains. "So, for us it's clearly a mixture of metabolic cues and light exposure that are important."The bacteria that live inside of our guts, however, most likely face similar daily challenges as those experienced by cyanobacteria because we give them food during the day when we eat but not during the night. "It's still an open question whether the bacteria that live inside us have ways of keeping track of time," Rust says.
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Genetically Modified
| 2,015 |
December 7, 2015
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https://www.sciencedaily.com/releases/2015/12/151207113839.htm
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Modified mosquitoes could help fight against malaria
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For the first time, malarial mosquitoes have been modified to be infertile and pass on the trait rapidly -- raising the possibility of reducing the spread of disease.
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The mosquito species Now, a team of researchers led by Imperial College London have genetically modified Within a few years, the spread could drastically reduce or eliminate local populations of the malaria-carrying mosquito species. Their findings represent an important step forward in the ability to develop novel methods of vector control.Normally, each gene variant has a 50 per cent chance of being passed down from parents to their offspring. In the Imperial team's experiments with The technique uses recessive genes, so that many mosquitoes will inherit only one copy of the gene. Two copies are needed to cause infertility, meaning that mosquitoes with only one copy are carriers, and can spread the gene through a population.This is the first time the technique has been demonstrated in "The field has been trying to tackle malaria for more than 100 years. If successful, this technology has the potential to substantially reduce the transmission of malaria," said co-author Professor Andrea Crisanti from the Department of Life Sciences at Imperial."As with any new technology, there are many more steps we will go through to test and ensure the safety of the approach we are pursuing. It will be at least 10 more years before gene drive malaria mosquitoes could be a working intervention," added Professor Austin Burt from Imperial's Department of Life Sciences.Many current measures to control malaria rely on reducing populations of malarial mosquitoes, such as insecticides and bed nets. These have proven very successful in reducing the spread of malaria, however these approaches face important costs and distribution challenges, as well as growing issues of resistance.A control measure relying on genetic spread through a targeted population of malaria mosquitoes could complement these interventions without adding dramatically to the health budget of resource-constrained countries."There are roughly 3,400 different species of mosquitoes worldwide, and while To test the gene drive, the team first identified three genes that impacted female fertility by disrupting the activity of suspected target genes. They then modified the genes with the CRISPR/Cas9 endonuclease, a type of DNA cutting tool that can be designed to target very specific parts of the genetic code.When chromosomes carrying these modified genes come into contact with chromosomes without the gene variant, an enzyme is produced that cuts it, causing a break. The broken chromosome uses the chromosome carrying the desired variant as a template to repair itself, copying in the code with the altered gene variant.The team aims to improve the expression of their gene drive elements, but also to find more genes to target, which would reduce the possibility of mosquitoes evolving resistance to the modification.Exploring target genes is also helping the researchers to learn more about basic mosquito biology. "We hope others will use our technique to understand how mosquitoes work, giving us more ammunition in the fight against malaria," said first author Andrew Hammond, also from Imperial's Department of Life Sciences.
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Genetically Modified
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December 2, 2015
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https://www.sciencedaily.com/releases/2015/12/151202132749.htm
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First direct evidence for synaptic plasticity in fruit fly brain
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Scientists at Cold Spring Harbor Laboratory (CSHL) have resolved a decades-long debate about how the brain is modified when an animal learns.
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Using newly developed tools for manipulating specific populations of neurons, the researchers have for the first time observed direct evidence of synaptic plasticity -- changes in the strength of connections between neurons -- in the fruit fly brain while flies are learning."We showed something that people have been hoping to see for a long time," says the team leader, CSHL Associate Professor Glenn Turner, "and we showed it quite definitively." The results appear online today in the journal Due to the relative simplicity of fruit fly neural anatomy -- there are just two synapses separating odor-detecting antenna from an olfactory-memory brain center called the mushroom body -- the diminutive insects have provided a powerful model organism for studying learning.Historically, researchers have monitored neurons in the mushroom body, as well as others to which they send signals, using a technique called calcium imaging. This approach enabled previous researchers to observe changes in neural activity that accompany learning. However this technique doesn't reveal precise how the electrical activity of the neurons is modified, since calcium is not the only ion involved in neuronal signaling.Additionally, it was unclear how the changes that had been seen were related to the behavior of the animal.Turner and colleagues at CSHL and the Howard Hughes Medical Institute's Janelia Research Campus were able to zoom in to a particularly important part of the fly brain where they were able to connect neural activity to behavior. Toshihide Hige, the lead author of the paper, used his expertise in electrophysiological recordings to directly examine changes in synaptic strength at this site.The researchers exposed fruit flies to a specific test odor and a very short time later subjected them to an artificial aversive cue. To do so they fired tiny beams of laser light at dopamine-releasing neurons in the mushroom body that were genetically engineered to become active in response to the light. Just like our own neurons, dopamine-releasing neurons in the fly are involved in reward and punishment." Presenting the smell of cherries, for example, which is normally an attractive odor to flies, while at the same time stimulating a particular dopamine neuron, trains the fly to avoid cherry odor," Turner explains.In addition to the dopamine neurons, the team identified neurons that represented the test odor and neurons that represented the flies' behavioral response to that odor. These neurons are connected to each other, while the dopamine neurons, which represent the punishment signal, modulate that connection. The team then made recordings of the neurons representing the behavior. This enabled them to discover any changes to the synaptic inputs those neurons received from the odor-representing neurons before and after learning.Strikingly, the team found a dramatic reduction in the synaptic inputs upon subsequent presentations of the test odor, but not control odors. This drop reflected the decrease in the attractiveness of the odor that resulted from the learning. "The average drop in synaptic strength was around 80 percent -- that's huge," says Turner.In future studies, Turner plans to exploit powerful tools available for studying fruit fly genetics to better understand the genetic components of learning. "We now have a way of investigating synaptic changes with genetic tools to identify molecules involved in learning and really understand the phenomenon at a level that bridges molecular and physiological mechanisms," he says."That mechanistic level of understanding is going to be really important," he adds. "It's often at the level of molecules that you see really strong connections between The research described in the release was supported by the National Institutes of Health, the Howard Hughes Medical Institute, the Japan Society for the Promotion of Science, and the Uehara Memorial Foundation.
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Genetically Modified
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November 30, 2015
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https://www.sciencedaily.com/releases/2015/11/151130130025.htm
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Shining light on microbial growth and death inside our guts
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For the first time, scientists can accurately measure population growth rates of the microbes that live inside mammalian gastrointestinal tracts, according to a new method reported in
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The new method uses genetically modified fluorescing "The dream in this field is to make cell-based computers, using cells that can remember, count, sense, actuate and complete tasks in a programmable way," said Pamela Silver, Ph.D., who is senior author on the new study, a Wyss Institute Core Faculty member on the Institute's Synthetic Biology platform, the Eliot T. and Onie H. Adams Professorship of Biochemistry and Systems Biology at Harvard Medical School (HMS), and a founder of the HMS Department of Systems Biology. "This advance brings us another step closer to making that original dream a reality."Gut microbes -- which collectively contain a vast amount of genetic information known as the "microbiome" -- play hugely important roles in the lives of their hosts. These microbes undergo dynamic shifts in their rates of growth depending upon factors like host diet or the presence of antibiotics. Gaining a window into these fluctuating dynamics helps scientists understand how microbes grow and divide inside our guts during infection, antibiotic therapy, and other microbial imbalances caused by health issues such as irritable bowel syndrome, obesity, and cancer, which could help identify future therapies for treating these conditions.But in gastrointestinal microbiome research, an area rife with new discoveries and opportunities thanks to recent breakthroughs in our understanding of how influential these microbes are to our health, it has until now been very difficult to monitor microbial cells during their travels through mammalian gastrointestinal tracts. Microbial growth rates fluctuate in response to diet, wellness, exercise and the environment, and are affected by inter-organism competition inside the gut. Yet after entering the gut and before exiting, microbes pass through the "dark zone," where they cannot be accessed or analyzed using standard methods and without disrupting observation of natural conditions.That challenge inspired Cameron Myhrvold, a Hertz graduate fellow at the Wyss Institute and Harvard Medical School and the lead author on the new study, to work with Silver to develop the novel synthetic "mark and recapture" technique known as DCDC.Using a genetically engineered red-colored fluorescent protein controlled by a gene expression promoter as a visual flag, Myhrvold set out to quite literally mark and recapture "Many different approaches to managing gastrointestinal health -- such as the use of antibiotics, probiotics, genetically engineered bacteria, and therapeutics -- rely on us being able to tell how these treatments affect the growth, division and death of certain microbial populations in our guts," said Myhrvold. "Until now, we've been lacking a way to measure how growth dynamics are affected by our interventions."A major new finding resulting from the study is that initial The DCDC method, which could be adapted to monitor a wide range of microbes, could be applied broadly in gastrointestinal research to illuminate what happens in the "dark zone" of mammalian guts when diet, environment, and health conditions change or experimental interventions are introduced."This innovation could help us gain a better understanding of the microbes that comprise the microbiome, which live inside us and contribute so significantly to our health. It also is a harbinger of an entirely new class of 'cellular devices' -- literally comprised of living cells -- which can be programmed to sense and respond at will," said Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at HMS and Boston Children's Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
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Genetically Modified
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November 30, 2015
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https://www.sciencedaily.com/releases/2015/11/151130111253.htm
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Battle of the Sexes: How inhibition of male flower production lets female flowers emerge
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Most people don't know this, but the cucumbers we buy in the supermarket are purely female -- grown from plants which were carefully cross-bred to produce female-only flowers. But while farmers have long known that "femaleness" factors into agricultural success -- the greater the percentage of female flowers, the greater the yield of both seeds and fruit -- it is only recently that scientists have revealed the molecular basis of plant sex determination.
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In a study published in "Most plants are hermaphroditic, meaning that their individual flowers contain both male and female reproductive organs, which produce both pollen and seeds," says Perl-Treves. "My research, on the other hand, focuses on the minority of plant species: the ten percent of flowering plants whose flowers have only male, or only female reproductive structures. This is a hot topic, because the greater the percentage of female flowers, the greater the crop yield. Our study shows that a particular family of these plants possesses a specialized strategy for sex determination: they produce female flowers through an enzyme-driven mechanism that represses the emergence of male organs and promotes the development of an ovary."Perl-Treves is an expert on the molecular genetics of cucurbits -- a family of plants which includes cucumber, squash, watermelon and cantaloupe. In this and previous work performed together with his French colleagues, Dr. Abdelhafid Bendahmane and Dr. Catherine Dogimont, of the Institut National de la Recherche Agronomique (INRA), Perl-Treves isolated two of the three genes known to play a role in cucurbit sex expression (the third gene was isolated years ago by another Israeli, Dr. Tova Trebitsch). Now, Perl-Treves and his colleagues have deciphered the molecular mechanism that mediates cucumber sex determination."Our work focused on the androecy gene, which produces the phenotype of all-male flowers," Perl-Treves explains. "We discovered that it is this very gene that also controls the production of flowers that are female. It does so by producing an enzyme -- ACS11 -- that limits the biosynthesis of a natural plant hormone called ethylene. When ACS11 is active -- that is, when ethylene is produced at the correct location -- female flowers develop. However, when a mutation causes ACS11 to be inhibited, the result is a lower level of ethylene in the developing flower bud. Under these circumstances, male rather than female flowers result."Perl-Treves has not yet characterized the exact molecular mechanism by which ethylene represses the emergence of male flowers. However, he says that the discovery of this gene-mediated dynamic can already be of practical significance."Ethylene production can be quantitatively modified, thus switching the sex of a developing plant," he says, adding that, even before the isolation of the genes involved, sexual fine-tuning had already been accomplished through the use of classical cross-breeding techniques and chemical hormone treatments. "Now that we understand the very specific role this gene plays in sex determination, it may be possible to use direct DNA 'diagnostics' to select plants that are agriculturally advantageous. Although this study involves cucurbits, this approach could theoretically form the basis of strategies for improving the productivity of other crops. For example, in unisexual trees like the palm date and pistachio, DNA tests that predict tree's sex in the nursery would have great economic importance since it take years for the tree's gender to become apparent, and female trees are the ones needed to harvest fruit."The discovery may also create more efficient, genetics-based cross-breeding methods for commercial seed production."To create hybrid seeds by crosses, seed producers emasculate flowers by hand, which is a very labor intensive process," Perl-Treves explains. "Now that we know the cucurbits' mechanism for repressing maleness, this gene-based mechanism could conceivably be genetically engineered into non-cucurbit species some time in the future."After isolating the sex-determining gene in cucumbers, Perl-Treves's colleagues discovered the same gene in a cucurbit "cousin" -- the melon. Like a pair of concurrently-minted coins found in two separate archaeological sites, the discovery makes it possible to determine how long ago in botanical history this mechanism was known to occur."Melon and cucumber are two species that evolved from the same family," he says. "Based on the time that these two species are believed to have broken off from one another, we can estimate that this shared genetic mechanism has been determining the sex of plants for about ten million years."On a significantly shorter time scale, Perl-Treves says that while it took years of intensive gene mapping efforts to isolate the DNA responsible for sex determination, there is still a long scientific road ahead."Our future goal is to understand exactly how ethylene biosynthesis represses the male flowers, allowing females to emerge," he says. "This is just one of the developmental-genetic questions about plant reproduction that might someday yield significant biotechnological assets."
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Genetically Modified
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November 26, 2015
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https://www.sciencedaily.com/releases/2015/11/151126104207.htm
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DNA sequences in GMOs: Largest database now publicly available
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The JRC has published a new database, JRC GMO-Amplicons, which contains more than 240,000 DNA sequences appearing in genetically modified organisms (GMOs). It will help to verify the presence of GMOs in food, feed and environment. To date, this new database is the largest and most comprehensive in this area and could be key to developing new methods for detecting GMOs in food and feed.
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The number of genetically modified (GM) crops, their complexity and the related cultivation area are steadily increasing worldwide. In the EU, only one variety of maize (corn) is currently grown commercially but GM varieties of maize, cotton, soybean, oilseed rape and sugar beet are authorised for import into the EU for food and feed uses. The authorisation is granted for new products if they do not pose threats to human or animal health or to the environment.According to EU Regulation on labelling, labels have to specify if the product contains GMOs.Correct labelling requires methods for GMO detection, identification and quantification and allows consumers to make informed decisions. These methods detect one or more short DNA sequences (amplicons) characteristic of the GMO genomes, i.e. they are able to detect if GMOs are present in the product. The new JRC GMO-Amplicons database was compiled by collecting information from a large number of publicly available databanks through an automatic computer-based procedure, called "Bioinformatics pipeline," developed by the JRC experts. The database provides information on amplicons present in GMOs that are authorised in the EU and also those described either in a publication, patent, or public database (even if not authorised). This makes JRC GMO-Amplicons the most comprehensive source for the detection of DNA target sequences currently available.The new database is easily accessible via the web and helps laboratories to identify suitable target-sequences for developing detection methods, especially for unauthorised GMOs.The reliable detection of GMOs is pivotal for the enforcement of regulations on GMO authorisation and labelling. In the context of the GMO authorisation process, the European Union Reference Laboratory for GM Food and Feed of the JRC is responsible for validating, developing and optimising methods for the detection of GMOs, and harmonising their correct application throughout the EU. It also is responsible for making tools and methods available to the control laboratories.The JRC GMO-Amplicons database is the third publicly available tool that has been developed by the JRC in the GMO field, together with the JRC GMO-Matrix and the GMOMETHODS database, a decision support tool to optimise the detection of GMOs and the EU database of reference methods for GMO analysis, respectively. They all together will contribute to make the analysis of GMOs in the food chain more efficient and cost-effective.
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Genetically Modified
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November 23, 2015
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https://www.sciencedaily.com/releases/2015/11/151123202216.htm
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Trees created with enhanced resistance to greening
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After a decade of battling the highly destructive citrus greening bacterium, researchers with the University of Florida's Institute of Food and Agricultural Sciences have developed genetically modified citrus trees that show enhanced resistance to greening, and have the potential to resist canker and black spot, as well. However, the commercial availability of those trees is still several years away.
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Jude Grosser, a professor of plant cell genetics at UF's Institute of Food and Agricultural Sciences Citrus Research and Education Center, and Manjul Dutt, a research assistant scientist at the CREC, used a gene isolated from the Arabidopsis plant, a member of the mustard family, to create the new trees. Their experiment resulted in trees that exhibited enhanced resistance to greening, reduced disease severity and even several trees that remained disease-free after 36 months of planting in a field with a high number of diseased trees. The journal "Citrus crop improvement using conventional breeding methods is difficult and time consuming due to the long juvenile phase in citrus, which can vary from four to twelve years, "Grosser said. "Improvement of citrus through genetic engineering remains the fastest method for improvement of existing citrus cultivars and has been a key component in the University of Florida's genetic improvement strategy."Citrus greening threatens to destroy Florida's $10.7 billion citrus industry. The diseased bacterium first enters the tree via the tiny Asian citrus psyllid, which sucks on leaf sap and leaves behind the greening bacteria. The bacteria then move through the tree via the phloem -- the veins of the tree. The disease starves the tree of nutrients, damages its roots and the tree produces fruits that are green and misshapen, unsuitable for sale as fresh fruit or, for the most part, juice. Most infected trees eventually die and the disease has already affected millions of citrus trees in North America.Citrus greening was first detected in Florida in 2005. Florida has lost approximately 100,000 citrus acres and $3.6 billion in revenues since 2007, according to researchers with UF/IFAS.Grosser and Dutt's research team used sweet orange cultivars Hamlin and Valencia and created plants that defend themselves against pathogens utilizing a process called systemic acquired resistance, or SAR. SAR provides protection against a broad spectrum of microorganisms and is associated with the production of anti-pathogen proteins. Utilizing SAR has already resulted in the production of transgenic canker-resistant trees. Transgenic trees are those into which DNA from an unrelated organism has been artificially introduced.Disease resistance to greening, also known as huanglongbing or HLB, in this study was evaluated in two ways.First, in a greenhouse study conducted with Southern Gardens Citrus in Clewiston, several hundred trees (clones from several independent transgenic plant lines) were exposed continuously for two years to free-flying, greening-positive psyllids. Trees were routinely pruned and fertilized to stimulate new leaf production. These trees were evaluated every six months for two years for the presence of greening. The insects were also randomly evaluated during this study for the presence of the greening bacterium.Approximately 45 percent of the trees expressing the Arabidopsis gene tested negative for greening. In three of the transgenic lines, the greening bacterium was not detected at all. Control trees tested positive for the presence of greening within six months and remained positive for the entire duration of the study.In the second concurrent study, selected transgenic trees and controls were cloned, grown and planted in fields with a 90-percent HLB infection rate. These trees were similarly evaluated every six months for three years for the presence of the greening bacterium.In this study, one transgenic line remained greening-free for the duration of the study, except for the 24-month sampling period when it tested positive. A second line tested positive at the 30-month sampling period while a third line tested positive at 30 months, but was greening-free at 36 months. Neither of these lines declined in health, and both showed continued growth with periodic flushes."In addition to inducing resistance to greening, this transgenic line could potentially protect our trees from other important citrus fungal and bacterial diseases such as citrus canker and black spot," Dutt said.The next steps include transferring this gene into additional commercial varieties and rootstocks that are commonly grown in Florida. In addition, researchers must 'stack' this gene with another transgene that provides resistance to the greening bacterium by a completely different mechanism. That will prevent the pathogen from overcoming the resistance in the field. It will still be several years before such trees will be available for commercial use.
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Genetically Modified
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November 2, 2015
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https://www.sciencedaily.com/releases/2015/11/151102163720.htm
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Protecting plants from stealthy diseases
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Stealthy diseases sometimes trick plants by hijacking their defense signaling system, which issues an alarm that diverts plant resources for the wrong attack and allows the enemy pathogens to easily overrun plants.
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A team of international scientists led by Michigan State University, however, is helping plants counter these attacks by boosting plants' alert system. New research in the current issue of "This is the first example of using receptor engineering to fix a disease-vulnerable component of the plant immune system that is frequently hijacked by highly evolved pathogens to cause disease," said Sheng Yang He, an MSU Distinguished Professor in the MSU-Department of Energy Plant Research Laboratory. "This new strategy is different from conventional resistance gene-based crop breeding and is based on a deep understanding of a key component, the jasmonate receptor, of the plant immune system."This study may have significant practical implications and may serve as an example of finding and fixing disease-vulnerable components of the plant immune system. It also may provide a general strategy of producing a new generation of disease-resistant crop plants against many plant diseases, which collectively cause crop losses of more than $200 billion annually worldwide, added He, a Howard Hughes Medical Institute-Gordon and Betty Moore Foundation Plant Biology Investigator.Jasmonate regulates plant defenses against a wide variety of pathogens and insects. In an evolutionary arms race between plants and pathogens, however, a group of highly evolved pathogens produce a jasmonate-mimicking toxin, coronatine. The wily bacteria use this toxin to override the jasmonate receptor, which divert plant resources to allow these pathogens to waltz through the security door without tripping any alarms.To stem this hijacking, He and his team created an enhanced receptor, one that can still signal for insect defense but also has a greatly reduced sensitivity to coronatine toxin. The team's proof-of-concept demonstration shows that the coronatine-based takeover of the jasmonate receptor by bacterial pathogens can be stopped and that plants can be engineered to be resistant to both insects and pathogens, which has been one of the elusive goals of plant pathology/entomology research."It took many years of fundamental research by a number of laboratories, but we made a precise repair of the jasmonate decoding system so that it can now distinguish between endogenous jasmonate in plants and bacterial toxin coronatine," He said. "We show that modified Arabidopsis plants equipped with the repaired jasmonate decoding system not only protects against insects, but it also does not allow bacteria to cause disease."The concept of repairing plant defense system components is appealing and could become a new trend in future efforts to protect plants from numerous plant diseases.
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Genetically Modified
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November 2, 2015
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https://www.sciencedaily.com/releases/2015/11/151102131513.htm
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Engineers design magnetic cell sensors
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MIT engineers have designed magnetic protein nanoparticles that can be used to track cells or to monitor interactions within cells. The particles, described in
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"Ferritin, which is as close as biology has given us to a naturally magnetic protein nanoparticle, is really not that magnetic. That's what this paper is addressing," says Alan Jasanoff, an MIT professor of biological engineering and the paper's senior author. "We used the tools of protein engineering to try to boost the magnetic characteristics of this protein."The new "hypermagnetic" protein nanoparticles can be produced within cells, allowing the cells to be imaged or sorted using magnetic techniques. This eliminates the need to tag cells with synthetic particles and allows the particles to sense other molecules inside cells.The paper's lead author is former MIT graduate student Yuri Matsumoto. Other authors are graduate student Ritchie Chen and Polina Anikeeva, an assistant professor of materials science and engineering.Previous research has yielded synthetic magnetic particles for imaging or tracking cells, but it can be difficult to deliver these particles into the target cells.In the new study, Jasanoff and colleagues set out to create magnetic particles that are genetically encoded. With this approach, the researchers deliver a gene for a magnetic protein into the target cells, prompting them to start producing the protein on their own."Rather than actually making a nanoparticle in the lab and attaching it to cells or injecting it into cells, all we have to do is introduce a gene that encodes this protein," says Jasanoff, who is also an associate member of MIT's McGovern Institute for Brain Research.As a starting point, the researchers used ferritin, which carries a supply of iron atoms that every cell needs as components of metabolic enzymes. In hopes of creating a more magnetic version of ferritin, the researchers created about 10 million variants and tested them in yeast cells.After repeated rounds of screening, the researchers used one of the most promising candidates to create a magnetic sensor consisting of enhanced ferritin modified with a protein tag that binds with another protein called streptavidin. This allowed them to detect whether streptavidin was present in yeast cells; however, this approach could also be tailored to target other interactions.Because the engineered ferritins are genetically encoded, they can be manufactured within cells that are programmed to make them respond only under certain circumstances, such as when the cell receives some kind of external signal, when it divides, or when it differentiates into another type of cell. Researchers could track this activity using magnetic resonance imaging (MRI), potentially allowing them to observe communication between neurons, activation of immune cells, or stem cell differentiation, among other phenomena.Such sensors could also be used to monitor the effectiveness of stem cell therapies, Jasanoff says."As stem cell therapies are developed, it's going to be necessary to have noninvasive tools that enable you to measure them," he says. Without this kind of monitoring, it would be difficult to determine what effect the treatment is having, or why it might not be working.The researchers are now working on adapting the magnetic sensors to work in mammalian cells. They are also trying to make the engineered ferritin even more strongly magnetic.
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Genetically Modified
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October 29, 2015
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https://www.sciencedaily.com/releases/2015/10/151029102238.htm
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Microbiomes could hold keys to improving life as we know it
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A consortium of 48 scientists from 50 institutions in the United States -- including Pamela Silver, Ph.D., a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University -- are calling for a Unified Microbiome Initiative that would span national cross-institutional and cross-governmental agency support. The group, called the Unified Microbiome Initiative Consortium (UMIC), envisions that a coordinated effort would drive forward cutting edge microbiome research, enabling breakthrough advances across medicine, ecosystem management, sustainable energy and production of commodities. Their proposal was published online in the journal
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Microbial life forms including viruses, bacteria and fungi are the most diverse and abundant organisms on earth. They have shaped our evolutionary origins for billions of years and continue to have widespread impact on the planet, its environment and the species inhabiting it. Together, they make up microbiomes that influence each other, the environment, and the host organisms that these microbial communities thrive in. The UMIC foresees that the microbiomes populating our planet and its many diverse species and environments could be leveraged through genetic engineering for applications that improve the greater good, and that many milestones could be reached on this front within ten years."Microbes are everywhere. Therefore understanding microbiomes, whether they be the ones that live in and on our bodies or the ones in the environment, is essential to understanding life," said Silver, who in addition to being one of the faculty leaders on the Wyss Institute's Synthetic Biology platform, is also the Elliot T. and Onie H. Adams Professor of Biochemistry and Systems Biology at Harvard Medical School (HMS) and a founding member of the Department of Systems Biology at HMS.The UMIC consists of leading microbiologists, ecologists, physical scientists, engineers, and scientists in the emerging field of synthetic biology. The group coalesced during a series of coordinated but separately convened meetings held by The White House Office of Science and Technology Policy and The Kavli Foundation. The proposal in The power of genome sequencing and genetic engineering has enabled synthetic biologists like Silver and her colleagues on the Wyss Institute Synthetic Biology platform to begin harnessing these microbes for diverse applications that could impact our health, ecosystem, and production of food and energy sources."Understanding how [microbiomes] work might hold the key to advances as diverse as fighting antibiotic resistance and autoimmune diseases, reclaiming ravaged farmland, reducing fertilizer and pesticide use, and converting sunlight into useful chemicals," said Jeff F. Miller, Ph.D., Director of the California NanoSystems Institute and corresponding author of the By metabolic processes, microbes synthesize countless different molecules, which through genetic engineering could lead to colonies of microbial "workers" being used for the sustainable synthesis of pharmaceuticals, materials and chemical commodities. Genetically engineered microbes could also produce biofuels through metabolic processes and conversion of solar energy into liquid fuel, according to work already underway by Silver at the Wyss Institute and HMS.Microbes also play a vital role in balancing biogeochemical processes, such as removing carbon dioxide from the atmosphere. The interactions between soil, plant roots and microbes also play an important role in plant health and crop yield.Furthermore, the microbiomes in our gastrointestinal tracts regulate wide-ranging physiological, metabolic, immunologic, cognitive, behavioral, and psychiatric traits. Understanding and manipulating human microbiomes could be key to managing physical and mental health. Silver and her team have already begun developing several potential avenues for leveraging gut microbes to improve health. In collaboration with Wyss Core Faculty member James Collins, Ph.D., Silver has engineered genetically programmed bacterial "reporters" that can detect and record conditions in the gastrointestinal tract. And, working with Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., and Wyss Institute Senior Staff Scientist Jeffrey Way, Ph.D., Silver is developing consortia of synthetic microbes that could be used to treat gastrointestinal illness.Her expertise and experience in these emerging areas of synthetic biology has enabled Silver to contribute her thought leadership as a member of the UMIC to how the proposed Unified Microbiome Initiative could integrate focus areas to accelerate microbiome research."I'm interested in engineering microbes as a way to interrogate their behavior," said Silver. "The purpose of this unified initiative is to determine what are the big questions we have about the microbiome and what are the specific technologies we need in order to investigate those questions."Some of the big questions the group hopes to address through an organized coalition include understanding how microbes assemble into communities and what makes them resilient or resistant to perturbation, how genes in the microbiome interact with one another, which genes in the microbiome are associated with which organisms, as well as how we can beneficially harness the microbiomes of humans, animals, plants and environments.To find the answers to these questions, scientists must first be supported in the development of breakthrough technologies for investigating microbiomes. Specifically, the group recommends development of improved computational methods for analyzing and predicting the vast number of unknown genes and their functions comprising microbiomes; a transition from gene-specific to whole-genome based analysis through improved genome reference libraries and sequencing methods; developing high-powered imaging methods for visually interrogating communities of microbes down to the individual level; new adaptive modeling systems and data reporting tools; improved genetic engineering techniques for perturbing microbial communities; and novel methods to mimic natural environments for supporting microbiome growth in the laboratory, among others."Discovery of the importance of the existence and importance of the microbiome has provided a new frame of reference for our understanding of health and our environment," said Ingber, who in addition to directing the Wyss Institute is the Judah Folkman Professor of Vascular Biology at HMS and Boston Children's Hospital and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences. "A nation-wide coordinated effort to invest in understanding and leveraging microbiomes could open entirely new frontiers in biotechnology and medicine, and lead to solutions that would not be possible in any other way."
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Genetically Modified
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October 26, 2015
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https://www.sciencedaily.com/releases/2015/10/151026093250.htm
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Cellular stress management in people and plants
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In their research on the model plant thale cress (Arabidopsis thaliana), scientists from the Centre for Organismal Studies of Heidelberg University have discovered a major function of a fundamental cellular mechanism for stress management. They observed that the biochemistry and cell biology of plants and humans are quite similar. Their findings are significant for the stress biology of human cells as well as the development of agricultural crops that are highly resistant to their primary stressor, drought. The Heidelberg team under the direction of Prof. Dr. Rüdiger Hell and Dr. Markus Wirtz also cooperated with researchers from France and Norway in their investigations. Their results were published in the journal "Nature Communications."
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Proteins have many tasks to fulfil in the structure, function and regulation of cells. Once the proteins are formed, they are further adapted for their very specific jobs. "One of the most frequent changes is the attachment of an acetic acid residue on the amino-terminal end of the proteins. Lacking this modification, the plants cannot survive, and this same lack in certain proteins in humans leads to illness, developmental problems and cell death," explains Prof. Hell. Although up to 80 percent of proteins in the cytoplasm of human cells are modified by an acetic acid residue at their amino terminus, the function of this modification has only been studied for a handful of proteins.The Heidelberg researchers generated genetically modified plants with protein populations that carry less acetic acid residues and analysed the results. "The changed pattern of amino-terminal modification proteins by acetic acid surprisingly made the genetically modified plants proved to be more drought-resistant," continues Dr. Wirtz. The reason turned out to be mediated by the plant hormone abscisic acid, a key player in drought stress. The drought resistance was based on the constant activation of natural plant processes to counteract the stress, such as closing the stomata and lengthening the primary root.
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Genetically Modified
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October 22, 2015
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https://www.sciencedaily.com/releases/2015/10/151022141702.htm
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What you didn't know about naked mole-rats
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The naked mole-rat is a particularly ugly or cute animal, depending on your definition. It is tubular in shape, like the tunnels it creates, hairless and wrinkled, for wiggling through those tunnels, and has long, chisel-like front teeth. It looks somewhat like a walrus in miniature. And these rodents can chew through concrete!
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Do a Google search of the naked mole-rat, or read through a number of biology textbooks, and you will find numerous references to this African mammal as being "inbred" and "eusocial," meaning -- similar to some insects -- it has a fertile "queen" at the head of the colony, helpers who tend to her and may mate with her, and female "workers" who are sterile, expending their energy building tunnels and finding food.This social system is rare among animals, and almost unheard-of among mammals, so evolutionary biologists have long taken particular interest in the unusual eusocial mating system of the naked mole-rat and its essentially homogeneous genetics. Why would this rodent have evolved to socialize and mate so differently from other mammals? From a natural selection standpoint -- where advantageous traits are passed down to succeeding generations -- what is gained by limiting genetic diversity by limiting the breeding pool?Evolutionary biologists have puzzled over and debated this for decades. For this reason, the naked mole-rat has been an interesting oddball study model.Well, it turns out the long-held conventional wisdom about the naked mole-rat being inbred is wrong, according to a University of Virginia-led study published recently in the journal UVA biologist Colleen Ingram and a team of researchers from several U.S. universities and the American Museum of Natural History conducted genetics studies of different mole-rat populations from Africa, and compared them to the genetics of a long-studied mole-rat population. They found that the populations of mole-rats studied for decades are "inbred" only because they originally came from a small, genetically isolated population of naked mole-rats from south of Kenya's Athi River. The researchers discovered that larger wild populations from north of that river and from the Tana River region are genetically variable, like other mammals -- meaning they are not inbred, despite their unusual eusocial mating behavior."We now know, from looking at the big picture from a much larger geographic area than previously studied, that the naked mole-rat is not inbred at all," Ingram said. "What we thought we knew was based on early genetics studies of a small inbred sample from an otherwise genetically variable species. This shows that long-held assumptions, even from heavily studied model species, can and should always be questioned and further studied."It also suggests, she said, that laboratory animals, isolated and repeatedly re-bred for studies, might over time represent behaviors and genetics that are different from the diverse wild populations from which they originally came.The study also means that some biology websites and textbooks need updating.
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Genetically Modified
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October 21, 2015
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https://www.sciencedaily.com/releases/2015/10/151021120620.htm
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Teenagers and mutant tomatoes
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What started as a simple show and tell with heirloom tomatoes by Wake Forest University biology professors and students to teach about genetic diversity has grown into an interactive presentation that has reached thousands of public school students.
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Wake Forest biology professors Gloria Muday and Carole Gibson and their students use mutant tomatoes grown in the campus garden to teach fundamental biology concepts to local high school students. "Teaching with Tomatoes" is funded by the American Society of Plant Biology Education Foundation and has evolved over the years.College students lead high school students through a problem-based learning exercise highlighting a purple fruit mutant to help them understand genetic inheritance and how that is part of both traditional plant breeding and construction of genetically modified organisms (GMOs) and food in a changing climate.Students learn about dominant and recessive genes and the genetic influence on the characteristics we can see and the ones we cannot. They use Punnett squares to predict gene combinations, discuss the science behind GMO foods, and even extract the DNA from red and purple mutant fruits."The material we teach is integral to high school biology curriculum; they just might not have gotten there yet. The goal is to provide memorable examples, so that when the students reach their genetic unit, they can call on this experience to build a stronger understanding of these critical course concepts," explained Muday.Another goal is to help high schools students understand what GMO foods are, the potential of this technology to address central challenges in agriculture that are accentuated with global climate change, and the current evidence for the safety of this technology."The local students aren't the only ones who benefit from this experience," Muday said. "It's also a way for very talented Wake Forest students to learn through teaching these concepts to younger students and it helps cement the concepts for them as well."
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Genetically Modified
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October 19, 2015
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https://www.sciencedaily.com/releases/2015/10/151019123744.htm
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Genome-edited plants, without DNA
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The public and scientists are at odds over the safety of genetically modified (GM) food. According to a January 2015 Pew Research Center report, only 37% of the public believe that GM foods are safe which is in stark contrast to the support from88% of scientists. There is concern that adding DNA of different species will lead to unintended, undesirable consequences. Scientists at the IBS Center for Genome Engineering in South Korea have created a way to genetically modify plants using CRISPR-Cas9 without the addition of DNA. Because no DNA is used in this process, the resulting genome-edited plants could likely be exempt from current GMO regulations and given a warmer reception by the public.
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What makes this work so groundbreaking is that these genetic modifications look just like genetic variations resulting from the selective breeding that farmers have been doing for millennia. IBS Director of the Center for Genome Engineering Jin-Soo Kim explains that "the targeted sites contained germline-transmissible small insertions or deletions that are indistinguishable from naturally occurring genetic variation."CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeat, which refers to the unique repeated DNA sequences found in bacteria and archaea. CRISPR is now used widely for genome editing. What's crucial in genetic engineering is for the gene editing tool to be accurate and precise, which is where CRISPR-Cas9 excels. CRISPR-Cas9 uses a single guide RNA (sgRNA) to identify and edit the target gene and Cas9 (a protein) then cleaves the gene, resulting in site-specific DNA double-strand breaks (DSBs). When the cell repairs the DSB, the resulting fix is the intended genetic edit.The beauty of this research is that the IBS research team has elevated the process and no longer uses DNA, being unshackled from GMO regulations. To do this, purified Cas9 protein was mixed with sgRNAs targeting specific genes from three plant species to form preassembled ribonucleoproteins (RNPs). The IBS team used these Cas9RNPs to transfect several different plants including tobacco, lettuce and rice to achieve targeted mutagenesis in protoplasts. To test the efficacy of this process, the team delivered Cas9 RNPs to the protoplasts of the test plant species, and foundCas9 RNP-induced mutations 24 hours after transfection.These newly cloned lettuce cells showed no mosaicism which led the researchers to believe that the RGEN RNP may have cleaved the target site immediately after transfection and the indels occurred before cell division was completed.Finally, the team demonstrated that RGEN-induced mutations were maintained after regeneration. Using a Cas9 RNP, they disrupted a gene in lettuce called Brassinosteroid Insensitive 2 (BIN2) which regulates the signaling of brassinosteroid, a class of steroid hormones responsible for a wide range of physiological processes in the plant life cycle, including growth. They found that after cell division the lettuce cells maintained the disruption of the gene with a frequency of 46%. Importantly, there were no off-target indels. They grew full plants from the seeds of these genome edited and regenerated plants,which had the mutation from the previous generation. They were able to definitively show that Cas9 RNPs can be used to genetically modify plants, which Jin-Soo Kim points out,"paves the way for the widespread use of RNA-guided genome editing in plant biotechnology and agriculture."The IBS team's technique of genome editing without inserting DNA could be revolutionary for the future of the seed industry.The RGEN RNP process will enable us to produce plants that are heartier and more suited to climate change in order to feed Earth's increasing population. Currently European Union GMO regulations don't allow for food with added DNA. Since the Cas9 RNP technique does not use DNA, it may be able to avoid being in violation of these rules. In addition, using Cas9 RNP is cheaper, faster and more accurate to apply to plants than previous breeding techniques (like radiation-induced mutations). Large agribusiness companies have been able to afford the time and money necessary to create seeds for genetically modified food, but the Cas9 RNP technique could allow for a more decentralized gene-edited seed production industry.This process is ready for use to bolster plant output and create heartier crops in foods like tomatoes and lettuce. The application of the Cas9 RNP gene editing technique could be the next step in ending food shortages.
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Genetically Modified
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October 15, 2015
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https://www.sciencedaily.com/releases/2015/10/151015115946.htm
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Quantum physics meets genetic engineering
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Nature has had billions of years to perfect photosynthesis, which directly or indirectly supports virtually all life on Earth. In that time, the process has achieved almost 100 percent efficiency in transporting the energy of sunlight from receptors to reaction centers where it can be harnessed -- a performance vastly better than even the best solar cells.
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One way plants achieve this efficiency is by making use of the exotic effects of quantum mechanics -- effects sometimes known as "quantum weirdness." These effects, which include the ability of a particle to exist in more than one place at a time, have now been used by engineers at MIT to achieve a significant efficiency boost in a light-harvesting system.Surprisingly, the MIT researchers achieved this new approach to solar energy not with high-tech materials or microchips -- but by using genetically engineered viruses.This achievement in coupling quantum research and genetic manipulation, described this week in the journal Lloyd, a professor of mechanical engineering, explains that in photosynthesis, a photon hits a receptor called a chromophore, which in turn produces an exciton -- a quantum particle of energy. This exciton jumps from one chromophore to another until it reaches a reaction center, where that energy is harnessed to build the molecules that support life.But the hopping pathway is random and inefficient unless it takes advantage of quantum effects that allow it, in effect, to take multiple pathways at once and select the best ones, behaving more like a wave than a particle.This efficient movement of excitons has one key requirement: The chromophores have to be arranged just right, with exactly the right amount of space between them. This, Lloyd explains, is known as the "Quantum Goldilocks Effect."That's where the virus comes in. By engineering a virus that Belcher has worked with for years, the team was able to get it to bond with multiple synthetic chromophores -- or, in this case, organic dyes. The researchers were then able to produce many varieties of the virus, with slightly different spacings between those synthetic chromophores, and select the ones that performed best.In the end, they were able to more than double excitons' speed, increasing the distance they traveled before dissipating -- a significant improvement in the efficiency of the process.The project started from a chance meeting at a conference in Italy. Lloyd and Belcher, a professor of biological engineering, were reporting on different projects they had worked on, and began discussing the possibility of a project encompassing their very different expertise. Lloyd, whose work is mostly theoretical, pointed out that the viruses Belcher works with have the right length scales to potentially support quantum effects.In 2008, Lloyd had published a paper demonstrating that photosynthetic organisms transmit light energy efficiently because of these quantum effects. When he saw Belcher's report on her work with engineered viruses, he wondered if that might provide a way to artificially induce a similar effect, in an effort to approach nature's efficiency."I had been talking about potential systems you could use to demonstrate this effect, and Angela said, 'We're already making those,'" Lloyd recalls. Eventually, after much analysis, "We came up with design principles to redesign how the virus is capturing light, and get it to this quantum regime."Within two weeks, Belcher's team had created their first test version of the engineered virus. Many months of work then went into perfecting the receptors and the spacings.Once the team engineered the viruses, they were able to use laser spectroscopy and dynamical modeling to watch the light-harvesting process in action, and to demonstrate that the new viruses were indeed making use of quantum coherence to enhance the transport of excitons."It was really fun," Belcher says. "A group of us who spoke different [scientific] languages worked closely together, to both make this class of organisms, and analyze the data. That's why I'm so excited by this."While this initial result is essentially a proof of concept rather than a practical system, it points the way toward an approach that could lead to inexpensive and efficient solar cells or light-driven catalysis, the team says. So far, the engineered viruses collect and transport energy from incoming light, but do not yet harness it to produce power (as in solar cells) or molecules (as in photosynthesis). But this could be done by adding a reaction center, where such processing takes place, to the end of the virus where the excitons end up.The research was supported by the Italian energy company Eni through the MIT Energy Initiative. In addition to MIT postdocs Nimrod Heldman and Patrick Rebentrost, the team included researchers at the University of Florence, the University of Perugia, and Eni.
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Genetically Modified
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October 9, 2015
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https://www.sciencedaily.com/releases/2015/10/151009083159.htm
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A cure for vitamin B6 deficiency?
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Plant scientists engineered the cassava plant to produce higher levels of vitamin B6 in its storage roots and leaves. This could help to protect millions of people in Africa from serious deficiencies.
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In many tropical countries, particularly in sub-Saharan Africa, cassava is one of the most important staple foods. People eat the starchy storage roots but also the leaves as a vegetable. Both have to be cooked first to remove the toxic cyanide compounds that cassava produces.But the roots have a disadvantage: although rich in calories, in general they contain only few vitamins. Vitamin B6 in particular is present in only small amounts, and a person for whom cassava is a staple food would have to eat about 1.3 kg of it every day for a sufficient amount of this vital vitamin.Vitamin B6 deficiency is prevalent in several African regions where cassava is often the only staple food people's diet. Diseases of the cardiovascular and nervous systems as well as are associated with vitamin B6 deficiency.Plant scientists at ETH Zurich and the University of Geneva have therefore set out to find a way to increase vitamin B6 production in the roots and leaves of the cassava plant. This could prevent vitamin B6 deficiency among people who consume mostly cassava.Their project has succeeded: in the latest issue of Nature Biotechnology, the scientists present a new genetically modified cassava variety that produces several-fold higher levels of this important vitamin."Using the improved variety, only 500 g of boiled roots or 50 g of leaves per day is sufficient to meet the daily vitamin B6 requirement," says Wilhelm Gruissem, professor of plant biotechnology at ETH Zurich. The basis for the new genetically modified cassava variant was developed by Professor Teresa Fitzpatrick at the University of Geneva. She discovered the biosynthesis of vitamin B6 in the model plant thale cress (Arabidopsis thaliana). Two enzymes, PDX1 and PDX2, are involved in the synthesis of the vitamin. With the introduction of the corresponding genes for the enzymes, into the cassava genome, the researchers produced several new cassava lines that had increased levels of vitamin B6.To determine if the increased production of the vitamin in the genetically modified cassava was stable without affected the yield, the plant scientists conducted tests in the greenhouse and in field trials over the course of several years. "It was important to determine that the genetically modified cassava consistently produced high vitamin B6 levels under different conditions," says Gruissem.Measurements of the metabolites confirmed that cassava lines produced several times more vitamin B6 in both roots and leaves than normal cassava. The researchers also attributed the increased production to the activity of the transferred genes, regardless of whether the plants were grown in a greenhouse or the field. The increased vitamin B6 trait remained stable even after the cassava was multiplied twice by vegetative propagation.Previously, the researchers had analysed several hundred different cassava varieties from Africa for its natural vitamin B6 content -- none had a level as high as the genetically modified variety.Vitamin B6 from the genetically modified varieties is bioavailable, which means that humans can absorb it well and use it, as was confirmed by a research team at the University of Utrecht."Our strategy shows that increasing vitamin B6 levels in an important food crop using Arabidopsis genes is stable, even under field conditions. Making sure that the technology is readily available to laboratories in developing countries is equally important," says Hervé Vanderschuren, who led the cassava research programme at ETH Zurich and recently became a professor of plant genetics at the University of Liège.It is still unclear when and how vitamin B6-enhanced cassava will find its way to farmers and consumers. The new trait should be crossed in varieties preferred by farmers using traditional plant breeding or introduced into selected varieties using genetic engineering.Vanderschuren hopes this can be performed in African laboratories. He has previously trained scientists on site and organised workshops to build platforms for the genetic modification of crop plants in Africanlaboratories. "We hope that these platforms can help spread the technology to farmers and consumers."The method for increasing vitamin B6 has not been patented because the gene construct and technology should be available freely to all interested parties.One huge hurdle, however, is the distribution and use of the new variety: "There are at least two obstacles: legislation for transgenic crops in developing countries and implementation of a cassava seed system to give all farmers access to technologies," says Vanderschuren.He is currently supervising a project in India in conjunction with the School of Agricultural, Forest and Food Sciences (HAFL) in Zollikofen, which he hopes will result in guidelines for the development of sustainable seed system for cassava in India. "Our work in Africa will also benefit from this project," he asserts.Individual national organisations as well as the FAO and other NGOs are currently organising the spread of cassava stem cuttings for cultivation in Africa. However, a better and more efficient organisation for the distribution of healthy plant material is urgently needed, says the researcher.On the legislative side, the cultivation of genetically modified cassava (and other crops) is not yet regulated everywhere. In numerous African countries, such as Uganda, Kenya and Nigeria, the governments have now enacted legislation for field trials of genetically modified plants. "This is an important step to ensure that improved varieties can be tested under field conditions," says Vanderschuren. "In order to allow the cultivation of genetically modified plants, the respective parliaments will have to develop further legislation."Vitamin B6 is a mixture of three similar molecules, namely pyridoxol, pyridoxine and pyridoxamine. These are the precursors of pyridoxal phosphate, one of the most important co-enzymes in the body involved in the assembly and modification of proteins. The human body cannot produce vitamin B6, which is why it must be supplied with the food. A high vitamin B6 content is found in soya beans, oats, beef liver and brown rice, for example. Avocados, nuts and potatoes are also good sources. The daily requirement of an adult is approximately 1.5 mg to 2 mg.
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Genetically Modified
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October 8, 2015
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https://www.sciencedaily.com/releases/2015/10/151008173517.htm
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Plant biosensor could help African farmers fight parasitic 'witchweed'
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Engineering and biology professors at the University of Toronto have developed a new strategy for helping African farmers fight a parasitic plant that devastates crops.
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Plants in the genus U of T chemical engineering professor Alexei Savchenko, along with professor Peter McCourt in the Department of Cell and Systems Biology, have created a genetically engineered plant biosensor, a tool that will help them hunt for molecules that could prevent The duo has been studying the biochemical pathways used by Savchenko and McCourt hope to outwit But in order to determine what false signal to send, the scientists first needed to better understand how The next step was to clone and introduce the most sensitive receptor into McCourt and Savchenko are now screening a variety of chemicals in search of ones that would mimic the plant hormones. Their genetically engineered "We have shown that this receptor is very important for
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Genetically Modified
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October 2, 2015
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https://www.sciencedaily.com/releases/2015/10/151002082305.htm
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Studying cardiac arrhythmias in nematodes
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Researchers at the Goethe University have developed a simple model using the nematode
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Cardiac arrhythmias often have genetic causes. The same mutation is often detected in patients with the same type of arrhythmia. However, it is not clear from the outset whether other mutations in the same gene have the same effects. The effects of the arrhythmia could also differ depending on the type of mutation. This knowledge could definitely be significant for treatment. This is because a type of medication that works particularly well for a specific mutation could be less beneficial for other mutations. Researchers have long been searching for a simple model that can be used to create certain genetic defects and in which the efficacy of substances can be tested.The research group, led by Alexander Gottschalk at the Institute of Biochemistry and the Buchmann Institute at the Goethe University, used the nematode The researchers used optogenetic techniques, since the feeding apparatus, i.e. the pharynx, does not naturally pump as regularly as required in order to recognize arrhythmias. They introduced photo-activated ion channels into the muscle cells using a genetic approach. In this way, the apparatus can be transformed into a light-activated muscle pump with highly regular action. They then introduced various ion channel mutations, which are responsible for the so-called Timothy syndrome (LQT8) in humans. In practice, the mutated pharynx then demonstrated aberrant pump behavior."We were able to improve or reverse these arrythmic effects using a substance that is already known to be pharmacologically active, and which is administered to patients with Timothy syndrome in a modified form," explains Prof Alexander Gottschalk. The goal is to use the worm to search for new active substances for other types of arrhythmia. These could even potentially be patient-specific if the exact mutation is transferred to the worm. The ease of genetic mutability of the nematode is highly advantageous in this regard when compared to a mouse model, which would be very difficult to generate. In order to facilitate the search for new medications, the researchers also developed a new optical method with which several animals can be analyzed in parallel.
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Genetically Modified
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September 25, 2015
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https://www.sciencedaily.com/releases/2015/09/150925131415.htm
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Root microbiome engineering improves plant growth
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Humans have been breeding crops until they're bigger and more nutritious since the early days of agriculture, but genetic manipulation isn't the only way to give plants a boost. In a review paper published on September 25 in
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Only a few published studies have looked at the effects of artificially selecting microbiomes. In their own labs, the authors--Ulrich Mueller of the University of Texas at Austin and Joel Sachs of the University of California, Riverside--have seen microbiome engineering to be successful with "My hope is that others will become interested in optimizing methods in other systems," says Mueller. "For agricultural applications, I would start with artificial selection of root microbiomes in a greenhouse environment, using cash crops such as lettuce, cucumber, or tomatoes, learn from these greenhouse experiments, then gauge whether any of these principles can be applied to outdoor agriculture and horticulture."Microbiome experiments can be tricky and affect reproducibility because of the complexity of propagating entire microbial communities between plants or between animals. The reason grasses and honeybees are attractive pilot organisms is because their microbiomes can be manipulated to be heritable. By testing this in organisms with stable genetics, it is easier to see the effects of adding specific bacterial communities."Selecting artificial microbiomes may be a cheaper way to help curb plant and animal diseases rather than pesticides and antibiotics or creating genetically modified organisms," Mueller says. "The methods to generate host-mediated artificial selection on root microbiomes are super simple (all you need is a syringe and a filter), and any farmer in any location could potentially do this to engineer microbiomes that are specific to the problems of the specific location where the farmer attempts to grow food."
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Genetically Modified
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September 23, 2015
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https://www.sciencedaily.com/releases/2015/09/150923134110.htm
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Viruses join fight against harmful bacteria
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In the hunt for new ways to kill harmful bacteria, scientists have turned to a natural predator: viruses that infect bacteria. By tweaking the genomes of these viruses, known as bacteriophages, researchers hope to customize them to target any type of pathogenic bacteria.
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To help achieve that goal, MIT biological engineers have devised a new mix-and-match system to genetically engineer viruses that target specific bacteria. This approach could generate new weapons against bacteria for which there are no effective antibiotics, says Timothy Lu, an associate professor of electrical engineering and computer science and biological engineering."These bacteriophages are designed in a way that's relatively modular. You can take genes and swap them in and out and get a functional phage that has new properties," says Lu, the senior author of a paper describing this work in the Sept. 23 edition of the journal These bacteriophages could also be used to "edit" microbial communities, such as the population of bacteria living in the human gut. There are trillions of bacterial cells in the human digestive tract, and while many of these are beneficial, some can cause disease. For example, some reports have linked Crohn's disease to the presence of certain strains of "We'd like to be able to remove specific members of the bacterial population and see what their function is in the microbiome," Lu says. "In the longer term you could design a specific phage that kills that bug but doesn't kill the other ones, but more information about the microbiome is needed to effectively design such therapies."The paper's lead author is Hiroki Ando, an MIT research scientist. Other authors are MIT research scientist Sebastien Lemire and Diana Pires, a research fellow at the University of Minho in Portugal.The Food and Drug Administration has approved a handful of bacteriophages for treating food products, but efforts to harness them for medical use have been hampered because isolating useful phages from soil or sewage can be a tedious, time-consuming process. Also, each family of bacteriophages can have a different genome organization and life cycle, making it difficult to engineer them and posing challenges for regulatory approval and clinical use.The MIT team set out to create a standardized genetic scaffold for their phages, which they could then customize by replacing the one to three genes that control the phages' bacterial targets.Many bacteriophages consist of a head region attached to a tail that enables them to latch onto their targets. The MIT team began with a phage from the T7 family that naturally kills "You keep the majority of the phage the same and all you're changing is the tail region, which dictates what its target is," Lu says.To find genes to swap in, the researchers combed through databases of phage genomes looking for sequences that appear to code for the key tail fiber section, known as gp17.After the researchers identified the genes they wanted to insert into their phage scaffold, they had to create a new system for performing the genetic engineering. Existing techniques for editing viral genomes are fairly laborious, so the researchers came up with an efficient approach in which they insert the phage genome into a yeast cell, where it exists as an "artificial chromosome" separate from the yeast cell's own genome. During this process the researchers can easily swap genes in and out of the phage genome."Once we had that method, it allowed us very easily to identify the genes that code for the tails and engineer them or swap them in and out from other phages," Lu says. "You can use the same engineering strategy over and over, so that simplifies that workflow in the lab."In this study, the researchers engineered phages that can target pathogenic Yersinia and Klebsiella bacteria, as well as several strains of One advantage of the engineered phages is that unlike many antibiotics, they are very specific in their targets. "Antibiotics can kill off a lot of the good flora in your gut," Lu says. "We aim to create effective and narrow-spectrum methods for targeting pathogens."Lu and his colleagues are now designing phages that can target other strains of harmful bacteria, which could have applications such as spraying on crops or disinfecting food, as well as treating human disease. Another advantage of this approach is that all of the phages are based on an identical genetic scaffold, which could streamline the process of getting regulatory approval, Lu says.
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Genetically Modified
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September 21, 2015
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https://www.sciencedaily.com/releases/2015/09/150921133837.htm
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Targeting DNA: Protein-based sensor could detect viral infection or kill cancer cells
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MIT biological engineers have developed a modular system of proteins that can detect a particular DNA sequence in a cell and then trigger a specific response, such as cell death.
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This system can be customized to detect any DNA sequence in a mammalian cell and then trigger a desired response, including killing cancer cells or cells infected with a virus, the researchers say."There is a range of applications for which this could be important," says James Collins, the Termeer Professor of Medical Engineering and Science in MIT's Department of Biological Engineering and Institute of Medical Engineering and Science (IMES). "This allows you to readily design constructs that enable a programmed cell to both detect DNA and act on that detection, with a report system and/or a respond system."Collins is the senior author of a Sept. 21 "The technologies are out there to engineer proteins to bind to virtually any DNA sequence that you want," says Shimyn Slomovic, an IMES postdoc and the paper's lead author. "This is used in many ways, but not so much for detection. We felt that there was a lot of potential in harnessing this designable DNA-binding technology for detection."To create their new system, the researchers needed to link zinc fingers' DNA-binding capability with a consequence -- either turning on a fluorescent protein to reveal that the target DNA is present or generating another type of action inside the cell.The researchers achieved this by exploiting a type of protein known as an "intein" -- a short protein that can be inserted into a larger protein, splitting it into two pieces. The split protein pieces, known as "exteins," only become functional once the intein removes itself while rejoining the two halves.Collins and Slomovic decided to divide an intein in two and then attach each portion to a split extein half and a zinc finger protein. The zinc finger proteins are engineered to recognize adjacent DNA sequences within the targeted gene, so if they both find their sequences, the inteins line up and are then cut out, allowing the extein halves to rejoin and form a functional protein. The extein protein is a transcription factor designed to turn on any gene the researchers want.In this paper, they linked green fluorescent protein (GFP) production to the zinc fingers' recognition of a DNA sequence from an adenovirus, so that any cell infected with this virus would glow green.This approach could be used not only to reveal infected cells, but also to kill them. To achieve this, the researchers could program the system to produce proteins that alert immune cells to fight the infection, instead of GFP."Since this is modular, you can potentially evoke any response that you want," Slomovic says. "You could program the cell to kill itself, or to secrete proteins that would allow the immune system to identify it as an enemy cell so the immune system would take care of it."The MIT researchers also deployed this system to kill cells by linking detection of the DNA target to production of an enzyme called NTR. This enzyme activates a harmless drug precursor called CB 1954, which the researchers added to the petri dish where the cells were growing. When activated by NTR, CB 1954 kills the cells.Future versions of the system could be designed to bind to DNA sequences found in cancerous genes and then produce transcription factors that would activate the cells' own programmed cell death pathways.The researchers are now adapting this system to detect latent HIV proviruses, which remain dormant in some infected cells even after treatment. Learning more about such viruses could help scientists find ways to permanently eliminate them."Latent HIV provirus is pretty much the final barrier to curing AIDS, which currently is incurable simply because the provirus sequence is there, dormant, and there aren't any ways to eradicate it," Slomovic says.While treating diseases using this system is likely many years away, it could be used much sooner as a research tool, Collins says. For example, scientists could use it to test whether genetic material has been successfully delivered to cells that scientists are trying to genetically alter. Cells that did not receive the new gene could be induced to undergo cell death, creating a pure population of the desired cells.It could also be used to study chromosomal inversions and transpositions that occur in cancer cells, or to study the 3-D structure of normal chromosomes by testing whether two genes located far from each other on a chromosome fold in such a way that they end up next to each other, the researchers say.
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Genetically Modified
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September 18, 2015
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https://www.sciencedaily.com/releases/2015/09/150918105022.htm
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Harvesting clues to GMO dilemmas from China's soybean fields
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China's struggle -- mirrored across the globe -- to balance public concern over the safety of genetically modified (GM) crops with a swelling demand for affordable food crops has left a disconnect: In China's case, shrinking fields of domestic soybean -- by law non-GM -- and massive imports of cheaper soybeans that are the very GM crop consumers profess to shun.
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Researchers at Michigan State University (MSU) take a first look at how China's soybean farmers are reacting when their crop struggles in the global market, and their choices' global environmental implications. The study is published in this week's journal The study has discovered what Chinese farmers are growing on lands once dominated by non-GM soy, as well as farmers bucking that trend and planting more. Researchers say these farming choices may offer solutions to a national dilemma."Many studies have focused on the global expansion of GM crops. However, the spatial and temporal changes of non-GM crops are not clear, although they have significant socioeconomic and environmental impacts as well as policy implications in the telecoupled world," said Jianguo "Jack" Liu, Rachel Carson Chair in Sustainability at MSU's Center for Systems Integration and Sustainability (CSIS). "Understanding the finer points of growing soybeans will be a crucial step to managing a global enterprise."Demand for soybean as food, feed and oil has soared as China's economy booms and eating habits change. China is now the world's largest soybean importer -- bringing in more than 80 percent of the soybeans consumed, mostly from Brazil and the United States. Those imported crops are GM crops.Jing Sun, a research associate in CSIS, and his colleagues found that soybean farming in China is generally struggling as farmers switch to more profitable crops, with soybean fields shrinking and becoming more fragmented. But Sun also discovered surprising pockets of resilience and identified strengths in soybean cultivation that may point a way to give Chinese soybean consumers what they say they want."Cost versus food safety concerns is a dilemma in China, and consumers are pretending not to notice the soybeans they are getting are genetically modified," Sun said. "Our work will help inform the Chinese government on the status of local soybean crops, which is an issue that transcends the GM controversy, and includes environmental concerns."Sun and colleagues scrutinized satellite data of the nation's leading soybean-growing region, Heilongjiang Province in northeastern China. There they found farmers converting fields from soybean to corn, but not without environmental consequence. Unlike soybeans, corn cannot use nitrogen in the soil, so requires more fertilizers that can cause pollution.Yet even as daunting market pressures reduce soy plantings, Sun's analysis found surprising hotspots of soybeans. Turns out soybean farming does have advantages that may point the way to a resurgence. Farmers in the north found soybeans more forgiving of cold springs and short growing seasons that can cause corn to fail. And for some, soybean farming is a powerful tradition.The authors say China's current dependence on foreign imports to fill its burgeoning soybean demand -- and its decrease in domestic production -- comes with potential costs around the globe, including the possibility of Amazon rainforest deforestation as Brazil ramps up soybean production to meet demand.
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Genetically Modified
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