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September 17, 2015
https://www.sciencedaily.com/releases/2015/09/150917160029.htm
Naturally occurring 'GM' butterflies produced by gene transfer of wasp-associated viruses
Research teams from the University of Valencia and the University of Tours have discovered that genes originating from parasitic wasps are present in the genomes of many butterflies. These genes were acquired through a wasp-associated virus that integrates into DNA. Wasp genes have now been domesticated and likely play a role in in protecting butterflies against other pathogenic viruses. These results, published in
To reproduce, braconid wasps lay their eggs inside caterpillars and inject a 'giant virus' named bracovirus to circumvent the caterpillars' immune response. Bracoviruses can integrate into the DNA of parasitized caterpillars and control caterpillar development, enabling wasp larvae to colonize their host.Bracovirus genes can be detected in the genomes of several species of butterfly and moth, including the famous Monarch (Given that tens of thousands of parasitic wasp species, each associated with a unique bracovirus, parasitize virtually all lepidopteran species, it is likely that the described phenomenon is general and that different gene transfers occur regularly in nature. Beyond the interest these lateral gene transfers evoke in evolutionary biology, these results highlight the risk gene transfers could cause, in case GM-parasitoid wasps are produced, as genes artificially introduced into wasp species used for biological control could be transferred into the genomes of the targeted pests. Production of GM wasps expressing insecticide resistance for biological control of pests, for example, could lead to involuntary transmission of this resistance to the herbivorous insects.
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September 16, 2015
https://www.sciencedaily.com/releases/2015/09/150916184901.htm
California sage-grouse remain genetically diverse, for now
Genetic diversity is essential for a species to be able to adapt to environmental change, and when habitat loss divides a population into small, isolated fragments, that can spell trouble. Northeastern California is at the far western end of the range of Greater Sage-Grouse (
Every spring, sage-grouse gather at breeding sites called leks, where males put on elaborate displays to attract females. Davis and her colleagues collected blood from 167 grouse at 13 lek sites between 2007 and 2009.Their results suggest that there is a continuing exchange of genes between California leks, and possibly even with the adjacent Nevada population. "Sage-grouse occupy the western edge of their distribution in northeastern California and our study area was dominated by invasive annual grasses and encroaching conifer which has led to declines in sage-grouse populations," explains Davis. "Our study found that despite population declines and habitat loss, leks were not genetically differentiated, which was unexpected."This may sound like good news, but it doesn't mean we can stop worrying about California's sage-grouse population. In a species where dispersal, the movement of individuals between breeding areas is limited, it can take several generations for effects of habitat fragmentation on genetic diversity to be detectable, and in the meantime the amount of suitable habitat in California continues to shrink."Although our results suggest that sage-grouse have tolerated some degree of habitat fragmentation without losing genetic diversity, continued habitat loss and deterioration will likely result in additional declines in this population," says Davis. "From a management perspective, we suggest that maintaining and improving habitat quality and connectivity of sage-grouse habitats in northeastern California will be critical for maintaining gene flow and will be necessary to sustain sage-grouse in northeastern California." This will mean knitting isolated population fragments back together, creating corridors of healthy sagebrush habitat so that dispersal can continue. Sage-grouse face an uncertain future throughout their range, and no one population or lek is expendable if these iconic western birds are going to continue to thrive.
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September 16, 2015
https://www.sciencedaily.com/releases/2015/09/150916112621.htm
Synthetic biology needs robust safety mechanisms before real world application
Targeted cancer treatments, toxicity sensors and living factories: synthetic biology has the potential to revolutionize science and medicine. But before the technology is ready for real-world applications, more attention needs to be paid to its safety and stability, say experts in a review article published in
Synthetic biology involves engineering microbes like bacteria to program them to behave in certain ways. For example, bacteria can be engineered to glow when they detect certain molecules, and can be turned into tiny factories to produce chemicals.Synthetic biology has now reached a stage where it's ready to move out of the lab and into the real world, to be used in patients and in the field. According to Professor Pamela Silver, one of the authors of the article from Harvard Medical School in the US, this move means researchers should increase focus on the safety of engineered microbes in biological systems like the human body."Historically, molecular biologists engineered microbes as industrial organisms to produce different molecules," said Professor Silver. "The more we discovered about microbes, the easier it was to program them. We've now reached a very exciting phase in synthetic biology where we're ready to apply what we've developed in the real world, and this is where safety is vital."Microbes have an impact on health; the way they interact with animals is being ever more revealed by microbiome research -- studies on all the microbes that live in the body -- and this is making them easier and faster to engineer. Scientists are now able to synthesize whole genomes, making it technically possible to build a microbe from scratch."Ultimately, this is the future -- this will be the way we program microbes and other cell types," said Dr. Silver. "Microbes have small genomes, so they're not too complex to build from scratch. That gives us huge opportunities to design them to do specific jobs, and we can also program in safety mechanisms."One of the big safety issues associated with engineering microbial genomes is the transfer of their genes to wild microbes. Microbes are able to transfer segments of their DNA during reproduction, which leads to genetic evolution. One key challenge associated with synthetic biology is preventing this transfer between the engineered genome and wild microbial genomes.There are already several levels of safety infrastructure in place to ensure no unethical research is done, and the kinds of organisms that are allowed in laboratories. The focus now, according to Dr. Silver, is on technology to ensure safety. When scientists build synthetic microbes, they can program in mechanisms called kill switches that cause the microbes to self-destruct if their environment changes in certain ways.Microbial sensors and drug delivery systems can be shown to work in the lab, but researchers are not yet sure how they will function in a human body or a large-scale bioreactor. Engineered organisms have huge potential, but they will only be useful if proven to be reliable, predictable, and cost effective. Today, engineered bacteria are already in clinical trials for cancer, and this is just the beginning, says Dr. Silver."The rate at which this field is moving forward is incredible. I don't know what happened -- maybe it's the media coverage, maybe the charisma -- but we're on the verge of something very exciting. Once we've figured out how to make genomes more quickly and easily, synthetic biology will change the way we work as researchers, and even the way we treat diseases."
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September 9, 2015
https://www.sciencedaily.com/releases/2015/09/150909090825.htm
Peering into fish brains to see how they work
The newest research group at Norwegian Nobel laureates May-Britt and Edvard Moser's Kavli Institute for Systems Neuroscience uses transgenic zebrafish to unlock the secrets of the brain.
One of the fundamental challenges facing neuroscientists who want to understand how the brain works is actually figuring out how the brain is wired together and how neurons interact.Norwegian Nobel laureates and neuroscientists May-Britt and Edvard Moser of the Norwegian University of Science and Technology solved this problem by learning how to record from individual neurons in the rat brain while the rats move freely in space. They used the recordings to make the discovery that won them the Nobel Prize: They were able to see that certain neurons in the entorhinal cortex fired in such a way to create a grid pattern that could be use to navigate, like an internal GPS.The newest group leader of the Mosers' Kavli Institute for Systems Neuroscience, Emre Yaksi, has taken a very different approach to the problem of seeing what's going on inside the brain. Instead of studying rats or mice, Yaksi has roughly 90 different kinds of genetically modified zebrafish that he can breed to create different fish with desired characteristics.Young, larval zebrafish are completely transparent, so Yaksi needs only a regular optical microscope to see what's happening inside their little fishy heads. Some of Yaksi's fish have a genetic modification that makes their neurons light up as they send a signal to another neuron. This is what makes circuits and connections visible to researchers, he says."We are interested in understanding the universal circuit architectures (in the brain) that can do interesting computations," Yaksi says. Even though fish are quite different from humans, their brains have many similar structures, and "in the end fish also have to find food, they also have to find a mate, they have to avoid dangers, and they build brain circuits that can generate all these behaviours, quite like humans do."Yaksi came to the Kavli Institute in early 2015 from an Assistant Professor position at Neuroelectronics Research Flanders in Belgium, where he had been a group leader and interim director since 2010.Along with Yaksi's team of researchers came a 900 kg anti-vibration table the size of a billiards table. The table was so big and heavy the only way to get it into the laboratory was to remove windows from the third floor lab and hoist it in with a crane.Yaksi's group needs the table to reduce vibrations so they can use the highly sensitive optical microscopes to peer into zebrafish brains. The larval fish are so small that even slight vibrations from cars or trucks driving by on the streets below are enough to make the microscopes bounce away from their tiny brain targets.Zebrafish brains are small, with just 10,000 to 20,000 neurons, a number that is dwarfed by the human brain, which has an estimated 80 billion neurons. Nevertheless, the measurements Yaksi and his colleagues make, results in huge reams of data.One 30 minute recording can generate so much data that it takes easily a week to process it, he said. For this reason, Yaksi's research group is composed of a multidisciplinary team of engineers, physicists and life scientists who are trained to develop and use computational tools to analyze these big datasets.And because some of the zebrafish have been genetically modified so that their neurons light up with a fluorescent protein when the neurons are active, Yaksi and his colleagues often work in low light or darkness. It's especially noticeable when he takes visitors into the muted darkness of the laboratory, where many of the fanciest microscopes are contained in boxes open on the front, designed to limit the amount of external light.Other zebrafish have been genetically modified so that shining a blue light into their brains activates certain neurons -- which allows researchers to map connections between neurons, Yaksi said.Most of the research being done by Yaksi's group is basic research, with findings that advance our understanding of the brain computations but don't specifically have any immediate clinical implications.But Yaksi's wife and colleague, Nathalie Jurisch-Yaksi, is working with medical doctors to develop genetically modified zebrafish that will help shed light on brain diseases such as epilepsy."Most of the people in my lab are doing very basic research, trying to ask how does the brain work, how is it connected, how is it built," Yaksi said. "But Nathalie is working with medical doctors here at NTNU, we are really trying to reach out to clinicians."For example, he said, if a brain disorder such as epilepsy has a genetic component, that same genetic mutation can be created in the group's transgenic zebrafish facility so that the team can study what causes the seizures in a diseased brain and how the seizures can be prevented.
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August 28, 2015
https://www.sciencedaily.com/releases/2015/08/150828112737.htm
DNA 'clews' used to shuttle CRISPR-Cas9 gene-editing tool into cells
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have for the first time created and used a nanoscale vehicle made of DNA to deliver a CRISPR-Cas9 gene-editing tool into cells in both cell culture and an animal model.
The CRISPR-Cas system, which is found in bacteria and archaea, protects bacteria from invaders such as viruses. It does this by creating small strands of RNA called CRISPR RNAs, which match DNA sequences specific to a given invader. When those CRISPR RNAs find a match, they unleash Cas9 proteins that cut the DNA. In recent years, the CRISPR-Cas system has garnered a great deal of attention in the research community for its potential use as a gene editing tool -- with the CRISPR RNA identifying the targeted portion of the relevant DNA, and the Cas protein cleaving it.But for Cas9 to do its work, it must first find its way into the cell. This work focused on demonstrating the potential of a new vehicle for directly introducing the CRISPR-Cas9 complex -- the entire gene-editing tool -- into a cell."Traditionally, researchers deliver DNA into a targeted cell to make the CRISPR RNA and Cas9 inside the cell itself -- but that limits control over its dosage," says Chase Beisel, co-senior author of the paper and an assistant professor in the department of chemical and biomolecular engineering at NC State. "By directly delivering the Cas9 protein itself, instead of turning the cell into a Cas9 factory, we can ensure that the cell receives the active editing system and can reduce problems with unintended editing.""Our delivery mechanism resembles a ball of yarn, or clew, so we call it a nanoclew," says Zhen Gu, co-senior author of the paper and an assistant professor in the joint biomedical engineering program at NC State and UNC-CH. "Because the nanoclew is made of a DNA-based material, it is highly biocompatible. It also self-assembles, which makes it easy to customize."The nanoclews are made of a single, tightly-wound strand of DNA. The DNA is engineered to partially complement the relevant CRISPR RNA it will carry, allowing the CRISPR-Cas9 complex -- a CRISPR RNA bound to a Cas9 protein -- to loosely attach itself to the nanoclew. "Multiple CRISPR-Cas complexes can be attached to a single nanoclew," says Wujin Sun, lead author of the study and Ph.D. student in Gu's lab.When the nanoclew comes into contact with a cell, the cell absorbs the nanoclew completely -- swallowing it and wrapping it in a protective sheath called an endosome. But the nanoclews are coated with a positively-charged polymer that breaks down the endosome, setting the nanoclew free inside the cell. The CRISPR-Cas9 complexes can then free themselves from the nanoclew to make their way to the nucleus. And once a CRISPR-Cas9 complex reaches the nucleus, gene editing begins.To test the nanoclew CRISPR-Cas delivery system, the researchers treated cancer cell cultures and tumors in mice. The relevant cancer cells had been modified to express a fluorescent protein. In short, they glowed. The CRISPR RNAs on the nanoclews were designed to target the DNA in the cancer cell that was responsible for making the fluorescent proteins. If the glowing stopped, the nanoclews worked."And they did work. More than a third of cancer cells stopped expressing the fluorescent protein," Beisel says."This study is a proof of concept, and additional work needs to be done -- but it's very promising," Gu says.
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August 28, 2015
https://www.sciencedaily.com/releases/2015/08/150828102254.htm
Mathematician reveals the mechanism for sustaining biological rhythms
Our bodies have a variety of biological clocks that follow rhythms or oscillations with periods ranging from seconds to days. For example, our hearts beat every second, and cells divide periodically. The circadian clock located in the hypothalamus generates twenty-four hour rhythms, timing our sleep and hormone release. How do these biological clocks or circuits generate and sustain the stable rhythms that are essential to life?
Jae Kyoung Kim, who is an assistant professor in the Department of Mathematical Sciences at KAIST, has predicted how these biological circuits generate rhythms and control their robustness, utilizing mathematical modeling based on differential equations and stochastic parameter sampling. Based on his prediction, using synthetic biology, a research team headed by Matthew Bennett of Rice University constructed a novel biological circuit that spans two genetically engineered strains of bacteria, one serves as an activator and the other as a repressor to regulate gene expression across multiple cell types, and found that the circuit generates surprisingly robust rhythms under various conditions.The results of the research conducted in collaboration with KAIST (Korea Institute of Science and Technology), Rice University, and the University of Houston were published in The top-down research approach, which focuses on identifying the components of biological circuits, limits our understanding of the mechanisms in which the circuits generate rhythms. Synthetic biology, a rapidly growing field at the interface of biosciences and engineering, however, uses a bottom-up approach.Synthetic biologists can create complex circuits out of simpler components, and some of these new genetic circuits are capable of fluctuation to regulate gene production. In the same way that electrical engineers understand how an electrical circuit works as they construct batteries, resistors, and wires, synthetic biologists can understand better about biological circuits if they put them together using genes and proteins. However, due to the complexity of biological systems, both experiments and mathematical modeling need to be applied hand in hand to design these biological circuits and understand their function.In this research, an interdisciplinary approach proved that a synthetic intercellular singling circuit generates robust rhythms to create a cooperative microbial system. Specifically, Kim's mathematical analysis suggested, and experiments confirmed, that the presence of negative feedback loops in addition to a core transcriptional negative feedback loop can explain the robustness of rhythms in this system. This result provides important clues about the fundamental mechanism of robust rhythm generation in biological systems.Furthermore, rather than constructing the entire circuit inside a single bacterial strain, the circuit was split among two strains of Escherichia coli bacterium. When the strains were grown together, the bacteria exchanged information, completing the circuit. Thus, this research also shows how, by regulating individual cells within the system, complex biological systems can be controlled, which in turn influences each other (e.g., the gut microbiome in humans).
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August 27, 2015
https://www.sciencedaily.com/releases/2015/08/150827154251.htm
Modified bacteria become a multicellular circuit
Rice University scientists have made a living circuit from multiple types of bacteria that prompts the bacteria to cooperate to change protein expression.
The subject of a new paper in The researchers' goal is to modify biological systems by controlling how bacteria influence each other. This could lead to bacteria that, for instance, beneficially alter the gut microbiome in humans.Humans' stomachs have a lot of different kinds of bacteria, said Rice synthetic biologist Matthew Bennett. "They naturally form a large consortium. One thought is that when we engineer bacteria to be placed into guts, they should also be part of a consortium. Working together allows them to effect more change than if they worked in isolation."In the proof-of-concept study, Bennett and his team created two strains of genetically engineered bacteria that regulate the production of proteins essential to intercellular signaling pathways, which allow cells to coordinate their efforts, generally in beneficial ways.The ability to engineer DNA so cells produce specific proteins has already paid dividends, for example, by manipulating bacteria to produce useful biofuels and chemicals."The main push in synthetic biology has been to engineer single cells," Bennett said. "But now we're moving toward multicellular systems. We want cells to coordinate their behaviors in order to elicit a populational response, just the way our bodies do."Bennett and his colleagues achieved their goal by engineering common The bacteria worked together by doing opposite tasks: One was an activator that up-regulated the expression of targeted genes, and the other was a repressor that down-regulated genes. Together, they created oscillations -- rhythmic peaks and valleys -- of gene transcription in the bacterial population.The two novel strains of bacteria sent out intercellular signaling molecules and created linked positive and negative feedback loops that affected gene production in the entire population. Both strains were engineered to make fluorescent reporter genes so their activities could be monitored. The bacteria were confined to microfluidic devices in the lab, where they could be monitored easily during each hourslong experiment.When the bacteria were cultured in isolation, the protein oscillations did not appear, the researchers wrote.Bennett said his lab's work will help researchers understand how cells communicate, an important factor in fighting disease. "We have many different types of cells in our bodies, from skin cells to liver cells to pancreatic cells, and they all coordinate their behaviors to make us work properly," he said. "To do this, they often send out small signaling molecules that are produced in one cell type and effect change in another cell type."We take that principle and engineer it into these very simple organisms to see if we can understand and build multicellular systems from the ground up."Ultimately, people might ingest the equivalent of biological computers that can be programmed through one's diet, Bennett said. "One idea is to create a yogurt using engineered bacteria," he said. "The patient eats it and the physician controls the bacteria through the patient's diet. Certain combinations of molecules in your food can turn systems within the synthetic bacteria on and off, and then these systems can communicate with each other to effect change within your gut."Ye Chen, a graduate student in Bennett's lab at Rice, and Jae Kyoung Kim, an assistant professor at KAIST and former postdoctoral fellow at Ohio State University, are lead authors of the paper. Co-authors are Rice graduate student Andrew Hirning and Krešimir Josi?, a professor of mathematics at the University of Houston. Bennett is an assistant professor of biochemistry and cell biology.The National Institutes of Health, the Robert A. Welch Foundation, the Hamill Foundation, the National Science Foundation and the China Scholarship Council supported the research.
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August 26, 2015
https://www.sciencedaily.com/releases/2015/08/150826135724.htm
Methanotrophs: Could bacteria help protect our environment?
New insight into methanotrophs, bacteria that can oxidise methane, may help us develop an array of biotechnological applications that exploit methane and protect our environment from this potent greenhouse gas.
Publishing in They have identified a new family of copper storage proteins called Csp that are present in a range of bacteria. These proteins store metal in a way that has not been seen previously and their widespread presence amongst diverse bacteria raises important questions about how bacteria use copper ions, which can also be toxic to cells.Methane availability is rising as the extraction of natural gas booms, and more methane is escaping into the atmosphere. Methanotrophs are the primary biological mechanism for mitigating the release of methane by consuming it for carbon and energy. These organisms also have great potential in the biotechnological utilisation of methane, a readily renewable carbon source, for the production of bulk and fine chemicals and sustainable energy.To oxidise methane, methanotrophs use an enzyme called methane monooxygenase whose essential cofactor is copper (some can also use iron). Understanding how methanotrophs handle copper is therefore of great importance for all potential applications of these organisms.The scientists describe the discovery and characterisation of Csp1 from a methanotroph that can bind large quantities of copper and propose this is a protein that accumulates copper for methane oxidation.Lead author Chris Dennison, Professor of Biological Chemistry at Newcastle University explained: "Methane is such a useful and plentiful commodity but we need more cost effective methods to unlock its potential. Using bacteria could be the best option so a better knowledge of how these bacteria operate is required."As copper is so important for the oxidation of methane, all potential applications based on this reactivity requires knowing how methanotrophs acquire and store copper. The discovery of the Csps adds a new dimension to our understanding of this complex process."Co-author Colin Murrell, Professor in Environmental Microbiology at the University of East Anglia, commented: "We have known that copper is a vital element for biological methane oxidation for over thirty years and this new information will really help us to formulate new strategies for exploiting these bacteria both in the laboratory and in the environment."Metalloproteomics was used to discover Csp1 in a highly complex mixture of proteins. The analysis of recombinant Csp1 using an array of biochemical and biophysical techniques has allowed copper binding by Csp1 to be understood at the molecular level. This includes determination of Csp1 crystal structures using the facilities at Diamond Light Source. A genetically modified methanotroph has been generated to demonstrate the physiological function of Csp1.Dr Neil Paterson, a post-doctoral research associate at Diamond Light Source, said: "The ability of Diamond Light Source to provide tuneable X-ray energy allowed us to use the intrinsic copper ions within the protein to solve the crystal structure by X-ray diffraction and also define their oxidation state through X-ray fluorescence spectroscopy."Csp1 possesses a four-helix bundle fold, a well-established structural motif for proteins. The striking feature of Csp1 is that multiple cysteine residues, known to avidly bind copper, point into the core of the bundle that suggested a novel way of storing a metal. Copper-binding studies and the crystal structure of the protein with copper provide a detailed insight into how the four-helix bundle of Csp1 can be filled with copper ions.
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August 20, 2015
https://www.sciencedaily.com/releases/2015/08/150820144735.htm
Regulatory, certification systems creating paralysis in use of genetically altered trees
Myriad regulations and certification requirements around the world are making it virtually impossible to use genetically engineered trees to combat catastrophic forest threats, according to a new policy analysis published this week in the journal
In the United States, the time is ripe to consider regulatory changes, the authors say, because the federal government recently initiated an update of the overarching Coordinated Framework for the Regulation of Biotechnology, which governs use of genetic engineering.North American forests are suffering from an onslaught of threats including local and imported pests, as well as the impacts of a shifting climate. These threats pose "a real and present danger" to the future of many of our forest trees, notes Steven Strauss, a distinguished professor of forest biotechnology at Oregon State University and lead author on the analysis."The forest health crisis we're facing makes it clear that regulations must change to consider catastrophic losses that could be mitigated by using advanced forest biotechnologies, including genetic engineering," Strauss said. "With the precision enabled by new advances in genetic engineering - and their ability to make changes more rapidly and with less disruption to natural tree genetics than hybrid breeding methods - they can provide an important new tool."In their analysis, Strauss and coauthors Adam Costanza, of the Institute of Forest Biosciences in Cary, North Carolina, and Armand Séguin of Natural Resources Canada in Quebec, argue that new regulatory approaches should be implemented in the United States and globally that focus on the product, not the process - and consider need, urgency and genetic similarity of modifications to those used in breeding.The researchers note the striking discrepancy between the speed at which pests and changing climates are affecting trees and modifying both natural and planted forests, and the onerous and slow pace of regulatory review of genetically engineered trees that could be used to help fight these threats."If we have a technology that can help stop a forest health crisis, we should also have a regulatory system that can respond in a time frame that can make a difference," said Costanza, who is president of the Institute of Forest Biosciences.The authors stress that they are not advocating for separate regulations for genetically engineered trees. Rather, they call for an approach that would give agencies the option to fast-track field research for products intended to address forest health problems or that use methods that modify natural genes and thus are comparable in scope to those of conventional breeding."Obviously, these changes will take time and require wide-ranging input," said Strauss, a professor in OSU's College of Forestry, "but we need to start now. We depend on forests for so many ecological, social and economic values - and all of these are being threatened."Why should we tie up a major tool like genetic engineering in excessive red tape?"The authors point out that sustainable forest certification systems also are in need of a policy update. All major systems ban genetically engineered trees and will not certify any land as sustainable if genetically engineered trees are grown at all - even if the trees are being used solely for research or are designed to help stop a forest threat.
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August 14, 2015
https://www.sciencedaily.com/releases/2015/08/150814145759.htm
Microbe that bolsters isobutanol production created
Another barrier to commercially viable biofuels from sources other than corn has fallen with the engineering of a microbe that improves isobutanol yields by a factor of 10.
The finding of the Department of Energy's BioEnergy Science Center, published in the journal Isobutanol is attractive because its energy density and octane values are much closer to gasoline and it is useful not only as a direct replacement for gasoline but also as a chemical feedstock for a variety of products. For example, isobutanol can be chemically upgraded into a hydrocarbon equivalent for jet fuel.While the earlier work by BESC researchers at DOE's Oak Ridge National Laboratory and the University of California at Los Angeles was important from a proof-of-principle perspective, this new result represents a significant gain."When we reported our initial finding four years ago, we were using Consolidated bioprocessing refers to the bundling of several processes in a single microbe that can be used to extract sugar from a plant's cellulose and convert those sugars into a biofuel. This approach can be used to combine several steps -- pretreatment, enzyme treatment and fermentation -- to produce biofuel at a lower cost. The process also helps overcome the challenges of recalcitrance, or a plant's natural defenses to being chemically dismantled. Recalcitrance is one of the primary economic barriers to using lignocellulosic biomass such as corn stover and switchgrass as a feedstock for biofuels.While the previous genetically engineered microbe achieved conversion results of 0.6 gram of isobutanol per liter, "In addition to this development, which moves the BESC team closer to the production goal of more than 20 grams per liter, the prospects of commercial realization of this approach are greatly enabled by the fact that the microbe works at temperatures high enough to keep competing bugs from contaminating the microbial fermentation tanks and interfering with the conversion process," said Paul Gilna, director of BESC.Authors note that microbial engineering challenges remain, but they are encouraged by this finding. Other authors of the paper, titled "Consolidated bioprocessing of cellulose to isobutanol using
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August 13, 2015
https://www.sciencedaily.com/releases/2015/08/150813142535.htm
Genetically engineered yeast produces opioids
For thousands of years, people have used yeast to ferment wine, brew beer and leaven bread.
Now researchers at Stanford have genetically engineered yeast to make painkilling medicines, a breakthrough that heralds a faster and potentially less expensive way to produce many different types of plant-based medicines.Writing today in Hydrocodone and its chemical relatives such as morphine and oxycodone are opioids, members of a family of painkilling drugs sourced from the opium poppy. It can take more than a year to produce a batch of medicine, starting from the farms in Australia, Europe and elsewhere that are licensed to grow opium poppies. Plant material must then be harvested, processed and shipped to pharmaceutical factories in the United States, where the active drug molecules are extracted and refined into medicines."When we started work a decade ago, many experts thought it would be impossible to engineer yeast to replace the entire farm-to-factory process," said senior author Christina Smolke, an associate professor of bioengineering at Stanford.Now, though the output is small -- it would take 4,400 gallons of bioengineered yeast to produce a single dose of pain relief -- the experiment proves that bioengineered yeast can make complex plant-based medicines."This is only the beginning," Smolke said. "The techniques we developed and demonstrate for opioid pain relievers can be adapted to produce many plant-derived compounds to fight cancers, infectious diseases and chronic conditions such as high blood pressure and arthritis."Many medicines are derived from plants, which our ancestors chewed or brewed into teas, or later refined into pills using chemical processes to extract and concentrate their active ingredients. Smolke's team is modernizing the process by inserting precisely engineered snippets of DNA into cells, such as yeast, to reprogram the cells into custom chemical assembly lines to produce medicinal compounds.An important predecessor to the Stanford work has been the use of genetically engineered yeast to produce the anti-malarial drug artemisinin. Traditionally artemisinin has been sourced from the sweet wormwood tree in similar fashion to how opiates are refined from poppy. Over the last decade, as yeast-based artemisinin production has become possible, about one third of the world's supply has shifted to bioreactors.The artemisinin experiments proved that yeast biosynthesis was possible, but involved adding only six genes. The Stanford team had to engineer 23 genes into yeast to create their cellular assembly line for hydrocodone."This is the most complicated chemical synthesis ever engineered in yeast," Smolke said.Her team found and fine-tuned snippets of DNA from other plants, bacteria and even rats. These genes equipped the yeast to produce all the enzymes necessary for the cells to convert sugar into hydrocodone, a compound that deactivates pain receptors in the brain."Enzymes make and break molecules," said Stephanie Galanie, a PhD student in chemistry and a member of Smolke's team. "They're the action heroes of biology."To get the yeast assembly line going, the Stanford team had to fill in a missing link in the basic science of plant-based medicines.Many plants, including opium poppies, produce (S)-reticuline, a molecule that is a precursor to active ingredients with medicinal properties. In the opium poppy, (S)-reticuline is naturally reconfigured into a variant called (R)-reticuline, a molecule that starts the plant down a path toward the production of molecules that can relieve pain.Smolke's team and two other labs recently independently discovered which enzyme reconfigures reticuline, but even after the Stanford bioengineers added this enzyme into their microbial factory, the yeast didn't create enough of the opioid compound. So they genetically tweaked the next enzyme in the process to boost production. Down the line they went, adding enzymes, including six from rats, in order to craft a molecule that emerged ready to plug pain receptors in the brain.In their "We want there to be an open deliberative process to bring researchers and policymakers together," Smolke said. "We need options to help ensure that the bio-based production of medicinal compounds is developed in the most responsible way."Smolke said that in the United States, where opioid medicines are already widely available, the focus is on potential misuse. But the World Health Organization estimates that 5.5 billion people have little or no access to pain medications."Biotech production could lower costs and, with proper controls against abuse, allow bioreactors to be located where they are needed," she said.In addition to bioengineering yeast to convert sugar into hydrocodone, the Stanford team developed a second strain that can process sugar into thebaine, a precursor to other opioid compounds. Bio-produced thebaine would still need to be refined through sophisticated processes in pharmaceutical factories, but it would eliminate the time delay of growing poppies."The molecules we produced and the techniques we developed show that it is possible to make important medicines from scratch using only yeast," she said. "If responsibly developed, we can make and fairly provide medicines to all who need."
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August 13, 2015
https://www.sciencedaily.com/releases/2015/08/150813142529.htm
When fruit flies get sick, their offspring become more diverse
New research from North Carolina State University and Reed College shows that when fruit flies are attacked by parasites or bacteria they respond by producing offspring with greater genetic variability. This extra genetic variability may give the offspring an increased chance of survival when faced with the same pathogens. These findings demonstrate that parents may purposefully alter the genotypes of their offspring.
Fruit flies' reproductive cells are usually haploid, meaning that there is only one copy of each chromosome in the cell's nucleus instead of two. During meiosis, the form of cell division that creates eggs in females and sperm in males, female fruit flies produce eggs that contain only one set of chromosomes -- each chromosome in the set may be a copy of the mother's chromosome or a copy of the father's chromosome. Or they may be a mixture of both chromosomes due to a process known as recombination. Under normal conditions each offspring of a female fruit fly has a 25 percent chance of getting a maternal copy of a chromosome, a 25 percent chance of receiving a paternal copy, and a 50 percent chance of receiving a recombinant chromosome.In theory, under conditions in which organisms face new threats, such as those posed by parasites or pathogens, it could be advantageous to have offspring with more recombinant chromosomes. These offspring would have more novel combinations of alleles (versions of particular genes), increasing the chances that at least some of them would be well adapted to these threats.Nadia Singh, an assistant professor of biological sciences at NC State, and her colleague and co-author of a paper describing the work, Todd Schlenke of Reed College, wanted to see if fruit flies have evolved such a strategy for coping with infections by bacteria or parasitic wasps. Singh and Schlenke exposed fruit flies to two different pathogenic bacteria, as well as to the parasitic wasp Leptopilina clavipes, which lays its eggs inside fruit fly larvae and devours the fly from the inside out unless it is killed by the fly immune system.The findings, which appear in "We believe that this is an example of what has been called transmission distortion. In this case, something is signaling these female fruit flies to produce a higher proportion of offspring with recombined chromosomes than they would normally," says Singh. "The result is that they're hedging their bets, genetically speaking -- creating a large number of very different offspring means that at least some of those offspring may be genetically better suited to surviving future threats from these bacteria or parasites."Even more interesting was the discovery that this signal may somehow be transmitted even when the female is exposed to the threat in the larval stage -- well before egg production (and the associated chromosomal recombination) begins."It is interesting that stresses occurring early in development can influence a host's reproductive machinery later in life -- we don't know yet what the infection signal is or how it is maintained across metamorphosis" says Schlenke. "And there's no reason to think that this type of reproductive response to infection is unique to flies," adds Singh. "We want to know whether other species do this, because it represents a novel way that parents can influence the potential fitness of their offspring."
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August 13, 2015
https://www.sciencedaily.com/releases/2015/08/150813123053.htm
Biochemist studies oilseed plants for biofuel, industrial development
A Kansas State University biochemistry professor has reached a milestone in building a better biofuel: producing high levels of lipids with modified properties in oil seeds.
Timothy Durrett, assistant professor of biochemistry and molecular biophysics, and collaborators at Michigan State University and the University of Nebraska, Lincoln have modified The goal of the research is to alter oilseeds to produce large amounts of modified oil that can be used as improved biofuels or even industrial and food-related applications. The research recently appeared in the journal Industrial Crops and Products and on the front cover of the "Reducing our dependence on fossil fuel-derived carbon is always good," Durrett said. "Using alternative sources of fuel is the obvious way to reduce our dependence. But even other applications, such as using it for lubricants or as feedstocks for the chemical industry, would help reduce our dependence on fossil-derived carbon."Camelina can grow on poorer quality farmland, needs little irrigation or fertilizer, and produces seeds that can provide gallons of oil, Durrett said. It also can be rotated with wheat and could become a biofuel crop for semi-arid regions, including western Kansas and Colorado.The camelina genome was recently sequenced, which has greatly helped Durrett and collaborators as they improve camelina's oil properties to produce low-viscosity oil -- the kind of oil needed for biofuel. By modifying the oilseed biochemistry in camelina, the researchers were able to get very high levels of the modified oil, which are called acetyl-TAGS. In the best camelina lines, about 85 percent of the oil was comprised of the modified acetyl-TAGs.One of the team's goals is to make commercial products using oils from the engineered plants. The researchers are analyzing these oils because their acetyl-TAGs possess unusual structures and have high value-added properties."The basic problem is that most of our oilseed crops -- such as canola or soybean -- produce just a few fatty acids because we use them for nutritional needs," Durrett said. "That's great for a source of food, but makes doing any sort of chemistry more complicated."The researchers think that camelina producing acetyl-TAGs is a renewable resource with potential industrial uses, including plasticizers, biodegradable lubricants and food emulsifiers."The food industry uses similar compounds already," Durrett said. "What we need to do is first of all see if our oil is safe and can match those specifications. Probably one of the most valuable parts of this research is that we can generate meaningful data sets because of the oil's properties and we can learn more about the oil itself and what it can do."
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August 13, 2015
https://www.sciencedaily.com/releases/2015/08/150813074718.htm
Progress toward the perfect pea
A group at the John Innes Centre has developed peas that will help animals absorb more protein from their diet. The study is published in
Pea and other legume seeds contain several proteins that stop nutrients being absorbed fully in the intestines. One such class of molecule is the protease inhibitors. These slow down the rate at which humans, poultry or livestock digest proteins by incapacitating the enzymes that break them down. Previous nutritional studies with broiler chickens have shown that peas with proteins which disrupt digestion can reduce protein availability by up to 10%.Dr Claire Domoney's group has identified and studied peas with mutations in genes coding for the seed protease inhibitors, known as the trypsin/chymotrypsin inhibitors. They found three types of mutation, one of which was in a wild relative of pea, and which completely wiped out the seed's ability to inhibit protein digestion. The other two mutations were generated by mutagenesis and were also effective in reducing the inhibitors, although less dramatically so.Peas provide a valuable and nutritious crop for human and pet food and animal feed. Dr Domoney's results provide proof of principle for the ways in which food and feedstuffs can be improved through large-scale genetic approaches. The research can be extended to more proteins in pea and other legume crops, where food or feed use may be limited by the same or different seed proteins. Removal of allergenic proteins, for example, is an important goal for improving many food and feed crops.Dr Claire Domoney said: 'The discovery of a wild pea line, a Pisum elatius line from Turkey which lacks a protein defined as an 'anti-nutrient', is a clear example of the value of diverse germplasm collections. Being able to generate and/or discover genetic variation for traits of interest to growers is essential for improving crop traits. In our case, the wild pea mutant has been crossed readily with the cultivated species, Pisum sativum, providing a headstart for breeders. Mutagenised resources, such as that at INRA, are also an invaluable resource for novel variation. We are now in a good position with new technologies to be able to screen very large numbers of lines for small changes in genes of interest.'Breeders, including Limagrain and Wherry & Sons, are already showing interest in the new peas. As non-GM methods were used, Dr Domoney expects widespread adoption of the variant pea lines and that the novel peas could reach the market within five years.Mr Peter Smith, Arable Crops Director at Wherry & Sons Ltd, said: 'The value of genetics and targeted research in pulse crops aids the UK industry in achieving specific needs. The removal of inhibitors in peas is an example of one of many traits which should enable the industry to move forward with a nutritionally improved crop benefiting throughout the food chain. As pulses potentially become grown on a wider scale in the UK we must remain focused on producing a better product in comparison to imported pulses and protein crops.'
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August 12, 2015
https://www.sciencedaily.com/releases/2015/08/150812151214.htm
Genetic analysis supports elevating Cape Parrot to new species
In support of previous research, the Cape Parrot should be elevated to the species level, according to a new genetic analysis study publish August 12, 2015 in the open-access journal
The Cape Parrot is currently considered a The author's data analysis identified the Cape Parrot as genetically distinct from the other P. robustus subspecies. Their analysis places the most recent common ancestor between the Cape Parrot and
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August 4, 2015
https://www.sciencedaily.com/releases/2015/08/150804093723.htm
New biosensors for managing microbial 'workers'
Super productive factories of the future could employ fleets of genetically engineered bacterial cells, such as common E. coli, to produce valuable chemical commodities in an environmentally friendly way. By leveraging their natural metabolic processes, bacteria could be re-programmed to convert readily available sources of natural energy into pharmaceuticals, plastics and fuel products.
"The basic idea is that we want to accelerate evolution to make awesome amounts of valuable chemicals," said Wyss Core Faculty member George Church, Ph.D., who is a pioneer in the converging fields of synthetic biology, metabolic engineering, and genetics. Church is the Robert Winthrop Professor of Genetics at Harvard Medical School and Professor of Health Sciences and Technology at Harvard and MIT.Critical to this process of metabolically engineering microbes is the use of biosensors. Made of a biological component -- such as a fluorescent protein -- and a 'detector' that responds to the presence of a specific chemical, biosensors act as the switches and levers that turn programmed functions on and off inside the engineered cells. They also can be used to detect which microbial 'workers' are producing the most voluminous amounts of a desired chemical. In this way, they can be thought of as the medium for two-way communication between humans and cells.But so far, scientists have only had access to a limited variety of biosensors that have little relevance to the bio-manufacturing of valuable chemicals. Now, Wyss Institute researchers led by Church have developed a new suite of such sensors, reported in "We can communicate with cells much more effectively, and vice versa," said the study's first author Jameson Rogers, a graduate researcher at the Wyss Institute who is pursuing his Ph.D. in Engineering Sciences from Harvard University. "If we compared this to controlling a computer, it's almost like we have only had the up and down arrows available to us, and now suddenly we have doubled our control capabilities by adding the left and right arrows as well."The Wyss team aims to leverage the new biosensors to aid in their efforts to develop renewable chemical production strategies using genetically engineered microbes.Linked to green fluorescent protein (GFP), the biosensors can be used to trigger individual cells to give off visible fluorescence in a rate directly proportional to how well they are able to produce a desired chemical commodity. Using the new biosensors, the most efficient microbial workers are easily identified so that they can serve as the predecessors for colonies of engineered bacteria that evolve to become more efficient at producing renewable chemicals with each subsequent generation. This drastically reduces the bottleneck of the design-build-test cycle, which has historically been caused by engineers having to sift through teeming bacteria colonies to find top producers.The findings could also lead to new applications in environmental monitoring using genetically engineered microbes to issue warning signals in the presence of pollutants or toxins, and could unlock new fundamental insights into metabolic pathways."Our team is developing several different ways to make even more custom biosensors," said Church. "We're trying to control biological processes and we need new ways to get our hands in at the molecular level -- we're now reaching in deeper than we've previously been able to, and we still have many interesting new approaches.""With this work, George and his team are bringing us closer to a sustainable future in which we would rely on bio-manufacturing for the clean production of chemical and pharmaceutical commodities," said Wyss Institute Founding Director Donald E. Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School 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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July 27, 2015
https://www.sciencedaily.com/releases/2015/07/150727135723.htm
Consumers don't view GMO labels as negative 'warnings'
A new study released just days after the U.S. House passed a bill that would prevent states from requiring labels on genetically modified foods reveals that GMO labeling would not act as warning labels and scare consumers away from buying products with GMO ingredients.
The study, presented at the annual conference of the Agricultural and Applied Economics Association, held in San Francisco on July 27, relies on five years of data (2003, 2004, 2008, 2014 and 2015) and includes 2,012 responses to a representative, statewide survey of Vermont residents. It focuses on the relationship between two primary questions: whether Vermonters are opposed to GMO's in commercially available food products; and if respondents thought products containing GMO's should be labeled.Results showed no evidence that attitudes toward GMO's are strengthened in either a positive or negative way due to a desire for labels that indicate the product contains GM ingredients. On average across all five years of the study, 60 percent of Vermonters reported being opposed to the use of GMO technology in food production and 89 percent desire labeling of food products containing GMO ingredients. These numbers have been increasing slightly since 2003. In 2015, the percentages were 63 and 92 percent, respectively.Responses varied slightly by demographic groups. For example, given a desire for positive GMO labels, opposition to GMO decreased in people with lower levels of education, in single parent households, and those earning the highest incomes. Opposition to GMO increases in men and people in the middle-income category. No changes were larger than three percentage points."When you look at consumer opposition to the use of GM technologies in food and account for the label, we found that overall the label has no direct impact on opposition. And it increased support for GM in some demographic groups, " said Jane Kolodinsky, author of the study and professor and chair of the Department of Community Development and Applied Economics at the University of Vermont. "This was not what I hypothesized based on the reasoning behind the introduction of The Safe and Accurate Food Labeling bill. We didn't find evidence that the labels will work as a warning."Proponents of the U.S. Senate-bound bill, which if enacted would nullify Vermont's GMO labeling law that has yet to take effect, argue that mandating labels on foods containing GMOs is misleading, because it suggests to consumers that GMOs are somehow risky to eat. Rep. Peter Welch, D-Vt., co-sponsor of the Genetically Engineered Food Right-to-Know Act, disagrees, saying last week that, "the consumer can decide whether he or she wants to purchase that product. It's the market that ultimately decides."Paul Burns, executive director of the Vermont Public Interest Research Group (VPIRG), said the GMO labels that Vermont's law would require were never intended to be a warning, and that Kolodinsky's study demonstrates that they will not act as such. "But they will provide important information so that consumers who have legitimate health or environmental concerns about GMOs can make informed purchasing decisions," he added.In her presentation in San Francisco, "An Investigation of the Endogeneity of Attitudes Towards Genetic Modification and Demand for GM Food Labels," Kolodinsky said the findings provide evidence, that in Vermont, GMO food labels would provide consumers with information on which to base their purchasing decisions. Consumers who wish to avoid GMO ingredients would do so, she added, and those who either want GMO ingredients or are indifferent can also make that choice. "The label would not signal to consumers that GMO ingredients are inferior to those produced using other agricultural production methods," she said."We need more evidence to determine which position is correct," Kolodinsky said at the conference. "This study adds to the GM labeling evidence by showing that, in the only U.S. State that has passed a mandatory positive GM labeling law, the label will not act as a 'warning label.' When only the label is considered, it has no impact on consumer opposition. And there is some evidence that the label will increase consumer confidence in GM technology among certain groups."
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July 23, 2015
https://www.sciencedaily.com/releases/2015/07/150723083853.htm
Tool developed for more accurate interpretation of biomedical research
Investigators affiliated with VIB and UGent recently achieved great success with a study involving biomedical research on mouse models. The research group of Prof Peter Vandenabeele (VIB/UGent) recently used tangible examples to demonstrate how the side effects of genetic modification of mice can complicate the interpretation of biomedical research. The team developed a web tool that allows scientists to estimate the impact of this phenomenon more accurately. Their findings were recently published in the medical journal Immunity and received ample attention by a preview in Immunity and a comment in The Scientist.
Tom Vanden Berghe (VIB/UGent): "Our research will have a profound retro-active impact on the interpretation of a great deal of scientific research. In addition, it will also aid in explaining controversies in scientific literature surrounding certain disease models. Finally, in the long term, these results can contribute to an improved translation of findings from lab animals to humans."Tests on mice are an important tool for research into diseases and drugs. By deactivating a specific gene in mouse strains, the investigators can study the effect of this gene on the development of a disease.However, mouse models alone are not sufficient to reach irrefutable scientific conclusions. Clinical studies using human cells remain essential to validate the research results. These studies often produce different conclusions. An important reason for this is that the genetic modification of mouse strains not only changes the target gene, but also causes changes in the neighboring genes. Geneticists are familiar with this phenomenon, but it is sometimes overlooked.In order to clarify this problem, the research group of Prof Peter Vandenabeele (VIB/UGent) performed a comparative analysis on the genetic information from various mouse strains.Peter Vandenabeele (VIB/UGent): "Our bioinformatics analysis revealed that each mouse strain contains approximately one thousand genes that result in an abnormal protein. About a hundred of these could actually be attributed to a functional defect. In the first generation of a genetically modified mouse strain, the so-called recombinant congenic mice, we almost always see various other defective genes close to the inactivated gene. This means that in certain cases, researchers cannot be certain whether the inactivated gene, or the dysfunctional neighboring genes (or a combination of both) is/are responsible for the observed effect."Post-doctoral researcher Tom Vanden Berghe supported this supposition with several tangible examples. In this way, he illustrated how this strongly underestimated problem in fundamental scientific research can result in false positives and premature conclusions.Tom Vanden Berghe then worked with bio-informaticists Liesbet Martens and Paco Hulpiau to develop a web tool that helps researchers to estimate the impact of this phenomenon correctly. The tool gives researchers insight into the possible abnormalities and the potential effect of these on their research results. Tak Wah Mak, a top-scientist from Ontario Cancer Institute, concludes his preview on Vanden Berghe's article as follows "The wake-up call represented by this Immunity article on the importance of the passenger genome therefore does a great public service to the research community involved in the analysis and generation of gene targeted mice."
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July 22, 2015
https://www.sciencedaily.com/releases/2015/07/150722144640.htm
Soybean oil causes more obesity than coconut oil, fructose
A diet high in soybean oil causes more obesity and diabetes than a diet high in fructose, a sugar commonly found in soda and processed foods, according to a just published paper by scientists at the University of California, Riverside.
The scientists fed male mice a series of four diets that contained 40 percent fat, similar to what Americans currently consume. In one diet the researchers used coconut oil, which consists primarily of saturated fat. In the second diet about half of the coconut oil was replaced with soybean oil, which contains primarily polyunsaturated fats and is a main ingredient in vegetable oil. That diet corresponded with roughly the amount of soybean oil Americans currently consume.The other two diets had added fructose, comparable to the amount consumed by many Americans. All four diets contained the same number of calories and there was no significant difference in the amount of food eaten by the mice on the diets. Thus, the researchers were able to study the effects of the different oils and fructose in the context of a constant caloric intake.Compared to mice on the high coconut oil diet, mice on the high soybean oil diet showed increased weight gain, larger fat deposits, a fatty liver with signs of injury, diabetes and insulin resistance, all of which are part of the Metabolic Syndrome. Fructose in the diet had less severe metabolic effects than soybean oil although it did cause more negative effects in the kidney and a marked increase in prolapsed rectums, a symptom of inflammatory bowel disease (IBD), which like obesity is on the rise.The mice on the soybean oil-enriched diet gained almost 25 percent more weight than the mice on the coconut oil diet and 9 percent more weight than those on the fructose-enriched diet. And the mice on the fructose-enriched diet gained 12 percent more weight than those on a coconut oil rich diet."This was a major surprise for us -- that soybean oil is causing more obesity and diabetes than fructose -- especially when you see headlines everyday about the potential role of sugar consumption in the current obesity epidemic," said Poonamjot Deol, the assistant project scientist who directed the project in the lab of Frances M. Sladek, a professor of cell biology and neuroscience.The paper, "Soybean oil is more obesogenic and diabetogenic than coconut oil and fructose in mouse: potential role for the liver," was published July 22 in the journal In the U.S. the consumption of soybean oil has increased greatly in the last four decades due to a number of factors, including results from studies in the 1960s that found a positive correlation between saturated fatty acids and the risk of cardiovascular disease. As a result of these studies, nutritional guidelines were created that encouraged people to reduce their intake of saturated fats, commonly found in meat and dairy products, and increase their intake of polyunsaturated fatty acids found in plant oils, such as soybean oil.Implementation of those new guidelines, as well as an increase in the cultivation of soybeans in the United States, has led to a remarkable increase in the consumption of soybean oil, which is found in processed foods, margarines, salad dressings and snack foods. Soybean oil now accounts for 60 percent of edible oil consumed in the United States. That increase in soybean oil consumption mirrors the rise in obesity rates in the United States in recent decades.During the same time, fructose consumption in the United States significantly increased, from about 37 grams per day in 1977 to about 49 grams per day in 2004.The research outlined in the paper is believed to be the first side-by-side look at the impacts of saturated fat, unsaturated fat and fructose on obesity, diabetes, insulin resistance and nonalcoholic fatty liver disease, which along with heart disease and hypertension, are referred to as the Metabolic Syndrome.The study also includes extensive analysis of changes in gene expression and metabolite levels in the livers of mice fed these diets. The most striking results were those showing that soybean oil significantly affects the expression of many genes that metabolize drugs and other foreign compounds that enter the body, suggesting that a soybean oil-enriched diet could affect one's response to drugs and environmental toxicants, if humans show the same response as mice.The UC Riverside researchers also did a study with corn oil, which induced more obesity than coconut oil but not quite as much as soybean oil. They are currently doing tests with lard and olive oil. They have not tested canola oil or palm oil.The researchers cautioned that they didn't study the impacts of the diets on cardiovascular diseases and note in the paper that the consumption of vegetable oils could be beneficial for cardiac health, even if it also induces obesity and diabetes.They also noted that there are many different types of saturated and unsaturated fats. This is particularly true for the saturated fats in animal products that were associated with heart disease in the studies in the 1960s: they tend to have a longer chain length than the saturated fats in coconut oil.The latest paper relates to previously released findings by scientists in Sladek's lab and at the UC Davis West Coast Metabolomics Center, which compared regular soybean oil to a new genetically modified soybean oil.That research, presented at a conference in March, found that the new genetically modified, high oleic soybean oil (Plenish), which has a lower amount of polyunsaturated fatty acid than traditional soybean oil, is healthier than regular soybean oil but just barely. Using mice, the researchers found that the Plenish oil also induces fatty liver although somewhat less obesity and diabetes. Importantly, it did not cause insulin resistance, a pre-diabetic condition. It should be noted that both the regular soybean oil and Plenish are from soybeans that are genetically modified to be resistant to the herbicide RoundUp.The researchers are now finalizing a manuscript about these findings that also incorporates tests done with olive oil.
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July 17, 2015
https://www.sciencedaily.com/releases/2015/07/150717142439.htm
Dairy products boost effectiveness of probiotics
The success of probiotics for boosting human health may depend partly upon the food, beverage, or other material carrying the probiotics, according to research published on July 10th in
"Our findings indicate that the manner in which a probiotic is delivered--whether in food or supplement form--could influence how effective that probiotic is in delivering the desired health benefits," said corresponding author Maria Marco, PhD, an associate professor in the Department of Food Science and Technology, at the University of California at Davis.In the study, the researchers investigated the probiotic strain, The investigators also took a census of the microbiota before and after ingestion of "Strains of According to the researchers, dairy products are the most popular food matrices for probiotic strains. "Remarkably, the question of whether it makes any difference to consume probiotics in dairy products rather than other foods or nutritional supplements has not been systematically or mechanistically investigated in clinical or preclinical studies. "Because we know that bacteria can adapt to their surroundings, we thought the conditions that probiotics are exposed to prior to ingestion might influence their capacity to maintain or improve human health."
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July 14, 2015
https://www.sciencedaily.com/releases/2015/07/150714131556.htm
Environment, not distance, triggers genetic differences in 'sky island' birds
Genomic sequencing of White-breasted nuthatches populating isolated mountains in Southern Arizona shows pressure to adapt to unique habitats prompts genetic branching among clades of the birds, rather than distances separating the "sky islands" where they live.
"Non-random gene flow is causing these birds to become genetically distinct based on certain environments," said Joseph Manthey, doctoral student at the University of Kansas' Biodiversity Institute. "As the nuthatches can fly, their ability to disperse suggested they'd either be able to move easily between nearby sky islands or not at all because of distances between them. So I was expecting a pattern of isolation-by-distance -- or that some sky island populations were genetically distinct due to isolation from other populations. "Instead, the researchers found variations in temperature and rainfall-triggered genetic differences between the clades of nuthatches -- not expanses separating them. The Madrean Sky Islands feature changes in habitat along elevational gradients in mountains."In this region, habitat at the base of the mountains is desert, while the higher elevations have coniferous forests. In this way, they act as islands to species that require the forests to survive," Manthey said.Manthey's paper, co-authored by Robert Moyle, associate professor of ecology and evolutionary biology, has been hailed as a "blueprint" for future isolation-by-environment studies. It soon will be published in the peer-reviewed journal The research stands out because of its detailed analysis of the nuthatches' genetic profiles. The investigators examined single nucleotide polymorphisms -- or, mutations at a single spot in the nuthatches' genome. "We were looking for loci that might be under selection, or genetic locations that are important for adaptation to specific environments," Manthey said.He added the new technique differs from previous landscape genetics studies identifying genetic variation because earlier efforts didn't pinpoint where variations happened in the genome or if they were close to specific genes.The researchers used the KU Genome Sequencing Core's resources, including an Illumina HiSeq2500, which takes genomic samples and gives back millions to billions of short sequences of the genome. The instrument incorporates fluorescent dyes during replication, which is taking place in millions of genetic fragments at a time and snaps pictures of each of the fluorescence events.In this way, the investigators were able to isolate genetic changes and tie those to unique environmental factors in the Madrean Sky Islands.Manthey is conducting similar studies in the sky islands on other species of bird, as well as ants and pine species, to see if these results hold true beyond the nuthatches."This region is the only biodiversity hotspot of North America, which is an area that contains a high level of biodiversity, as well as being threatened with destruction, either through human landscape change or climate change," he said. "Understanding more about limitations of how plants and animals are able to disperse through this landscape gives us insights into how species will react to the inevitable future changes and how we may better conserve these natural resources."
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July 9, 2015
https://www.sciencedaily.com/releases/2015/07/150709132444.htm
Basic computing elements created in bacteria
The "friendly" bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.
In a paper published in the journal These basic computing elements will allow the bacteria to sense, memorize, and respond to signals in the gut, with future applications that might include the early detection and treatment of inflammatory bowel disease or colon cancer.Researchers have previously built genetic circuits inside model organisms such as "We wanted to work with strains like The team developed a series of genetic parts that can be used to precisely program gene expression within the bacteria. "Using these parts, we built four sensors that can be encoded in the bacterium's DNA that respond to a signal to switch genes on and off inside These can be food additives, including sugars, which allow the bacteria to be controlled by the food that is eaten by the host, Voigt adds.To sense and report on pathologies in the gut, including signs of bleeding or inflammation, the bacteria will need to remember this information and report it externally. To enable them to do this, the researchers equipped The researchers also implemented a technology known as CRISPR interference, which can be used to control which genes are turned on or off in the bacterium. The researchers used it to modulate the ability of The researchers demonstrated that their set of genetic tools and switches functioned within The researchers now plan to expand the application of their tools to different species of "We aim to expand our genetic toolkit to a wide range of bacteria that are important commensal organisms in the human gut," Lu says.The concept of using microbes to sense and respond to signs of disease could also be used elsewhere in the body, he adds.In addition, more advanced genetic computing circuits could be built upon this genetic toolkit in "For example, we want to have high sensitivity and specificity when diagnosing disease with engineered bacteria," Lu says. "To achieve this, we could engineer bacteria to detect multiple biomarkers, and only trigger a response when they are all present."
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July 7, 2015
https://www.sciencedaily.com/releases/2015/07/150707134832.htm
Unlocking lignin for sustainable biofuel
Turning trees, grass, and other biomass into fuel for automobiles and airplanes is a costly and complex process. Biofuel researchers are working to change that, envisioning a future where cellulosic ethanol, an alcohol derived from plant sugars, is as common and affordable at the gas station as gasoline.
The key to making this vision a reality? Unraveling the tightly wound network of molecules -- cellulose, hemicellulose, and lignin -- that make up the cell wall of plants for easier biofuel processing.Using high-performance computing, a group of researchers at the US Department of Energy's (DOE's) Oak Ridge National Laboratory (ORNL) provided insight into how this might be accomplished, simulating a well-established genetic modification to the lignin of an aspen tree in atomic-level detail. The team's conclusion -- that hydrophobic, or water repelling, lignin binds less with hydrophilic, or water attracting, hemicellulose -- points researchers toward a promising way to engineer better plants for biofuel. Their results were published in the November 2014 edition of Physical Chemistry Chemical Physics.The study is important because lignin -- which is critical to the survival of plants in the wild -- poses a problem for ethanol production, preventing enzymes from breaking down cellulose into simple sugars for fermentation.Jeremy Smith, the director of ORNL's Center for Molecular Biophysics and a Governor's Chair at the University of Tennessee, led the project. His team's simulation of a genetically modified lignin molecule linked to a hemicellulose molecule adds context to work conducted by researchers at DOE's BioEnergy Science Center (BESC), who demonstrated that genetic modification of lignin can boost the amount of biofuel derived from plant material without compromising the structural integrity of the plant. BESC is supported by DOE's Office of Science."BESC scientists created lots of different lignins randomly through genetic modification," Smith said. "They found one that worked for them, but they wanted to know why it worked."To find the answer, Smith's team turned to Titan, a 27-petaflop supercomputer at the Oak Ridge Leadership Computing Facility (OLCF), a DOE Office of Science User Facility.Aspens are among the most widespread trees in North America, with a habitable zone that extends across the northern United States and Canada. As part of the genus Populus, which includes poplars and cottonwoods, they are known for their fast growth and ability to adapt to diverse environments -- two qualities that make them prime candidates for cellulosic ethanol. Compared to traditional biofuel crops like corn and sugarcane, aspens require minimal care; they also can be grown in areas where food crops cannot grow.But the hardiness that allows aspens to thrive in nature makes them resistant to enzymatic breakdown during fermentation, an important step for converting biomass into ethanol. This problem can be traced to the molecular makeup of the plant cell wall, where lignin and hemicellulose bond to form a tangled mesh around cellulose.Cellulose, a complex carbohydrate made up of glucose strands, comprises nearly half of all plant matter. It gives plants their structure, and it's the critical substance needed to make cellulosic ethanol. To break down cellulose, one must get past lignin, a waste product of biofuel production that requires expensive treatments to isolate and remove. By throwing a wrench in the plant cell's lignin assembly line, BESC scientists found they could boost biofuel production by 38 percent.In nature, lignin adds strength to cellulosic fibers and protects the plant from predators and disease. Lignin molecules consist of multiple chemical groups made up of carbon, oxygen, and hydrogen that are assembled within the cell during a process called biosynthesis. During assembly, enzymes catalyze molecules into more complex units. By suppressing a key enzyme, Cinnamyl-alcohol dehydrogenase, BESC scientists created an "incomplete" lignin molecule. Instead of a hydrophilic alcohol group (an oxygen-hydrogen molecule bound to a hydrogen-saturated carbon atom), the final lignin polymer contained a hydrophobic aldehyde group (a carbon atom double-bonded to an oxygen atom)."We wanted to see if there was a difference in the lignin-hemicellulose network if you substituted water-resisting aldehydes in the lignin for water-attracting alcohols," said Loukas Petridis, an ORNL staff scientist. "Geneticists knew the modified plant could be more easily broken down, but they didn't have an atomic-level explanation that a supercomputer like Titan can provide."Using a molecular dynamics code called NAMD, the team ran simulations of the wild lignin and the genetically modified lignin in a water cube, modeling the presence of the aldehydes by altering the partial charges of the oxygen and hydrogen atoms on the modified lignin's allylic site.The team simulated multiple runs of each 100,000-atom system for a few hundred nanoseconds, tracking the position of atoms in time increments of a femtosecond, or 1 thousand trillionth of a second. A comparison of the simulations showed weaker interaction between hemicellulose and the modified lignin than with wild lignin, suggesting that hydrophobic lignin interacts less with hydrophilic hemicellulose."From this you could make the testable assumption that making lignin more hydrophobic may lead to plants that are easier to deconstruct for biofuel," Petridis said. "That's the kind of rational insight we can provide using computer simulation."It took a decade of work to determine all the steps of lignin biosynthesis and find ways to manipulate genes. In the future, we hope to circumvent some of the work by continuing to test our models against experiment and making good suggestions about genes using supercomputers. That's where the predictive power of molecular dynamic codes like NAMD comes in."The project allocation was part of the 59 million processor hours awarded to Smith's team on Titan in 2014 through DOE's Office of Advanced Scientific Computing Research (ASCR) Leadership Computing Challenge, or ALCC, program.Moving forward, Smith's group seeks to further validate molecular dynamics simulations as a predictive tool by modeling a genetically modified form of switchgrass, another plant targeted for cellulosic ethanol."This modification is a bit more subtle and more complex to simulate," Petridis said. "Finding out how good a predictive tool NAMD can be is the next step."
Genetically Modified
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July 4, 2015
https://www.sciencedaily.com/releases/2015/07/150704082402.htm
Climate change is turning male dragon lizards into females
A climate-induced change of male dragons into females occurring in the wild has been confirmed for the first time, according to University of Canberra research recently published on the cover of international journal
The researchers, who have long studied Australia's bearded dragon lizards, have been able to show that a reptile's sex determination process can switch rapidly from one determined by chromosomes to one determined by temperature.Lead author Dr Clare Holleley, a postdoctoral research fellow at the University of Canberra's Institute for Applied Ecology, explained: "We had previously been able to demonstrate in the lab that when exposed to extreme temperatures, genetically male dragons turned into females.""Now we have shown that these sex reversed individuals are fertile and that this is a natural occurring phenomenon."Using field data from 131 adult lizards and controlled breeding experiments, Dr Holleley and colleagues conducted molecular analyses which showed that some warmer lizards had male chromosomes but were actually female."By breeding the sex reversed females with normal males, we could establish new breeding lines in which temperature alone determined sex. In doing so, we discovered that these lizards could trigger a rapid transition from a genetically-dependent system to a temperature-dependent system," she said."We also found that sex-reversed mothers -- females who are genetic males -- laid more eggs than normal mothers," Dr Holleley said. "So in a way, one could actually argue that dad lizards make better mums."University of Canberra Distinguished Professor Arthur Georges, senior author of the paper, also highlighted the importance that these discoveries have in the broader context of sex determination evolution."The mechanisms that determine sex have a profound impact on the evolution and persistence of all sexually reproducing species," Professor Georges said."The more we learn about them, the better-equipped we'll be to predict evolutionary responses to climate change and the impact this can have on biodiversity globally."
Genetically Modified
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June 19, 2015
https://www.sciencedaily.com/releases/2015/06/150619103353.htm
Successful ovulation of 100 eggs from one female mouse
The average number of eggs for genetically modified mice (knockout mice) obtained using previous methods of superovulation induction is about 20 but in reality the number is often much smaller, about 10 or less. However, researchers at Kumamoto University have developed a method of ultra-superovulation and have successfully obtained the ovulation of 100 eggs from a single female mouse.
Normal 2-cell stage embryo growth and offspring from these eggs has been confirmed using in vitro fertilization and embryo transfer. This achievement is expected to become a very useful technology for future mass production of knockout mice.The ultra-superovulation induced method was developed by Prof. Naomi Nakagata and Dr. Toru Takeo from the Division of Reproductive Engineering in the Center for Animal Resources and Development (CARD) of Kumamoto University, Japan. The results were published in The number human protein coding genes, which account for less than 2% of the human genome, have recently been found to number over 20,000. The scientific community uses knockout mice to analyze basal phenotypes (the appearance of genetic characteristics) to analyze the function of such a large number of genes. For this reason, efficient production of knockout mice is necessary.In conventional induced superovulation methods pregnant mare serum gonadotropin (PMSG), a follicle stimulating hormone (FSH), is administered to knockout mice with the intention of developing a large number of ovarian follicles. However, the actual number of eggs obtained from one female mouse was limited to 30 at most.Professor Nakagata and his colleagues came up with the idea of adding inhibin antiserum to the superovulation process. The hormone inhibin is released from the gonads during development and is a secretion regulator of FSH. FSH is secreted from the pituitary gland and limits the number of eggs produced during ovulation. The use of an inhibin antiserum promotes excessive secretion of FSH by neutralizing inhibin in the body of female knockout mice. Furthermore, by administering PMSG simultaneously the mice developed a large number of follicles leading to successful ovulation of 100 or more eggs from one knockout mouse, approximately 3-4 times that of conventional methods."With our newly developed method, it is possible to reduce the number of female knockout mice used in egg collection by 1/3 -- 1/4 or less." said Dr. Takeo, who was involved in the development of the procedure. "Reducing the number of experimental animals is one of the most important pillars in the welfare of laboratory animals. Not only from the life science research viewpoint, but also from the social concern for the welfare of laboratory animals. This outcome is very meaningful, and we hope this achievement will contribute to the promotion of various studies of international acclaim."By allowing a large number of ovulation ovum from a small number of female mice, it makes it easier to perform IVF and embryo transfers. Therefore, it becomes possible to improve the efficiency of collecting, preserving and providing knockout mouse.Prof. Nakagata anticipates that his ultra-superovulation induction method has a very high potential to be applied to rats, hamsters, and guinea pigs, but this has not yet been established. He expects to spread the range of the method into these other laboratory animals soon.The ovulation-inducing agent is scheduled to be released from the collaborating pharmaceutical company in the future.
Genetically Modified
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June 16, 2015
https://www.sciencedaily.com/releases/2015/06/150616102357.htm
Scientists use molecular 'lock and key' for potential control of GMOs
Researchers at the University of California, Berkeley, have developed an easy way to put bacteria under a molecular lock and key in order to contain its accidental spread. The method involves a series of genetic mutations that render the microbe inactive unless the right molecule is added to enable its viability.
The work appears in the journal The researchers worked with a strain of 'This approach is very robust and simple in that it only requires a few mutations in the genome,' said Anderson. 'The molecule serves as the key, and we engineer the lock.'Study lead author Gabriel Lopez, who started the project as a UC Berkeley graduate student in bioengineering, compared the approach to taking out a component in a car.'The car would still run if it lost its rear-view mirror, but it wouldn't go far without the camshaft or fuel tank,' said Lopez, now a postdoctoral researcher in Anderson's lab. 'Organisms are the same. Some parts are essential, and some aren't. Of the 4,000 genes in E.coli, about 300 are essential to its survival. What we're doing is putting an ignition switch onto a handful of the bacteria's essential genes. Without the right key, the bug won't live.'The technique turns the bacteria into a synthetic auxotroph, an organism modified to require a particular compound for its growth. It could potentially be applied to organisms being engineered to treat diseases, the researchers said. Because those pharmaceuticals entail the introduction of organisms into the body, mechanisms are needed to ensure that the organism is activated only when needed.Lopez said they added redundancy in the system by adding several lock-and-key combinations into one organism. Switching on a single gene improved viability 100 millionfold, and combining several gene locks resulted in a 10 billionfold increase in viability, according to the study.'This is just one instance of how you can do it, but my hope is that people will see this and realize we can use this lock-and-key approach with other proteins and other organisms,' said Lopez.The researchers noted that other approaches to biocontainment rely upon a 'kill switch' that poisons an organism. The concern, they said is that the organism may evolve a way to survive that signal. They noted that in their approach, the default state of their organism is death, and that researchers must actively turn on the genes to enable its survival. They distinguished their approach as being fast, cheap and easy to deploy, having been demonstrated in an industrially relevant organism.The inspiration came from techniques dating back to the 1940s, when early biochemists were researching the conditions that would enable microbes to live or die. Biologists discovered that mutating the genes of mold could alter their sensitivity to pH levels, temperature and other conditions.'I took those early tools used to figure out how biology works and applied those techniques for making biology work when, where and how we want,' said Lopez.The researchers cautioned that there is no one-size-fits-all solution to biocontainment. 'We have to look at what it is that we're worried about with which application in determining which biocontainment approach is relevant,' said Anderson.The lock-and-key approach, for instance, is not a practical answer for containing engineered DNA sequences from horizontal gene transfer, a situation in which genetic material could accidentally move from one organism to another, Anderson said.In addition, this technique is meant to prevent the accidental spread of an engineered organism, but it is not foolproof against intentional attempts to thwart the biosafety net.'We're never going to be able to solve the problem of a human actively hacking away at our safety systems,' said Lopez. 'Even if we could beat a human today, there will be better equipment and more knowledge 10 years from now, and that will be very hard to secure against.'
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June 11, 2015
https://www.sciencedaily.com/releases/2015/06/150611114411.htm
Winner doesn't always take all
The bacterium
There are numerous genetic variants and strains of Olaya Rendueles, a postdoctoral researcher at ETH, has now delivered the first experimental evidence of the accuracy of this theory in real bacterial life. The post-doctoral researcher works in the group of Professor Gregory J. Velicer at ETH Zurich's Institute of Integrative Biology. Velicer owns probably on of the largest collections of In order to identify the factors responsible for the wide diversity observed in soil bacteria, Rendueles compared the competitive abilities of a number of The researcher organised a sort of tournament across a number of petri dishes. First, she checked which strain prevailed in a one-to-one duel. Here, she found that the more competitive strain always prevailed and destroyed the weaker one. Diversity was therefore lost.However, this was not so if the less competitive strain outnumbered the stronger strain by a ratio of 99:1. In this case, the weaker strain prevailed. Experts use the term 'positive frequency-dependent selection' to describe this selective advantage due to numerical superiority.When Rendueles arranged the duels in a chequerboard fashion over four fields, with the weaker strain predominating on a white field and the stronger strain predominating on the black field, then the numerically superior strain always prevailed in the respective field.If the less competitive strain prevailed in its field thanks to its numerical superiority, then it successfully held on to this field. The more competitive strain could not take over this niche. A social barrier between the genetically different strains hindered the assault. Rendueles discovered that although two different strains can fight one another when single individuals are in direct contact, they cannot fight remotely; for example, by using antibiotics to kill the opponent. Overall, diversity was therefore retained across the total population, which encompassed all four fields.For Rendueles, this is a clear indication that positive frequency-dependent selection can maintain genotypic diversity within a population, provided the weaker variants of a species can hold on in niches that are not accessible to the dominant strain."This is the first experimental evidence of this theoretically predicted mechanism," says the postdoctoral researcher. She adds that it would have been a different story were the population evenly distributed; for example, in aqueous solution as found in the sea. In such a situation, where all the strains present are able to mix, only the most competitive or numerically superior strain of bacteria survive. This inevitably leads to a reduction in genetic diversity.Experimental proof of the hypothesis -- that positive frequency-dependent selection acts as a mechanism for maintaining diversity -- is important because until now an older, well-established theory, namely negative frequency-dependent selection, was considered the main mechanism by which diversity is maintained. In this negative form of selection, rare gene variants enjoy an advantage over frequent, dominant variants because they fall victim to predators less often. For example, different colour variants of a butterfly population may escape a predator because they are better camouflaged than the majority of the population. This selective advantage persists only for as long as the camouflage gene variant remains rare.On the other hand, until now positive frequency-dependent selection has been seen as diversity-reducing ('winner takes all'). "We can now demonstrate that positive frequency-dependent selection maintains diversity by enabling weaker gene variants to survive if they are numerically superior to dominant variants," says Rendueles.The researchers are confident that this mechanism applies not only to
Genetically Modified
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June 10, 2015
https://www.sciencedaily.com/releases/2015/06/150610131630.htm
Genetically modified fish on the loose?
Genetically modified fish that overexpress growth hormone have been created for more than 25 years, but unlike many domesticated crops, transgenic fish have yet to enter commercial production. Because of the difficulty inherent in eradicating an established fish population, efforts are under way to model the threat posed by possible invasions.
In an article for an upcoming issue of The genetically modified salmonids the authors studied possess a suite of traits that may, under different conditions and at different life stages, render them more or less fit than wild-type salmon. For instance, the authors report that growth hormone-transgenic salmon exhibit enhanced feeding motivation. This altered feeding behavior could help them outcompete wild-type fish for food. However, more aggressive feeding might expose the transgenic fish to greater predation risk, thereby reducing their net fitness. Unraveling the net consequences of such opposing effects poses a significant challenge for regulators and decisionmakers, the authors say.Also troublesome for modeling is the wide range of possible invasion scenarios. Even though many transgenic lines are expected to have reduced fitness compared with wild-type conspecifics, they could become established in alternative niches. As the authors put it, 'Many novel genotypes in the form of invasive species can successfully establish in new ecosystems even without having a specific evolutionary history in those locations.' Further complicating matters is the possibility of transgenic fishes' adapting to the local habitats and selection pressures of the ecosystems they invade.To address these wide-ranging concerns, the authors suggest a modeling approach that relies on the assessment of transgenic and surrogate strains in a broad array of conditions designed to simulate natural ecosystems. However, they caution, whether such risk assessments will sufficiently reduce uncertainty and preserve ecosystems 'remains a significant objective for further research.'
Genetically Modified
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June 10, 2015
https://www.sciencedaily.com/releases/2015/06/150610093000.htm
Coral colonies more genetically diverse than assumed
Coral colonies are more genetically diverse than it has been assumed to date. This is the conclusion drawn by biologists at Ruhr-Universität Bochum, who have conducted comprehensive studies into the genetic variability in individual colonies of different reef-forming coral species. "However, this doesn't mean we should expect that this variability can compensate for corals dying worldwide due to climate change," says Maximilian Schweinsberg from the Department of Animal Ecology, Evolution and Biodiversity, headed by Prof Dr Ralph Tollrian. In collaboration with colleagues, the researchers published their report in the journal "Molecular Ecology."
"The ongoing climate change and the environmental change resulting thereof have an increasingly severe impact on coral reefs," explains Schweinsberg. The basis for adapting to the change is genetic diversity. Individual coral colonies can be comprised of millions of polyps. To date, it has been assumed that they originate through the proliferation of one larva and are therefore genetically identical. In isolated cases, however, the researchers found genetically different polyps inside a colony. But it was unclear how frequently this phenomenon occurred.The genetic variability can be caused by two processes: by spontaneous genetic mutations in individual colony sections or by different corals coalescing during their development stage. In the first case, the resulting coral colonies are called mosaics, in the second case chimera. The biologists from Bochum have studied 222 coral colonies of five different species. In each species, they found genetically different polyps; the frequency of this phenomenon varied between 24 and 47 per cent. The majority of the genetically variable coral colonies were mosaics. However, chimera also occurred in all species.In stony corals, individual polyps release nutrients for the colony, presumably feeding the genetically less well adapted polyps. Thus, the colony's genetically "weaker" specimens can survive. If the environmental conditions change, for example due to climate change, new genetic patterns become necessary. Polyps that were poorly adapted to the old conditions may now gain an advantage. Accordingly, genetic diversity in colonies increases the probability of being equipped for different situations.
Genetically Modified
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June 2, 2015
https://www.sciencedaily.com/releases/2015/06/150602092733.htm
New information changes few opinions on GMOs, global warming
First impressions are important. So much so that even armed with new information, many people won't change their minds about genetically modified foods and global warming, a new University of Florida study shows.
In fact, some grow even more stubborn in their beliefs that GMOs are unsafe, said Brandon McFadden, an assistant professor in food and resource economics in the UF Institute of Food and Agricultural Sciences.After they read scientific information stating that genetically modified foods are safe, 12 percent of the study's participants said they felt such foods were less safe -- not more, much to McFadden's astonishment.That's partly because people form beliefs and often never let go of them, he said."This is critical and hopefully demonstrates that as a society we should be more flexible in our beliefs before collecting information from multiple sources," McFadden said. "Also, this indicates that scientific findings about a societal risk likely have diminishing value over time."For the study, published in the current issue of the journal To assess their beliefs about genetically modified foods, participants were asked to respond to statements such as: "Genetically modified crops are safe to eat." To gauge their beliefs about humans and global warming, they responded to statements such as: "Earth is getting warmer because of human actions."Then they were given scientific information about genetically modified foods and global warming.For example, researchers showed them this quote from the National Research Council regarding genetically modified food: "To date, no adverse health effects attributed to genetic engineering have been documented in the human population."Respondents read several quotes about global warming, including this one from the American Association for the Advancement of Science: "The scientific evidence is clear: Global climate change caused by human activities is occurring now, and it is a growing threat to society."After reading statements from scientific groups, participants were asked about their beliefs regarding the safety of genetically modified foods. The choices ranged from "much less safe" to "much more safe."The results showed that before they received the information, 32 percent believed GM foods were safe to eat; 32 percent were not sure and 36 percent did not believe GM foods were safe to eat. After they received scientific information, about 45 percent believed genetically modified foods were safer to eat and 43 percent were not swayed by the information.Then they were asked to assess the extent to which they believe human involvement caused global warming. They were given choices ranging from "much less involved" to "much more involved."The study showed that before they received the information, 64 percent believed human actions are causing global warming; 18 percent were not sure and 18 percent did not believe human actions are to blame. After receiving scientific information about global warming, about 50 percent of participants believed even more strongly that human actions lead to global warming, while 44 percent were not swayed by the information, the study showed."Possibly, the best indicator for whether a person will adopt scientific information is simply what a person believes before receiving the information," McFadden said.
Genetically Modified
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May 28, 2015
https://www.sciencedaily.com/releases/2015/05/150528142907.htm
Quasi-sexual gene transfer drives genetic diversity of hot spring bacteria
New work from a team including Carnegie's Devaki Bhaya and Michelle Davison used massive DNA sequencing of bacterial populations that grow in the hot springs in Yellowstone National Park to determine their genetic diversity and explore the underlying evolutionary dynamics. They found an unexpectedly high degree of sharing and exchange of genetic material between the tiny, green, photosynthetic cyanobacteria
The team discovered that the pattern of differences in genome organization between various individuals of the same species indicates that the bacteria transfer DNA, including whole genes, back and forth. This swapping or "recombination" allows gene variations to spread rapidly through a population. Their findings are published by There is a great deal of small-scale genetic diversity in naturally occurring bacterial populations--as opposed to the carefully managed bacterial clones used in laboratory research and clinical work. Bacterial populations in the natural environment represent a dynamic genetic resource that changes over time, but the quantification of this diversity, and the exact mechanisms creating its dynamics, has remained elusive."Biologists have long been interested in determining the evolutionary and ecological forces that drive the population genetics of bacterial communities," Bhaya explained.The research team, which also included lead author Michael Rosen as well as Daniel Fisher, both of the Applied Physics Department at Stanford University, set out to investigate this question by combining the power of so-called "deep sequencing" ( highly detailed and extensive DNA sequence determination) with powerful statistical analysis.Several possible scenarios were considered. For instance, one theory predicts that bacterial populations are genetically diverse because they adapt to their surrounding conditions on a very small-scale, local level, leading to the establishment of distinct subpopulations, called ecotypes.Another possibility was that all of the diversity in the bacterial genes is 'neutral'--no particular version of a gene makes an organism more or less fit for its environment. Bacteria reproduce by asexual division, which means that each new generation is stuck with a nearly exact replica of its sole parent's genetic material. Genetic changes can occur through mutation or the transfer of segments of DNA between individual organisms.Using sophisticated statistical analysis of the massive "DNA deep sequencing" data enabled the team to trace the evolutionary forces that shaped these natural Rather, the population occupies a broad niche that includes a range of environmental conditions. Diversity is created by frequent swapping of genetic material between organisms. This apparently happens often enough that the population can be viewed as "quasi-sexual" in comparison to organisms like humans, where the process of sexual reproduction, specifically fertilization, combines genes from two parents.In sexual reproduction, new combinations of genes are the rule. Although this is not generally true for bacterial populations, for these particular hot spring bacteria, new combinations are also the rule, rather than the exception. Since DNA moves between individuals, a new generation will not be stuck with just a copy of its parental genes. Because of this level of variation, natural selection acts on the level of individual genes, not the whole genome. Transfers of DNA happen so much that bacteria can have all sorts of different combinations of genes and gene variants."Without deep sequencing and careful analysis, we never would have been able to detect and identify the forces at work and it will be exciting to discover if these insights extend to other microbial communities," Bhaya noted. "Microbial diversity is found everywhere from deep sea vents to the human gut or in association with plant roots. Using methods such as single cell sequencing, proteomics, and microscopy will allow exploration of this invisible and important world with great accuracy and depth."
Genetically Modified
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May 28, 2015
https://www.sciencedaily.com/releases/2015/05/150528142859.htm
New findings shed light on complexities of emerging zoonotic malaria
Zoonotic malaria has been shown to be caused by two genetically distinct
The new study, led by researchers at the London School of Hygiene & Tropical Medicine and University of Malaysia Sarawak (UNIMAS), used sensitive genotyping methods to analyse samples of 599 Senior author, David Conway, Professor of Biology at the London School of Hygiene & Tropical Medicine, said: "We were very surprised to find that knowlesi malaria is really two separate zoonoses going on at the same time. There is a lot of genetic diversity within each of the parasite types, but the high level of divergence between them indicates they are probably different sub-species being transmitted separately, within the same areas."In most places we surveyed, both parasite types coexist and infect people. If zoonotic transmission continues to be common, it becomes more likely that the two types may hybridise genetically, leading to new possibilities for parasite adaptation to humans or additional mosquito vectors. However, as parasite mating occurs within the mosquito, hybridisation would depend on whether the same vector species is sometimes infected by both types, which needs investigation."Study lead author, Paul Divis, from the London School of Hygiene & Tropical Medicine and UNIMAS, said: "Hybridisation between species or sub-species has been seen in other parasites that are associated with the emergence of novel pathogenicity. Therefore, the transmission of two types of Although the conclusions from the data were highly significant, the authors note that further work is needed to understand the divergence between the parasite subpopulations more precisely by analysis of whole genome sequences, and by studying parasites from more locations in different parts of south-east Asia.
Genetically Modified
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May 28, 2015
https://www.sciencedaily.com/releases/2015/05/150528124208.htm
Scientists see a natural place for 'rewilded' plants in organic farming
One of the key elements of organic agriculture, as defined by the International Federation of Organic Agriculture Movements (IFOAM), is that it rejects unpredictable technologies, such as genetic engineering. But what if adding a gene from undomesticated plants to bring back a natural trait isn't unpredictable, argue Danish scientists, ethicists, and legal experts in a review published May 28 in
The concept behind "rewilding" is that grocery-brand fruits and vegetables have been made weak by generations of breeding for traits that yield the best harvest, and so a way to toughen them up would be to add genes found in their wild cousins, which are less bountiful but more resilient to pests, drought, and other challenges."The corn we eat does not live in nature anymore," says senior author Michael Palmgren, a plant and environmental scientist at University of Copenhagen. "It's like how we turned a wolf into a poodle. During breeding you select for specific characteristics, but then you risk losing others because you're not selecting for them. If you wanted to strengthen a dog, you would breed it with a wolf."Theoretically, corn-strengthening mutations could occur naturally through long-term breeding programs, and so the question for debate is whether hastening the process through genetic engineering, ethically and legally, would be able to benefit organic farmers who are not allowed to use the pesticides, weed-killers, and fertilizers that define conventional agriculture.While no "rewilded" crops have yet been created by inserting a trait, a 2014 Nature Biotechnology paper (10.1038/nbt.2969) showed that it is possible to make bread wheat crop resistant to mildew by removing DNA from three locations, thereby allowing offspring of this plant to pass on this benefit. This product could have been made through traditional breeding, so it challenges the unpredictability that is currently associated with genetic engineering."In current legislations, a plant is considered natural if it's mutated by chemicals and radiation--that happens in nature," Palmgren says. "If you can make a precise mutation that has the same effect and you don't introduce new material, then this type of plant should also be an exception."He specifically collaborated with ethicists and legal experts to determine that yes, this type of precise "rewilding" is in accordance with values of organic agriculture. They believe that, at least outside of the European Union where there are fewer restrictions on genetically modified organisms (GMOs), it would be legally compatible to introduce this technology without labeling the plants as GMOs."Originally, when the whole idea of transgenic plants came up--that you can take a gene from a bacteria or a fish and put it in a corn--we as plant scientists were excited about the technology and didn't understand the objections," Palmgren says. "This is a new program, and I've learned to have discussions and debates with people in other fields from the beginning so that we do not repeat past mistakes that affected public opinion."
Genetically Modified
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May 27, 2015
https://www.sciencedaily.com/releases/2015/05/150527150946.htm
Diagnosing cancer with lumninescent bacteria: Engineered probiotics detect tumors in liver
Engineers at MIT and the University of California at San Diego (UCSD) have devised a new way to detect cancer that has spread to the liver, by enlisting help from probiotics -- beneficial bacteria similar to those found in yogurt.
Many types of cancer, including colon and pancreatic, tend to metastasize to the liver. The earlier doctors can find these tumors, the more likely that they can successfully treat them."There are interventions, like local surgery or local ablation, that physicians can perform if the spread of disease in the liver is confined, and because the liver can regenerate, these interventions are tolerated. New data are showing that those patients may have a higher survival rate, so there's a particular need for detecting early metastasis in the liver," says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Electrical Engineering and Computer Science at MIT.Using a harmless strain of Previous studies had shown that bacteria can penetrate and grow in the tumor microenvironment, where there are lots of nutrients and the body's immune system is compromised. Because of this, scientists have been trying for many years to develop bacteria as a possible vehicle for cancer treatment.The MIT and UCSD researchers began exploring this idea a few years ago, but soon expanded their efforts to include the concept of creating a bacterial diagnostic. To turn bacteria into diagnostic devices, the researchers engineered the cells to express the gene for a naturally occurring enzyme called lacZ that cleaves lactose into glucose and galactose. In this case, lacZ acts on a molecule injected into the mice, consisting of galactose linked to luciferin, a luminescent protein naturally produced by fireflies. Luciferin is cleaved from galactose and excreted in the urine, where it can easily be detected using a common laboratory test.At first, the researchers were interested in developing these bacteria for injection into patients, but then decided to investigate the possibility of delivering the bacteria orally, just like the probiotic bacteria found in yogurt. To achieve that, they integrated their diagnostic circuits into a harmless strain of E. coli called Nissle 1917, which is marketed as a promoter of gastrointestinal health.In tests with mice, the researchers found that orally delivered bacteria do not accumulate in tumors all over the body, but they do predictably zero in on liver tumors because the hepatic portal vein carries them from the digestive tract to the liver."We realized that if we gave a probiotic, we weren't going to be able to get bacteria concentrations high enough to colonize the tumors all over the body, but we hypothesized that if we had tumors in the liver they would get the highest dose from an oral delivery," says Bhatia, who is a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.This allowed the team to develop a diagnostic specialized for liver tumors. In tests in mice with colon cancer that has spread to the liver, the probiotic bacteria colonized nearly 90 percent of the metastatic tumors.In the mouse experiments, animals that were given the engineered bacteria did not exhibit any harmful side effects.The researchers focused on the liver not only because it is a natural target for these bacteria, but also because the liver is hard to image with conventional imaging techniques like CT scanning or magnetic resonance imaging (MRI), making it difficult to diagnose metastatic tumors there.With the new system, the researchers can detect liver tumors larger than about one cubic millimeter, offering more sensitivity than existing imaging methods. This kind of diagnostic could be most useful for monitoring patients after they have had a colon tumor removed because they are at risk for recurrence in the liver, Bhatia says.Andrea Califano, a professor of biological sciences at Columbia University, says the study is "seminal and thought-provoking in terms of clearing a new path for investigating what can be done for early detection of cancer," adding that the therapeutic possibilities are also intriguing."These bacteria could be engineered to cause genetic disruption of cancer cell function, deliver drugs, or reactivate the immune system," says Califano, who was not involved in the research.The MIT team is now pursuing the idea of using probiotic bacteria to treat cancer, as well as for diagnosing it.The research was funded by the Ludwig Center for Molecular Oncology at MIT, a Prof. Amar G. Bose Research Grant, the National Institutes of Health through the San Diego Center for Systems Biology, and the Koch Institute Support Grant from the National Cancer Institute.
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May 21, 2015
https://www.sciencedaily.com/releases/2015/05/150521104924.htm
Field study shows how a GM crop can have diminishing success at fighting off insect pest
A new study from North Carolina State University and Clemson University finds the toxin in a widely used genetically modified (GM) crop is having little impact on the crop pest corn earworm (
At issue is genetically engineered corn that produces a In the late 1990s, scientists found that Cry1Ab was also fairly affective against More than 15 years later, another NC State researcher wanted to see if Gould's predictions held up."We wanted to do an observational study in the field to see how, if at all, things have changed since the work done in the '90s -- was there any indication that zea was becoming resistant," says Dominic Reisig, an associate professor of entomology at NC State and lead author of a paper describing the new study.Reisig and his collaborator, Francis Reay-Jones of Clemson, evaluated corn crop sites in both North Carolina and South Carolina over two years -- and the results were fairly stark.In the late 1990s, Cry1Ab reduced both the number of "There was a warning that zea could develop a resistance to this toxin," Reisig says. "But no changes were made in how to manage Cry1Ab, and now it appears that zea has developed resistance."However, Reisig notes that they cannot say "Our focus was on determining if there were real-world effects, and there were," Reisig says. "This may also explain why zea -- a significant cotton pest -- is becoming less responsive to a related toxin used in GM cotton called Cry1Ac."This finding is of limited economic impact at the moment," Reisig says. "Because agriculture companies have already developed new, more effective Bt toxins for use against "But the study is important. The methods that are agreed upon to show resistance are somewhat arbitrary. The agreed upon metrics for demonstrating field fitness are laboratory studies with an agreed upon diagnostic dose of the toxin. I, and many others, feel that field observations are screaming that changes are happening, but that this is largely ignored. That was one reason for the study."These findings are a reminder that we need to pay attention to potential clues about developing resistance," Reisig says. "We can't expect there to always be a new GM toxin available to replace the old one."The paper, "Inhibition of Helicoverpa zea Growth by Transgenic Corn Expressing Bt Toxins and Development of Resistance to Cry1Ab," is published in the journal
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May 21, 2015
https://www.sciencedaily.com/releases/2015/05/150521082308.htm
Phages transducing antibiotic resistance detected in chicken meat
Antimicrobial resistance in bacteria poses a global threat to public health. Common antibiotics are often ineffective in treating infectious diseases because pathogens acquire resistance genes. These antimicrobial resistance genes are obtained in different ways.
"The most frequent way is the transfer via mobile genetic elements such as plasmids, or via transposons, the so-called jumping genes," explains Friederike Hilbert, scientist at the Institute of Meat Hygiene at the Vetmeduni Vienna. "Transfer of resistances via phages was thought to play a minor role so far."Hilbert and her colleagues isolated phages from 50 chicken samples purchased from Austrian supermarkets, street markets and butchers. They found phages in 49 samples. "Phages do not pose a risk to humans because they can only infect bacteria. No other cells or organisms can be infected."Their analysis showed that one quarter of the phages under study were able to transduce antimicrobial resistance to "This mechanism could also be important in clinical settings, where multiresistant pathogens are on the rise. We assume that phages acquire resistance genes from already resistant bacteria and then transfer those genes to other bacteria," says Hilbert. "Our results could explain why resistances spread so rapidly among bacteria."Scientists have known for a while that phages are able to transduce genes but this was considered a rare event for genes encoding resistance to antibiotics. Newer DNA analyses show, however, that phages leave their signature in bacterial genomes. This way of transfer is presumably more frequent than thought. Phages may therefore play a major role in bacterial evolution.Compared to bacteria, phages are significantly more resistant to disinfectants. Alcohol, in particular, is hardly active against phages. "Common disinfection methods are often inappropriate against phages," Hilbert underlines. The food industry and also hospitals may choose disinfectants that are active against bacteria, but might be ineffective against phages.Treating bacterial infections with phages has become a promising alternative combating antimicrobial-resistant pathogens where phages directly combat bacteria. Hilbert recommends to test therapeutic phages for their ability to transfer resistance genes. The combination of phages and multiresistant pathogens could otherwise result in a hazardous cocktail of phages transferring multiresistance genes."
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May 12, 2015
https://www.sciencedaily.com/releases/2015/05/150512104039.htm
Mining pollution alters fish genetics in southwest England
Pollution from historic mining activities in south west England has led to a reduction in genetic diversity of brown trout according to new research from the University of Exeter. The findings, which will be published on Friday 15 May in the journal
The prevalence of metal contaminants in rivers across the south west of England is directly linked to mining activities dating back hundreds of years. Exposure to high concentrations of metals can be detrimental to fish health, negatively impacting their genetic diversity and population structure.Josephine Paris, lead author and postgraduate researcher at the University of Exeter said: "Our research shows that brown trout populations have been severely affected by both historical and contemporary mining practices. The effects of both metal contamination and changes in environmental geochemistry have driven dramatic changes in the genetic architecture of these fish. In the case of the Industrial Revolution, these shifts have occurred in less than 200 years, showing the speed and magnitude at which human activity can alter the genetics of species."To investigate the genetic impacts of metal pollution, the researchers compared DNA samples from fifteen brown trout populations from heavily-polluted and 'clean' rivers.Genetic analysis revealed that all trout populations from metal contaminated rivers derived from a single common ancestor approximately 960 years ago, during the medieval period when tin mining in the region is first documented. Metal contamination at this time led to genetically distinct populations in different rivers.Around 150 years ago, during the Industrial Revolution, further genetic separation occurred when rivers were again polluted with significantly increased levels of metal contaminants. During this period, trout numbers substantially declined in heavily polluted areas like the River Hayle. Those trout that remained were less genetically diverse than trout in clean rivers.Co-author Dr Andrew King Research Fellow in Biosciences at the University of Exeter said: "Trout in the metal contaminated rivers have evolved to live in water with metal concentrations that kill metal naïve fish. The metal contaminated populations are genetically distinct from one another and we think this is a response to the unique cocktail of metals found in each river. This raises the interesting question as to whether the ability to live in contaminated water has evolved once or multiple times."The River Camel and the River Fal are considered 'clean' rivers, although they do contain some metals due to the underlying geology and ancient mining activity. Other rivers, including the River Hayle and the Red River, are known as 'metal rivers' as they contain significantly elevated levels of metal contaminants.The research was conducted by Josephine Paris, PhD Biosciences student, Dr. Andrew King and Dr. Jamie Stevens of the Molecular Ecology and Evolution Group at the University of Exeter. Human mining activity across the ages determines the genetic structure of modern brown trout (
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May 11, 2015
https://www.sciencedaily.com/releases/2015/05/150511114436.htm
Water fleas genetically adapt to climate change
The water flea has genetically adapted to climate change. Biologists from KU Leuven, Belgium, compared 'resurrected' water fleas -- hatched from 40-year-old eggs -- with more recent specimens. The project was coordinated by Professor Luc De Meester from the Laboratory of Aquatic Ecology, Evolution and Conservation.
The water flea has genetically adapted to climate change. Biologists from KU Leuven, Belgium, compared 'resurrected' water fleas -- hatched from forty-year-old eggs -- with more recent specimens. The project was coordinated by Professor Luc De Meester from the Laboratory of Aquatic Ecology, Evolution and Conservation.The water flea As the dormant eggs remain viable for a long time researchers can use resurrection ecology to examine the evolution of water fleas in a changing climate. Biologist Aurora Geerts explains: "When water fleas reproduce asexually, their offspring is genetically identical to the mother. But when they mate, this results in genetic variation. The genetically fittest water fleas -- the ones that are best adapted to the environment -- survive and lay dormant eggs. When we hatch the dormant eggs of water fleas from the past and compare them with the contemporary population, we can reconstruct the evolutionary changes that occurred in that population and examine how they have adapted to the rising temperature of the water in which they live."The biologists used dormant eggs from Felbrigg Hall, a shallow lake in England: "Both the water flea population and the changes in temperature of that lake are well-documented. Over a period of forty years the average temperature near Felbrigg Hall has risen with 1.15 degrees Celsius. In addition, the number of heat waves has tripled. This causes stress to animals that live in such shallow water. From a Felbrigg Hall sediment core we selected dormant eggs from sediment layers matching the period 1955-1965 and a more recent layer from 1995-2005. We collected eggs from both time periods and hatched them. Then we examined the heat tolerance of the resulting populations from these two time periods by scoring the temperature at which the water fleas lost motor function and fainted. The critical maximum temperature for activity for the water fleas from the recent sediment layer is half a degree more than 40 years ago."In another experiment, the biologists examined whether current populations of the water flea The findings indicate that water flea populations can adapt quite rapidly to rising temperatures. The study is the first to show that animal populations can adapt and already have adapted to higher temperatures and increased heat wave frequencies -- two results of climate change -- by means of evolutionary changes in their heat tolerance.The capacity for genetic adaption is, however, not enough to guarantee success, Geerts adds: "Climate change may have an impact on other factors as well. The water flea might be exposed to more enemies, less food, or an increased sensitivity to parasites. But our results show that we need to take into account the evolutionary dynamics of a species if we want to predict how it will respond to climate change."
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May 7, 2015
https://www.sciencedaily.com/releases/2015/05/150507135925.htm
Evolution in action: Mate competition weeds out genetically modified fish from population
Purdue University research found that wild-type zebrafish consistently beat out genetically modified Glofish in competition for female mates, an advantage that led to the disappearance of the transgene from the fish population over time.
The study, the first to demonstrate evolutionary outcomes in the laboratory, showed that mate competition trumps mate choice in determining natural selection. "Mating success is actually a stronger force of evolution than survival of the fittest," said William Muir, professor of animal sciences. "If an organism can't get a mate, it can't pass its genes on. In terms of evolution, whether it survives or not doesn't matter."Muir and Richard Howard, professor emeritus of biology, conducted a long-term study of mating success in mixed populations of wild-type zebrafish and Glofish -- zebrafish containing a transgene cloned from a sea anemone that produces a fluorescent red protein. Although female zebrafish strongly preferred the neon red males to their brown, wild-type counterparts, the females were coerced into spawning with the wild-type males who aggressively chased away their transgenic rivals.As a result, the rate at which the red transgenic trait appeared in offspring fell rapidly over 15 generations of more than 18,500 fish and ultimately disappeared in all but one of 18 populations. "The females didn't get to choose," Muir said. "The wild-type males drove away the reds and got all the mates. That's what drove the transgene to extinction."Except for their mating competitiveness, wild-type males and Glofish males were similar in fitness -- that is, their health, fertility and lifespan -- which was unexpected since genetically modifying an organism often decreases its ability to flourish, Muir said."Natural selection has had billions of years to maximize an organism's fitness for its environment," he said. "Changing its genetics in any way almost always makes an organism less fit for the wild. You've 'detuned' it."The similarity of the wild-type zebrafish and Glofish made it possible to test mate competition and mate choice simultaneously, which few studies have done, Howard said."I've lectured on evolution for 25 years and never found a study that linked the mechanisms of evolution with the pattern of evolutionary outcomes," he said. "This study puts the whole story together."The study also showed the effectiveness of a model Muir developed to assess the potential risk posed to natural populations by transgenic organisms. The model, which measures six fitness components, can be used to predict what would happen if a particular transgene were released in the wild. Its premise lies in a simple principle: If a transgene makes an organism fitter than wild types for an environment, it could pose a risk to natural populations or the ecosystem. If a transgene makes the organism less fit, the gene will be weeded out of the population over time."Darwin was right: Survival of the fittest works," Muir said. "If we make a transgenic organism that has reduced fitness in the wild, evolution takes over and removes it. Nature experiments with mutations all the time, and it only saves the best of the best."Based on the model, the researchers predicted that wild-type males would chase other males and females more than Glofish males would, have greater success in securing mates and produce more offspring. The laboratory findings confirmed their predictions.The study shows that if Glofish were released into the wild, the transgenic trait would eventually disappear as the result of sexual selection. Muir stressed that "the model does not say that even if we find no risks, we should release transgenic fish into the wild. It simply says what would likely happen if we did."The model can be applied to genetically modified plants as well as animals and is one tool used by the U.S. Food and Drug Administration to assess potential risks posed by transgenic organisms, he said.Glofish are the only transgenic animals approved for sale to the public by the FDA.
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May 6, 2015
https://www.sciencedaily.com/releases/2015/05/150506133621.htm
Blocking obesity-associated protein stops dangerous fat formation, mouse study shows
By changing mouse genes to block a protein associated with obesity, Oxford University scientists have prevented fat from forming around the animals' internal organs, even when the animals eat an unhealthy diet. The study in
Visceral fat deposits around internal organs in the stomach are particularly harmful: they are associated with insulin resistance, type-2 diabetes and heart disease. The study, conducted in close collaboration with researchers at the at the French Institute of Health and Medical research (INSERM) in Paris, shows that changing the pattern of fat deposition from around the stomach to under the skin starts a chain of events which result in insulin sensitivity being maintained, reducing the chances of type-2 diabetes.Researchers already know that visceral fat attracts special M1-type macrophages (immune cells that attack infections and damaged cells). These M1-type macrophages produce harmful proteins that promote insulin resistance. 'We've previously found that a protein called interferon regulatory factor-5 (IRF-5) seems to push macrophages to change from a more 'peaceful', M2-type to the more aggressive M1-type', said Professor Irina Udalova at the Kennedy Institute of Rheumatology at Oxford University, 'so we wondered if 'deleting' IRF-5 might have a beneficial effect'.To test this idea, the two research teams fed the mice that were lacking the gene coding for IRF-5 with a healthy diet or a high-fat one. The mice with genetic changes were no different from standard lab mice when both the groups ate the healthy diet. Both groups of mice gained weight when they ate the high-fat diet. However, the mice with the altered gene piled on the fat under the skin, rather than around the internal organs in their stomach. The size of the fat cells in the stomach was also smaller in these mice, because there was more collagen (a 'scaffolding' protein that provides the structure for many parts of the body) deposits, holding the fat cells in.'The mice without IRF-5 still got fat, but what was different was where they deposited this fat. We know that people who put on fat around their belly have a higher risk of developing obesity-related illnesses such as type-2 diabetes, compared to people who put on weight around their thighs. But we can't change the pattern of fat deposition in people, which we can now do in these mice. So this turned out to be an excellent way of testing if changing the pattern of fat deposition actually changes the factors that lead to type-2 diabetes', said Professor Udalova.The researchers tested this idea by giving the mice a very sweet drink, containing glucose. They then tracked how quickly the glucose was broken down by insulin. Obesity can make the body less sensitive to insulin, which means that it takes longer for the glucose to disappear from the blood stream. This loss of sensitivity can eventually lead to type-2 diabetes. Despite being fatter, the mice without IRF-5 did better than the standard mice on this glucose challenge test.Researchers at INSERM also found that IRF-5 levels were elevated in fatty tissue from very obese people, especially in their visceral fat. A gene analysis of this group of people found that the higher the levels of IRF-5, the lower the levels of another protein produced by macrophages, transforming growth factor beta (TGFbeta). By mimicking the environment in fatty tissue in a test-tube, the researchers also found that artificially increasing the levels of IRF-5 in cells from thin people reduced the levels of TGFbeta, similar to what was found in the obese people. The researchers think that reducing IRF-5 levels sets off a chain of events, starting with increased TGFbeta levels. Increased TGFbeta in turn leads to more collagen being deposited, which results in 'remodelling' of abdominal fat deposits, and the release of other chemicals that maintain insulin sensitivity.'We found that the mice without IRF-5 were essentially healthy, despite being significantly fatter. Blocking IRF-5's activity may however have other side-effects, such as increasing allergies. So more work is needed to understand if changing levels of IRF-5 (by using new drugs to target the protein) in humans would be a good way of treating the problem of obesity and obesity associated metabolic diseases. But the results show very clearly that where you get fat matters a lot', said Professor Udalova.
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May 6, 2015
https://www.sciencedaily.com/releases/2015/05/150506111325.htm
From the depths of a microscopic world, spontaneous cooperation
Maybe it's not such a dog-eat-dog world after all. A clever combination of two different types of computer simulations enabled a group of Illinois researchers to uncover an unexpectedly cooperative group dynamic: the spontaneous emergence of resource sharing among individuals in a community. Who were the members of this friendly, digitally represented collective?
The finding, initially predicted by mathematical models and then confirmed through empirical testing, was reported recently in "We thought, can we marry these two approaches?" said Cole. "Let's put a whole bunch of cells in a shared environment and simulate the glucose and oxygen concentrations outside." Cole merged the two models, eventually developing an entirely new simulation code, in order to predict how bacteria within colonies access and metabolize resources as the colony expands.Bacteria such as Luthey-Schulten is a faculty member at the Carl R. Woese Institute for Genomic Biology (IGB). In the Luthey-Schulten lab's work, colony growth was simulated in 3D, which allowed Cole and others to model what would happen as the colony grew larger, making it harder for oxygen to penetrate to inside layers, or for glucose from the growth substrate to reach the top.Allowing these resource disparities to emerge in the model revealed something unexpected and novel, yet intuitive. The model predicted that the bacteria would spontaneously begin to cooperate to make the most of their resources.In the simulated colonies, cells at the bottom, lacking oxygen, would break down glucose into acetate. Cells at the top would take up that acetate and use their access to oxygen to complete its breakdown, extracting the remaining available energy from the original glucose substrate. Cells in the outermost ring, with access to both glucose and oxygen, exhibited the most growth and reproduction."As soon as I saw it, I thought, it makes perfect sense," said Cole. "It has to be going on at some level, and I'm sure it's testable."To test the model's predictions, Luthey-Schulten, Cole and colleagues ventured into empirical work: they grew and monitored bacterial colonies in the lab, in conditions that matched those they had simulated. With microscopy support from Miyandi Sivaguru, assistant director of the IGB Core Facilities, they used a genetically engineered fluorescent dye to visually track bacterial cells that used acetate as a fuel source. The fluorescent label could be seen in the upper layers of cells in the middle of the colony, just as the simulation predicted.One striking feature of both the simulated and real colonies in the study is that cooperative task specialization was able to quickly emerge among genetically identical or near-identical cells. The authors hope that the model can be adapted to reveal new insights into the behavior of other groups of cells, including cancer-causing tumors.
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April 29, 2015
https://www.sciencedaily.com/releases/2015/04/150429104804.htm
How does a honeybee queen avoid inbreeding in her colony?
Recombination, or crossing-over, occurs when sperm and egg cells are formed and segments of each chromosome pair are interchanged. This process plays an crucial role in the maintenance of genetic variation. Matthew Webster and Andreas Wallberg at the Biomedical Centre, Uppsala University, have studied recombination in honeybees. The extreme recombination rates found in this species seem to be crucial for their survival.
Like other social insects, honeybees live in colonies consisting mainly of closely related members of the worker caste. High genetic diversity among the workers is important for the whole colony's survival. There are several theories as to why: for example, a genetically variable workforce may be best equipped to perform the diverse tasks required in the colony, and diverse colonies may also be less susceptible to disease. But how can the queen, the colony's only fertile female, prevent inbreeding and maintain genetic variation?The queen bee solves the problem in two ways. One is through polyandry. She mates with a score of drones and uses their sperm to fertilize the eggs randomly so that workers often have different fathers. The second is through extremely high rates of recombination.By sequencing the entire genome of 30 African honeybees, the research team has been able to study recombination at a level of detail not previously possible. The frequency of recombination in the honeybee is higher than measured in any other animal and is more than 20 x higher than in humans.Recombination affects how efficiently natural selection can promote favorable genetic variants. In line with this, the researchers have found that genes involved in the new adaptations to the environment in honeybees also undergo more recombination. But recombination is not entirely risk free."Recombination is not only beneficial for bees. When parts of chromosomes broken and exchanged, errors can sometimes occur during their repair due to a process called "GC-biased gene conversion," says Matthew Webster.This process leads to gradual fixation of mutations that may be harmful to the honeybee. Although a similar process occurs in humans, it is more than ten times stronger in honeybees. Over time, recombination is expected to lead to a deterioration of the gene pool, a process that seems to have accelerated in bees. The extreme recombination rates -- crucial for maintaining genetically diverse honeybee colonies -- come with a high price."There are no free lunches. Not even for a honeybee," says Matthew Webster.
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April 28, 2015
https://www.sciencedaily.com/releases/2015/04/150428125042.htm
Genetically modified crops to fight spina bifida
Genetically modified crops are usually designed to have herbicide tolerance and insect resistance, but there are other applications of such engineered plants, such as the incorporation of genes for specific nutrients. Research published in the
The first commercially available GM crop was the FLAVR SAVR tomato in 1994 but by 2012 some 170 million hectares of GM crops were being grown worldwide in 28 countries by 17 million farmers. There are various crop plants being developed that are enriched in iron and zinc, vitamin A and other nutrients. Two well-known GM rice crops that were designed to improve nutrition levels in the food are in development. The first, so-called Golden rice, is an entirely safe, pro-vitamin A enriched rice and will be introduced soon with the potential to save the lives of hundreds of thousands of children who might otherwise die of malnutrition. By contrast, folate biofortified rice (FBR) is still at the laboratory phase of development, although proof-of-concept has been well established.Hans De Steur and colleagues at Ghent University, Belgium and Liaoning Academy of Agricultural Sciences, China, suggest that in regions of high folate-deficiency risk, such as Balrampur (India) and Shanxi (China) there are many years lost of healthy life because of a lack of this vitamin. About 50% to 70% and up to 85% of all neural tube defects arise because of maternal folate deficiency.The standard metric used in research, as described by the World Health Organization (WHO) is the DALY Disability-Adjusted Life Year. This equates to the sum of Years of Life Lost (YLL) due to premature mortality and the Years Lost due to Disability (YLD) for people living with a given health condition and so combines morbidity and mortality. The team's work shows that folate biofortification could help avoid 29 to 111 DALYs each year in Balrampur per 1000 births and between 47 and 104 DALYs in Shanxi. In absolute figures, China and India have 16000 and 18000 NTDs births per annum, and account for about 12% of the global estimated number of NTDs, i.e., nearly 300 000 NTDs per year.
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April 24, 2015
https://www.sciencedaily.com/releases/2015/04/150424105348.htm
Psychology of the appeal of being anti-GMO
A team of Belgian philosophers and plant biotechnologists have turned to cognitive science to explain why opposition to genetically modified organisms (GMOs) has become so widespread, despite positive contributions GM crops have made to sustainable agriculture. In a paper published April 10 in
"The popularity and typical features of the opposition to GMOs can be explained in terms of underlying cognitive processes. Anti-GMO messages strongly appeal to particular intuitions and emotions," says lead author Stefaan Blancke, a philosopher with the Ghent University Department of Philosophy and Moral Sciences. "Negative representations of GMOs--for instance, like claims that GMOs cause diseases and contaminate the environment--tap into our feelings of disgust and this sticks to the mind. These emotions are very difficult to counter, in particular because the science of GMOs is complex to communicate."Examples of anti-GMO sentiment are present around the world--from the suspension of an approved genetically modified eggplant in India to the strict regulations on GM crops in Europe. Contributing to this public opposition, the researchers suspect, is a lack of scientific understanding of genetics (not even half of the respondents in a US survey rejected the claim that a fish gene introduced into a tomato would give it a fishy taste) as well as moral objections to scientists "playing God.""Anti-GMO arguments tap into our intuitions that all organisms have an unobservable immutable core, an essence, and that things in the natural world exist or happen for a purpose," Blancke explains "This reasoning of course conflicts with evolutionary theory--the idea that in evolution one species can change into another. It also makes us very susceptible to the idea that nature is a force that has a purpose or even intentions that we shouldn't' meddle with."While religious beliefs, particularly those that hold a romantic view of nature, have been accused of generating some of the negativity around GMOs, Blancke and his co-authors argue that there's more to the story. Using ideas from the cognitive sciences, evolutionary psychology, and cultural attraction theory, they propose that it is more a matter of messages competing for attention--in which environmental groups are simply much better at influencing people's gut feelings about GMOs than the scientific community."For a very long time people have only been hearing one side," Blancke says. "Scientists aren't generally involved with the public understanding of GMOs, not to mention the science of GMOs is highly counterintuitive and therefore difficult to convey to a lay audience--so they have been at a disadvantage form the start."The researchers believe that understanding why people are against GMOs is the first step toward identifying ways to counteract negative messages. Blancke and co-author Geert De Jaeger, a plant biotechnologist, started in their community by developing a public lecture to dispel myths about GMOs. They urge others to build science education programs that can help balance out anti-GMO campaigns."We want to bring the two sides more together," Blancke says. "You cannot say every GMO is bad. You have to look at each case separately to make a judgement."
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April 24, 2015
https://www.sciencedaily.com/releases/2015/04/150424085013.htm
Discovery of a protein capable of regulating DNA repair during sperm formation
Researchers from the Universitat Autònoma de Barcelona (UAB) Department of Cellular Biology, Physiology and Immunology, and the UAB Institute of Biotechnology and Biomedicine, led by Dr Ignasi Roig, discovered that the signalling route -- a cascade activation of several molecules -- triggered by the ATM protein regulates DNA repair during the production of spermatocytes by meiosis, the cell division process which yields spermatozoa.
In experiments conducted with genetically modified mice, researchers observed that when the ATM protein is eliminated, or its activation is reduced, spermatocytes (precursors of spermatozoa) which present breakage in the genome do not block their cellular cycle and therefore do not have the capacity to progress more than normal, given that they do not correctly repair DNA breakage.Therefore, the research shows that these mutations affecting the signalling route which depends on the ATM protein, as well as the drugs inhibiting the function of this signalling route such as some anti-tumour drugs, could produce infertility problems in humans.The discovery will allow to delve deeper into the mechanisms regulating the formation of gametes (eggs and sperm). It is known that the ATM protein is one of the main proteins involved in DNA repair in somatic cells (any of the cells forming part of our organism, except for germline cells). This study, published recently in Sexual reproduction requires the fusion of two gametes (egg and sperm) which combine their genetic material to produce an embryo. Therefore, the number of chromosomes of these cells must be reduced by half through a specialised cell division called meiosis. At the beginning of meiosis, germline cells intentionally generate multiple double chain breakages along the whole DNA genome. The reparation of these DNA breakages, through a process called homologous recombination, allows homologous chromosomes to pair up and guarantee a balanced segregation during the meiotic division and thereby avoid the formation of gametes with an incorrect number of chromosomes which could result in chromosome disorders due to the presence of aneuploids (such as Down's Syndrome and other similar disorders), or in spontaneous abortions.Since these repair errors in DNA breakage can generate instability in the genome, the process of repairing the breakages is a highly regulated one. It is therefore essential that there be control mechanisms capable of detecting errors in this process and halting the cell cycle with the aim of allowing the cell to repair the breakages or, if not possible, to eliminate the damaged cell.The project's leading researcher is Dr Ignasi Roig, lecturer of the Unit of Cytology and Histology at the Department of Cellular Biology, Physiology and Immunology (UAB), and researcher of the Genome Instability and Integrity group at the Institute of Biotechnology and Biomedicine (IBB) of the Universitat Autònoma de Barcelona. In addition to Dr Roig, Sarai Pacheco and Marina Marcet Ortega, also belonging to the same research group, participated in the study. Researchers from the Howard Hughes Medical Institute (New York) and the Memorial Sloan-Kettering Cancer Center (New York) also formed part of the team.
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April 21, 2015
https://www.sciencedaily.com/releases/2015/04/150421084204.htm
Horizontal gene transfer: Sweet potato naturally 'genetically modified'
Sweet potatoes from all over the world naturally contain genes from the bacterium Agrobacterium. Researchers from UGent and the International Potato Institute (CIP) publish this discovery on the website of
The researchers discovered the foreign DNA sequences of The sequences appeared to be present in each of the 291 tested sweet potato cultivars and even in some wild related species. Different research methods confirmed the same conclusion: the specific sequences are not due to contamination, but they are part of the sweet potato genome.The genes in the foreign DNA sequences were also shown to be active in sweet potato, which can indicate that they provide a positive characteristic which was selected for by the farmers during domestication.It is not the first time that researchers find bacterial, fungal or viral DNA in the genome of plants or animals. High throughput genome analyses in recent years find more and more examples of possible "horizontal gene transfers." In a horizontal gene transfer there is exchange of genes between different species -- in contrast to normal gene transfer from parents to progeny which occurs within one species.Finding similar sequences is not a full proof that they are the result of horizontal gene transfer, but in the case of sweet potato there are strong indications that this has happened. Indeed, The mechanism that
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April 20, 2015
https://www.sciencedaily.com/releases/2015/04/150420122836.htm
Genetic code of Upland cotton cracked
In a groundbreaking achievement led by an international team that includes Clemson scientist Chris Saski, the intricately woven genetic makeup of Upland cotton has been decoded for the first time in the ancient plant's history.
Saski participated in sequencing the genome, which is a crucial stepping-stone toward further advancements of understanding the inner workings of one of the most complex and treasured plants on the planet.The future implications of Saski's research in the short and long terms are both financial and holistic. Upland cotton, which accounts for more than 90 percent of cultivated cotton worldwide and has a global economic impact of $500 billion, is the main source of renewable textile fibers.The genome sequence, unveiled in the scientific journal "From the discovery standpoint -- having a solid foundation to begin measuring genetic diversity and how the genes are organized -- this is a game-changer," said Saski, director of Clemson's Genomics and Computational Biology Laboratory. "With a genome map and genetically diverse populations, you can reveal the biology and DNA signature underlying cotton fiber development. Then you can use this information to breed cotton lines with advanced fiber elongation and fiber strength, which are crucial to the industry. This first draft of the genome sequence is a solid foundation for unlocking cotton's mysteries."Upland cotton came into existence more than a million years ago when two separate species hybridized, creating a plant that has multiple genomes. Unlike humans, who have two sets of chromosomes (from a mother and a father), the Upland cotton genome is configured with four sets, adding multiple layers of complexity for scientists such as Saski."You can only imagine the confounding problems that can occur when you have multiple genomes," said Saski. "I'm interested in the process underlying polyploidization and how a better understanding of this complexity can be leveraged to breed better cotton."Saski's U.S based consortium, which includes Brian Scheffler of the U.S. Department of Agriculture, David Stelly of Texas A&M, Don Jones of Cotton Inc. and Jeffrey Chen of the University of Texas at Austin, traveled to Nanjing Agriculture University in eastern China. There they worked with a team led by professors Tianzhen Zhang and Ruiqiang Li to assemble the draft genome."China is the largest cotton-producing country in the world," said Saski, whose initial research on the project began more than four years ago. "In the end, we were successful in setting the stage for using DNA information to inform and benefit breeders."Upland cotton is one of South Carolina's foundational commodity crops. It has been grown since the time of the American Revolution, and it remains a staple crop to this day. It is also South Carolina's leading agricultural export.Cotton breeders are being challenged to release new varieties suitable for drought-like conditions and high salinity soils, and that are also better able to resist constant threats from pests and diseases."The techniques and approach Saski and his collaborators are applying to decode the complex cotton genome will have a profound impact on the way cotton is improved through breeding," said Stephen Kresovich, Coker Chair of Genetics and director of Clemson's Institute of Translational Genomics. "These insights will also advance our understanding of polyploidy genetics, which is so common in crop plants."The cotton genome that produces spinnable fibers is extremely complex because of the presence of multiple genomes, a phenomenon that occurs in about 80 percent of all plant species."Saski and his colleagues have developed innovative strategies to dissect the cotton genome using comparative genomics, genetics, computational biology and high-performance computing," said Kresovich. "The results of this work will have a direct impact in the discovery of novel traits in cotton and related species and will set the stage for accelerated agronomic improvement. As the future unfolds, South Carolina will certainly be a major benefactor."
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April 15, 2015
https://www.sciencedaily.com/releases/2015/04/150415103318.htm
Plant oils used for novel bio-based plastics
Researchers have developed a new way to use plant oils like olive and linseed oil to create polyurethane, a plastic material used in everything from foam insulation panels to tires, hoses and sealants.
The researchers, led by Michael Kessler, Berry Family director and professor in Washington State University's School of Mechanical and Materials Engineering, have published a paper on the work in the journal ACS Polyurethane is extremely tough and corrosion- and wear-resistant, but researchers would like a more environmentally friendly alternative to the petroleum-based product. About 14 million tons of polyurethane was produced in 2010, and production is expected to increase by almost 30 percent by 2016.While there are already some polyurethanes made from plant materials, Kessler's research group developed a new method that uses vegetable oils to create materials with a wide variety of flexibility, stiffness and shapes. Plant oils are inexpensive, readily available, renewable and can be genetically engineered.In the study, the researchers made polyurethane using olive, canola, grape seed, linseed and castor oils. While other researchers have struggled with using petroleum-based solvents, the WSU researchers, working with colleagues from Iowa State and from Cairo universities, didn't use solvents or a catalyst in their production.To make polyurethane, manufacturers combine two types of chemical compounds in a reaction. One of the chemicals is a polyol, which is a compound with multiple hydroxyl functional groups that are available for reaction.Some oils, like linseed oil, have five or six reactive sites, making the material stiffer. Others, such as olive oil, have fewer reactive sites, making the material more flexible."What's new about this is specifically the way we make the polyols," said Kessler, who compared the process to building with Legos. "It is the same concept with these chemical groups. They click together and form a chemical bond."The novelty of this particular work is that these polyurethanes are using a new chemistry made by a combination of castor oil fatty acid and modified vegetable oils," he said.Kessler, who is director of the Center for Bioplastics and Biocomposites, hopes that the method is appealing to the plastics industry. The center, a collaboration between WSU and Iowa State University, is the first industry and university cooperative research center devoted to the development of biologically based plastics.It got underway earlier this year with a grant from the National Science Foundation and brings together partners to conduct research that is particularly relevant for industry with a high potential for commercialization. A total of 24 companies are members of the center.
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April 9, 2015
https://www.sciencedaily.com/releases/2015/04/150409143031.htm
Mountain gorillas: Lots of deleterious genetic variation disappeared from population thanks to inbreeding
The first project to sequence whole genomes from mountain gorillas has given scientists and conservationists new insight into the impact of population decline on these critically endangered apes. While mountain gorillas are extensively inbred and at risk of extinction, research published today in
"Mountain gorillas are among the most intensively studied primates in the wild, but this is the first in-depth, whole-genome analysis," says Dr Chris Tyler-Smith, corresponding author from the Wellcome Trust Sanger Institute. "Three years on from sequencing the gorilla reference genome, we can now compare the genomes of all gorilla populations, including the critically endangered mountain gorilla, and begin to understand their similarities and differences, and the genetic impact of inbreeding."The number of mountain gorillas living in the Virunga volcanic mountain range on the borders of Rwanda, Uganda and the Democratic Republic of Congo plummeted to approximately 253 in 1981 as a result of habitat destruction and hunting. Since then, conservation efforts led by the Rwanda Development Board and conservation organizations like the Gorilla Doctors (a partnership between the non-profit Mountain Gorilla Veterinary Project and the UC Davis Wildlife Health Center), and supported by tourists keen to see the gorillas made famous by late primatologist Dian Fossey, have bolstered numbers to approximately 480 among the Virunga population.Researchers interested to learn how such a small gene pool would affect the mountain gorillas were surprised to find that many harmful genetic variations had been removed from the population through inbreeding, and that mountain gorillas are genetically adapting to surviving in small populations."This new understanding of genetic diversity and demographic history among gorilla populations provides us with valuable insight into how apes and humans, their closely related cousins, adapt genetically to living in small populations," says Dr Aylwyn Scally, corresponding author from the Department of Genetics at the University of Cambridge. "In these data we can observe the process by which genomes are purged of severely deleterious mutations by a small population size."Using blood samples collected over several years by the Rwanda Development Board, The Institut Congolese pour la Conservation du Nature and by Gorilla Doctors, which treats wild gorillas injured by snares, researchers were able to sequence the whole genomes of seven mountain gorillas for the first time. Previously, only easily obtainable but poor-quality DNA from faecal and hair samples have been analysed at a handful of genetic loci. Scientists could now see that these mountain gorillas, along with eastern lowland gorillas, their closely related neighbours, were two to three times less genetically diverse than gorillas from larger groups in western regions of central Africa.While there are concerns that this low level of genetic diversity may make the mountain gorillas more vulnerable to environmental change and to disease, including cross-infectious strains of human viruses, the inbreeding has, in some ways, been genetically beneficial. Fewer harmful loss-of-function variants were found in the mountain gorilla population than in the more numerous western gorilla populations. These variants stop genes from working and can cause serious, often fatal, health conditions.By analysing the variations in each genome, researchers also discovered that mountain gorillas have survived in small numbers for thousands of years. Using recently-developed methods, researchers were able to determine how the size of the population has changed over the past million years. According to their calculations, the average population of mountain gorillas has numbered in the hundreds for many thousands of years; far longer than previously thought."We worried that the dramatic decline in the 1980s would be catastrophic for mountain gorillas in the long term, but our genetic analyses suggest that gorillas have been coping with small population sizes for thousands of years," says Dr Yali Xue, first author from the Sanger Institute. "While comparable levels of inbreeding contributed to the extinction of our relatives the Neanderthals, mountain gorillas may be more resilient. There is no reason why they should not flourish for thousands of years to come."It is hoped that the detailed, whole-genome sequence data gathered through this research will aid conservation efforts. Now that a genome-wide map of genetic differences between populations is available, it will be possible to identify the origins of gorillas that have been illegally captured or killed. This will enable more gorillas to be returned to the wild and will make it easier to bring prosecutions against those who poach gorillas for souvenirs and bush meat."Our dedicated programme of clinical monitoring and intervention in cooperation with the Rwanda Development Board, the Institut Congolese pour la Conservation du Nature and local communities is helping to ensure the health and sustainability of endangered mountain gorillas," says Dr Mike Cranfield, Co-Director of Gorilla Doctors. "Detailed genetic data help us trace where confiscated gorillas came from, and allows the assessment of the genetic health of the population as well as their susceptibility to certain health issues."
Genetically Modified
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March 31, 2015
https://www.sciencedaily.com/releases/2015/03/150331215848.htm
The nature of nurture is all about your mother, study says
When it comes to survival of the fittest, it's all about your mother -- at least in the squirrel world.
New research from the University of Guelph shows that adaptive success in squirrels is often hidden in the genes of their mother."Some squirrels are genetically better at being mothers than others," said Andrew McAdam, a professor in U of G's Department of Integrative Biology and co-author of the study published in The research team analyzed 24 years' worth of data from a population of North American red squirrels in Canada's Yukon and measured maternal genetic effects in squirrel offspring."We provide evidence that genetic differences in the nurturing ability of red squirrels affect the fitness of their offspring," said McAdam. He worked on the study with Eryn McFarlane, a former Guelph graduate student and lead author of the paper who is now at Uppsala University in Sweden.Biologists have debated "nature vs. nurture" for decades, McAdam said. "Are we born a blank slate or is our destiny in life written out for us in terms of our genetics?"It's widely recognized that mothers make important contributions to attributes of their developing offspring."But our study is the first to measure how important these genes in the mothers are to the evolutionary success of their offspring."Researchers tracked squirrels throughout their lifetime by marking each animal and using radio collars to find their nests. "It was a collaboration with researchers from three Canadian universities," McAdam said, crediting his PhD adviser, University of Alberta professor Stan Boutin, with establishing the project.At first, the researchers found no evidence for the heritability of fitness. "This is not uncommon, but it's depressing for someone interested in studying adaptation," McAdam said."But Eryn noticed that there seemed to be a difference in fitness among squirrels that depended on who their mother was, and decided to look and see whether those differences among mothers were due to genetics."They discovered a hidden source of adaptive potential that has not been measured before, McAdam said. "It wasn't in the genes of the offspring -- it was hidden in the genes of their mothers."These maternal genetic effects on offspring fitness can drive evolution even when offspring genes have no direct effect on fitness, he said."It represents a previously undocumented source of adaptive potential in wild populations."Although they don't know all attributes that make for a "better mother," the researchers found that genetically gifted mothers often give birth earlier in the breeding season and their pups are more successful in establishing territories. "This is just one attribute. We also know that there are still more yet to be discovered.""What is clear is that the benefits of good mothering early in life are compounded across a whole lifetime."
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March 24, 2015
https://www.sciencedaily.com/releases/2015/03/150324111510.htm
What is the definition of 'natural' foods? Consumers want to know
After decades of debate there remains no generally accepted definition of a "natural" food product. Regulatory agencies have refused to settle the issue but may be under new pressure from consumer lawsuits, according to a new study in the
"Consumers don't agree on a definition either, yet clearly believe that 'natural' is important," writes author Ross D. Petty (Babson College). "In 2009, 30% of newly launched foods claimed to be natural but by 2013 this dropped to 22%, possibly due to an increase in the number of consumer lawsuits. Lawyers are increasingly willing to take cases which regulatory agencies have abandoned."In 1973, the Federal Trade Commission warned that no other area of national health was as abused by deception as nutrition, but by 1983 the FTC had given up on the issue of defining "natural" products. The FDA required in 1977 that artificial flavors be identified as such, but refused to define "natural." When federal district courts in 2014 questioned the legality of promoting genetically modified ingredients as natural, the FDA declined to give an opinion. The US Department of Agriculture fared better, requiring that "natural" meats be free of substances such as artificial flavoring. The industry itself sporadically addressed the "natural" problem, with the Council of Better Business Bureaus advising Nutrasweet to cease claiming it was "made from natural ingredients."Industry progress in general, however, has been limited. With no regulations to fall back on, consumers have begun resorting to legal action, petitioning the FDA in 2001 to act against "natural" food products that hid genetically modified ingredients. Next came the "Sugar Wars," with the Sugar Association and Equal suing Splenda for claiming it was natural. Splenda resisted, and as of April 2014, no natural community class action lawsuit has actually gone to trial."Though natural food lawsuits to date have disappointed, they encourage marketers to drop the claim of being natural or reformulate their products to avoid future lawsuits. Perhaps this will persuade the FDA or FTC to consider creating, finally, a definition for the meaning of natural," concludes the author.
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March 24, 2015
https://www.sciencedaily.com/releases/2015/03/150324084812.htm
Engineers develop new yeast strain to enhance biofuel and biochemical production
Researchers in the Cockrell School of Engineering at The University of Texas at Austin have used a combination of metabolic engineering and directed evolution to develop a new, mutant yeast strain that could lead to a more efficient biofuel production process that would make biofuels more economically competitive with conventional fuels. Their findings were published online in the journal
Beyond biofuels, the new yeast strain could be used in biochemical production to produce oleochemicals, chemicals traditionally derived from plant and animal fats and petroleum, which are used to make a variety of household products.Hal Alper, associate professor in the McKetta Department of Chemical Engineering, and his team have engineered a special type of yeast cell, "Our re-engineered strain serves as a stepping stone toward sustainable and renewable production of fuels such as biodiesel," Alper said. "Moreover, this work contributes to the overall goal of reaching energy independence."Previously, the Alper team successfully combined genetically engineered yeast cells with ordinary table sugar to produce what Alper described as "a renewable version of sweet crude," the premium form of petroleum. Building upon this approach, the team used a combination of evolutionary engineering strategies to create the new, mutant strain of "This significant improvement in our cell-based platform enables these cells to compete in the biofuels industry," Alper said. "We have moved to concentration values that begin to align with those in other industrial fuel processes."Alper and his team improved the performance of The researchers used these high-performing cells, cells that produced more lipids and at a faster rate, to obtain the final yeast with improved function."We were able to iterate the strain through a process of directed evolution, which involves mutation and selection, and with each cycle we were able to get things better and better," Alper said.In addition to using lipids for biofuels, the cell-based platform is able to produce oleochemicals, including nutritional polyunsaturated fatty acids, waxes, lubricants, oils, industrial solvents, cosmetics and a type of vitamin supplements called nutraceuticals.The researchers' method and platform are patent pending. Alper's lab is continuing to work on ways to improve how the yeast strain converts sugar into lipids, and on the types of lipid products they can produce.
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March 16, 2015
https://www.sciencedaily.com/releases/2015/03/150316160339.htm
Consumers willing to spend more for biotech potato products
New research from an Iowa State University economist found consumers were willing to spend more for genetically modified potato products with reduced levels of a chemical compound linked to cancer.
Wallace Huffman, Charles F. Curtiss Distinguished Professor in Agriculture and Life Sciences who contributed to the project, said the findings underscore the importance of efforts to educate consumers on the use of biotechnology in the production of healthful food."This is a complicated issue so it's important for consumers to get information on how the technology works and its potential benefits," Huffman said.Acrylamide is a chemical compound that studies have linked to the formation of cancer in animals, and the FDA has encouraged Americans to cut back on foods that contain the substance. It accumulates naturally in starchy foods cooked at high temperatures, such as roasted nuts and coffee beans or the crusts of bread. Potato products like french fries and potato chips make up the biggest source of acrylamide consumption in the United States, Huffman said.Potato growers have tried conventional plant breeding techniques to cut down on the formation of acrylamide, but biotechnology and genetic modification have yielded more promising results, he said.Huffman's research attempts to gauge consumer attitudes toward experimental genetically modified potato products. Genetically modified food has sparked controversy among some, but the results of the research showed a willingness among consumers to pay more for genetically modified potato products that reduce the formation of acrylamide than for conventional potatoes. That provides evidence that consumers are willing to pay more for enhanced food safety, even when it's delivered through biotech methods, Huffman said.For instance, participants were willing to pay $1.78 more for a five-pound bag of potatoes after they received information from a scientific perspective on hazards associated with acrylamide exposure and a potato industry perspective on dramatically reducing acrylamide in potato products using biotechnology. Likewise, the participants were willing to pay an extra $1.33 for a package of frozen french fries after they received materials explaining the scientific implications of human exposure to acrylamide."There was a really strong effect from the industry and scientific perspectives," Huffman said. "Another interesting finding was that social and demographic concerns didn't seem to matter regarding willingness to pay for genetically modified products."The study included approximately 300 people in the Boston, Los Angeles and Des Moines areas. The subjects participated in an experimental auction market for various potato products both before and after receiving informational materials on acrylamide and the biotechnology used to reduce its formation. Each participant received some combination of information from the perspective of potato growers, food scientists and environmental groups.While scientific and industry perspectives had a substantial effect on consumers' willingness to buy genetically modified products, the environmental information had a negative impact, Huffman said.Huffman was one of 24 investigators on the project, which was funded jointly by the U.S. Department of Agriculture's National Institute of Food and Agriculture and the University of Wisconsin. ISU economics graduate assistants Jonathan McFadden and Katie Lacy also contributed to the project.
Genetically Modified
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March 16, 2015
https://www.sciencedaily.com/releases/2015/03/150316121915.htm
Jailbreaking yeast could amp up wine's health benefits, reduce morning-after headaches
University of Illinois scientists have engineered a "jailbreaking" yeast that could greatly increase the health benefits of wine while reducing the toxic byproducts that cause your morning-after headache.
"Fermented foods -- such as beer, wine, and bread -- are made with polyploid strains of yeast, which means they contain multiple copies of genes in the genome. Until now, it's been very difficult to do genetic engineering in polyploid strains because if you altered a gene in one copy of the genome, an unaltered copy would correct the one that had been changed," said Yong-Su Jin, a U of I associate professor of microbial genomics and principal investigator in the Energy Biosciences Institute.Recently scientists have developed a "genome knife" that cuts across multiple copies of a target gene in the genome very precisely -- until all copies are cut. Jin's group has now used this enzyme, RNA-guided Cas9 nuclease, to do precise metabolic engineering of polyploid The possibilities for improved nutritive value in foods are staggering, he said. "Wine, for instance, contains the healthful component resveratrol. With engineered yeast, we could increase the amount of resveratrol in a variety of wine by 10 times or more. But we could also add metabolic pathways to introduce bioactive compounds from other foods, such as ginseng, into the wine yeast. Or we could put resveratrol-producing pathways into yeast strains used for beer, kefir, cheese, kimchee, or pickles -- any food that uses yeast fermentation in its production."Another benefit is that winemakers can clone the enzyme to enhance malolactic fermentation, a secondary fermentation process that makes wine smooth. Improper malolactic fermentation generates the toxic byproducts that may cause hangover symptoms, he said.Jin stressed the genome knife's importance as a tool that allows genetic engineers to make these extremely precise mutations."Scientists need to create designed mutations to determine the function of specific genes," he explained. "Say we have a yeast that produces a wine with great flavor and we want to know why. We delete one gene, then another, until the distinctive flavor is gone, and we know we've isolated the gene responsible for that characteristic."The new technology also makes genetically modified organisms less objectionable, he said. "In the past, scientists have had to use antibiotic markers to indicate the spot of genetic alteration in an organism, and many persons objected to their use in foods because of the danger of developing antibiotic resistance. With the genome knife, we can cut the genome very precisely and efficiently so we don't have to use antibiotic markers to confirm a genetic event."The research was reported in a recent issue of
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March 10, 2015
https://www.sciencedaily.com/releases/2015/03/150310123357.htm
Microbial soil cleanup at Fukushima
Proteins from salt-loving, halophilic, microbes could be the key to cleaning up leaked radioactive strontium and caesium ions from the Fukushima Dai-ichi Nuclear Power Plant incident in Japan. The publication of the X-ray structure of a beta-lactamase enzyme from one such microbe, the halophile Chromohalobacter sp. 560, reveals it to have highly selective cesium binding sites.
A collaboration between researchers at the Japan Atomic Energy Agency in Tokai, Ibaraki, Kyushu Synchrotron Light Research Center in Saga, Kagoshima University, and Florida State University, Tallahassee, USA, has led to a 1.8 to 2.9 angstrom resolution structure for this enzyme. Anomalous X-ray diffraction also revealed binding sites in the protein for Sr2+ and Cs+ ions, the team reports.The team demonstrated how they could locate caesium ions in a specific site within the protein even in the presence of a nine-fold molar excess of sodium ions, which would normally out-compete any binding site. Intriguingly, the presence of strontium and caesium ions does not diminish the activity of the enzyme determined using isothermal titration calorimetry. "The observation of a selective and high-affinity caesium-binding site provides important information that is useful for the design of artificial caesium-binding sites that may be useful in the bioremediation of radioactive isotopes," the team explains.It is well known that proteins from halophilic bacteria have an abundance of acidic amino acids and so present an acidic surface that can interact with a range of metal ions. There are twelve types of such enzymes recorded in the Protein Data Bank that can bind to sodium, magnesium, potassium, calcium, iron, zinc, strontium and cadmium ions. Indeed, the presence of these materials in various enzymes is usually a prerequisite for their structure and functionality. Because of this metal affinity, the team reasoned that proteins from halophiles might be useful as molecular mops for separating precious metals from mixtures or in remediation when toxic metals ions must be extracted selectively from a site. More specifically, the proteins could act as models for artificial reagents to be used in this context.With respect to the Fukushima incident, the team explains that most of the radioactive caesium was deposited on the land at the site. Amounting to 2.4 petabequerels (PBq) of radioactivity and it is fixed in soil particles, comprising weathered biotite, a micaceous mineral found in many igneous and metamorphic rocks. Much of the soil has been removed, but the issue of extracting the radioactive elements for safe disposal has not been addressed. Moreover, the soil that remains at the site is also contaminated and no cost-effective method for extracting the caesium that leeches from it into the environment has been demonstrated.The team suggests that protein absorbents related to the beta-lactamase from Chromohalobacter might be designed using the techniques of synthetic biology, the most likely approach being to engineer a native protein to make the affinity site described by the team. The genes for such an agent might then be engineered into new breeds of plant that could be grown on the site. With the protein absorbents expressed in plant roots, caesium could be extracted from the soil efficiently, the plants harvested and their new radioactive cargo disposed of safely, leaving behind improved soil."Although the removal of caesium is an important theme for us, public acceptance for the use of genetically engineered plants is not strong enough here in Japan, so we are going to shift our theme for finding useful sites to gather other rare materials using engineered proteins derived from the structural information of the halophilic proteins," team member Ryota Kuroki said.
Genetically Modified
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March 7, 2015
https://www.sciencedaily.com/releases/2015/03/150307095940.htm
Experimental drug turns 'bad' white fat into 'good' brown-like fat
An experimental drug causes loss of weight and fat in mice, a new study has found. The study results will be presented Friday at the Endocrine Society's 97th annual meeting in San Diego.
Known as GC-1, the drug reportedly speeds up metabolism, or burning off, of fat cells."GC-1 dramatically increases the metabolic rate, essentially converting white fat, which stores excess calories and is associated with obesity and metabolic disease, into a fat like calorie-burning brown fat," said study author Kevin Phillips, PhD, a researcher at Houston Methodist Research Institute, Houston.Until several years ago, scientists thought that only animals and human infants have energy-burning, "good" brown fat."It is now clear," Phillips said, "that human adults do have brown fat, but appear to lose its calorie-burning activity over time."White adipose tissue, or fat, becomes a "metabolic villain," as Phillips called it, when the body has too much of it. Some published research shows that people who have more brown fat have a reduced risk of obesity and diabetes. Researchers are now working on ways to "brown" white fat, or convert it into brown fat.GC-1 works, according to Phillips, by activating the receptors for thyroid hormone, which play a role in regulating metabolism--the body's conversion of food into energy. Thyroid hormone receptors also help with adaptive thermogenesis, in which the body converts excess energy (calories and fat) to heat.Phillips said he and other researchers at Houston Methodist Research Institute have tested the drug in hundreds of mice, with partial research funding from the National Institutes of Health. Obese mice, both genetically obese and those with diet-induced obesity, received GC-1 treatment daily.Genetically obese mice lost weight and more than 50 percent of their fat mass in approximately two weeks, Phillips reported. Treated mice also showed antidiabetic effects, such as a sixfold improvement or better in insulin sensitivity (how well the body clears glucose from the bloodstream). He said mice with diet-induced obesity experienced similar improvements.The drug also induced adaptive thermogenesis in fat cells isolated from mice. Cells grown in culture in a dish, as well as tissue samples taken from obese mice, showed evidence of white-fat browning."Our data demonstrate that GC-1 is a novel fat-browning agent that may have use in the treatment of obesity and metabolic disease," Phillips said.The drug has not yet undergone testing for weight loss in humans. GC-1 is being tested in clinical trials for lowering cholesterol, under the name sobetirome. However, Phillips said the doses of sobetirome used in the cholesterol-lowering studies are much lower than what would be needed for weight loss.
Genetically Modified
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March 5, 2015
https://www.sciencedaily.com/releases/2015/03/150305152111.htm
How healthy is genetically modified soybean oil?
Soybean oil accounts for more than 90 percent of all the seed oil production in the United States. Genetically modified (GM) soybean oil, made from seeds of GM soybean plants, was recently introduced into the food supply on the premise that it is healthier than conventional soybean oil.
But is that premise true?Just barely, say scientists at the University of California, Riverside and their colleagues at UC Davis. The researchers compared the effects of both oils in experiments performed in the lab on mice. They found that the GM soybean oil is just as unhealthy as regular soybean oil in that it also induces obesity, diabetes and fatty liver. GM soybean oil does, however, have one advantage: it does not cause insulin resistance -- the inability to efficiently use the hormone insulin."While genetic modification of crops can introduce new beneficial traits into existing crops, the resulting products need to be tested for long-term health effects before making assumptions about their impact on human health," said senior investigator Frances Sladek, a professor of cell biology and neuroscience at UC Riverside.Study results will be presented tomorrow, March 6, at the Endocrine Society's 97Naturally high in unsaturated fats, vegetable oils were once thought to be healthy, and were hydrogenated to increase their shelf-life and temperature stability. The hydrogenation, however, generated Soybean oil, the most common vegetable oil used in the United States, contains about 55 percent linoleic acid, a polyunsaturated fat."Our previous results on mice showed that replacing some of the fat in a diet high in saturated fats from coconut oil with soybean oil -- to achieve a level common in the American diet -- causes significantly more weight gain, adiposity, diabetes and insulin resistance than in mice fed just the high-fat coconut oil diet," Sladek said.To determine whether linoleic acid was responsible for the metabolic effects of soybean oil, the researchers designed a parallel diet in which regular soybean oil was replaced, on a per gram basis, with GM soybean oil. The GM soybean oil has a fatty acid composition (low linoleic acid) similar to that of olive oil. The GM plants were developed by DuPont to reduce "The GM soybean oil has 0 grams Deol and the rest of the research team found to their surprise that the parallel diet containing GM soybean oil induced weight gain and fatty liver essentially identical to that of a diet with regular soybean oil, with the exception that the mice remained insulin sensitive and had somewhat less adipose (fat) tissue."These results indicate that linoleic acid may contribute to insulin resistance and adiposity but that another as yet unidentified component of the soybean oil affects the liver and overall weight gain," Deol said.In their experiments, the researchers gave four groups of mice different diets for 24 weeks. Each group was comprised of 12 mice. The control group received a low-fat diet (5 percent of daily calories from fat). The other groups received a diet with 40 percent of daily calories from fat, an amount common in the American diet. One diet was high in saturated fat from coconut oil, and one had 41 percent of the saturated fat replaced with regular soybean oil. The fourth group had 41 percent of the saturated fat replaced with the GM soybean oil. The body weights, food intake, glucose tolerance and insulin sensitivity of all the mice were tracked.What the researchers found was that mice fed a diet with either of the soybean oils had worse fatty liver, glucose intolerance and obesity than the group that got all their fat from coconut oil. But the mice whose diet included the GM soybean oil had less fat tissue than the animals that ingested regular soybean oil. These mice weighed about 30 percent more than the controls that ate a low-fat diet, while the group on the diet containing regular soybean oil weighed 38 percent more than controls. The mice on the diet that was primarily coconut oil weighed only about 13 percent more than controls. Unlike the diet with regular soybean oil, the diet with the new GM soybean oil did not lead to insulin resistance."While the GM soybean oil may have fewer negative metabolic consequences than regular soybean oil, it may not necessarily be as healthy as olive oil, as has been assumed by its fatty acid composition, and it is certainly less healthy than coconut oil which is primarily saturated fat," Sladek said. "It is important to understand the metabolic effects and health impact of the GM soybean oil before it is widely adopted as a healthier alternative to regular soybean oil. It is equally important to understand the health effects of regular soybean oil, which is ubiquitous in the American diet and seems to be much more detrimental to metabolic health than saturated fat."Sladek and Deol were joined in the research by Jane R. Evans, Antonia Rizo and Cynthia Perez at UCR; and Johannes Fahrmann, Dimitry Grapov, Jun Yang and Oliver Fiehn at UC Davis who performed extensive analysis on the liver and blood samples from these mice."To our knowledge this is the first in-depth analysis of the metabolic effects of GM soybean oil, and the first metabolomics analysis comparing soybean oil -- regular and GM -- to coconut oil," Deol said.
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March 4, 2015
https://www.sciencedaily.com/releases/2015/03/150304124137.htm
Dog DNA tests alone not enough for healthy pedigree, experts say
Breeding dogs on the basis of a single genetic test carries risks and may not improve the health of pedigree lines, experts warn.
Only a combined approach that makes use of DNA analysis, health screening schemes and pedigree information will significantly reduce the frequency of inherited diseases.This approach will also improve genetic diversity, which helps to counteract the risk of disorders, researchers say.Scientists at the University of Edinburgh's Roslin Institute made the recommendations having reviewed the various approaches that are being taken to minimise potential defects in pedigree animals.Pedigree dog breeds are created for desirable physical and behavioural characteristics, which often stem from breeding between closed familial lines over years and -- in some cases -- centuries.This approach means that inherited diseases can become more common in pedigree populations. Around half of all King Charles Cavalier Spaniels, for instance, are affected by an inherited heart murmur that can be life-threatening.Health screening dogs before selecting animals to breed from has already helped to reduce the prevalence of some diseases, such as floating knee-cap in the Dutch Kooiker breed.DNA tests are now available to help identify dogs carrying gene mutations that are known to cause some severe illnesses. It is hoped that this technology will help to eliminate disease-causing genes from pedigree lines.But ruling out breeding dogs solely on the basis of a single failed DNA test result will reduce the gene pool of pedigree lines and make inbreeding more common, researchers say. It could also inadvertently increase the prevalence of other genetic diseases which have not been tested for.The researchers recommend limiting the use of individual stud dogs to promote more diversity in pedigree lines.They also recommend cross-breeding to introduce even greater genetic diversity. Breeding the offspring that result from cross-breeding with the original pedigree for ten generations can produce animals that share 99.9 per cent of their genetic material with purebred animals, but that lack the gene faults that cause disease.This approach has been successful in generating Dalmatians lacking a genetic defect that causes kidney stones, which is common in the breed.Dr Lindsay Farrell, of The Roslin Institute, said: "Although carrying a specific genetic variant may raise the likelihood that an animal will suffer from the associated disease, it is not guaranteed. When making breeding decisions, genetic testing needs to be considered alongside health screening and family history. That will help to keep as much genetic diversity as possible in our pedigree dogs and, at the same time, reduce the prevalence of inherited diseases."Professor Kim Summers, of The Roslin Institute, said: "Breeders are keen to embrace DNA testing to improve the health of their breed. We need to make sure that these powerful technologies are used to best advantage."
Genetically Modified
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March 2, 2015
https://www.sciencedaily.com/releases/2015/03/150302123253.htm
Genetically speaking, mammals are more like their fathers
You might resemble or act more like your mother, but a novel research study from UNC School of Medicine researchers reveals that mammals are genetically more like their dads. Specifically, the research shows that although we inherit equal amounts of genetic mutations from our parents -- the mutations that make us who we are and not some other person -- we actually "use" more of the DNA that we inherit from our dads.
The research, published in the journal "This is an exceptional new research finding that opens the door to an entirely new area of exploration in human genetics," said Fernando Pardo-Manuel de Villena, PhD, professor of genetics and senior author of the paper. "We've known that there are 95 genes that are subject to this parent-of-origin effect. They're called imprinted genes, and they can play roles in diseases, depending on whether the genetic mutation came from the father or the mother. Now we've found that in addition to them, there are thousands of other genes that have a novel parent-of-origin effect."These genetic mutations that are handed down from parents show up in many common but complex diseases that involve many genes, such as type-2 diabetes, heart disease, schizophrenia, obesity, and cancers. Studying them in genetically diverse mouse models that take parent-of-origin into account will give scientists more precise insights into the underlying causes of disease and the creation of therapeutics or other interventions.The key to this research is the Collaborative Cross -- the most genetically diverse mouse population in the world, which is generated, housed, and distributed from UNC. Traditional lab mice are much more limited in their genetic diversity, and so they have limited use in studies that try to home in on important aspects of diseases in humans. The Collaborative Cross bred together various wild type mice to create wide diversity in the mouse genome. Pardo-Manuel de Villena said that this diversity is comparable to the variation found in the human genome. This helps scientists study diseases that involve various levels of genetic expression across many different genes.Gene expression connects DNA to proteins, which then carry out various functions inside cells. This process is crucial for proper human health. Mutations that alter gene expression are called regulatory mutations."This type of genetic variation is probably the most important contributor -- not to simple Mendelian diseases where there's just one gene mutation [such as cystic fibrosis] -- but to much more common and complex diseases, such as diabetes, heart disease, neurological conditions, and a host of others," Pardo-Manuel de Villena said. "These diseases are driven by gene expression, not of one gene but of hundreds or thousands of genes."The Collaborative Cross and the expertise we have at UNC allow us to look at different gene expression for every gene in the genome of every kind of tissue," said Pardo-Manuel de Villena, who directs the Collaborative Cross.For the "We found that the vast majority of genes -- about 80 percent -- possessed variants that altered gene expression," Crowley said. "And this was when we discovered a new, genome-wide expression imbalance in favor of the dad in several hundred genes. This imbalance resulted in offspring whose brain gene expression was significantly more like their father's."For every gene a scientist is interested in, Pardo-Manuel de Villena's team can create mice that have low, intermediate, or high expression of genes. And they can explore if that expression is associated with a specific disease."This expression level is dependent on the mother or the father," Pardo-Manuel de Villena said. "We now know that mammals express more genetic variance from the father. So imagine that a certain kind of mutation is bad. If inherited from the mother, the gene wouldn't be expressed as much as it would be if it were inherited from the father. So, the same bad mutation would have different consequences in disease if it were inherited from the mother or from the father."These types of genetic mutations across hundreds of genes are hard to study and a major bottleneck to realizing the promises of the post-genome era. But Pardo-Manuel de Villena said, "Thanks to the Collaborative Cross, the mouse can be used to model how these genes work and how they impact health and disease in any kind of tissue in the body."
Genetically Modified
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March 2, 2015
https://www.sciencedaily.com/releases/2015/03/150302071014.htm
Enhancing high-temperature tolerance in plants: Effective on rice and tomatoes
A research group at the Kobe University Graduate School of Agricultural Science Functional Phytochemistry Laboratory has identified for the first time that the (
Plants essentially have a high-temperature resistance function. It is switched off during normal conditions. However, it is switched on during periods of high temperature. The study started out by hypothesizing that if the signal chemicals in plants that switchs the function on could be identified, then plants' stress response to high temperature could be artificially controlled.It is known that some plants' high-temperature resistance function is also switched on when oxidative treatment is applied. The study group assumed that a chemical compound, generated through oxidation of fatty acids in plants by reactive oxygen, triggers the switch. Through their experiments, the group has identified that the (Acquired thermotolerance in plants in a non-genetically modified way. It will be easier for this method to find acceptance in Japan where consumers are less accepting of genetically-modified crops.Since the (The effects of the (A patent for the work was issued in September, 2014.
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February 26, 2015
https://www.sciencedaily.com/releases/2015/02/150226144859.htm
Fighting Colorado potato beetle with RNA interference
Colorado potato beetles are a dreaded pest of potatoes all over the world. Since they do not have natural enemies in most potato producing regions, farmers try to control them with pesticides. However, this strategy is often ineffective because the pest has developed resistances against nearly all insecticides. Now, scientists from the Max Planck Institutes of Molecular Plant Physiology in Potsdam-Golm and Chemical Ecology in Jena have shown that potato plants can be protected from herbivory using RNA interference (RNAi). They genetically modified plants to enable their chloroplasts to accumulate double-stranded RNAs (dsRNAs) targeted against essential beetle genes. (
RNA interference (RNAi) is a type of gene regulation that naturally occurs in eukaryotes. In plants, fungi and insects it also is used for protection against certain viruses. During infection, many viral pathogens transfer their genetic information into the host cells as double-stranded RNA (dsRNA). Replication of viral RNA leads to high amounts of dsRNA which is recognized by the host's RNAi system and chopped up into smaller RNA fragments, called siRNAs (small interfering RNAs). The cell then uses siRNAs to detect and destroy the foreign RNA.But the RNAi mechanism can also be exploited to knock down any desired gene, by tailoring dsRNA to target the gene's messenger RNA (mRNA). When the targeted mRNA is destroyed, synthesis of the encoded protein will be diminished or blocked completely. Targeting an essential gene of a crop pest can turn dsRNA into a precise and potent insecticide.Some crop plants have recently been engineered by modifying their nuclear genomes to produce dsRNA against certain insects. "This never resulted in full protection from herbivory," says Ralph Bock of the Max Planck Institute of Molecular Plant Physiology, "because the plant's own RNAi system prevents the accumulation of sufficient amounts of dsRNA. We wanted to circumvent this problem by producing dsRNA in the chloroplasts instead." These organelles, which perform photosynthesis in green plants, are descendants of formerly free-living cyanobacteria, which are prokaryotes that lack an RNAi system. Presuming that chloroplasts would accumulate high amounts of dsRNA, the scientists in Ralph Bock's group decided to generate so-called transplastomic plants. In such plants, the chloroplast genome is the target of genetic modification instead of the nuclear genome.To test this system on a real insect pest, the scientists chose the Colorado potato beetle. This little striped beetle was introduced into Europe accidentally at the end of the 19th century. Nowadays, it is a worldwide pest and can cause massive damage in agriculture. Besides potato leaves the adult beetle and its larvae also feed on other nightshade crops, like tomato, bell pepper and tobacco. The pest is difficult to control because of the widespread occurrence of insecticide resistance. "By using chloroplast transformation we generated potato plants that accumulate high amounts of long stable dsRNAs targeting essential genes in the beetle," says Ralph Bock.The efficacy of the dsRNAs as an insecticide was tested at the Max Planck Institute for Chemical Ecology in Jena. Larvae were fed on detached potato leaves and the mortality was monitored for nine days. The leaves were taken from transplastomic dsRNA plants, conventional transgenic dsRNA plants with a modified nuclear genome, and unmodified plants. For comparison, dsRNAs targeting two different genes were tested. "Transplastomic leaves producing dsRNA against the actin gene caused a mortality rate of 100% after five days of feeding," says Sher Afzal Khan from Jena. The actin gene encodes a structural protein that is essential for cell integrity. In contrast, plants with a modified nuclear genome expressed much less dsRNA and only slightly slowed down the beetles' growth.These recent results show that changing the target of transformation from the nuclear genome to the chloroplast genome overcomes the major hurdle towards exploiting RNAi for crop protection. As many insect pests increasingly develop resistances against chemical pesticides and Bt toxins, RNAi represents a promising strategy for pest control. This technology allows for precise protection without chemicals and without production of foreign proteins in the plant.
Genetically Modified
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February 26, 2015
https://www.sciencedaily.com/releases/2015/02/150226141412.htm
Living in genetic comfort zone: How to avoid influence of genetic variation
The phenotype of organisms is shaped by the interaction between environmental factors and their genetic constitution. A recent study by a team of population geneticists at the Vetmeduni Vienna shows that fruit flies live in a sort of genetic comfort zone at a specific temperature. The scientists found that, despite their underlying genetic differences, two separate strains of flies had a very similar gene expression pattern at 18°C. This effect of 'canalization', which has also been described in humans, allows organisms to continue to grow and develop stable even in the face of genetic and environmental stress. The results were published in the journal PLOS Genetics.
The information encoded in the DNA of an organism is not sufficient to determine the expression pattern of genes. This fact has been known even before the discovery of epigenetics, which refers to external modifications to the DNA that turn genes "on" or "off." These modifications do not change the DNA sequence, but instead, they affect how genes are expressed. Another, less known mechanism called canalization keeps organisms robust despite genetic mutations and environmental stressors. If an organism experiences environmental or genetic perturbations during its development, such as extreme living conditions or genetic mutations, canalization acts as a way of buffering these disturbances. The organism remains stable and can continue to develop without recognizable changes.Christian Schlötterer at the Institute of Population Genetics and his colleagues studied the mechanism of canalisation in fruit flies. The researchers subjected two genetically distinct strains of fruit flies, Oregon and Samarkand, to different temperatures (13°C, 18°C, 23°C and 29°C). Subsequently, they analysed the variation in gene expression in response to the different temperatures. The results revealed a homogenous pattern of gene expression among the two strains at 18°C. No matter whether the flies were from the Oregon or to the Samarkand strain, their gene expression was almost indistinguishable."The flies' genetic comfort zone appears to be located at 18°C. "As soon as the flies leave the comfort zone, move to either higher or lower temperatures, the gene expression of the two strains varies dramatically" Schlötterer explains.The effect of canalization was first described in 1942, when researchers pointed out that organisms remain stable in their external appearance despite different environmental circumstances or genetic mutations. This sort of developmental buffering helps to stabilize organismal growth."If an organism develops along the canalization pathway, or along the comfort zone, mutations can accumulate without being expressed. Once an organisms leaves the canalized range, those hidden genetic variations can be expressed and become visible. The phenomenon is called decanalization," Schlötterer explains.A publication by U.S. researcher Greg Gibson in the journal "Genetic information alone does not determine whether we stay healthy or not. It is the complex interaction of environmental conditions and genetic variation that needs to be considered," says Schlötterer.
Genetically Modified
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February 25, 2015
https://www.sciencedaily.com/releases/2015/02/150225132251.htm
Regulating genome-edited crops that (according to current regulations) aren't GMOs
A survey of rice, wheat, barley, fruit, and vegetable crops found that most mutants created by advanced genetic engineering techniques may be out of the scope of current genetically modified organism (GMO) regulations. In a review of these findings, published in the February 25 issue of the Cell Press journal
"Modern genome editing technology has allowed for far more efficient gene modification, potentially impacting future agriculture," says Tetsuya Ishii, PhD, of Hokkaido University's Office of Health and Safety. "However, genome editing raises a regulatory issue by creating indistinct boundaries in GMO regulations because the advanced genetic engineering can, without introducing new genetic material, make a gene modification which is similar to a naturally occurring mutation."Under current regulations, a GMO is a living organism that has been altered by a novel combination of genetic material, including the introduction of a transgene. Advanced genetic engineering technologies, including ZFN, TALEN, and CRISPR/Cas9, raise regulatory issues because they don't require transgenes to make alterations to the genome. They can simply pluck out a short DNA sequence or add a mutation to an existing gene."Genome editing technology is advancing rapidly; therefore it is timely to review the regulatory system for plant breeding by genome editing," says Dr. Ishii. "Moreover, we need to clarify the differences between older genetic engineering techniques and modern genome editing, and shed light on various issues towards social acceptance of genome edited crops."In their study, Dr. Ishii and a member of his research staff, Motoko Araki, present four regulatory models in order to resolve the indistinct regulatory boundaries that genome editing has created in GMO regulations. They propose that the most stringent regulation (in which most of the mutants are subject to the regulations, whereas only a portion of deletion and insertion mutants fall outside the regulations) should be initially adopted and gradually relaxed because the cultivation and food consumption of genome-edited crops is likely to increase in the near future.While policy-level discussions about the regulations of genome-edited organisms are slowly taking place around the world, according to Dr. Ishii, his study will serve as a basis for the conversation with regulatory agencies in the world as well as the Japanese Ministry of the Environment.
Genetically Modified
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February 24, 2015
https://www.sciencedaily.com/releases/2015/02/150224182531.htm
Tissue engineering: Scientists grow leg muscle from cells in a dish
A team of researchers from Italy, Israel and the United Kingdom has succeeded in generating mature, functional skeletal muscles in mice using a new approach for tissue engineering. The scientists grew a leg muscle starting from engineered cells cultured in a dish to produce a graft. The subsequent graft was implanted close to a normal, contracting skeletal muscle where the new muscle was nurtured and grown. In time, the method could allow for patient-specific treatments for a large number of muscle disorders.
The results are published in The scientists used muscle precursor cells -- mesoangioblasts -- grown in the presence of a hydrogel (support matrix) in a tissue culture dish. The cells were also genetically modified to produce a growth factor that stimulates blood vessel and nerve growth from the host. Cells engineered in this way express a protein growth factor that attracts other essential cells that give rise to the blood vessels and nerves of the host, contributing to the survival and maturation of newly formed muscle fibres. After the graft was implanted onto the surface of the skeletal muscle underneath the skin of the mouse, mature muscle fibres formed a complete and functional muscle within several weeks. Replacing a damaged muscle with the graft also resulted in a functional artificial muscle very similar to a normal Tissue engineering of skeletal muscle is a significant challenge but has considerable potential for the treatment of the various types of irreversible damage to muscle that occur in diseases like Duchenne muscular dystrophy. So far, attempts to re-create a functional muscle either outside or directly inside the body have been unsuccessful. "The morphology and the structural organisation of the artificial organ are extremely similar to if not indistinguishable from a natural skeletal muscle," says Cesare Gargioli of the University of Rome, one of the lead authors of the study.In future, irreversibly damaged muscles could be restored by implanting the patient's own cells within the hydrogel matrix on top of a residual muscle, adjacent to the damaged area. "While we are encouraged by the success of our work in growing a complete intact and functional mouse leg muscle we emphasize that a mouse muscle is very small and scaling up the process for patients may require significant additional work," comments EMBO Member Giulio Cossu, one of the authors of the study. The next step in the work will be to use larger animal models to test the efficacy of this approach before starting clinical studies.
Genetically Modified
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February 19, 2015
https://www.sciencedaily.com/releases/2015/02/150219160514.htm
Gene may help reduce GM contamination
Genetically modified crops have long drawn fire from opponents worried about potential contamination of conventional crops and other plants. Now a plant gene discovered by University of Guelph scientists might help farmers reduce the risk of GM contamination and quell arguments against the use of transgenic food crops, says Sherif Sherif, lead author of a new research paper describing the findings.
This is believed to be the first-ever study to identify a gene involved in altering fruit trees that normally cross-pollinate -- needing one plant to fertilize another -- into self-pollinators, said Sherif.The paper was published recently in the journal Sherif said researchers might one day insert this gene into GM crops to prevent their pollen from reaching other plants.Plant agriculture professor Jay Subramanian, Sherif's PhD supervisor and a co-author on the paper, said: "There are a lot of transgenic crops worldwide. There is concern about pollen from them being able to fertilize something in the wild population, thus creating 'super weeds.'"The researchers found a gene making a protein that naturally allows a small handful of plants to self-pollinate and make fruit before the flower opens. Peaches, for example, have closed flowers, unlike their showy-flowered plum and cherry cousins that need pollen from another tree to fertilize and set fruit.Subramanian studies tree fruits at the Vineland Research and Innovation Centre in Vineland, Ont. Sherif worked with him on studies of plant responses to stresses such as drought or disease.Other co-authors on the paper are Guelph professors Jaideep Mathur, Department of Molecular and Cellular Biology and Gopi Paliyath, Department of Plant Agiruclture, along with Islam El-Sharkawy, a former research associate with Subramanian; and colleagues at the National University of Singapore.Besides aiding crop farmers and food producers, their discovery might be a boon to perfume-makers, said Subramanian.Used in fragrant perennials such as jasmine, the gene might keep flowers closed and allow growers to collect more of the aromatic compounds prized by perfume-makers. "That's when volatile compounds are peaking," said Subramanian. "When the flower opens, you lose almost 80 per cent of those volatiles."Most plants develop open flowers to attract pollinators, but it takes energy to make flowers as well as nectar and pollen. Subramanian said plants with closed flowers -- called cleistogamous, or Greek for "closed marriage" -- might have developed in environments lacking pollinators or under adverse conditions."This is the first time we know of that someone has shown that, using molecular tools, you can induce cleistogamy in plants," he said.
Genetically Modified
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February 16, 2015
https://www.sciencedaily.com/releases/2015/02/150216125425.htm
Mothers can pass traits to offspring through bacteria's DNA, mouse study shows
It's a firmly established fact straight from Biology 101: Traits such as eye color and height are passed from one generation to the next through the parents' DNA.
But now, a new study in mice by researchers at Washington University School of Medicine in St. Louis has shown that the DNA of bacteria that live in the body can pass a trait to offspring in a way similar to the parents' own DNA. According to the authors, the discovery means scientists need to consider a significant new factor -- the DNA of microbes passed from mother to child -- in their efforts to understand how genes influence illness and health.The study appears online Feb. 16 in "We have kept bacteria on one side of a line separating the factors that shape our development -- the environmental side of that line, not the genetic side," said co-senior author Herbert W. Virgin IV, MD, PhD. "But our results show bacteria stepping over the line. This suggests we may need to substantially expand our thinking about their contributions, and perhaps the contributions of other microorganisms, to genetics and heredity."Bacteria are most familiar through their roles in harmful infections. But scientists have realized that such bacteria are only a tiny fraction of the bacterial communities that live in and on our bodies. Most bacteria are commensal, which means they do not cause harm and often confer benefits.Commensal bacteria influence traits such as weight and behavior. But until now, researchers thought the bacteria that exerted these effects were acquired during a person's life. The study is the first to show that bacterial DNA can pass from parent to offspring in a manner that affects specific traits such as immunity and inflammation.The researchers linked commensal bacteria in mice to the animals' susceptibility to a gut injury. Mice with certain inherited bacteria are susceptible to the injury, which is caused by exposure to a chemical. Female mice pass the bacteria to their offspring, making them vulnerable to the injury. Others carrying different bacteria are less susceptible.In the short term, the findings may help scientists eliminate a significant "bug" in studies of genetically engineered mice. In several fields of research, scientists have been confronted intermittently with the sudden, unexplained appearance of new or altered traits in mice. The traits often spread from one mouse habitat to the next, suggesting a spreading microbial infection is responsible. But the traits also consistently pass from mother to offspring, suggesting a genetic cause.Thaddeus Stappenbeck, MD, PhD, a professor of pathology and immunology, and co-senior author Virgin, the Edward Mallinckrodt Professor of Pathology and head of the Department of Pathology and Immunology, encountered this problem in their studies of inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis. They were surprised to find that roughly half their mice had low levels in the gut of IgA, an antibody linked to these disorders.IgA helps defend the body against harmful invaders. It is commonly present in mucus made by the body in areas where the exterior world encounters the body's interior, such as the eyes, nose, throat and gut.When the scientists housed mice with low levels of the antibody with mice that had high levels of the antibody, all of the mice ended up with low antibody levels in a few weeks. When they bred the mice, the offspring whose mothers had low levels of the antibody also had low levels.Eventually, the scientists learned that one of the culprits likely responsible for the spread of low antibody levels is a bacterium called Sutterella. This bacterium and others found in the low-IgA mice could explain both ways that decreased antibody levels were spreading: Mice that were housed together acquired low antibody levels through normal spread of the bacteria, and mouse mothers passed the same bacteria to their descendants.The latter explanation involves a major change in thinking because it suggests that traits affected by bacteria can pass from mothers to their offspring in the same manner as traits affected by mouse DNA.To prove that this change in antibody levels represented a significant change in the mice that could be thought of as a trait, the researchers fed the mice a chemical they use to characterize the gut's response to injury as part of their studies of inflammatory bowel diseases. In mice with low levels of the antibody, the compound caused much more damage."The implications for mouse experiments are profound and could help us cut through some persistent sources of confusion," Stappenbeck said. "When we study mice, we have to account for the possibility that inherited bacteria and their genes could be influencing the trait we're trying to learn about."According to Stappenbeck, one way to do this will be to stop housing experimental and control mice in separate colonies. This would help ensure that any inherited microbes that influence a trait of interest are present in both groups.In the long term, Virgin expects the expanded model of heredity to produce a more complicated but also much more insightful picture of how human, bacterial and viral genes influence human health.This work was supported by the National Institutes of Health (NIH), grants AI08488702, T32AI007163, T32CA009547, and the William M. Keck Foundation.
Genetically Modified
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February 12, 2015
https://www.sciencedaily.com/releases/2015/02/150212131645.htm
A new model organism for aging research: The short-lived African killifish
Studying aging and its associated diseases has been challenging because existing vertebrate models (e.g., mice) are relatively long lived, while short-lived invertebrate species (e.g., yeast and worms) lack key features present in humans. Stanford University scientists have found a new middle ground with the development of a genome-editing toolkit to study aging in the naturally short-lived African turquoise killifish. The investigators hope these fish will be a valuable new model for understanding, preventing, and treating the diseases of old age. They present their work in the February 12 issue of
African turquoise killifish live in temporary ponds of water in Zimbabwe and Mozambique that disappear with the dry season. Consequently, unlike their counterparts in more permanent bodies of water, they have evolved a short lifespan of only 4-6 months, making them excellent candidate organisms for studying aging. However, until now, few genetic tools were available for studying them.Taking advantage of recently developed CRISPR/Cas-based genome editing techniques, the researchers generated the platform needed for the killifish to be used experimentally. "This means knowing the ensemble of its genes and being able to manipulate or mutate them in a variety of ways to better understand aging and diseases of old age," says senior author Dr. Anne Brunet, professor of genetics at Stanford School of Medicine, who has made the genetically engineered fish available to the entire research community.Some of the killifish mutants have already shown promise for studying aging and disease. "One of our killifish mutants recapitulates, but in a rapid manner, a human disease called Dyskeratosis congenita, which is due to deficits in a complex involved in maintaining the end of chromosomes, or telomeres," says lead author Dr. Itamar Harel, a postdoctoral research fellow in genetics. "These killifish mutants, like their human counterparts, have defects in blood, gut, and display fertility problems."Now that the team has generated the tools necessary to rapidly manipulate killifish, the model organism can be used to screen for genes and drugs that slow or reverse aging and age-related diseases."Understanding how the genome encodes for complex characteristics like lifespan is one of the biggest challenges of modern biology," Dr. Brunet notes. "This model system and the tools and resources we have created can help tackle this challenge."
Genetically Modified
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February 11, 2015
https://www.sciencedaily.com/releases/2015/02/150211083202.htm
The first kobuviruses described from Africa
An international team of researchers led by scientists at the German Leibniz Institute for Zoo and Wildlife Research (IZW) genetically describe the first kobuviruses to be reported from Africa. The results show that the viruses are less host-specific than previously assumed. The study has been published in the scientific journal
Current knowledge of the recently described genus Kobuvirus is limited. In humans and livestock, kobuviruses are known to cause gastroenteritis and hence are important for both health and economic reasons. To date, canine kobuvirus is known to infect domestic dogs in Europe, the USA and Asia. Before the current study, the only wild carnivore known to be infected with canine kobuvirus was the red fox in Europe, and Kobuvirus infection had not been reported from Africa.A team of researchers from the Tanzanian Wildlife Research Institute, the Ecosystem Alliance (USA) and the IZW investigated Kobuvirus infection in wild carnivores in the Serengeti National Park (NP) in Tanzania, East Africa, and in domestic dogs living in villages outside the park. Using state-of-the-art molecular techniques, the scientists were able to provide the complete Kobuvirus genome from three wild carnivore species, the spotted hyena, the side-striped jackal and golden jackal, and the local domestic dog.These species were infected with canine kobuvirus strains genetically distinct from those in geographical regions outside Africa. Interestingly, the strains infecting wild carnivores inside the Serengeti NP were genetically distinct from those infecting domestic dogs outside the park, and genetically distinct strains were detected in domestic dogs from different villages. By demonstrating for the first time canine kobuvirus in a non-canid host, the spotted hyena, the results of the study provide evidence that kobuviruses are less host-specific than previously thought.
Genetically Modified
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February 10, 2015
https://www.sciencedaily.com/releases/2015/02/150210142008.htm
Epigenetic breakthrough: A first of its kind tool to study the histone code
University of North Carolina scientists have created a new research tool, based on the fruit fly, to help crack the histone code. This research tool can be used to better understand the function of histone proteins, which play critical roles in the regulation of gene expression in animals and plants.
This work, published in the journal "People think cancer is a disease of uncontrolled proliferation, but that's just one aspect of it," said Robert Duronio, PhD, professor of biology and genetics and co-senior author. "Cancer is actually a disease of development in which the cells don't maintain their proper functions; they don't do what they're supposed to be doing." Somehow, the gene regulation responsible for proper cell development goes awry.One aspect of gene regulation involves enzymes placing chemical tags or modifications on histone proteins -- which control a cell's access to the DNA sequences that make up a gene. Properly regulated access allows cells to develop, function, and proliferate normally. The chemical modification of histones is thought to be a form of epigenetic information -- information separate from our DNA -- that controls gene regulation. This idea is based on the study of the enzymes that chemically modify histones. However, there is a flaw in this argument."In complex organisms, such as fruit flies, mice, and humans, scientists have only been able to This is crucial because therapies, such as cancer drugs, can target histones. With this new research tool, scientists will be able to better study thousands of enzyme-histone interactions important for human health."If you think of the genome as a recipe book, then you could say we've made it possible to know that there are hidden ingredients that help explain how specific recipes turn out correctly or not," said Greg Matera, PhD, professor of biology and genetics and co-senior author of the paper. "That's the first step in scientific discovery -- knowing that there are things we need to look for and then searching for them."Before now, a lot of this epigenetic research had been done in yeast -- single cell organisms that also use enzymes to lay chemical tags on histone proteins. This work has yielded many interesting findings and has led to the development of therapeutics. But some of this work has led to an oversimplification of human biology, leaving many questions about human health unanswered.For instance, in complex organisms, enzymes in cells typically do more than one thing. One likely reason for this is that animals undergo cellular differentiation; human life begins as a single cell that differentiates into the various cell types needed for different organs, body parts, blood, the immune system, etc. This differentiation has to be maintained throughout life."Because of this, animals likely have a greater requirement for epigenetic regulation than yeast do," Matera said. "Animal cells have to 'remember' that they must express genes in specific ways." When cancer cells start dividing rapidly to form tumors, these cells are actually reverting to an earlier time in their development when they were supposed to divide rapidly. The gene regulation that was supposed to rein them in has gone haywire.Whereas in yeast, a histone-modifying enzyme might have a single regulatory task, the human version of that same enzyme might have other regulatory tasks that involve additional proteins."In fact, maybe the really critical target of that one modifying enzyme is some other protein that we don't know about yet," Matera said. "And we need to know about it."The best way to figure that out would be to make it impossible for the enzyme to modify a histone by changing -- or mutating -- the histone protein. If a histone protein could be disabled in this way and cells still behaved normally, then that would mean there was some other protein that the enzyme acted on. To do this, however, would require replacing a histone gene with a genetically engineered one that could not be modified by an enzyme.The problem is that in animals, such as mice and humans, there are many histone genes and they are scattered throughout the genome. This makes replacing them with 'designer' histone genes difficult. In addition, other genes are located in between the histone genes. Therefore, deleting the portion of the chromosome with histone genes in order to replace them with a modified one would wind up deleting other genes vital for survival. This would make such an approach in, say, a mouse, useless."It has been technically impossible to do this kind of research in complex organisms," Duronio said. "But fruit flies have all their histone genes in one place on the chromosome; this makes it feasible to delete the normal genes and replace them with designer genes."Matera, Duronio, and McKay led an effort to delete the histone genes in fruit flies and replace them with specific designer histone genes they created. These new genes were created so they could not be the repositories of epigenetic tags or modifications. That is, the modifying enzyme would not be able to do its job on As shown in the Previously, in mammalian cells, other researchers had discovered that when you mutate a specific modifying enzyme, the result is death because the cells can't replicate.With their new fruit fly research model, the UNC researchers altered the histone gene so that this particular enzyme could not modify its histone protein target. The result was not death. In fact, the flies lived and flew as normal flies do. This meant that the enzyme, which was previously proven to be vital to life, must do something else very important."There must be another target for that modifying enzyme," Matera said. "There must be another hidden carrier of epigenetic information that we don't know about."McKay added, "This is a demonstration of the potential of our epigenetic platform. Going forward, we're going to do a lot more experiments to identify more discrepancies and hopefully other targets of these enzymes. We're on the ground floor of a long-term project."This research shows that the epigenetic recipe book for yeast is thin. The recipe book for humans, which is genetically akin to the one for fruit flies, is much thicker, more complex, and full of hidden ingredients scientists have yet to discover.Now, scientists have a tool to test the recipes.
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February 10, 2015
https://www.sciencedaily.com/releases/2015/02/150210130504.htm
Engineered insulin could offer better diabetes control
For patients with diabetes, insulin is critical to maintaining good health and normal blood-sugar levels. However, it's not an ideal solution because it can be difficult for patients to determine exactly how much insulin they need to prevent their blood sugar from swinging too high or too low.
MIT engineers hope to improve treatment for diabetes patients with a new type of engineered insulin. In tests in mice, the researchers showed that their modified insulin can circulate in the bloodstream for at least 10 hours, and that it responds rapidly to changes in blood-sugar levels. This could eliminate the need for patients to repeatedly monitor their blood sugar levels and inject insulin throughout the day."The real challenge is getting the right amount of insulin available when you need it, because if you have too little insulin your blood sugar goes up, and if you have too much, it can go dangerously low," says Daniel Anderson, the Samuel A. Goldblith Associate Professor in MIT's Department of Chemical Engineering, and a member of MIT's Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science. "Currently available insulins act independent of the sugar levels in the patient."Anderson and Robert Langer, the David H. Koch Institute Professor at MIT, are the senior authors of a paper describing the engineered insulin in this week's Patients with Type I diabetes lack insulin, which is normally produced by the pancreas and regulates metabolism by stimulating muscle and fat tissue to absorb glucose from the bloodstream. Insulin injections, which form the backbone of treatment for diabetes patients, can be deployed in different ways. Some people take a modified form called long-acting insulin, which stays in the bloodstream for up to 24 hours, to ensure there is always some present when needed. Other patients calculate how much they should inject based on how many calories they consume or how much sugar is present in their blood.The MIT team set out to create a new form of insulin that would not only circulate for a long time, but would be activated only when needed -- that is, when blood-sugar levels are too high. This would prevent patients' blood-sugar levels from becoming dangerously low, a condition known as hypoglycemia that can lead to shock and even death.To create this glucose-responsive insulin, the researchers first added a hydrophobic molecule called an aliphatic domain, which is a long chain of fatty molecules dangling from the insulin molecule. This helps the insulin circulate in the bloodstream longer, although the researchers do not yet know exactly why that is. One theory is that the fatty tail may bind to albumin, a protein found in the bloodstream, sequestering the insulin and preventing it from latching onto sugar molecules.The researchers also attached a chemical group called PBA, which can reversibly bind to glucose. When blood-glucose levels are high, the sugar binds to insulin and activates it, allowing the insulin to stimulate cells to absorb the excess sugar.The research team created four variants of the engineered molecule, each of which contained a PBA molecule with a different chemical modification, such as an atom of fluorine and nitrogen. They then tested these variants, along with regular insulin and long-acting insulin, in mice engineered to have an insulin deficiency.To compare each type of insulin, the researchers measured how the mice's blood-sugar levels responded to surges of glucose every few hours for 10 hours. They found that the engineered insulin containing PBA with fluorine worked the best: Mice that received that form of insulin showed the fastest response to blood-glucose spikes."The modified insulin was able to give more appropriate control of blood sugar than the unmodified insulin or the long-acting insulin," Anderson says.The new molecule represents a significant conceptual advance that could help scientists realize the decades-old goal of better controlling diabetes with a glucose-responsive insulin, says Michael Weiss, a professor of biochemistry and medicine at Case Western Reserve University."It would be a breathtaking advance in diabetes treatment if the Anderson/Langer technology could accomplish the translation of this idea into a routine treatment of diabetes," says Weiss, who was not part of the research team.Giving this type of insulin once a day instead of long-acting insulin could offer patients a better alternative that reduces their blood-sugar swings, which can cause health problems when they continue for years and decades, Anderson says. The researchers now plan to test this type of insulin in other animal models and are also working on tweaking the chemical composition of the insulin to make it even more responsive to blood-glucose levels."We're continuing to think about how we might further tune this to give improved performance so it's even safer and more efficacious," Anderson says.The research was funded by the Leona M. and Harry B. Helmsley Charitable Trust, the Tayebati Family Foundation, the National Institutes of Health, and the Juvenile Diabetes Research Foundation.
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February 10, 2015
https://www.sciencedaily.com/releases/2015/02/150210083541.htm
First humanized mouse model of Sjögren’s syndrome opens door to study other autoimmune diseases
Researchers at The Ohio State University have announced the development of the first chimeric mouse model of Sjögren's syndrome -- giving scientists an unprecedented look at the progression of the debilitating "dry eye" disease. Because the disease often doesn't respond to conventional immunosuppressive therapy, the model will also open the door for the development of new molecular-based, targeted drugs.
"While mouse models have existed for some time to study Sjögren's and other autoimmune diseases, an ideal model to use for early drug development was still lacking," said Nicholas Young, PhD, an immunologist with Ohio State's Wexner Medical Center who helped create and study the chimeric mice. "We're optimistic that the experimental platform resulting from this humanized mouse model will help jumpstart the creation of innovative therapies."The chimeric mouse is engineered by transplanting human cells to replicate the activity of Sjögren's syndrome (SjS), an autoimmune disease where out-of-control inflammatory cells from the immune system inexplicably destroy tear ducts and salivary glands, and impact the function of other organs.The research team hopes their new model will ultimately yield better insights and translate into more effective treatment options for the nearly 50 million Americans with some form of autoimmune disease.Mouse models help scientists understand the origins of human disease and help identify safe and effective treatments. Despite genetic and physiological similarities between mice and humans, there are enough differences that medical results seen in mice do not always translate over to humans. This can lead to unexpected side effects or a lack of efficacy once an experimental treatment reaches human testing."Let's face it, mice are not humans. We should not expect the drugs that are successful in treating mice to work identically in the human version of the same disease. Not surprisingly, many of them do not," said Young.Young is part of a team working under Wael Jarjour, MD, Director of Immunology and Rheumatology, that has been researching autoimmune diseases at Ohio State for the past 6 years. They saw an opportunity to fundamentally advance the conventional drug development process by creating a first-ever chimeric mouse model for Sjögren's.Named after the chimera of Greek mythology, chimeric mice are engineered to contain both genetically distinct human and mouse cells. The mice are immunological "blank slates" -- meaning their bodies don't react to the presence of human cells, but instead act as a surrogate allowing them to thrive, creating a mini-laboratory to study human cells in a living system. In the last decade, techniques and technology to create chimeric mice have advanced significantly, and they are used frequently in cancer studies, but not many other disease areas.In 2009, Jarjour and his research team were awarded a grant from The Medarva Foundation Fund (formerly known as the Richmond Eye and Ear Foundation Fund) to create this chimeric mouse model for Sjögren's.For the experiment, Young tapped into ResearchMatch, a research volunteer database supported by Ohio State's Center for Clinical and Translational Science, to collect peripheral blood mononuclear cells (PBMCs) from healthy volunteers or people with SjS. The research team then injected one set of mice with cells from people without SjS, and another group of mice with cells taken from people with the condition.While no difference was observed in the distribution of engrafted human cells, chimeric mice that were given PBMCs from SjS patients produced higher levels of cytokines, proteins associated with inflammation. Under a microscope, scientists could see that the inflammatory responses in the tear ducts and salivary glands of the SjS chimeras were also exaggerated."We showed that the organs in the SjS chimeric mice were selectively targeted, creating an ideal in vivo environment to test experimental therapeutics and investigate T-cell disease pathology," said Young. "While this system will allow us to conduct a much more accurate study of Sjögren's pathology, the versatility of this model is very exciting because it is applicable to other autoimmune disorders, including lupus."Lai-Chu Wu, DPhil, Associate Professor, Department of Molecular and Cellular Biochemistry and a collaborator on this project, added, "This chimeric mouse model also reveals intriguing therapeutic prospects that could lead to individualized patient care one day through the establishment of a fully functioning 'human' immune system."Young agrees, noting that it's only a matter of time before science figures out how to replicate the full range of the human immune response within a chimeric model -- and predicting that it will be a game-changer."Once that happens, the possibilities for testing and drug development would extend well beyond autoimmune disease and into just about every field of medicine," said Young.Nicholas Young is a Post-Doctoral Researcher at The Ohio State University Wexner Medical Center with the Department of Internal Medicine, Division of Immunology and Rheumatology. The study was published in the January issue of Clinical Immunology.Sjögrens syndrome is a common autoimmune disorder that typically attacks and progressively destroys moisture producing glands in the body, most commonly leading to dry eyes and mouth. Symptoms can develop slowly over several years, and the condition often goes undiagnosed, attributed instead to aging or other causes. Sjögren's syndrome affects about one percent of the United States population, and is one of the most prevalent autoimmune diseases in the country.
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February 4, 2015
https://www.sciencedaily.com/releases/2015/02/150204134119.htm
Scientists reprogram plants for drought tolerance
UC Riverside-led research in synthetic biology provides a strategy that has reprogrammed plants to consume less water after they are exposed to an agrochemical, opening new doors for crop improvement.
Crops and other plants are constantly faced with adverse environmental conditions, such as rising temperatures (2014 was the warmest year on record) and lessening fresh water supplies, which lower yield and cost farmers billions of dollars annually.Drought is a major environmental stress factor affecting plant growth and development. When plants encounter drought, they naturally produce abscisic acid (ABA), a stress hormone that inhibits plant growth and reduces water consumption. Specifically, the hormone turns on a receptor (special protein) in plants when it binds to the receptor like a hand fitting into a glove, resulting in beneficial changes -- such as the closing of guard cells on leaves, called stomata, to reduce water loss -- that help the plants survive.While it is true that crops could be sprayed with ABA to assist their survival during drought, ABA is costly to make, rapidly inactivated inside plant cells and light-sensitive, and has therefore failed to find much direct use in agriculture. Several research groups are working to develop synthetic ABA mimics to modulate drought tolerance, but once discovered these mimics are expected to face lengthy and costly development processes.The agrochemical mandipropamid, however, is already widely used in agricultural production to control late blight of fruit and vegetable crops. Could drought-threatened crops be engineered to respond to mandipropamid as if it were ABA, and thus enhance their survival during drought?Yes, according to a team of scientists, led by Sean Cutler at the University of California, Riverside.The researchers worked with The finding illustrates the power of synthetic biological approaches for manipulating crops and opens new doors for crop improvement that could benefit a growing world population."We successfully repurposed an agrochemical for a new application by genetically engineering a plant receptor -- something that has not been done before," said Cutler, an associate professor of botany and plant sciences. "We anticipate that this strategy of reprogramming plant responses using synthetic biology will allow other agrochemicals to control other useful traits -- such as disease resistance or growth rates, for example."Study results appear online Feb. 4 in Cutler explained that discovering a new chemical and then having it evaluated and approved for use is an extremely involved and expensive process that can take years."We have, in effect, circumvented this hurdle using synthetic biology -- in essence, we took something that already works in the real world and reprogrammed the plant so that the chemical could control water use," he said.Protein engineering is a method that enables the systematic construction of many protein variants; it also tests them for new properties. Cutler and his co-workers used protein engineering to create modified plant receptors into which mandipropamid could fit and potently cause receptor activation. The engineered receptor was introduced into
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February 2, 2015
https://www.sciencedaily.com/releases/2015/02/150202114547.htm
Engineers devise genetic 'on' switch made exclusively of RNA
All life processes depend on genes turning on and off. Cornell University scientists have created a new "on" switch to control gene expression -- a breakthrough that could revolutionize genetic engineering.
Synthetic biologists led by Julius Lucks, assistant professor of chemical and biomolecular engineering, have created a new genetic control mechanism made exclusively of ribonucleic acids (RNA). They call their engineered RNAs STARS -- Small Transcription Activating RNAs -- described online in "We've created a whole new toolset of regulation," said Lucks, who describes RNA as "the most engineerable molecule on the planet."RNA is a single-stranded version of its close cousin, DNA, which makes up the double-stranded genome of all living organisms. While DNA acts as nature's hard drive, storing the genes that make up our genome, RNA is part of the cellular computer that activates the hard drive by helping the cell tune the expression of specific genes, Lucks says. While RNA is known to do this in many ways, one thing it can't do in nature is start the process by turning on, or activating, transcription -- the first step in gene expression, and the core of many cellular programs.In the lab, Lucks and colleagues have assigned RNA this new role. They've engineered an RNA system that acts like a genetic switch, in which RNA tells the cell to activate the transcription of a specific gene. The STAR system involves placing a special RNA sequence upstream of a target gene that acts as a blockade and prevents the cell from transcribing that gene. When the STAR is present, it removes this blockade, turning on the downstream gene by allowing transcription to take place. The effect is like a lock-and-key system for turning genes on, with STARs acting as a set of genetic keys for unlocking cellular genetic programs."RNA is like a molecular puzzle, a crazy Rubik's cube that has to be unlocked in order to do different things," Lucks said. "We've figured out how to design another RNA that unlocks part of that puzzle. The STAR is the key to that lock."RNA is Lucks' favorite molecule because it's simple -- much simpler than a protein -- and its function can be engineered by designing its structure. In fact, new experimental and computational technologies, some developed by Lucks' lab, are now giving quick access to their structures and functions, enabling a new era of biomolecular design that is much more difficult to do with proteins.Lucks envisions RNA-only, LEGO-like genetic circuits that can act as cellular computers. RNA-engineered gene networks could also offer diagnostic capabilities, as similar RNA circuits have been shown to activate a gene only if, for example, a certain virus is present."This is going to open up a whole set of possibilities for us, because RNA molecules make decisions and compute information really well, and they detect things really well," Lucks said.The paper is called "Creating Small Transcription Activating RNAs," and its co-authors are postdoctoral associate James Chappell and graduate student Melissa Takahashi. Supporters include the National Science Foundation, the Defense Advanced Research Projects Agency and the Office of Naval Research.
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January 22, 2015
https://www.sciencedaily.com/releases/2015/01/150122084847.htm
Cell's recycling team helps sound alarm on pathogens
Just as households have garbage disposals and recycling bins for getting rid of everyday waste, the cell has its own system for cleaning up unnecessary or defunct components. This process, known as autophagy, is also an efficient method of eliminating unwanted visitors like viruses, bacteria, and parasites.
But when it comes to combatting a fungal invader, Duke researchers have found that the cleanup crew takes a less straightforward approach. Rather than killing fungal invaders directly, autophagy is used to chew up a molecule that would otherwise hold back the immune response. It's sort of like breaking the glass on an alarm to allow the button to be pushed.The finding appears January 22 in "The real frontline killers of fungi are (white blood cells called) neutrophils, but they are kept at bay by a molecule called A20," said Mari L. Shinohara, Ph.D., senior study author and assistant professor of immunology, molecular genetics and microbiology at Duke University School of Medicine."We found that when there is a fungal infection, the sentinels of war -- a special group of cells called tissue-resident macrophages -- use autophagy to get rid of the A20 molecules to quickly release an emergency signal," Shinohara said.The term autophagy (literally self-eating) was coined half a century ago by the Nobel laureate Christian de Duve to describe the process used by cells to break down and recycle their components. This self-digestion and recycling helps cells survive times when nutrients are low, and also enables them to remove dysfunctional organelles and proteins that could damage the cell.In recent years, scientists have discovered that autophagy plays a role in the immune response as well. They showed that the same cellular machinery that degrades unused proteins can also destroy viruses, bacteria and parasites. But it wasn't clear whether autophagy could target fungi for destruction.To explore this question, Shinohara and her colleagues started with a group of mice genetically engineered to lack a tiny spherical structure called the autophagosome that is responsible for engulfing unwanted materials for degradation -- the recycling bin. They infected these mice with Candida albicans, a fungal pathogen that causes opportunistic oral and genital infections in humans.The researchers found that mice lacking autophagosomes and unable to perform autophagy were more susceptible to fungal infection than normal mice. Masashi Kanayama, a postdoctoral fellow in Shinohara's lab and lead author of the study, then dissected the mouse mutants to determine what was happening at the cellular level. He discovered that fewer neutrophils had been recruited to fight off the infection.Neutrophils and macrophages are usually called to arms by a protein complex called NF-kappaB, which is a key regulator of the immune response. Because autophagy is known to specifically sequester certain proteins, Shinohara wondered whether it might be soaking up a protein that blocks NF-kappaB as a roundabout way to induce the immune response.Through a series of molecular biochemical assays, Shinohara and colleagues found that autophagy was indeed depleting A20, a known inhibitor of NF-kappaB. With A20 out of the picture, NF-kappaB was free to send out chemical signals known as chemokines to activate the antifungal arsenal to respond to the infection."We believe that autophagy provides an effective means of combating fungal infections," said Shinohara. "First, having a negative regulator like A20 ensures that there are fewer false alarms, and that fighters are only brought in when needed. Second, removing A20 is a quick and efficient way to induce an immune response, because it sets off a chain of actions that is already in place. Creating a protein from scratch would take much more time."
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January 21, 2015
https://www.sciencedaily.com/releases/2015/01/150121135619.htm
Biological safety lock for genetically modified organisms
The creation of genetically modified and entirely synthetic organisms continues to generate excitement as well as worry.
Such organisms are already churning out insulin and other drug ingredients, helping produce biofuels, teaching scientists about human disease and improving fishing and agriculture. While the risks can be exaggerated to frightening effect, modified organisms do have the potential to upset natural ecosystems if they were to escape.Physical containment isn't enough. Lab dishes and industrial vats can break; workers can go home with inadvertently contaminated clothes. And some organisms are meant for use in open environments, such as mosquitoes that can't spread malaria.So attention turns to biocontainment: building in biological safeguards to prevent modified organisms from surviving where they're not meant to. To do so, geneticists and synthetic biologists find themselves taking a cue from safety engineers."If you make a chemical that's potentially explosive, you put stabilizers in it. If you build a car, you put in seat belts and airbags," said George Church, Robert Winthrop Professor of Genetics at Harvard Medical School and core faculty member at the Wyss Institute.And if you've created the world's first genomically recoded organism, a strain of Church and colleagues report Jan. 21 in The A separate team reports in The two studies are the first to use synthetic nutrient dependency as a biocontainment strategy, and suggest that it might be useful for making genetically modified organisms safer in an open environment.In addition, "We now have the first example of genome-scale engineering rather than gene editing or genome copying," said Church. "This is the most radically altered genome to date in terms of genome function. We have not only a new code, but also a new amino acid, and the organism is totally dependent on it."Church's team, led by first authors Dan Mandell and Marc Lajoie, HMS research fellows in genetics, also made the The modifications offer theoretically safer Scientists have been exploring two main biocontainment methods, but each has weaknesses. Church was determined to fix them.One method involves turning normally self-sufficient organisms like Altering the genetics of Another pitfall of making auxotrophs is that some Church believes his team protected against those possibilities because it had to make 49 genetic changes to the Church's solution also took care of concerns he had with another biocontainment technique, in which genetic "kill switches" make bacteria vulnerable to a toxin so spills can be quickly neutralized. "All you have to do to kill a kill switch is turn it off," which can be done in any number of ways, Church said. Routing around the dependency on the artificial amino acid is much harder.Church determined that another key to making a successful "synthetic auxotroph" was to ensure that the "If you put it off on the periphery, like on the paint job of your car, the car will still run," he explained. "You have to embed the dependency smack in the middle of the engine, like the crank shaft, so it now has a particular part you can only get from, say, one manufacturer in Europe."The need to choose a process essential to They ended up with three successful redesigned essential proteins and two dependent As it was, the escape rate--the number of The group grew a total of 1 trillion The weaknesses in Church's methods remain to be seen. For now, he is satisfied with the results his group has obtained by pushing the limits of available testing."As part of our dedication to safety engineering in biology, we're trying to get better at creating physically contained test systems to develop something that eventually will be so biologically contained that we won't need physical containment anymore," said Church.In the meantime, he said, "we can use the physical containment to debug it and make sure it actually works."This work was funded by the U.S. Department of Energy (grant DE-FG02-02ER63445).
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January 21, 2015
https://www.sciencedaily.com/releases/2015/01/150121135617.htm
Synthetic amino acid enables safe, new biotechnology solutions to global problems
Scientists from Yale have devised a way to ensure genetically modified organisms (GMOs) can be safely confined in the environment, overcoming a major obstacle to widespread use of GMOs in agriculture, energy production, waste management, and medicine.
The Yale researchers rewrote the DNA of a strain of bacteria so that it requires the presence of a special synthetic amino acid that does not exist in nature to activate genes essential for growth. Amino acids are the building blocks of proteins, which carry out life's functions. This new method of bio-containment, reported online on Jan. 21 in the journal "This is a significant improvement over existing biocontainment approaches for genetically modified organisms," said Farren Isaacs, assistant professor in the Department of Molecular, Cellular, and Developmental Biology and the Systems Biology Institute at West Campus, and senior author of the paper. "This work establishes important safeguards for organisms in agricultural settings, and more broadly, for their use in environmental bioremediation and even in medical therapies."Isaacs, Jesse Rinehart, Alexis Rovner, and fellow synthetic biologists at Yale call these new bacteria genomically recoded organisms (GROs) because they have a new genetic code devised by the team of researchers. The new code allowed the team to link growth of the bacteria to synthetic amino acids not found in nature, establishing an important safeguard that limits the spread and survival of organisms in natural environments.In a second study, Isaacs, Ryan Gallagher, and Jaymin Patel at Yale devised a strategy to layer multiple safeguards that also limit growth of GMOs to environments that contain a different set of synthetic molecules. Published Jan. 21 in the journal These safe GMOs will improve efficiency of such engineered organisms, which are now being used in closed systems, such as the production of pharmaceuticals, fuels, and new chemicals. Concerns about use of GMOs in open environments, however, has limited their adoption in other areas.The authors also say that the new code paired with artificial amino acids will allow scientists to create safer GMOs for use in open systems, which include improved food production, designer probiotics to combat a host of diseases, and specialized microorganisms that clean up oil spills and landfills."As synthetic biology leads to the emergence of more sophisticated GMOs to address these grand challenges, we must assume a proactive role in establishing safe and efficacious solutions for biotechnology, similar to those who worked to secure the Internet in the 1990s." Isaacs said.
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January 13, 2015
https://www.sciencedaily.com/releases/2015/01/150113090428.htm
GMOs with health benefits have a large market potential
Genetically modified crops with an increased vitamin and/or mineral content have large potential to improve public health, but their availability for consumers is still hampered, as a result of the negative public opinion. Research from Ghent University, recently published in Nature Biotechnology, has demonstrated that these crops have a promising market potential.
Over the last years, various GM crops with health benefits have been developed in which genes, mostly originating from other organisms, have been added. Notable examples include rice enriched with pro-vitamin A (also known as 'Golden Rice') and folate-enriched rice, developed at Ghent University.Fifteen years after the development of 'Golden Rice', which was the first GMO with health benefits, the developers of such transgenic biofortified crops have little reason to celebrate. To date, none of these GMOs are approved for cultivation, unlike GMOs with agronomic traits. Despite this, six major staple crops have been successfully biofortified with one or more vitamins or minerals. Clearly, these GMOs with health benefits have great potential. In a recent study, from Ghent University, not only the impact of GM crops on human health, but also their market potential was convincingly demonstrated.Research at UGent reveals that consumers are willing to pay more for GMOs with health benefits, with premiums ranging from 20% to 70%. This differs from GMOs with farmer benefits, which are only accepted by consumers when they are offered at a discount.Especially in regions, such as China and Brazil -- which are considered as key target markets for these nutritionally improved crops -- , where a large part of the population suffers from nutrient deficiencies, the potential market share of these GMOs is high.Several studies show that these GMOs have positive impacts on human health. As expected, the enhancement of multiple micronutrients in the same crop by genetic modification, yields the best results. This method generates aggregated health benefits at a relatively low cost.Although GMOs with health benefits are not a panacea for eliminating malnutrition, they offer a complementary and cost-effective alternative when other strategies are less successful or feasible.
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January 6, 2015
https://www.sciencedaily.com/releases/2015/01/150106154710.htm
Mouse cell line developed to fast-track research in BRAF melanoma
Melanoma in humans is on the rise, with one in 50 individuals likely to have the disease. By developing cell lines that grow readily in culture, Dartmouth investigators led by Constance Brinckerhoff, PhD have created a fast-track research tool that remains applicable to many scientists who use mouse melanoma as a model system. The findings were first published in May 2014 in
"The ability to study these mouse melanoma cell lines both in culture and in mice with an intact immune system is an experimental advantage," explained Brinckerhoff.The team developed a protocol that allows mouse BRAF melanoma cells to grow readily in culture and to be transplanted in syngeneic mice. The cell lines are genetically compatible with a strain of mice that are immunologically competent, while human cells need to be placed into immunologically weakened mice in order to grow.Since publication, there have been worldwide requests for the cell lines and Brinckerhoff's team is developing additional characterization of the cells. Brinckerhoff reports, "More than 20 labs have contacted us since the paper was published and the feedback we've received indicates investigators worldwide are seeing experimental advantages in using the new cell lines. For years, the lack of mouse cell lines that harbor the BRAF mutation has been a barrier to rapidly moving research forward."
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December 18, 2014
https://www.sciencedaily.com/releases/2014/12/141218081123.htm
Protection of mouse gut by mucus depends on microbes
The quality of the colon mucus in mice depends on the composition of gut microbiota, reports a Swedish-Norwegian team of researchers from the University of Gothenburg and the Norwegian University of Life Sciences in Oslo. The work, published in
"Genetically similar mice with subtle but stable and transmissible intestinal microbiota showed unexpectedly large differences in the inner colon mucus layer. The composition of the gut microbiota has significant effects on mucus properties," says Malin E.V. Johansson from the University of Gothenburg who led the study.By sequencing the microbiota and examining the 16S ribosomal RNA genes, the researchers discovered that two mouse colonies maintained in two different rooms in the same specific pathogen-free facility had different gut microbiota. They also had a mucus structure that was specific for each colony. Whereas one colony developed mucus that was not penetrable to bacteria, the other colony had an inner mucus layer permeable to bacteria.Each group of mice had a stable population of bacteria that could be maternally transmitted: The group with impenetrable mucus had increased amounts of Erysipelotrichi bacteria, while the other group had higher levels of Proteobacteria and TM7 bacteria in the distal colon mucus. Free-living mice from the forest had mucus similar in composition to that found in mice in the non-penetrable colony. The authors also showed that the bacterial composition could be modulated to a small extent through the diet."The results from the free-living mice strongly argue for the importance of a well-developed inner mucus layer that efficiently separates bacteria from the host epithelium for the overall health of the mice," says Johansson.The different mucus properties were recreated by transplanting the microbial communities into germ-free mice. "After recolonisation of germ-free mice with the different microbiota we observed the same structural and functional differences in their mucus properties," added Johansson.Mucus is our outermost barrier to our microbiota in the gut. If the mucus fails to offer a protective barrier it can allow more bacteria to come in contact with our epithelium in a way that can trigger colon inflammation. Diseases such as ulcerative colitis show an increased incidence in the Western world and this study emphasizes the importance of the composition of the microbiota for an impenetrable protective mucus barrier.
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December 16, 2014
https://www.sciencedaily.com/releases/2014/12/141216144111.htm
The sense of smell uses fast dynamics to encode odors
Neuroscientists from the John B. Pierce Laboratory and Yale School of Medicine have discovered that mice can detect minute differences in the temporal dynamics of the olfactory system, according to research that will be published on December 16 in the open access journal
The research team used light in genetically-engineered mice to precisely control the activity of neurons in the olfactory bulbs in mice performing a discrimination task. This approach to controlling neural activity, called optogenetics, allows for much more precise control over the activity of neurons of the olfactory system than is possible by using chemical odors. The "light-smelling" mice were able to detect differences as small as 13 milliseconds between the dynamics of these "virtual odors."Because olfactory bulbs exhibit dynamic neural activations in the range of many tens of milliseconds, the 13 millisecond detection limit suggested that mice should be able to discriminate these dynamics. The researchers tested this hypothesis by recording brief "movies" of the dynamic activity in the olfactory bulbs of one group of mice and projecting them back onto the olfactory bulbs of another group of naïve mice. The naïve mice were indeed able to discriminate between the movies, demonstrating that the neural dynamics of the bulb contain fundamental information about odors."This data is very exciting as it shows for the first time that the temporal dynamics of bulbar neural activity are meaningful to the animal," remarked Associate Professor Justus Verhagen, the lead author on the paper. "Before optogenetics arrived as a new tool we had no means to test if this was true, we could read out the dynamic activity but could not impose it back on the brain and ask questions about its role in odor discrimination ."These new findings build upon earlier evidence that olfactory processing in mice included temporal information about sniffs. "We knew from prior work by the team of Dr. Dima Rinberg that mice could accurately determine when their olfactory system was stimulated relative to the timing of sniffs. We now know that mice can also obtain this information directly by comparing the timing of activities among neurons. We hence think that the neural population dynamics are important for the sense of smell both independently of and relative to sniffing. Thus, a sniff can be the "start" signal from which the brain begins to analyze the times at which different neurons turn on, but the brain can also do this independently of the sniff by using the earliest neural activations themselves as "start" signals. Combined these mechanisms provide for a very robust means for the brain to use time information. However, we don't yet know how these two forms of temporal information may interact."Dr. Verhagen's lab is one of several at Yale and the John B. Pierce Laboratory that are studying the neurobiology of food and flavor perception. His lab is unique in applying the power of optogenetics in mice to study the spatio-temporal capabilities of the olfactory neural circuitry that underlies these vital perceptual functions.
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December 16, 2014
https://www.sciencedaily.com/releases/2014/12/141216140743.htm
Can returning crops to their wild states help feed the world?
To feed the world's growing population--expected to reach nine billion by the year 2050--we will have to find ways to produce more food on less farmland, without causing additional harm to the remaining natural habitat. A feature review, to be published on December 16th in the Cell Press journal
Michael G. Palmgren of the University of Copenhagen and his colleagues suggest that the most efficient way to regain those lost properties is by reinserting good genes back into our crops after isolating them from related plants or to by using precision methods to repair faulty genes. "Once the genes that have been mutated unintentionally have been identified, the next step would be to reestablish wild-type properties. Rewilding would allow crop plants not only to better utilize available resources in the environment and have higher nutritional value, but also to better resist diseases, pests, and weeds," says Palmgren.While this back-to-nature breeding has great potential, there is one hitch, because crops restored to a more natural state in this manner would be classified, under current definitions, as genetically modified organisms (GMOs). "Studies tell us that many consumers look with some reservation upon GMO-based products, in part because they are considered alien," says Palmgren. "Rewilded crops represent a different path, yet if branded as GM products may likely face considerable challenges for market penetration."Palmgren notes that a discussion about which products should be labeled as GMOs is necessary. "It may be useful to distinguish between the product (the plant) and the process (the breeding technology)," he says. If a crop regains beneficial properties of a wild relative, such as disease resistance, it makes little sense to consider one plant as natural and the other as alien purely based on the method used to reach the same end result.The bottom line for Palmgren is this: the plants we eat and depend on are not the same as those originally found in the wild, whether they've been genetically modified or not. "Reintroduction of some of the lost properties does not make our crops alien," he says.
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December 15, 2014
https://www.sciencedaily.com/releases/2014/12/141215185024.htm
Novel tool to study life-threatening arrhythmias: A genetically engineered pig
Researchers at NYU Langone Medical Center have developed the first large animal model of an inherited arrhythmic syndrome -- an advance that will lead to a better understanding of the biologic mechanisms important in normal heart conduction and rhythm. The novel pig model points the way toward development of better treatments for inherited forms of life-threatening arrhythmias, which are a significant cause of sudden cardiac death.
The findings, published online in "By developing a genetically engineered pig sodium channelopathy model, we are now able to examine the mechanisms responsible for lethal arrhythmias in a human-like heart and investigate new therapies aimed at reducing sudden cardiac death," said lead author David S. Park, MD, PhD, assistant professor, Leon H. Charney Division of Cardiology, Department of Medicine at NYU Langone.Until now, researchers have primarily used cultured heart cells and mouse models to study cardiac arrhythmias. "But because of similarities of the pig heart to human hearts, research with the pig model will prove invaluable in gaining further insights into the mechanisms that underlie life-threatening arrhythmias," said Glenn I. Fishman, MD, the study's senior author, and Director of the Leon H. Charney Division of Cardiology at NYU Langone.Both Drs. Fishman and Park envision a future where novel therapies, such as drugs that can enhance cardiac sodium channel expression or radiofrequency ablation procedures, can first be tested in the pig model before application to patients. "A better understanding of arrhythmia mechanisms should yield better therapies in the future," said Dr. Park.
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December 15, 2014
https://www.sciencedaily.com/releases/2014/12/141215114242.htm
Ancient wisdom boosts sustainability of biotech cotton
Advocates of biotech crops and those who favor traditional farming practices such as crop diversity often seem worlds apart, but a new study shows that these two approaches can be compatible. An international team led by Chinese scientists and Bruce Tabashnik at the University of Arizona's College of Agriculture and Life Sciences discovered that the diverse patchwork of crops in northern China slowed adaptation to genetically engineered cotton by a wide-ranging insect pest. The results are published in the advance online edition of
Genetically engineered cotton, corn and soybean produce proteins from the widespread soil bacterium To delay resistance, farmers plant refuges of insect host plants that do not make Bt toxins, which allows survival of insects that are susceptible to the toxins. When refuges near Bt crops produce many susceptible insects, it reduces the chances that two resistant insects will mate and produce resistant offspring. In the United States, Australia and most other countries, farmers were required to plant refuges of non-Bt cotton near the first type of Bt cotton that was commercialized, which produces one Bt toxin named Cry1Ac. Planting such non-Bt cotton refuges is credited with preventing evolution of resistance to Bt cotton by pink bollworm (Yet in China, the world's number one cotton producer, refuges of non-Bt cotton have not been required. The Chinese approach relies on the previously untested idea that refuges of non-Bt cotton are not needed there because the most damaging pest, the cotton bollworm (Tabashnik used computer simulations to project the consequences of different assumptions about the effects of natural refuges in northern China. The simulations mimic the biology of the cotton bollworm and the planting patterns of the 10 million farmers in northern China from 2010 to 2013, where Bt cotton accounts for 98 percent of all cotton, but cotton represents only 10 percent of the area planted with crops eaten by the cotton bollworm."Because nearly all of the cotton is Bt cotton, the simulations without natural refuges predicted that resistant insects would increase from one percent of the population in 2010 to more than 98 percent by 2013," said Tabashnik, who heads the UA's Department of Entomology and also is a member of the UA's BIO5 Institute. "Conversely, resistance barely increased under the most optimistic scenario modeled, where each hectare of the 90 percent natural refuge was equivalent to a hectare of non-Bt cotton refuge."In a third scenario, the researchers used field data on emerging cotton bollworms from different crops to adjust the contribution of each hectare of natural refuge relative to non-Bt cotton. These data were provided by co-author Kongming Wu of the Institute of Plant Protection in Beijing. By this method, the total natural refuge area was equivalent to a 56 percent non-Bt cotton refuge, and 4.9 percent of the insects were predicted to be resistant by 2013.To distinguish between these possibilities, a team led by co-author Yidong Wu of China's Nanjing Agricultural University tracked resistance from 2010 to 2013 at 17 sites in six provinces of northern China. Insects were collected from the field and more than 70,000 larvae were tested in laboratory feeding experiments to determine if they were resistant. This extensive monitoring showed that the percentage of resistant insects increased from one percent of the population in 2010 to 5.5 percent in 2013.The field data imply that the natural refuges of non-Bt crops other than cotton delayed resistance with an effect similar to that of a 56 percent non-Bt cotton refuge, just as the model predicted."Our results mean we are getting a better understanding of what is going on," Tabashnik said. "We'd like to encourage further documentation work to track these trends. The same kind of analysis could be applied in areas in the U.S. where the natural refuge strategy is used."Natural refuges help, but are not a permanent solution," he added. "The paper indicates that if the current trajectory continues, more than half of the cotton bollworm population in northern China will be resistant to Bt cotton in a few years."To avoid this, the authors recommend switching to cotton that produces two or more Bt toxins and integrating Bt cotton with other control tactics, such as biological control by predators and parasites."The most important lesson is that we don't need to choose between biotechnology and traditional agriculture," Tabashnik said. "Instead, we can use the best practices from both approaches to maximize agricultural productivity and sustainability."
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December 11, 2014
https://www.sciencedaily.com/releases/2014/12/141211141837.htm
Biologists map crocodilian genomes
A Texas Tech University biologist led a team of more than 50 scientists who mapped the genomes of three crocodilians.
By mapping these genomes, scientists may better understand the evolution of birds, which are the toothy predators' closest living relatives, said David Ray, an associate professor of biology. The team completed genomes of a crocodile, an alligator and a true gharial to complete the genomic family portrait."One of the major finds in our case was that crocodilian genomes change very slowly when compared to birds," Ray said. "We compared both birds and crocodilians to turtles, which are the closest living relatives of the group that includes both birds and crocodilians. We found that they evolved slowly also. The best explanation for this is that the common ancestor of all three was a 'slow evolver,' which in turn suggests that rapid evolution is something that evolved independently in birds."Research began in 2009 as an attempt to map only 1 percent of crocodilian DNA. However, shortly after starting, the price for mapping a million bases dropped from $1,000 eventually down to $1."We had proposed to sequence about 2.4 million bases from the three crocodilians in the original proposal," Ray said. "By the time we got the funds, it became clear that we could easily accomplish a thousand times that much and could afford to sequence an entire genome of 3 billion bases."Ray said that when biologists look at a group of organisms, they look for what makes that group unique as well as what all members of one group of organisms share that other groups do not. The best way to do that is to examine their closest relatives."Technically, birds' closest relatives are the dinosaurs," he said. "So we can only look at their fossils and this can provide only limited information on their biology when compared to examining organisms that are alive today. We get insight into differences in behavior, structures that don't fossilize, and in our case, the makeup of the genome."Ray said he and other scientists were surprised to see how genetically uniform the alligators that the group sequenced were. Initially, the group suspected severe hunting during most of the 20th century may be to blame."Because alligators underwent a severe population decline, we first thought that might be what happened," he said. "However, we see the same pattern in all three species and the likelihood that all three were subject to the same genetic bottlenecks is small. We suggested instead that change just occurs slowly in crocodilians. In other words, it wasn't that the genetic differences were reduced because of overhunting. Rather, the amount of variation in crocodilians is low because change simply occurs slowly in these genomes."The DNA in alligators, crocodiles and gharials is about 93 percent identical across the genome. By comparison, a human shares about 93 percent of his or her DNA with a macaque."The difference is that humans and macaques shared a common ancestor around 23 million years ago while alligators and crocodiles shared a common ancestor in the much more distant past, around 90 million years ago," he said. "That means that things are changing in primate genomes about four times faster than in crocodilians."Ed Green, an assistant professor of biomolecular engineering at University of California, Santa Cruz, has worked on several mammalian genomes, including that of Neanderthals. He said he didn't expect such slow genetic changes seen in these reptiles."Crocodilian genomes are really interesting because they appear to have changed so little over time," Green said. "From the perspective of someone who knows a lot about mammalian genomes, reptiles are strange in how static they are. Crocs and gators are especially static."Like most genome projects, the assembly and annotation is only the beginning. There is some fascinating biology in Crocodylia like temperature-dependent sex determination. Male and female crocodilians are genetically identical, and we'd love to know how that works. We're also now in the position to start looking hard at the genomes of the common ancestor of crocs and birds. Not much is known about the biology of this creature, called an archosaur. But we may hope to learn a lot about it by reconstructing its genome from the living genomes of its living descendants, the crocs and birds."Their research, largely funded by the National Science Foundation, will appear Friday (Dec. 12) in the peer-reviewed journal,
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December 8, 2014
https://www.sciencedaily.com/releases/2014/12/141208145755.htm
Visualizing DNA double-strand break process for the first time
Scientists from the Spanish National Cancer Research Centre (CNIO), led by Guillermo Montoya, have developed a method for producing biological crystals that has allowed scientists to observe --for the first time-- DNA double chain breaks. They have also developed a computer simulation that makes this process, which lasts in the order of millionths of a second, visible to the human eye. The study is published today by the journal
"We knew that enzymes, or proteins, endonucleases, are responsible for these double strand breaks, but we didn't know exactly how it worked until now," said Montoya. "In our study, we describe in detail the dynamics of this basic biological reaction mediated by the enzyme I-Dmol. Our observations can be extrapolated to many other families of endonucleases that behave identically."DNA breaks occur in several natural processes that are vital for life: mutagenesis, synthesis, recombination and repair. In the molecular biology field, they can also be generated synthetically. Once the exact mechanism that produces these breaks has been uncovered, this knowledge can be used in multiple biotechnological applications: from the correction of mutations to treat rare and genetic diseases, to the development of genetically modified organisms.Enzymes are highly specialised dynamic systems. Their nicking function could be compared, said Montoya, to a specially designed fabric-cutting machine that "it would only make a cut when a piece of clothing with a specific combination of colours passed under the blade."In this case, researchers concentrated on observing the conformational changes that occurred in the I-Dmol active site; the area that contains the amino acids that act as a blade and produces DNA breaks.By altering the temperature and pH balance, the CNIO team has managed to delay a chemical reaction that typically occurs in microseconds by up to ten days. Under those conditions, they have created a slow-motion film of the whole process."By introducing a magnesium cation we were able to trigger the enzyme reaction and subsequently to produce biological crystals and freeze them at -200ºC," said Montoya. "In that way, we were able to collect up to 185 crystal structures that represent all of the conformational changes taking place at each step of the reaction."Finally, using computational analysis, the researchers illustrated the seven intermediate stages of the DNA chain separation process. "It is very exciting, because the elucidation of this mechanism will give us the information we need to redesign these enzymes and provide precise molecular scissors, which are essential tools for modifying the genome," he concluded.
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December 3, 2014
https://www.sciencedaily.com/releases/2014/12/141203142451.htm
Study set to shape medical genetics in Africa
Researchers from the African Genome Variation Project (AGVP) have published the first attempt to comprehensively characterise genetic diversity across Sub-Saharan Africa. The study of the world's most genetically diverse region will provide an invaluable resource for medical researchers and provides insights into population movements over thousands of years of African history. These findings appear in the journal
"Although many studies have focused on studying genetic risk factors for disease in European populations, this is an understudied area in Africa," says Dr Deepti Gurdasani, lead author on the study and a Postdoctoral Fellow at the Wellcome Trust Sanger Institute. "Infectious and non-infectious diseases are highly prevalent in Africa and the risk factors for these diseases may be very different from those in European populations.""Given the evolutionary history of many African populations, we expect them to be genetically more diverse than Europeans and other populations. However we know little about the nature and extent of this diversity and we need to understand this to identify genetic risk factors for disease."Dr Manjinder Sandhu and colleagues collected genetic data from more than 1800 people -- including 320 whole genome sequences from seven populations -- to create a detailed characterisation of 18 ethnolinguistic groups in Sub-Saharan Africa. Genetic samples were collected through partnerships with doctors and researchers in Ethiopia, the Gambia, Ghana, Kenya, Nigeria, South Africa and Uganda.The AGVP investigators, who are funded by the Wellcome Trust, the Bill and Melinda Gates Foundation and the UK Medical Research Council, found 30 million genetic variants in the seven sequenced populations, a fourth of which have not previously been identified in any population group. The authors show that in spite of this genetic diversity, it is possible to design new methods and tools to help understand this genetic variation and identify genetic risk factors for disease in Africa."The primary aim of the AGVP is to facilitate medical genetic research in Africa. We envisage that data from this project will provide a global resource for researchers, as well as facilitate genetic work in Africa, including those participating in the recently established pan-African Human Heredity and Health in Africa (H3Africa) genomic initiative," says Dr Charles Rotimi, senior author from the Centre for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health, USA.The authors also found evidence of extensive European or Middle Eastern genetic ancestry among several populations across Africa. These date back to 9,000 years ago in West Africa, supporting the hypothesis that Europeans may have migrated back to Africa during this period. Several of the populations studied are descended from the Bantu, a population of agriculturists and pastoralists thought to have expanded across large parts of Africa around 5,000 years ago.The authors found that several hunter-gatherer lines joined the Bantu populations at different points in time in different parts of the continent. This provides important insights into hunter-gatherer populations that may have existed in Africa prior to the Bantu expansion. It also means that future genetic research may require a better understanding of this hunter-gatherer ancestry."The AGVP has provided interesting clues about ancient populations in Africa that pre-dated the Bantu expansion," says Dr Manjinder Sandhu, lead senior author from the Wellcome Trust Sanger Institute, UK and the Department of Medicine, University of Cambridge. "To better understand the genetic landscape of ancient Africa we will need to study modern genetic sequences from previously under-studied African populations, along with ancient DNA from archaeological sources."The study also provides interesting clues about possible genetic loci associated with increased susceptibility to high blood pressure and various infectious diseases, including malaria, Lassa fever and trypanosomiasis, all highly prevalent in some regions of Africa. These genetic variants seem to occur with different frequencies in disease endemic and non-endemic regions, suggesting that this may have occurred in response to the different environments these populations have been exposed to over time."The AGVP has substantially expanded on our understanding of African genome variation. It provides the first practical framework for genetic research in Africa and will be an invaluable resource for researchers across the world. In collaboration with research groups across Africa, we hope to extend this resource with large-scale sequencing studies in more of these diverse populations," says Dr Sandhu.
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December 1, 2014
https://www.sciencedaily.com/releases/2014/12/141201113253.htm
Natural 'high' could avoid chronic marijuana use
Replenishing the supply of a molecule that normally activates cannabinoid receptors in the brain could relieve mood and anxiety disorders and enable some people to quit using marijuana, a Vanderbilt University study suggests.
Cannabinoid receptors are normally activated by compounds in the brain called endocannabinoids, the most abundant of which is 2-AG. They also are "turned on" by the active ingredient in marijuana.Sachin Patel, M.D., Ph.D., and his colleagues developed a genetically modified mouse with impaired ability to produce 2-AG in the brain. The mice exhibited anxiety-like behaviors, and female mice also displayed behaviors suggestive of depression.When an enzyme that normally breaks down 2-AG was blocked, and the supply of the endocannabinoid was restored to normal levels, these behaviors were reversed, the researchers reported on Nov. 26 in the online edition of the journal If further research confirms that some people who are anxious and depressed have low levels of 2-AG, this method of "normalizing 2-AG deficiency could represent a viable ... therapeutic strategy for the treatment of mood and anxiety disorders," they concluded.However, this approach has not been tested in humans, they cautioned.Relief of tension and anxiety is the most common reason cited for chronic marijuana use. Thus, restoring depleted levels of 2-AG also "could be a way to help people using marijuana," added Patel, the paper's senior author and professor of Psychiatry and of Molecular Physiology and Biophysics.Chronic use of marijuana down-regulates cannabinoid receptors, and thus paradoxically increases anxiety. This can lead to a "vicious cycle" of increasing marijuana use that in some cases leads to addiction.Patel and his colleagues previously have found cannabinoid receptors in the central nucleus of the amygdala of the mouse. The amygdala is a key emotional hub in the brain involved in regulating anxiety and the flight-or-fight response.They also have found that chemically modified inhibitors of the COX-2 enzyme they developed relieve anxiety behaviors in mice by activating natural "endocannabinoids" without gastrointestinal side effects. Clinical trials of some of these potential drugs could begin in the next several years.Cyclooxygenase (COX) enzymes produce pro-inflammatory prostaglandins and are the target of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), used to relieve pain and inflammation. It has been known for several years that COX-2 inhibition also activates endocannabinoids.
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November 18, 2014
https://www.sciencedaily.com/releases/2014/11/141118104845.htm
Helping wheat defend itself against damaging viruses
Wheat diseases caused by a host of viruses that might include wheat streak mosaic, triticum mosaic, soil-borne mosaic and barley yellow dwarf could cost producers 5 to 10 percent or more in yield reductions per crop, but a major advance in developing broad disease-resistant wheat is on the horizon.
John Fellers, molecular biologist for the U.S. Department of Agriculture's Agricultural Research Service, and Harold Trick, plant geneticist for Kansas State University, have led an effort to develop a patent-pending genetic engineering technology that builds resistance to certain viruses in the wheat plant itself. And although genetically engineered wheat is not an option in the market today, their research is building this resistance in non-genetically engineered wheat lines as well."(Wheat viruses) are a serious problem," Trick said. "Wheat streak mosaic virus is one of the most devastating viruses we have. It's prevalent this year. In addition to that, we have several other diseases, triticum mosaic virus and soil-borne mosaic virus, that are serious diseases."Knowing how costly these diseases can be for producers, Fellers has worked on finding solutions for resistance throughout his career. As a doctoral student at the University of Kentucky, he used a technology in his research called pathogen-derived resistance, or RNA-mediated resistance -- a process that requires putting a piece of a virus into a plant to make it resistant to that particular virus. Most of the viruses that infect wheat are RNA viruses, he said."The plant has its own biological defense system," Fellers said. "We were just triggering that with this technology."Now Fellers, with the help of Trick, his wheat transformation facility and K-State graduate students, have developed transgenic wheat lines that contain small pieces of wheat streak mosaic virus and triticum mosaic virus RNA."It's kind of like forming a hairpin of RNA," Fellers said. "What happens is the plant recognizes this RNA isn't right, so it clips a piece of it and chops it up, but then it keeps a copy for itself. Then we have a resistance element."Fellers compared the process to the old days of viewing most wanted posters on the post office wall. The piece of foreign RNA from the virus, which is a parasite, is one of those most wanted posters. Because the virus is a parasite, it has to seize or hijack part of the plant system to make proteins that it needs to replicate.When the virus comes into the plant, the plant holds up that poster from the post office wall, recognizes the virus, and doesn't allow the virus to replicate and go through its lifecycle.Trick said it wasn't difficult to incorporate the RNA into the wheat, as it involved a standard transformation process where the DNA encoding the RNA was introduced into plant cells, plants were regenerated from these transformed cells, and then the transgenic plants underwent testing for disease resistance."The problem with this technology is the most wanted poster is only for one individual," Trick added. "If we were trying to target multiple genes, we'd have to make another vector for a second virus, then create that transgenic, which we have done. So, we have different plants that are genetically resistant to wheat streak mosaic virus and plants that are resistant to triticum mosaic virus. We would like to get something that has broad resistance to many different viruses."Knowing again that the viruses are parasites that rely on part of the plant system to replicate, it may be possible to shut off these plant systems to prevent viral replication, Trick said, which in essence means making a most wanted poster for specific plant genes.Fellers and Trick have made additional transgenic plants with a most wanted poster for these plant genes and tested their new plants for resistance to a number of wheat viruses."We're now able to target barley yellow dwarf and soil-borne mosaic viruses," Fellers said. "We've also done mixed infection tests with wheat streak mosaic and triticum mosaic (viruses), and our initial results now are that they're all resistant. We're very cautious, but our initial indications show we have come up with something that provides broad resistance to these four viruses. We thought it was important enough to file for a patent."Fellers said this work is a proof of concept, meaning it shows that researchers have an ability now to address these virus issues. The fact that the process uses genetic engineering would mean that getting broad-resistance wheat would take some time considering the public and industry would have to accept it first.However, Trick said they are now pursuing a non-genetically engineered method that involves turning off specific plant genes using mutations. With this method, the researchers could develop the technology and incorporate it into the K-State breeding program without regulations."We would hope the turn around time would be quick, but it's still classical breeding," Fellers said of using mutations. "It's a matter of developing markers and getting them in the varieties. We have been using Jagger and Karl 92, varieties that are already past their prime, so we have to get them in some newer varieties."
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November 17, 2014
https://www.sciencedaily.com/releases/2014/11/141117084715.htm
Insect-resistant maize could increase yields and decrease pesticide use in Mexico
Although maize was originally domesticated in Mexico, the country's average yield per hectare is 38% below the world's average. In fact, Mexico imports 30% of its maize from foreign sources to keep up with internal demand.
To combat insect pests, Mexican farmers rely primarily on chemical insecticides. Approximately 3,000 tons of active ingredient are used each year just to manage the fall armyworm (While integrated pest management (IPM) programs -- which aim to minimize economic damage and lower environmental and health risks -- are widely used in crops such as tomatoes, broccoli, and peppers, IPM is highly uncommon in Mexican maize crops.In order to understand why, an expert panel composed of Mexican researchers and crop advisers gathered information from 2010-2013 regarding the main pests that reduce maize production, and the main methods being used to control these pests. Their findings are published in a free, open-access article in the The authors found the diversity of growing conditions to be the greatest obstacle for implementing IPM programs for Mexico's 2 million growers, many of whose fields are only two hectares or less.Another obstacle, according to the authors, is the lack of insect-resistant maize varieties, such as Bt hybrids. These varieties, which are genetically modified to express proteins from the bacterium "According to our estimates, 3,000 tons of organophosphate active ingredient is sold in Mexico each year to control ONLY fall armyworm, ONLY on corn," said Professor Urbano Nava-Camberos of the Universidad Juárez del Estado de Durango, and one of the co-authors. "In addition, applications are also made to cutworms, corn rootworms, borers, and corn earworms that do not necessarily coincide with the fall armyworm applications. However, all of these insect pests can be effectively controlled with Bt corn and integrated pest management programs.""There are a few solutions that can be immediately implemented to diminish the environmental impact of corn pests, including the use of Bt corn," added another co-author, crop consultant Guadalupe Pellegaud. "Unfortunately, people who oppose the introduction of this technology in Mexico do not seem to realize that a far greater environmental impact is done by applying more than 3,000 tons of insecticide active ingredient each year."
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November 17, 2014
https://www.sciencedaily.com/releases/2014/11/141117084625.htm
On a safari through the genome: Genes offer new insights into the distribution of giraffes
The Giraffe (
Like most other giraffes, these subspecies are now mainly found in nature reserves. Until recently, scientists assumed a clear demarcation of their ranges: Angola Giraffes occur in Namibia and northern Botswana, while South African Giraffes reside in southern Botswana and South Africa. "However, according to our studies, the distribution areas prove to be much more complex. South African Giraffes also occur in northeastern Namibia and northern Botswana, and Angola Giraffes can be found in northwestern Namibia and southern Botswana, as well," explains the study's author, Friederike Bock from the Biodiversity and Climate Research Center (BiK-F). A look at the new distribution map reveals the presence of a population of Angola Giraffes in the Central Kalahari Game Reserve, the world's second-largest national park, quasi nestled between two populations of the South African Giraffe, with both subspecies living side by side.According to the research team, the fact that two genetically distinct subspecies could develop within the same region may be explained by the local geographic conditions that prevailed approximately 500,000 to two million years ago. Back then, the mountain range along the East African Rift Valley was sinking, creating vast wetlands and lakes, such as the paleo lake Makgadikgadi. According to Professor Dr. Axel Janke from the BiK-F, "these large bodies of water may have separated the populations for long periods of time. Moreover, female giraffes likely do not migrate across long distances, thereby contributing to a clear separation of the maternal lines." Today, there no longer exist any barriers that prevent the possible mingling of both subspecies; an investigation of these processes is however subject to further genetic analyses.For the study, the researchers created a profile of the subspecies' mitochondrial DNA, using tissue samples from about 160 giraffes from various populations across the entire African continent. On the basis of this genetic material, inherited from the maternal side, the often similarly marked subspecies can be uniquely identified genetically and the relationships between various populations can be clearly demonstrated. "Our focus was on giraffes in southern Africa, in particular in Botswana and South Africa. There, we sampled populations that had not been genetically analyzed before," says Bock.According to estimates by the World Conservation Organization IUCN, the world's giraffe population is about 100,000 individuals -- showing a decreasing trend. In Botswana alone, the population has dwindled by more than half in recent years. In order to achieve effective protection measures that will preserve the majority of the giraffe's subspecies, it is indispensable to gain knowledge that allows their reliable identification as well as detailed information regarding their distribution. The surprising results concerning the distribution of the two subspecies in Namibia and Botswana emphasize the importance of additional taxonomic research on all giraffe subspecies.
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November 11, 2014
https://www.sciencedaily.com/releases/2014/11/141111111317.htm
Controlling genes with your thoughts
It sounds like something from the scene in Star Wars where Master Yoda instructs the young Luke Skywalker to use the force to release his stricken X-Wing from the swamp: Marc Folcher and other researchers from the group led by Martin Fussenegger, Professor of Biotechnology and Bioengineering at the Department of Biosystems (D-BSSE) in Basel, have developed a novel gene regulation method that enables thought-specific brainwaves to control the conversion of genes into proteins -- called gene expression in technical terms.
"For the first time, we have been able to tap into human brainwaves, transfer them wirelessly to a gene network and regulate the expression of a gene depending on the type of thought. Being able to control gene expression via the power of thought is a dream that we've been chasing for over a decade," says Fussenegger.A source of inspiration for the new thought-controlled gene regulation system was the game Mindflex, where the player wears a special headset with a sensor on the forehead that records brainwaves. The registered electroencephalogram (EEG) is then transferred into the playing environment. The EEG controls a fan that enables a small ball to be thought-guided through an obstacle course.The system, which the Basel-based bioengineers recently presented in the journal A light then literally goes on in the implant: an integrated LED lamp that emits light in the near-infrared range turns on and illuminates a culture chamber containing genetically modified cells. When the near-infrared light illuminates the cells, they start to produce the desired protein.The implant was initially tested in cell cultures and mice, and controlled by the thoughts of various test subjects. The researchers used SEAP for the tests, an easy-to-detect human model protein which diffuses from the culture chamber of the implant into the mouse's bloodstream.To regulate the quantity of released protein, the test subjects were categorised according to three states of mind: bio-feedback, meditation and concentration. Test subjects who played Minecraft on the computer, i.e. who were concentrating, induced average SEAP values in the bloodstream of the mice. When completely relaxed (meditation), the researchers recorded very high SEAP values in the test animals. For bio-feedback, the test subjects observed the LED light of the implant in the body of the mouse and were able to consciously switch the LED light on or off via the visual feedback. This in turn was reflected by the varying amounts of SEAP in the bloodstream of the mice."Controlling genes in this way is completely new and is unique in its simplicity," explains Fussenegger. The light-sensitive optogenetic module that reacts to near-infrared light is a particular advancement. The light shines on a modified light-sensitive protein within the gene-modified cells and triggers an artificial signal cascade, resulting in the production of SEAP. Near-infrared light was used because it is generally not harmful to human cells, can penetrate deep into the tissue and enables the function of the implant to be visually tracked.The system functions efficiently and effectively in the human-cell culture and human-mouse system. Fussenegger hopes that a thought-controlled implant could one day help to combat neurological diseases, such as chronic headaches, back pain and epilepsy, by detecting specific brainwaves at an early stage and triggering and controlling the creation of certain agents in the implant at exactly the right time.
Genetically Modified
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November 6, 2014
https://www.sciencedaily.com/releases/2014/11/141106101736.htm
Diversity outbred mice better predict potential human responses to chemical exposures
A genetically diverse mouse model is able to predict the range of response to chemical exposures that might be observed in human populations, researchers from the National Institutes of Health have found. Like humans, each Diversity Outbred mouse is genetically unique, and the extent of genetic variability among these mice is similar to the genetic variation seen among humans.
Using these mice, researchers from the National Toxicology Program (NTP), an interagency program headquartered at the National Institute of Environmental Health Sciences (NIEHS), were able to identify specific genes or chromosomal regions that make some mice more susceptible, and others more resistant, to the toxic effects of benzene. Benzene is a common air pollutant and human carcinogen found in crude oil, gasoline, and cigarette smoke, and naturally produced by wildfires and volcanoes.The scientists found that, like humans, each Diversity Outbred mouse developed at The Jackson Laboratory, Bar Harbor, Maine, responded to the effects of the chemical exposure differently. Exposure responses were assessed by measuring the frequency of micronucleated red blood cells, a biological marker of chromosomal damage, which is a hallmark of benzene exposure. The researchers measured the levels of this biomarker in each mouse before and after exposure.Some mice demonstrated extraordinary sensitivity to the exposure, while others showed no response. The range of response from lowest to highest was approximately 5-fold. Since the researchers knew the genetic makeup of each mouse, they could pinpoint the regions involved in susceptibility or resistance to the chemical exposure, and then look for related genetic regions in human chromosomes."This paper points out the significant genetic differences that are found throughout every population that must to be taken into account when extrapolating data from animals to humans," said Linda Birnbaum, Ph.D., director of NTP and NIEHS. "The Diversity Outbred mouse is a useful model for predicting the range of response that might be observed in humans following exposure to a chemical."Benzene was selected by NTP as a case study for testing the mouse model, because there is an abundance of animal and human toxicity data for comparison. Benzene can affect people differently, depending on the level and duration of exposure, making it important to accurately estimate the levels at which it may cause harm to the most susceptible individuals."These genetically diverse mice provided a reproducible response to benzene exposure across two independently exposed groups, suggesting that each group of genetically unique mice demonstrated the same range of differential susceptibility, much like what you would find in human epidemiology studies," said Jef French, Ph.D., lead author on the paper. "It's important to be able to accurately measure the impact of exposure and to develop appropriate permissible safety levels for toxic compounds. This model can help us do that with greater accuracy."These results may lead to further research to better understand genetically regulated responses to toxicity in humans, as well as mechanisms of susceptibility and resistance to environmental exposures as they relate to disease. "In addition to informing the design of human epidemiology studies evaluating associations between chemical exposures and biological effects in diverse populations, the Diversity Outbred mouse model may also provide valuable data for use by regulators and manufacturers conducting chemical risk assessments," said co-author Kristine Witt of NTP.The paper is available online in the journal Next spring, the NIEHS Division of Extramural Research and Training plans to hold a meeting to look at the Diversity Outbred mouse model and other population-based rodent models that can be used to advance the field of environmental health sciences.
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November 2, 2014
https://www.sciencedaily.com/releases/2014/11/141102160103.htm
'Wimpy' antibody protects against kidney disease in mice
An antibody abundant in mice and previously thought to offer poor assistance in fighting against infection may actually play a key role in keeping immune responses in check and preventing more serious self-inflicted forms of kidney disease, researchers say.
Led by researchers at the University of Cincinnati (UC) and Cincinnati Children's Hospital Medical Center and published online Nov. 2, 2014, in the journal "Antibodies protect against pathogens, in large part, by clumping them together and by activating other defenses, including a set of serum proteins, known as complement, and cells that have antibody-binding molecules on their surface called Fc receptors," says Fred Finkelman, MD, Walter A. and George McDonald Foundation Chair of Medicine and professor of medicine and pediatrics at UC.Finkelman is also an immunobiology researcher at Cincinnati Children's Hospital Medical Center. Richard Strait, MD, an assistant professor of pediatrics at UC and an attending physician at Cincinnati Children's, is the first author of the research published in "Surprisingly, most of the antibody made by mice is IgG1, which is relatively defective in its ability to clump pathogens, activate complement, and activate cells by binding to their Fc receptors," says Finkelman, also a physician at the Cincinnati Department of Veterans Affairs (VA) Medical Center. "Humans have a similar type of antibody, called IgG4, which is also relatively defective in these abilities."Why should you have such a wimpy antibody? It's the antibody made in the largest amount. Our thought was that in biology, you don't get anything for free," says Finkelman. "If an antibody can kill bacteria and viruses very well, it might also cause inflammation that can harm the animal that makes it. So maybe you need some of these wimpy antibodies to protect against that type of self-inflicted damage."Researchers tested their hypothesis by studying what happens when genetically bred mice that cannot make IgG1 are injected with a foreign protein that would spur a normal mouse's immune system to produce IgG1. The genetically bred mouse instead produced another antibody known as IgG3, which affected capillaries in the kidneys and ultimately led to renal failure."The mouse's kidneys turned yellow because they essentially shut off blood flow and within a few days there was total destruction of the filtering part of the kidney called the glomerulus," explains Finkelman.However, injecting IgG1 into mice that could not make the antibody prevented them from developing kidney disease, says Finkelman."These findings support our hypothesis about the reason for making antibodies such as mouse IgG1 and human IgG4," says Finkelman. "They also demonstrate a new type of kidney disease that can be caused by certain types of antibody, such as mouse IgG3, even without complement or Fc receptors. In addition, our findings suggest that antibodies such as human IgG4 might be useful for treating people who have diseases caused by other types of antibody."These diseases include myasthenia gravis and blistering skin diseases, says Finkelman.Myasthenia gravis is a chronic autoimmune neuromuscular disease characterized by varying degrees of weakness of the skeletal (voluntary) muscles of the body. Individuals with the ailment lose the ability to contract their muscles because their body produces an antibody that destroys acetylcholine receptors in muscle."The nerves in their muscles continue to fire and they release the chemical acetylcholine, but there is not much for the acetylcholine to bind to," says Finkelman. "These people become very weak and can actually die because they can no longer swallow well or breathe well."Individuals with blistering skin diseases make antibodies against the molecules that hold skin cells together, says Finkelman. As a result, the skin cells separate from each other, forming blisters."People can lose a lot of fluid and can get infected very easily," says Finkelman. "These are very serious diseases and the treatment is not very good."
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October 30, 2014
https://www.sciencedaily.com/releases/2014/10/141030142206.htm
Genetic factors behind surviving or dying from Ebola shown in mouse study
A newly developed mouse model suggests that genetic factors are behind the mild-to-deadly range of reactions to the Ebola virus.
People exposed to Ebola vary in how the virus affects them. Some completely resist the disease, others suffer moderate to severe illness and recover, while those who are most susceptible succumb to bleeding, organ failure and shock.In earlier studies of populations of people who have contracted Ebola, these differences are not related to any specific changes in the Ebola virus itself that made it more or less dangerous; instead, the body's attempts to fight infection seems to determine disease severity.In the Oct. 30 edition of Research on Ebola prevention and treatment has been hindered by the lack of a mouse model that replicates the main characteristics of human Ebola hemorrhagic fever. The researchers had originally obtained this genetically diverse group of inbred laboratory mice to study locations on mouse genomes associated with influenza severity.The research was conducted in a highly secure, state-of-the-art biocontainment safety level 4 laboratory in Hamilton, Mont. The scientists examined mice that they infected with a mouse form of the same species of Ebola virus causing the 2014 West Africa outbreak. The study was done in full compliance with federal, state, and local safety and biosecurity regulations. This type of virus has been used several times before in research studies. Nothing was done to change the virus.Interestingly, conventional laboratory mice previously infected with this virus died, but did not develop symptoms of Ebola hemorrhagic fever.In the present study, all the mice lost weight in the first few days after infection. Nineteen percent of the mice were unfazed. They not only survived, but also fully regained their lost weight within two weeks. They had no gross pathological evidence of disease. Their livers looked normal.Eleven percent were partially resistant and less than half of these died. Seventy percent of the mice had a greater than 50 percent mortality. Nineteen percent of this last group had liver inflammation without classic symptoms of Ebola, and thirty-four percent had blood that took too long to clot, a hallmark of fatal Ebola hemorrhagic fever in humans. Those mice also had internal bleeding, swollen spleens and changes in liver color and texture.The scientists correlated disease outcomes and variations in mortality rates to specific genetic lines of mice."The frequency of different manifestations of the disease across the lines of these mice screened so far are similar in variety and proportion to the spectrum of clinical disease observed in the 2014 West African outbreak," Rasmussen said.While acknowledging that recent Ebola survivors may have had immunity to this or a related virus that saved them during this epidemic, Katze said, "Our data suggest that genetic factors play a significant role in disease outcome."In general, when virus infection frenzied the genes involved in promoting blood vessel inflammation and cell death, serious or fatal disease followed. On the other hand, survivors experienced more activity in genes that order blood vessel repair and the production of infection-fighting white blood cells.The scientists note that certain specialized types of cells in the liver could also have limited virus reproduction and put a damper on systemic inflammation and blood clotting problems in resistant mice. Susceptible mice had widespread liver infection, which may explain why they had more virus in their bodies and poorly regulated blood coagulation. The researchers also noticed that spleens in the resistant and susceptible mice took alternate routes to try to ward off infection."We hope that medical researchers will be able to rapidly apply these findings to candidate therapeutics and vaccines," Katze said. They believe this mouse model can be promptly implemented to find genetic markers, conduct meticulous studies on how symptoms originate and take hold, and evaluate drugs and that have broad spectrum anti-viral activities against all Zaire ebolaviruses, including the one responsible for the current West African epidemic.
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October 30, 2014
https://www.sciencedaily.com/releases/2014/10/141030133530.htm
Making lab-grown tissues stronger
Lab-grown tissues could one day provide new treatments for injuries and damage to the joints, including articular cartilage, tendons and ligaments.
Cartilage, for example, is a hard material that caps the ends of bones and allows joints to work smoothly. UC Davis biomedical engineers, exploring ways to toughen up engineered cartilage and keep natural tissues strong outside the body, report new developments this week in the journal "The problem with engineered tissue is that the mechanical properties are far from those of native tissue," said Eleftherios Makris, a postdoctoral researcher at the UC Davis Department of Biomedical Engineering and first author on the paper. Makris is working under the supervision of Professor Kyriacos A. Athanasiou, a distinguished professor of biomedical engineering and orthopedic surgery, and chair of the Department of Biomedical Engineering.While engineered cartilage has yet to be tested or approved for use in humans, a current method for treating serious joint problems is with transplants of native cartilage. But it is well known that this method is not sufficient as a long-term clinical solution, Makris said.The major component of cartilage is a protein called collagen, which also provides strength and flexibility to the majority of our tissues, including ligaments, tendons, skin and bones. Collagen is produced by the cells and made up of long fibers that can be cross-linked together.Researchers in the Athanasiou group have been maintaining native cartilage in the lab and culturing cartilage cells, or chondrocytes, to produce engineered cartilage."In engineered tissues the cells produce initially an immature matrix, and the maturation process makes it tougher," Makris said.Knee joints are normally low in oxygen, so the researchers looked at the effect of depriving native or engineered cartilage of oxygen. In both cases, low oxygen led to more cross-linking and stronger material. They also found that an enzyme called lysyl oxidase, which is triggered by low oxygen levels, promoted cross-linking and made the material stronger."The ramifications of the work presented in the PNAS paper are tremendous with respect to tissue grafts used in surgery, as well as new tissues fabricated using the principles of tissue engineering," Athanasiou said. Grafts such as cadaveric cartilage, tendons or ligaments -- notorious for losing their mechanical characteristics in storage -- can now be treated with the processes developed at UC Davis to make them stronger and fully functional, he said.Athanasiou also envisions that many tissue engineering methods will now be altered to take advantage of this strengthening technique.
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October 29, 2014
https://www.sciencedaily.com/releases/2014/10/141029145444.htm
New way of genome editing cures hemophilia in mice; may be safer than older method
The ability to pop a working copy of a faulty gene into a patient's genome is a tantalizing goal for many clinicians treating genetic diseases. Now, researchers at the Stanford University School of Medicine have devised a new way to carry out this genetic sleight of hand.
The approach differs from that of other hailed techniques because it doesn't require the co-delivery of an enzyme called an endonuclease to clip the recipient's DNA at specific locations. It also doesn't rely on the co-insertion of genetic "on" switches called promoters to activate the new gene's expression.These differences may make the new approach both safer and longer-lasting. Using the technique, the Stanford researchers were able to cure mice with hemophilia by inserting a gene for a clotting factor missing in the animals."It appears that we may be able to achieve lifelong expression of the inserted gene, which is particularly important when treating genetic diseases like hemophilia and severe combined immunodeficiency," said Mark Kay, MD, PhD, professor of pediatrics and of genetics. "We're able to do this without using promoters or nucleases, which significantly reduces the chances of cancers that can result if the new gene inserts itself at random places in the genome."Using the technique, Kay and his colleagues were able to insert a working copy of a missing blood-clotting factor into the DNA of mice with hemophilia. Although the insertion was accomplished in only about 1 percent of liver cells, those cells made enough of the missing clotting factor to ameliorate the disorder.Kay is the senior author of the research, which will be published Oct. 29 in The Stanford discovery may offer an alternative to a genome-editing technique called CRISPR/Cas9 that relies on an ancient, protective response developed by bacteria to fight off viral attack. Every time a bacterium defeats a virus, it saves a tiny portion of the invader's DNA in its own genome, like a genetic feather in its cap. (Accumulations of these viral regions are called clustered regularly interspaced short palindromic regions, or CRISPR.) When that virus comes around again, the cell uses the snippets of saved genetic material to identify and latch onto matching regions in the viral genome. Once attached, it cuts the viral genes at precise locations with a protein called Cas9.Researchers around the world have begun to use the CRISPR/Cas9 technique not just to permanently disable genes for study in laboratory animals, but also to insert new, modified genes into the animals' genomes. This allows the rapid creation of genetically modified laboratory animals; what used to take months or years can now take days or weeks.However, the technique requires not just the gene for the Cas9 nuclease, which itself could integrate into the recipient's genome, but also a promoter to drive the expression of the genes. Researchers are concerned that, if used in humans, Cas9 may cut the DNA at unexpected locations, which could disrupt or kill the cell. Alternatively, the promoter of the new gene could adversely affect the expression of nearby genes, causing cancers or other diseases. The foreign bacterial proteins could also cause an immune reaction in patients."Site-specific gene targeting is one of the fastest growing fields in gene therapy and genome engineering," said Barzel. "But the use of nucleases and promoters may have significant adverse effects. I wanted to come up with a novel gene-targeting scheme that involved no vector-borne promoter and did not require the use of an endonuclease."The technique devised by the researchers uses neither nucleases to cut the DNA nor a promoter to drive expression of the clotting factor gene. Instead, the researchers hitch the expression of the new gene to that of a highly expressed gene in the liver called albumin. The albumin gene makes the albumin protein, which is the most abundant protein in blood. It helps to regulate blood volume and to allow molecules that don't easily dissolve in water to be transported in the blood.The researchers used a modified version of a virus commonly used in gene therapy called adeno-associated virus, or AAV. In the modified version, called a viral vector, all viral genes are removed and only the therapeutic genes remain. They also relied on a biological phenomenon known as homologous recombination to insert the clotting factor gene near the albumin gene. By using a special DNA linker between the genes, the researchers were able to ensure that the clotting factor protein was made hand-in-hand with the highly expressed albumin protein.During homologous recombination, which is a natural repair process, the cell takes advantage of the fact that it has two copies of every chromosome. By lining up the damaged and undamaged chromosomes, the cell can crib off the intact copy to repair the damage without losing vital genetic information. Kay and Barzel used this natural process of recombination to copy sequences from the viral vector into the genome at places designated by the researchers -- in this case, after the albumin gene.When they tested their approach in newborn laboratory mice with hemophilia, they found that the animals began to express levels of clotting factor that were between 7 and 20 percent of normal. That amount of clotting factor has been shown in previous studies to be therapeutic in mice. They further showed, surprisingly, that the technique worked as well in adult animals, even though the gene was successfully inserted in fewer than 1 in every 100 liver cells."We expected this approach to work best in newborn animals because the liver is still growing," said Kay, who is also the Dennis Farrey Family Professor of Pediatrics. "However, because homologous recombination has been thought to occur mostly in proliferating cells, we didn't expect it to work as well as it did in adult animals."Kay has been involved in gene therapy for hemophilia for many years. In 2006, he was a leader of a team of investigators that used AAV to provide a clotting factor gene to patients with hemophilia B. This form of hemophilia is less common than hemophilia A, which affects about 1 in every 25,000 newborn boys (because the condition is caused by a faulty gene on the X chromosome, it rarely affects girls). However, hemophilia B is an easier target to treat because the gene for the missing clotting factor is smaller and easier to manipulate with gene therapy.As with many viruses, there are different strains of AAV. Unfortunately, the expression of the clotting factor with the strain of AAV used in the 2006 study lasted only a few months in humans, in contrast to the long-lived expression in animals. Recently another, similar clinical trial was launched in the United Kingdom using a different strain of AAV, and expression of the clotting factor was still observed in each of six people treated more than two years after receiving the modified virus. However, in both these trials, the clotting factor gene was not inserted into the genome, but was instead maintained as a separate, free-floating copy."The real issue with AAV is that it's unclear how long gene expression will last when the gene is not integrated into the genome," said Kay, who is also a member of the Stanford Cancer Institute, the Stanford Child Health Research Institute and Stanford Bio X. "Infants and children, who would benefit most from treatment, are still growing, and an unintegrated gene could lose its effectiveness because it's not copied from cell to cell. Furthermore, it's not possible to re-administer the treatment because patients develop an immune response to AAV. But with integration we could get lifelong expression without fear of cancers or other DNA damage."The researchers are now planning to test the technique in mice with livers made up of both human and mouse cells, a model which they recently were able to show may be a good surrogate to further predict what will happen in humans.
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October 23, 2014
https://www.sciencedaily.com/releases/2014/10/141023111052.htm
First protein microfiber engineered: New material advances tissue engineering and drug delivery
Researchers at the New York University Polytechnic School of Engineering have broken new ground in the development of proteins that form specialized fibers used in medicine and nanotechnology. For as long as scientists have been able to create new proteins that are capable of self-assembling into fibers, their work has taken place on the nanoscale. For the first time, this achievement has been realized on the microscale -- a leap of magnitude in size that presents significant new opportunities for using engineered protein fibers.
Jin Kim Montclare, an associate professor of chemical and biomolecular engineering at the NYU School of Engineering, led a group of researchers who published the results of successful trials in the creation of engineered microfiber proteins in the journal Many materials used in medicine and nanotechnology rely on proteins engineered to form fibers with specific properties. For example, the scaffolds used in tissue engineering depend on engineered fibers, as do the nanowires used in biosensors. These fibers can also be bound with small molecules of therapeutic compounds and used in drug delivery.Montclare and her collaborators began their experiments with the intention of designing nanoscale proteins bound with the cancer therapeutic curcumin. They successfully created a novel, self-assembling nanoscale protein, including a hydrophobic pore capable of binding small molecules. To their surprise, after incubating the fibers with curcumin, the protein not only continued to assemble, but did so to a degree that the fibers crossed the diameter barrier from the nanoscale to the microscale, akin to the diameter of collagen or spider silk."This was a surprising and thrilling achievement," said Montclare, explaining that this kind of diameter increase in the presence of small molecules is unprecedented. "A microscale fiber that is capable of delivering a small molecule, whether it be a therapeutic compound or other material, is a major step forward."Montclare explained that biomaterials embedded with small molecules could be used to construct dual-purpose scaffolds for tissue engineering or to deliver certain drugs more efficiently, especially those that are less effective in an aqueous environment. Using microscopy, the team was able to observe the fibers in three dimensions and to confirm that the curcumin, which fluoresces when bound to structural protein, was distributed homogeneously throughout the fiber.Despite the enormity of the jump from nano- to microscale, the research team believes they can devise even larger fibers. The next step, Montclare says, is developing proteins that can assemble on the milliscale, creating fibers large enough to see with the naked eye. "It's even possible to imagine generating hair out of cell assembly," she says.Researchers from three institutions collaborated on this work. In addition to Montclare, NYU School of Engineering doctoral candidate Jasmin Hume, graduate student Rudy Jacquet, and undergraduate student Jennifer Sun co-authored the paper. Richard Bonneau, an associate professor in NYU's Department of Biology and a member of the computer science faculty at NYU's Courant Institute of Mathematical Sciences, and postdoctoral scholar P. Douglas Renfrew also contributed, along with M. Lane Gilchrist, associate professor of chemical engineering at City College of New York and master's degree student Jesse A. Martin, also from City College. Their work was supported by the Army Research Office and the National Science Foundation.
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October 17, 2014
https://www.sciencedaily.com/releases/2014/10/141017092630.htm
First step: From human cells to tissue-engineered esophagus
In a first step toward future human therapies, researchers at The Saban Research Institute of Children's Hospital Los Angeles have shown that esophageal tissue can be grown in vivo from both human and mouse cells. The study has been published online in the journal
The tissue-engineered esophagus formed on a relatively simple biodegradable scaffold after the researchers transplanted mouse and human organ-specific stem/progenitor cells into a murine model, according to principal investigator Tracy C. Grikscheit, MD, of the Developmental Biology and Regenerative Medicine program of The Saban Research Institute and pediatric surgeon at Children's Hospital Los Angeles.Progenitor cells have the ability to differentiate into specific types of cell, and can migrate to the tissue where they are needed. Their potential to differentiate depends on their type of "parent" stem cell and also on their niche. The tissue-engineering technique discovered by the CHLA researchers required only a simple polymer to deliver the cells, and multiple cellular groupings show the ability to generate a replacement organ with all cell layers and functions."We found that multiple combinations of cell populations allowed subsequent formation of engineered tissue. Different progenitor cells can find the right 'partner' cell in order to grow into specific esophageal cell types -- such as epithelium, muscle or nerve cells -- and without the need for exogenous growth factors. This means that successful tissue engineering of the esophagus is simpler than we previously thought," said Grikscheit.She added that the study shows promise for one day applying the process in children who have been born with missing portions of the organ, which carries food, liquids and saliva from the mouth to the stomach. The process might also be used in patients who have had esophageal cancer -- the fastest growing type of cancer in the U.S. -- or otherwise damaged tissue, for example from accidentally swallowing caustic substances."We have demonstrated that a simple and versatile, biodegradable polymer is sufficient for the growth of tissue-engineered esophagus from human cells," added Grikscheit. "This not only serves as a potential source of tissue, but also a source of knowledge, as there are no other robust models available for studying esophageal stem cell dynamics. Understanding how these cells might behave in response to injury and how various donor cell types relate could expand the pool of potential donor cells for engineered tissue."Additional contributors include first author Ryan G. Spurrier, MD, Allison L. Speer, MD, Xiaogang Hou, PhD and Wael N. El-Nachef, MD, of The Saban Research Institute of Children's Hospital Los Angeles. The study was supported by grants from the California Institute for Regenerative Medicine.
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October 16, 2014
https://www.sciencedaily.com/releases/2014/10/141016123534.htm
Are male brains wired to ignore food for sex? Nematode study points to basic biological mechanisms
Choosing between two good things can be tough. When animals must decide between feeding and mating, it can get even trickier. In a discovery that might ring true even for some humans, researchers have shown that male brains -- at least in nematodes -- will suppress the ability to locate food in order to instead focus on finding a mate.
The results, which appear today in the journal "While we know that human behavior is influenced by numerous factors, including cultural and social norms, these findings point to basic biological mechanisms that may not only help explain some differences in behavior between males and females, but why different sexes may be more susceptible to certain neurological disorders," said Douglas Portman, Ph.D., an associate professor in the Department of Biomedical Genetics and Center for Neural Development and Disease at the University of Rochester and lead author of the study.The findings were made in experiments involving The study published today focuses on the activity of a single pair of neurons found in There are two sexes of It has been previously observed that males and hermaphrodites act differently when exposed to food. If placed at a food source, the hermaphrodites tend to stay there. Males, however, will leave food source and "wander" -- scientist believe they do this because they are in search of a mate.The Rochester researchers discovered that the sensory mechanisms -- called chemoreceptors -- of the AWA neurons were regulated by the sexual identity of these cells, which, in turn, controls the expression of a receptor called ODR-10. These receptors bind to a chemical scent that is given off by food and other substances.In hermaphrodites, more of the ODR-10 receptors are produced, making the worms more sensitive -- and thereby attracted -- to the presence of food. In males, fewer of these receptors are active, essentially suppressing their ability -- and perhaps desire -- to find food. However, when males were deprived of food, they produced dramatically higher levels of this receptor, allowing them to temporarily focus on finding food.To confirm the role of these genetic differences between the sexes on behavior, the researchers designed a series of experiments in which they observed the activity of The males were placed in their own individual food sources at the periphery of the dish. As a further obstacle between the males and their potential mates, an additional ring of food surrounded the hermaphrodites in the center of the dish. The males in the experiment consisted of two categories, one group with a normal genetic profile and another group that had been engineered by the researchers to overexpress the ODR-10 receptor, essentially making them more sensitive to the smell of food.The researchers found that the normal worms left their food source and eventually made their way to the center of the dish where they mated with the hermaphrodites. The genetically engineered males were less successful at finding a mate, presumably because they were more interested in feeding. By examining the genetic profile of the resulting offspring, the scientists observed that the normal males out-produced the genetically engineered males by 10 to one.In separate experiments, the researchers were also able to modify the behavior of the hermaphrodites by suppressing the ODR-10 receptors, causing them to act like males and abandon their food source."These findings show that by tuning the properties of a single cell, we can change behavior," said Portman. "This adds to a growing body of evidence that sex-specific regulation of gene expression may play an important role in neural plasticity and, consequently, influence differences in behaviors -- and in disease susceptibility -- between the sexes."
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October 14, 2014
https://www.sciencedaily.com/releases/2014/10/141014211755.htm
Using test tube experiments to study how bacterial species evolve antibiotic resistance
Given a critical change in the environment, how exactly, do species adapt?
Professor Tom Vogwill and colleagues wanted to get at the heart of this evolutionary question by measuring the growth rates and DNA mutations of 8 different species of Pseudomonas bacteria. They controlled a single but vital variable during growth, the dose of the antibacterial drug rifampicin.Overall, they challenged 480 populations from 8 different strains of Pseudomonas (3840 total) with adapting to the minimal concentration of rifampicin that is needed to completely inhibit the growth of the ancestral strain of each species. They carried out the experiment over 30 generations of bacteria. Next, the authors selected 75 randomly chosen rifampicin-resistant mutants from 8 different clonal bacterial strains and sequenced the rpoB gene in all 600 mutants, identifying 47 different mutations. They measured both the growth rates of the clones in the presence of rifampicin, and the DNA mutations of a gene, rpoB, a known mediator of drug resistance.They found that most of these rpoB mutations occurred only once, some occurred multiple times in a single strain, and others occurred multiple times in multiple strains. However, in agreement with the prevailing hypothesis, populations of the same strain tended to evolve in parallel. Despite that fact the 8 bacterial strains are genetically very different from each other, they also found that the same mutations have different effects on fitness in the different strains, indicating that the genetic make-up is an important fitness factor. Finally, the authors demonstrated that the growth rates varied more within species than between species."Antibiotic resistance often evolves by mutations in genes that are conserved across bacteria, raising the possibility that resistance evolution might follow similar paths across bacteria," said colleague Craig MacLean. "Our study provides good evidence that the rest of the genome influences which resistance mutations are observed, and how these mutations influence Darwinian fitness. These findings imply that we need to be cautious when trying to extrapolate our understanding of the genetics of antibiotic resistance between bacterial strains or species."The breadth of the study shows how the powerful new tool of experimental evolution can provide important insights into the relationships between DNA mutations, growth and evolution.
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