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October 14, 2014 | https://www.sciencedaily.com/releases/2014/10/141014152538.htm | Potential drug could ease impact of bacterial lung infections in cystic fibrosis patients, tests suggest | By screening over 2,000 approved drugs and natural products, scientists have shown that tannic acid may help ease the impact of bacterial lung infections in cystic fibrosis patients. Tests completed using experimentally modified frog oocytes show that tannic acid counteracts the harmful effect of an enzyme produced by the bacterium | From an early age, the lungs of individuals with cystic fibrosis (CF) are colonised and infected by bacteria, a common example being In patients suffering from CF, the cystic fibrosis "transmembrane conductance regulator" (CFTR) channels are faulty, causing a thick mucus to build up in their lungs. In these experiments, the authors used oocytes from the Xenopus type of frog -- that had been genetically modified to express CFTR channels on their cell surface -- to measure the effect that SMaseC has on CFTR channels. They saw that the SMaseC enzyme suppresses CFTR channel activity in these experimentally modified frog oocytes, and also in a human lung cell line.These results suggest that the SMaseC enzyme, produced by the S. aureas bacterium, may reduce any residual channel activity in CF patients. The problems originating from genetic defects in CFTR channels are likely made greater if the enzyme reduces the function of the CFTR channel even further.SMaseC also suppresses a type of voltage-gated potassium channel, known as the Kv1.3 channel, in immune cells. Suppression of these potassium channels is known to weaken host immunity, which would make it more difficult for the CF patients to recover from lung infections.To try and counteract the effects of the enzyme, the researchers went on to test a collection of approved drugs and natural products in a chemical library. They found that tannic acid -- a readily available and inexpensive natural product that has been used to treat disease as far back as 1850 -- stopped SMaseC from having a negative effect on both the CFTR and the Kv1.3 channels. "We hope to test whether the application of the SMaseC inhibitor tannic acid, in conjunction with effective antibiotic treatment and supportive measures, will provide a significant therapeutic improvement over current treatments for cystic fibrosis," Dr. Zhe Lu, the senior author, says. His team is also working hard to understand the exact mechanism by which tannic acid counters the negative actions of SMaseC. | Genetically Modified | 2,014 |
October 8, 2014 | https://www.sciencedaily.com/releases/2014/10/141008153507.htm | Drug used for another disease slows progression of Parkinson's | A new study from UCLA found that a drug being evaluated to treat an entirely different disorder helped slow the progression of Parkinson's disease in mice. | The study, published in the October edition of the journal though the exact cause of Parkinson's is unknown, evidence points to an accumulation of alpha-synuclein, which has been found to be common to all people with the disorder. The protein is thought to destroy the neurons in the brain that make dopamine, a neurotransmitter that helps regulate a number of functions, including movement and coordination. Dopamine deficiency is associated with Parkinson's disease.Gaucher disease is a rare genetic disorder in which the body cannot produce enough of an enzyme called β-glucocerebrosidase, or GCase. Researchers seeking genetic factors that increase people's risk for developing Parkinson's have determined that there may be a close relationship between Gaucher and Parkinson's due to a GCase gene. Mutation of this gene, which leads to decreased GCase activity in the brain, has been found to be a genetic risk factor for Parkinson's, although the majority of patients with Parkinson's do not carry mutations in the Gaucher gene."This is the first time a compound targeting Gaucher disease has been tested in a mouse model of Parkinson's disease and was shown to be effective," said the study's senior author, Marie-Francoise Chesselet, the Charles H. Markham Professor of Neurology at UCLA and director of the UCLA Center for the Study of Parkinson's Disease. "The promising findings in this study suggest that further investigation of this compound in Parkinson's disease is warranted."In the study, the researchers used mice that were genetically engineered to make too much alpha-synuclein which, over time, led the animals to develop deficits similar to those observed in humans with Parkinson's. The researchers found that the mice's symptoms improved after they received AT2101 for four months.The researchers also observed that AT2101 was effective in treating Parkinson's in mice even though they did not carry a mutant version of the Gaucher gene, suggesting that the compound may have a clinical effect in the broader Parkinson's population.AT2101 is a first-generation "pharmacological chaperone" -- a drug that can bind malfunctioning, mutated enzymes and lead them through the cell to their normal location, which allows the enzymes to carry on with their normal work. This was the first time that a pharmacological chaperone showed promise in a model of Parkinson's, according to Chesselet.Parkinson's disease affects as many as 1 million Americans, and 60,000 new cases are diagnosed each year. The disorder continues to puzzle scientists. There is no cure and researchers have been unable to pin down its cause and no drug has been proven to stop the progression of the disease, which causes tremors, stiffness and other debilitating symptoms. Current Parkinson's treatments only address its symptoms. | Genetically Modified | 2,014 |
October 3, 2014 | https://www.sciencedaily.com/releases/2014/10/141003214349.htm | RCas9: A programmable RNA editing tool | A powerful scientific tool for editing the DNA instructions in a genome can now also be applied to RNA, the molecule that translates DNA's genetic instructions into the production of proteins. A team of researchers with Berkeley Lab and the University of California (UC) Berkeley has demonstrated a means by which the CRISPR/Cas9 protein complex can be programmed to recognize and cleave RNA at sequence-specific target sites. This finding has the potential to transform the study of RNA function by paving the way for direct RNA transcript detection, analysis and manipulation. | Schematic shows how RNA-guided Cas9 working with PAMmer can target ssRNA for programmable, sequence-specific cleavage.Led by Jennifer Doudna, biochemist and leading authority on the CRISPR/Cas9 complex, the Berkeley team showed how the Cas9 enzyme can work with short DNA sequences known as "PAM," for protospacer adjacent motif, to identify and bind with specific site of single-stranded RNA (ssRNA). The team is designating this RNA-targeting CRISPR/Cas9 complex as RCas9."Using specially designed PAM-presenting oligonucleotides, or PAMmers, RCas9 can be specifically directed to bind or cut RNA targets while avoiding corresponding DNA sequences, or it can be used to isolate specific endogenous messenger RNA from cells," says Doudna, who holds joint appointments with Berkeley Lab's Physical Biosciences Division and UC Berkeley's Department of Molecular and Cell Biology and Department of Chemistry, and is also an investigator with the Howard Hughes Medical Institute (HHMI). "Our results reveal a fundamental connection between PAM binding and substrate selection by RCas9, and highlight the utility of RCas9 for programmable RNA transcript recognition without the need for genetically introduced tags."From safer, more effective medicines and clean, green, renewable fuels, to the clean-up and restoration of our air, water and land, the potential is there for genetically engineered bacteria and other microbes to produce valuable goods and perform critical services. To exploit the vast potential of microbes, scientists must be able to precisely edit their genetic information.In recent years, the CRISPR/Cas complex has emerged as one of the most effective tools for doing this. CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, is a central part of the bacterial immune system and handles sequence recognition. Cas9 -- Cas stands for CRISPR-assisted -- is an RNA-guided enzyme that handles the sniping of DNA strands at the specified sequence site.Together, CRISPR and Cas9 can be used to precisely edit the DNA instructions in a targeted genome for making desired types of proteins. The DNA is cut at a specific location so that old DNA instructions can be removed and/or new instructions inserted.Until now, it was thought that Cas9 could not be used on the RNA molecules that transcribe those DNA instructions into the desired proteins."Just as Cas9 can be used to cut or bind DNA in a sequence-specific manner, RCas9 can cut or bind RNA in a sequence-specific manner," says Mitchell O'Connell, a member of Doudna's research group and the lead author of a paper in In an earlier study, Doudna and her group showed that the genome editing ability of Cas9 is made possible by presence of PAM, which marks where cutting is to commence and activates the enzyme's strand-cleaving activity. In this latest study, Doudna, Mitchell and their collaborators show that PAMmers, in a similar manner, can also stimulate site-specific endonucleolytic cleavage of ssRNA targets. They used Cas9 enzymes from the bacterium "While RNA interference has proven useful for manipulating gene regulation in certain organisms, there has been a strong motivation to develop an orthogonal nucleic-acid-based RNA-recognition system such as RCas9," Doudna says. "The molecular basis for RNA recognition by RCas9 is now clear and requires only the design and synthesis of a matching guide RNA and complementary PAMmer."The researchers envision a wide range of potential applications for RCas9. For example, an RCas9 tethered to a protein translation initiation factor and targeted to a specific mRNA could essentially act as a designer translation factor to "up-" or "down-" regulate protein synthesis from that mRNA."Tethering RCas9 to beads could be used to isolate RNA or native RNA-protein complexes of interest from cells for downstream analysis or assays," Mitchell says. "RCsa9 fused to select protein domains could promote or exclude specific introns or exons, and RCas9 tethered to a fluorescent proteins could be used to observe RNA localization and transport in living cells." | Genetically Modified | 2,014 |
October 2, 2014 | https://www.sciencedaily.com/releases/2014/10/141002084129.htm | Space not only rules genes, but mind as well | Changes in spatial distribution of genetic material can lead to neuropsychiatric disorders, as discovered by Spanish-Polish team of researchers. The investigationof the genetically modified laboratory mice define new directions in the fight against neuropsychiatric disorders in humans; they also suggest that the results of some previous studies of mouse behavior might be misinterpreted. | Some mental disorders are genetic. Researchers from the Nencki Institute of Experimental Biology in Warsaw and the Spanish Instituto de Neurociencias de Alicante (INA) have shown, however, that the relationship between the psyche and genes may be more subtle than previously thought. In genetically modified laboratory mice, they found changes in the spatial distribution of genetic material fibers in neurons -- and the accompanying disturbances in behavior. The results of the team headed by prof. Angel Barco (INA) have been published in the famous magazine "Nature Communications.""DNA in the cells is not naked -- it is wrapped around proteins called histones to form chromatin fibers," begins to explain Dr. Adriana Magalska of Nencki Institute and immediately adds: "Most people certainly are familiar with a picture of human chromosomes that resemble the letter X. This is properly coiled chromatin that is responsible for the characteristic packing of the genetic material."To be able to observe the chromatin, the researchers marked it with green fluorescent protein (GFP). GFP is a non-toxic protein, which when illuminated by laser light emits green fluorescence. In molecular biology it is used to mark specific types of cells and to study gene activity. It has so many uses that for its discovery, the Nobel Prize was awarded.In the mice studied by the Polish-Spanish team, the gene producing GFP works only in neurons and remains inactive when the mice are given one of the antibiotics, doxycycline. So, if the mouse receives the antibiotic from birth, the gene remains inactive and the animal develops normally. At a time convenient for researchers, doxycycline can be discontinued, to activate the production of GFP in neurons. Then one can see what changes have occurred in these cells as a result of the conducted experiments. Most importantly, through the use of genetic engineering, in these genetically modified mice GFP is coupled to one of the histones of chromatin. This means that in practice all the chromatin of transgenic mice is labeled with GFP protein."Normal nuclei of mouse neurons contain regions of highly condensed chromatin called chromocenters that can be observed under a microscope as bright, spherical objects after cells are labeled with DNA stain. They contain genes that are inactive," says Grzegorz Wilczynski, Assoc. Professor at Nencki Institute.A custom-made proprietary software for image analysis, created by Dr. Blazej Ruszczycki from the Nencki Institute, has allowed researchers to transform a sequence of microscopic images to three-dimensional visualization. This visualization allowed Polish scientists to find marked differences in the spatial structure of the chromatin in transgenic mice producing activated GFP gene fused with a histone. The three-dimensional structure of the chromatin in the nucleus of the neurons of transgenic mice was found to be different than in wild type mice: chromocenters were bigger, not tightly focused, but more "fuzzy." It was also found that the modified spatial configuration of chromatin affects the production of certain proteins, which in turn leads to different than normal behavior of the mice."Transgenic mice were found to have significantly lower levels of serotonin and dopamine receptors. Both proteins are involved, inter alia, in emotional processes, including depressive disorders," says Dr. Magalska.The Spanish part of the team carried out accurate tests of animal behavior. The results were unequivocal. Compared with the wild-type, the modified mice were hyperactive, showed signs of autism, had trouble with remembering and making new interactions with other individuals.The results of the Spanish-Polish team mean that the activation of the gene that produces GFP combined with histone leads in mouse neurons to epigenetic changes, i.e. changes in which the activation and deactivation of the genes is determined not by DNA sequence, but by its immediate surroundings. These changes affect neuronal function, which results in the appearance of behavioral disorders in mice."If the changes in the spatial orientation of the DNA fibers result in neuropsychological impairment in mice, it seems likely that they may also lead to them in humans. This may be important, for example, to autism. The finding points to future areas of research, with potentially important implications for the development of modern medicine," says Prof. Wilczynski.But the Polish-Spanish publication is also important for another reason. For years in laboratories around the world genetically modified mice are used in experiments on behavior. Until now, all scientists were convinced that the introduction of GFP does not affect the reactions of animals. It is already known that it is not. Some previously published scientific studies might therefore be based on improperly interpreted data. | Genetically Modified | 2,014 |
October 1, 2014 | https://www.sciencedaily.com/releases/2014/10/141001133414.htm | Gut bacteria are protected by host during illness | To protect their gut microbes during illness, sick mice produce specialized sugars in the gut that feed their microbiota and maintain a healthy microbial balance. This protective mechanism also appears to help resist or tolerate additional harmful pathogens, and its disruption may play a role in human diseases such as Crohn's disease, report scientists from the University of Chicago in | "Both hosts and their gut microbiota can suffer in the case of sickness, but this mutually beneficial relationship is guarded by the host," said study senior author Alexander Chervonsky, MD, PhD, chairman of the Committee on Immunology at the University of Chicago.When faced with systemic illness, animals eat less to conserve energy instead of foraging for food and to deprive pathogens of nutrients. However, this can harm beneficial gut bacteria, which have an important role in health and disease.To investigate how microbiota might be supported during illness, Chervonsky and his team focused on a potential internal resource produced by the host -- L-fucose, a sugar which has been shown to affect gut microbes. A host cannot use L-fucose for energy, but when bound to proteins, it can be used by microbes as a food source. Under normal conditions, however, the small intestine of mice produces almost no L-fucose.The team exposed different types of mice to a molecule that mimicked a systemic infection. The mice became sick -- eating less food, drinking less water and losing weight. Only a few hours after this induced sickness, the researchers observed that L-fucose was produced and present on almost every surface of the small intestine. This effect was seen only in response to illness.The researchers then tested genetically engineered mice lacking Fut2, the gene responsible for L-fucose production. Healthy under normal conditions, mice without Fut2 regained weight after induced sickness -- a measure of recovery -- much slower than their normal counterparts. However, only mice with both intact gut microbiota and the ability to produce L-fucose recovered efficiently."Mice that can produce L-fucose recover better than those that can't," Chervonsky said. "If you remove bacteria the effect goes away."The team used genetic analyses to confirm that gut microbes were affected metabolically by the production of L-fucose. As part of this analysis, they noted that sick mice without Fut2 had significantly greater expression of harmful microbial genes than normal mice. Hypothesizing that L-fucose production was somehow preventing opportunistic bacteria from expressing virulent genes, they exposed mice to a mild bacterial pathogen and then four days later induced sickness. Under this condition, mice without Fut2 lost significantly more weight than normal, suggesting that the production of L-fucose helps the host tolerate or resist additional harmful pathogens.Interestingly, around 20 percent of humans lack a functional gene to produce L-fucose, a problem that has been associated with the inflammatory bowel ailment known as Crohn's disease."We speculate that without L-fucose, the activation of virulence genes cannot be blocked, and that's why bacteria play a role in Crohn's disease," Chervonsky said. "Whether we can use this toward therapeutics in the future requires further study." | Genetically Modified | 2,014 |
September 26, 2014 | https://www.sciencedaily.com/releases/2014/09/140926101023.htm | No sign of health or nutrition problems from GMO livestock feed, study finds | A new scientific review from the University of California, Davis, reports that the performance and health of food-producing animals consuming genetically engineered feed, first introduced 18 years ago, has been comparable to that of animals consuming non-GE feed. | The review study also found that scientific studies have detected no differences in the nutritional makeup of the meat, milk or other food products derived from animals that ate genetically engineered feed.The review, led by UC Davis animal scientist Alison Van Eenennaam, examined nearly 30 years of livestock-feeding studies that represent more than 100 billion animals.Titled "Prevalence and Impacts of Genetically Engineered Feedstuffs on Livestock Populations," the review article is now available online in open-access form through the American Society of Animal Science.Genetically engineered crops were first introduced in 1996. Today, 19 genetically engineered plant species are approved for use in the United States, including the major crops used extensively in animal feed: alfalfa, canola, corn, cotton, soybean and sugar beet.Food-producing animals such as cows, pigs, goats, chickens and other poultry species now consume 70 to 90 percent of all genetically engineered crops, according to the new UC Davis review. In the United States, alone, 9 billion food-producing animals are produced annually, with 95 percent of them consuming feed that contains genetically engineered ingredients."Studies have continually shown that the milk, meat and eggs derived from animals that have consumed GE feed are indistinguishable from the products derived from animals fed a non-GE diet," Van Eenennaam said. "Therefore, proposed labeling of animal products from livestock and poultry that have eaten GE feed would require supply-chain segregation and traceability, as the products themselves would not differ in any way that could be detected."Now that a second generation of genetically engineered crops that have been optimized for livestock feed is on the horizon, there is a pressing need to internationally harmonize the regulatory framework for these products, she said."To avoid international trade disruptions, it is critical that the regulatory approval process for genetically engineered products be established in countries importing these feeds at the same time that regulatory approvals are passed in the countries that are major exporters of animal feed," Van Eenennaam said.Collaborating on the study was co-author Amy E. Young in the UC Davis Department of Animal Science.The review study was supported by funds from the W.K. Kellogg endowment and the California Agricultural Experiment Station of UC Davis. | Genetically Modified | 2,014 |
September 18, 2014 | https://www.sciencedaily.com/releases/2014/09/140918162311.htm | Sensing neuronal activity with light: New way of mapping neural networks in a living organism | For years, neuroscientists have been trying to develop tools that would allow them to clearly view the brain's circuitry in action -- from the first moment a neuron fires to the resulting behavior in a whole organism. To get this complete picture, neuroscientists are working to develop a range of new tools to study the brain. Researchers at Caltech have developed one such tool that provides a new way of mapping neural networks in a living organism. | The work -- a collaboration between Viviana Gradinaru (BS '05), assistant professor of biology and biological engineering, and Frances Arnold, the Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry -- was described in two separate papers published this month.When a neuron is at rest, channels and pumps in the cell membrane maintain a cell-specific balance of positively and negatively charged ions within and outside of the cell resulting in a steady membrane voltage called the cell's resting potential. However, if a stimulus is detected -- for example, a scent or a sound -- ions flood through newly open channels causing a change in membrane voltage. This voltage change is often manifested as an action potential -- the neuronal impulse that sets circuit activity into motion.The tool developed by Gradinaru and Arnold detects and serves as a marker of these voltage changes."Our overarching goal for this tool was to achieve sensing of neuronal activity with light rather than traditional electrophysiology, but this goal had a few prerequisites," Gradinaru says. "The sensor had to be fast, since action potentials happen in just milliseconds. Also, the sensor had to be very bright so that the signal could be detected with existing microscopy setups. And you need to be able to simultaneously study the multiple neurons that make up a neural network."The researchers began by optimizing Archaerhodopsin (Arch), a light-sensitive protein from bacteria. In nature, opsins like Arch detect sunlight and initiate the microbes' movement toward the light so that they can begin photosynthesis. However, researchers can also exploit the light-responsive qualities of opsins for a neuroscience method called optogenetics -- in which an organism's neurons are genetically modified to express these microbial opsins. Then, by simply shining a light on the modified neurons, the researchers can control the activity of the cells as well as their associated behaviors in the organism.Gradinaru had previously engineered Arch for better tolerance and performance in mammalian cells as a traditional optogenetic tool used to control an organism's behavior with light. When the modified neurons are exposed to green light, Arch acts as an inhibitor, controlling neuronal activity -- and thus the associated behaviors -- by preventing the neurons from firing.However, Gradinaru and Arnold were most interested in another property of Arch: when exposed to red light, the protein acts as a voltage sensor, responding to changes in membrane voltages by producing a flash of light in the presence of an action potential. Although this property could in principle allow Arch to detect the activity of networks of neurons, the light signal marking this neuronal activity was often too dim to see.To fix this problem, Arnold and her colleagues made the Arch protein brighter using a method called directed evolution -- a technique Arnold originally pioneered in the early 1990s. The researchers introduced mutations into the Arch gene, thus encoding millions of variants of the protein. They transferred the mutated genes into A paper describing the process and the bright new protein variants that were created was published in the September 9 issue of the "This experiment demonstrates how rapidly these remarkable bacterial proteins can evolve in response to new demands. But even more exciting is what they can do in neurons, as Viviana discovered," says Arnold.In a separate study led by Gradinaru's graduate students Nicholas Flytzanis and Claire Bedbrook, who is also advised by Arnold, the researchers genetically incorporated the new, brighter Arch variants into rodent neurons in culture to see which of these versions was most sensitive to voltage changes -- and therefore would be the best at detecting action potentials. One variant, Archer1, was not only bright and sensitive enough to mark action potentials in mammalian neurons in real time, it could also be used to identify which neurons were synaptically connected -- and communicating with one another -- in a circuit.The work is described in a study published on September 15 in the journal "What was interesting is that we would see two cells over here light up, but not this one over there -- because the first two are synaptically connected," Gradinaru says. "This tool gave us a way to observe a network where the perturbation of one cell affects another."However, sensing activity in a living organism and correlating this activity with behavior remained the biggest challenge. To accomplish this goal Gradinaru's team worked with Paul Sternberg, the Thomas Hunt Morgan Professor of Biology, to test Archer1 as a sensor in a living organism -- the tiny nematode worm After incorporating Archer1 into neurons that were a part of the worm's olfactory system -- a primary source of sensory information for Gradinaru next hopes to use tools like Archer1 to better understand the complex neuronal networks of mammals, using microbial opsins as sensing and actuating tools in optogenetically modified rodents."For the future work it's useful that this tool is bifunctional. Although Archer1 acts as a voltage sensor under red light, with green light, it's an inhibitor," she says. "And so now a long-term goal for our optogenetics experiments is to combine the tools with behavior-controlling properties and the tools with voltage-sensing properties. This would allow us to obtain all-optical access to neuronal circuits. But I think there is still a lot of work ahead."One goal for the future, Gradinaru says, is to make Archer1 even brighter. Although the protein's fluorescence can be seen through the nearly transparent tissues of the nematode worm, opaque organs such as the mammalian brain are still a challenge. More work, she says, will need to be done before Archer1 could be used to detect voltage changes in the neurons of living, behaving mammals.And that will require further collaborations with protein engineers and biochemists like Arnold."As neuroscientists we often encounter experimental barriers, which open the potential for new methods. We then collaborate to generate tools through chemistry or instrumentation, then we validate them and suggest optimizations, and it just keeps going," she says. "There are a few things that we'd like to be better, and through these many iterations and hard work it can happen."The work published in both papers was supported with grants from the National Institutes of Health (NIH), including an NIH/National Institute of Neurological Disorders and Stroke New Innovator Award to Gradinaru; Beckman Institute funding for the BIONIC center; grants from the U.S. Army Research Office as well as a Caltech Biology Division Training Grant and startup funds from Caltech's President and Provost, and the Division of Biology and Biological Engineering; and other financial support from the Shurl and Kay Curci Foundation and the Life Sciences Research Foundation. | Genetically Modified | 2,014 |
September 15, 2014 | https://www.sciencedaily.com/releases/2014/09/140915153836.htm | 'Most famous wheat gene' discovered, clears way for non-GMO breeding | Washington State University researchers have found "the most famous wheat gene," a reproductive traffic cop of sorts that can be used to transfer valuable genes from other plants to wheat. | The discovery clears the way for breeders to develop wheat varieties with the disease- and pest-resistance traits of other grasses, using a legion of genetic tools that can reduce crop losses and pesticide use while foregoing the cost, regulatory hurdles and controversy of Genetically Modified Organisms, or GMOs."The real exciting part of this gene is that it has tremendous potential for application," said Kulvinder Gill, a WSU professor, who reports his findings in the journal For some 35 million years, the wild ancestors of wheat routinely traded genes as they accidentally cross-bred with each other. But with the rise of agriculture and cultivated wheat 10,000 years ago, the plant's genetic structure changed. Instead of being diploid, with two sets of chromosomes like humans and most other living things, it became polyploid, with, in the case of bread wheat, seven sets of six related chromosomes.Starting in 1958, just five years after the discovery of DNA's double-helix structure, researchers suspected that a specific gene controls the orderly pairing of wheat chromosomes during reproduction."If this gene was not present, there would be chaos in the nucleus," said Gill. "Six chromosomes would pair with each other, and sometimes five chromosomes would go to one cell and one to the other, resulting in a sterile plant. Because of this gene, wheat can be fertile. Without this gene, it would be more like sugar cane, where it is a mess in the nucleus and it can only be vegetatively propagated."But the gene also prevents wheat from breeding with related ancestors that can contain a vast array of traits preferred by growers."This gene would not allow rye chromosomes to pair with wheat," said Gill. "We cannot get a single gene transfer into wheat as long as this gene is present."Interest in the gene, called Ph1, has spawned scores of research papers, making it what Gill called, "the most famous wheat gene."In 2006, British researchers writing in the journal "In this paper," said Gill, "we show that their gene is not the Ph1." Knowing their findings would be controversial, Gill and his colleagues spent a year repeating the experiments that led to their conclusion. They are now moving on."Now that we have the gene, we can actually use that gene sequence to temporarily silence the gene and make rye and other chromosomes pair with wheat and transfer genes by a natural method into wheat without calling it GMO," Gill said.Their first effort involves transferring a gene from jointed goatgrass, a wild relative of wheat, to confer resistance to stripe rust. The fungus is considered the world's most economically damaging wheat pathogen, costing U.S. farmers alone some $500 million in lost productivity in 2012.While facilitated by technology, the actual exchange of genetic material is similar to what has long taken place in nature, only faster. Incorporating the gene transfer into the overall breeding process, researchers can develop a new variety in five years, said Gill."If we let wheat evolve for another few millions years in the wild, maybe it will develop enough variation, but we don't have that kind of time," said Gill. "We need to solve this problem today." | Genetically Modified | 2,014 |
September 14, 2014 | https://www.sciencedaily.com/releases/2014/09/140914150749.htm | Blood-cleansing biospleen device developed for sepsis therapy | Things can go downhill fast when a patient has sepsis, a life-threatening condition in which bacteria or fungi multiply in a patient's blood -- often too fast for antibiotics to help. A new device inspired by the human spleen and developed by a team at Harvard's Wyss Institute for Biologically Inspired Engineering may radically transform the way doctors treat sepsis. | "Even with the best current treatments, sepsis patients are dying in intensive care units at least 30 percent of the time," said Mike Super, Ph.D., Senior Staff Scientist at the Wyss Institute. "We need a new approach." Sepsis kills at least eight million people worldwide each year and it's the leading cause of hospital deaths.The device, called a "biospleen," exceeded the team's expectations with its ability to cleanse human blood tested in the laboratory and increase survival in animals with infected blood, as reported in Sepsis occurs when a patient's immune system overreacts to a bloodstream infection, triggering a chain reaction that can cause inflammation, blood clotting, organ damage, and death. It can arise from a variety of infections, including appendicitis, urinary tract infections, skin or lung infections, as well as contaminated IV lines, surgical sites, and catheters.Identifying the specific pathogen responsible for sepsis can take several days, and in most patients the causative agent is never identified. If doctors are unable to pinpoint which types of bacteria or fungi are causing the infection, they treat sepsis patients empirically with broad-spectrum antibiotics -- but these often fail in many cases and they can have devastating side-effects. The sepsis treatment challenge continues to grow more complex as the prevalence of drug-resistant bacteria increases while the development of new antibiotics lags."This is setting the stage for a perfect storm," said Super, who was part of a team led by Wyss Institute Founding Director Don Ingber, M.D., Ph.D., that also included Wyss Institute Technology Development Fellow Joo Kang, Ph.D., and colleagues from Boston Children's Hospital, Harvard Medical School, and Massachusetts General Hospital.Kang, who is also a Research Associate at Harvard's School of Engineering and Applied Sciences (SEAS) and Research Fellow in the Vascular Biology Program at Boston Children's Hospital, set out with the team to build a fluidic device that works outside the body like a dialysis machine, and removes living and dead microbes of all varieties -- as well as toxins. They modeled it after the microarchitecture of the human spleen, an organ that removes pathogens and dead cells from the blood through a series of tiny interwoven blood channels.The biospleen is a microfluidic device that consists of two adjacent hollow channels that are connected to each other by a series of slits: one channel contains flowing blood, and the other has a saline solution that collects and removes the pathogens that travel through the slits. Key to the success of the device are tiny nanometer-sized magnetic beads that are coated with a genetically engineered version of a natural immune system protein called mannose binding lectin (MBL).In its innate state, MBL has a branch-like "head" and a stick-like "tail." In the body, the head binds to specific sugars on the surfaces of all sorts of bacteria, fungi, viruses, protozoa and toxins, and the tail cues the immune system to destroy them. However, sometimes other immune system proteins bind to the MBL tail and activate clotting and organ damage -- so Super used genetic engineering tools to lop off the tail and graft on a similar one from an antibody protein that does not cause these problems.The team then attached the hybrid proteins to magnetic beads 128 nanometers in diameter approximately one-five hundredths the width of a human hair to create novel beads that could be added to blood of an infected patient to bind to the pathogens and toxins without having to first identify the type of infectious agent. The sepsis device then has a magnet that pulls the pathogen-coated magnetic beads through the channels to cleanse the blood flowing through the device, which is then returned to the patient.The team first tested their blood-cleaning system using human blood in the laboratory that was spiked with pathogens. They were able to filter blood much faster than ever before, and the magnets efficiently pulled the beads -- coated with the pathogens -- out of the blood. In fact, more than 90 percent of key sepsis pathogens were bound and removed when the blood flowed through a single device at a rate of about a half to one liter per hour, and many devices can be linked together to obtain levels required for human blood cleansing at dialysis-like rates.Next they tested the device using rats that were infected with "We didn't have to kill the pathogens. We just captured and removed them," Super said. What's more, 90 percent of the treated animals survived compared to 14 percent of the controls -- and sure enough, thanks to the team's modified MBL, the immune system had not overreacted."Sepsis is a major medical threat, which is increasing because of antibiotic resistance. We're excited by the biospleen because it potentially provides a way to treat patients quickly without having to wait days to identify the source of infection, and it works equally well with antibiotic-resistant organisms," said Ingber, who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and the Vascular Biology Program at Boston Children's Hospital, as well as Professor of Bioengineering at SEAS. "We hope to move this towards human testing to advancing to large animal studies as quickly as possible." | Genetically Modified | 2,014 |
September 11, 2014 | https://www.sciencedaily.com/releases/2014/09/140911135438.htm | Evolutionary tools improve prospects for sustainable development | Solving societal challenges in food security, emerging diseases and biodiversity loss will require evolutionary thinking in order to be effective in the long run. Inattention to this will only lead to greater challenges such as short-lived medicines and agricultural treatments, problems that may ultimately hinder sustainable development, argues a new study published online today in | For the first time, scientists have reviewed progress in addressing a broad set of challenges in agriculture, medicine and environmental management using evolutionary approaches, approaches that consider species' evolutionary histories and the likelihood of rapid evolutionary adaptation to human activities.The study finds an urgent need for better implementation of these approaches, for example in managing the use of antibiotics and pesticides in order to reduce the escalating problem of resistance evolution. Furthermore, current efforts are found insufficient to reduce the accumulating costs from chronic disease and biodiversity loss, two challenges ultimately caused by exposure to food and environments to which people and threatened wildlife are poorly adapted.The study also assessed the potential for less commonly implemented strategies including gene therapies to treat human disease, the breeding of "climate change proof" crop varieties, such as flood tolerant rice, and translocating exotic strains for ecological restoration and forestry that will be better adapted to near-future conditions."Applying evolutionary biology has tremendous potential, because it takes into account how unwanted pests or pathogens may adapt rapidly to our interventions and how highly valued species including humans on the other hand are often very slow to adapt to changing environments through evolution. Not considering such aspects may result in outcomes opposite of those desired, making the pests more resistant to our actions, humans more exposed to diseases and vulnerable species less able to cope with new conditions," says biologist Peter Søgaard Jørgensen, one of the lead-authors and PhD from the Center for Macroecology, Evolution and Climate at the University of Copenhagen."To succeed in avoiding such unwanted outcomes however, we need to learn from successes and progress in all fields using evolutionary biology as a tool. Currently there is no such coordination, says Scott P. Carroll, lead-author and biologist at the University of California Davis and Director of the Institute for Contemporary Evolution. He continues:"A particular worry is that the unaddressed need for management of evolution that spans multiple sectors will lead to the spread of new infectious diseases and antimicrobial resistance genes between natural, human health and agricultural systems. It is clear that we need to strengthen evolutionary biology linkages across nature conservation, food production and human health and develop a shared strategy."Whereas we might have to wait for new solutions from human gene therapy, genetic engineering of crops and development of new medicines to replace old ones, many innovative solutions based on applying evolutionary biology already exist.For example, farmers in the United States and Australia have used planting of pest-friendly refuges to delay evolution of insect resistance to genetically engineered corn and cotton. These genetically modified crops kill certain pests, but without refuges the pests quickly adapt. Providing refuges of conventional plants has been especially effective for suppressing resistance in the pink bollworm, an invasive pest of cotton.However, Peter Jørgensen also cautions: "In many cases, decision makers must pay more attention to assuring that long-term benefits of applying these solutions do not come at a short-term cost for some individuals, for example from yield loss due to localised effects of pests in a particular year. By encouraging cost sharing, local communities and governments play a crucial role in ensuring that everybody gains from the benefits of using evolutionary biology to realise the long-term goals of sustainable development such as increasing food security, protecting biodiversity and improving human health and well-being."The article is published today in | Genetically Modified | 2,014 |
September 9, 2014 | https://www.sciencedaily.com/releases/2014/09/140909192212.htm | Less effective DNA repair process takes over as mice age | As we and other vertebrates age, our DNA accumulates mutations and becomes rearranged, which may result in a variety of age-related illnesses, including cancers. Biologists Vera Gorbunova and Andrei Seluanov have now discovered one reason for the increasing DNA damage: the primary repair process begins to fail with increasing age and is replaced by one that is less accurate. | The findings have been published in the journal "Scientists have had limited tools to accurately study how DNA repair changes with age," said Gorbunova. "We are now able to measure the efficiency with which cells in mice of different ages repair DNA breaks at the same place in the chromosome."Gorbunova explained that when mice are young, the breaks in DNA strands are repaired through a process called non-homologous end joining (NHEJ), in which the damage is repaired by gluing the DNA together with no or very little overlap. However, Gorbunova and Seluanov found that NHEJ began to fail as the mice got older, allowing a less reliable DNA repair process -- microhomology-mediated end joining (MMEJ) -- to take over. With MMEJ repairs, broken ends are glued together by overlapping similar sequences that are found within the broken DNA ends. This process leads to loss of DNA segments and the wrong pieces being stitched together.Gorbunova and her team were able to make their observations by working with genetically-modified mice whose cells produce green fluorescent protein (GFP) that glows each time the breaks are repaired. By tracking how many cells glowed green in different tissues, the researchers determined the efficiency of repair."We showed two things with these genetically-modified mice," said Gorbunova. "Not only did the efficiency of DNA repair decline with age, but the mice began using a sloppier repair mechanism, leading to more mutations, particularly in the heart and lungs."DNA breaks occur frequently because animal cells are under constant assault from routine activities in the environment -- whether by a blast of X-rays from a visit to the doctor or simply breathing in oxygen -- and, as a result, the DNA molecules often get damaged.Using the genetically modified mice, the research team can now look at how diet, medicines, and different genetic factors also affect DNA repair in mice."These mice may very well help us devise novel ways to prevent some of the illnesses associated with aging," said Gorbunova. | Genetically Modified | 2,014 |
September 8, 2014 | https://www.sciencedaily.com/releases/2014/09/140908121007.htm | Plant diversity in China vital for global food security | With climate change threatening global food supplies, new research claims the rich flora of China could be crucial to underpin food security in the future. | A team from the University of Birmingham and partners in China have identified 871 wild plant species native to China that have the potential to adapt and maintain 28 globally important crops, including rice, wheat, soybean, sorghum, banana, apple, citrus fruits, grape, stone fruits and millet. 42% of these wild plant species, known as crop wild relatives (CWR) occur nowhere else in the world.CWR are wild plant species closely related to crops which grow under a broad range of environmental conditions in their natural habitats and are therefore much more genetically variable. Their adaptive traits can be transferred to crops to improve tolerance to extreme environmental conditions and exposure to different pests and diseases, which helps sustain food production. Furthermore, they can be utilised to improve the nutritional and marketing qualities of crops.Examples of China's CWR successfully used to improve crops include: Oryza rufipogon, a wild relative of rice, utilised to confer tolerance to drought and aluminium toxicity; Glycine soja, used to improve protein content in soybean; and Vitis amurensis, a wild relative of grape, which has been used to improve cold tolerance.Worryingly, of these 871 CWR native to China, at least 17% are threatened with extinction in China and require urgent conservation action. This includes wild relatives of 16 crops that are globally threatened because they do not occur anywhere else in the world.The flora of China comprises more than 20,000 native higher plant species, a proportion of which have value as gene donors for crop improvement. However, until now, the full range of these potentially valuable CWR species had not been identified.The research carried out by academics from the University of Birmingham represents a significant contribution to global research in plant genetic resources for food and agriculture, particularly in the fight against the detrimental impacts of climate change on food security. The research in China is based upon methodologies developed and applied by the University's research team in Europe, but it is the first survey of its kind anywhere else in the world.Now a comprehensive database of CWR for China exists and the priority species have been identified, the next step is to systematically conserve their diversity in situ and via gene banks to ensure their wealth of resilient characteristics are available to plant breeders.Shelagh Kell, Research Fellow, School of Biosciences said "China has remarkable wild plant diversity. With more plant species than Europe and CWR of globally important food crops, its position as a provider of plant genetic resources for crop improvement is crucial to us all globally. Now that we have identified China's priority CWR and some of the hotspots in which they occur, stakeholders need to implement a strategy to secure their future."Conservation planning and plant breeding knowledge is very advanced but the politics of establishing a network for in situ protection of CWR and for accessing plant material for crop improvement is incredibly complex. However, urgent attention needs to be paid to China's CWR to ensure that they are adequately conserved, so that this diversity is available for use in crop improvement programmes before it is lost forever." | Genetically Modified | 2,014 |
September 2, 2014 | https://www.sciencedaily.com/releases/2014/09/140902092957.htm | Cultivating biodiversity: Sorghum example | It is difficult to distinguish the human impact on the effects of natural factors on the evolution of crop plants. A Franco-Kenyan research team has managed to do just that for sorghum, one of the main cereals in Africa. The scientists demonstrated how three societies living on the slopes of Mount Kenya have shaped the geographic distribution and structure of the genetic diversity of local varieties. Because of their practices for selecting and exchanging crop seeds for harvesting, the farmers in each ethnic group maintain varieties which are unique to them. These prove to be genetically and phenotypically differentiated, despite their close geographical proximity. This study sheds light on the debate on the ownership and redistribution of benefits from genetic resources. | Climate, environment and competition between species are well-known factors in the genetic evolution of plants. But crop plants are subject to an additional force: human action. Up to now, few studies have been able to distinguish the results of the domestication of the effects of natural constraints on crop diversity. To shed some light on this question, a Franco-Kenyan research team became interested in a particular territory: the eastern slopes of Mount Kenya. This territory offers both an ecologically homogeneous environment and brings together different ethnic groups, the Chuka, Mbeere and Tharaka peoples, making it possible to compare the influence of their different agricultural practices and traditional knowledge on the diversity of sorghum, a very important cereal in this area.Researchers from the IRD, Cirad and At the same time, the researchers inventoried and sampled the different varieties of sorghum grown by 130 Chuka, Mbeere and Tharaka households. DNA analysis of the 300 plants gathered has identified four genetic groups of sorghum. Two of them correspond to two introduced varieties. These are varieties that were genetically improved by NGOs or the national agricultural extension services. One of these varieties, which was introduced almost 15 years ago, seems to be more genetically diverse among the Chuka than with the other ethnic groups. This suggests that the practices of the three communities leave their "signature" in the genomes of sorghum populations.Using this multidisciplinary approach bringing together anthropologists, geneticists and agronomists, this work shows the role of human societies in the geographic distribution and evolution of the genetic diversity of crop plants. Identifying the factors that shape biodiversity locally helps to preserve them better in the future. Furthermore, this confirms the influence of local practices and knowledge on the diversity of life, which is a central issue in the debate on the ownership and redistribution of benefits from the use of genetic resources. | Genetically Modified | 2,014 |
September 2, 2014 | https://www.sciencedaily.com/releases/2014/09/140902092202.htm | War between bacteria, phages benefits humans | In the battle between our immune systems and cholera bacteria, humans may have an unknown ally in bacteria-killing viruses known as phages. In a new study, researchers from Tufts University, Massachusetts General Hospital, Partners In Health, Haiti's National Public Health Laboratory, and elsewhere, report that phages can force cholera bacteria to give up their virulence in order to survive. Importantly, the study -- published in eLife -- found that cholera's mutational escape from phage predation occurs during human infection. | First author Kimberley Seed, Ph.D., and corresponding author Andrew Camilli, Ph.D., both of Tufts University School of Medicine, and their co-authors analyzed phage resistance properties and DNA sequences of cholera bacteria taken from phage-positive stool samples from patients with cholera in Haiti and Bangladesh, two countries where cholera outbreaks are common at present.They first determined that cholera bacteria from Haiti changed its DNA in order to fight phages. They compared the bacteria from Haiti to bacteria from Bangladesh collected over many years to determine if the changes were happening on multiple occasions in both countries or only in isolated groups or cases.The research team discovered that across both time and geography, the cholera bacteria mutated during human infection in order to trade their virulence, or ability to persist and make a human sick, for the ability to defend against the phages. Alternatively, in some patients, the cholera bacteria mutated in a more conservative manner to retain virulence, yet sacrificed the ability to grow optimally in the environment. In either scenario, the cholera bacteria appear to have traded something important in order to survive the onslaught from phages."This is the first time we have seen cholera bacteria defend themselves from phages while infecting humans. This suggests that these phages are actively working in our favor, first by killing cholera bacteria within the patient, and second, by genetically weakening the bacteria that are shed by the infected patient such that they are less fit to survive in the environment or less able to cause infection in other people," said senior author Andrew Camilli, a Howard Hughes Medical Institute investigator, professor of molecular biology & microbiology at Tufts University School of Medicine, and member of the Molecular Microbiology program faculty at the Sackler School of Graduate Biomedical Sciences at Tufts University."This important finding suggests that we may be able to leverage the strength of phages for treating people with cholera or perhaps preventing cholera in people who may have been recently exposed as an alternative to antibiotics," he continued."Seeing this rapid evolutionary change in the cholera bacteria occurring during human infection suggests that the phages are posing a very strong threat. And to observe this in two different continents suggests that this is not a one-time find, but that it may be happening consistently during cholera outbreaks," said first author Seed, now assistant professor of molecular, cellular and developmental biology at University of Michigan. "Additionally, virtually all bacteria can be infected by phages, which are found wherever bacteria are. So this finding with cholera may be the start of a broader understanding of how phages and bacteria evolve."Previous work by Camilli and Seed, published last year in Nature, provided the first evidence that a phage could acquire a wholly functional and adaptive immune system. They observed that the phage could use this acquired immune system to disarm a phage defense system of the cholera bacteria, allowing the phage to ultimately destroy its bacterial host. This study bolstered the concept of using phage to prevent or treat bacterial infections, and extended the idea that phages can be extremely sophisticated bacterial predators. The team is now investigating the details of this particular arms race between phage and bacteria in hopes of better understanding how phage influence cholera outbreaks and how we can further leverage phages to treat or prevent infections.The World Health Organization reports that there are an estimated three-to five million cases of cholera cases and 100,000 to 120,000 deaths due to cholera each year. This summer, at least 67 people in Ghana have died of cholera while 6,000 others have been infected. In northern Cameroon, there are reports that 200 people have died and many more infected in the last few months. A current outbreak in South Sudan has taken 130 lives out of a total of more than 5,800 cases. In Haiti, since the beginning of the epidemic there (October 2010) and through March of this year, more than 8,500 people have died, out of more than 700,000 reported cases. | Genetically Modified | 2,014 |
August 31, 2014 | https://www.sciencedaily.com/releases/2014/08/140831150329.htm | Discovery reveals how bacteria distinguish harmful vs. helpful viruses | When they are not busy attacking us, germs go after each other. But when viruses invade bacteria, it doesn't always spell disaster for the infected microbes: Sometimes viruses actually carry helpful genes that a bacterium can harness to, say, expand its diet or better attack its own hosts. | Scientists have assumed the bacterial version of an immune system would robotically destroy anything it recognized as invading viral genes. However, new experiments at Rockefeller University have now revealed that one variety of the bacterial immune system known as the CRISPR-Cas system can distinguish viral foe from friend. And, the researchers report in a paper published August 31 in "Transcription -- an initial step in the process that reads genes, including those of viruses -- makes the difference," says researcher Luciano Marraffini, head of the Laboratory of Bacteriology. "The full genome of viruses in their lytic, or destructive phase, is transcribed. Meanwhile, a few of the genes from a virus are transcribed during its lysogenic, or dormant phase."Viruses in their lytic phase make copies of themselves using a cell's machinery before destroying it to liberate these new viruses. Viruses in their lysogenic phase, meanwhile, quietly integrate into a host's genetic material. And this is where they offer their potential benefit to the bacteria, which co-opt viral genes for their own ends. In fact, some disease-causing microbes, such as the bacterium responsible for diphtheria, must pick up the right virus in order to attack humans.Scientists have only discovered this adaptive bacterial immune system relatively recently. Its function relies on CRISPRs, sections of DNA that contain repeating sequences interspersed with unique sequences called spacers. (CRISPR stands for clustered regularly interspaced short palindromic repeats.) The spacer sequences match the sequences in the viral genetic code, making it possible for enzymes encoded by CRISPR-associated genes (Cas) to chop out single spacer sequences from the RNA transcribed from the CRISPR DNA. Other Cas enzymes then use these spacer sequences as guides to target invaders for destruction.The system can adapt to new invaders by acquiring new spacer sequences to target them. Recently, CRISPR-Cas systems have attracted significant scientific attention because their ability to make precisely targeted cuts in DNA can be put to use to genetically engineer all types of cells."Our understanding of CRISPR-Cas systems remains in the early stages, but, so far, it has generally been thought they lack a sophisticated way of discriminating their targets. In other words, once they target something, it will be chopped up," says the study's lead author, graduate student Gregory Goldberg. "For the first time, our work has shown that a CRISPR-Cas system, one found in Most previous work has focused on lytic viruses. However, Staphylococci host many viruses capable of entering a lysogenic phase. The researchers also uncovered a telling asymmetry in the Staphylococcal CRISPR system's ability to effectively target a sequence and its counterpart on two strands of complimentary DNA. They suspected this discrepancy arose because transcription proceeds in a single direction for most viral genes, meaning one of the two target strands is not transcribed."The big clue showed up when we isolated a mutant virus that managed to evade destruction. Sometimes viruses can do this through a mutation in a target sequence that prevents the system from identifying them. But when we sequenced the genome of this phage, we found a mutation in a region that promotes transcription instead," Goldberg says.In a series of experiments, he and colleagues tested their hypothesis that the Staphylococcal CRISPR-Cas system, known as Type III-A, can tolerate an infection by a lysogenic virus, so long as the target sequences are not transcribed. They engineered a target sequence that would undergo transcription only in the presence of a specific chemical. As a result, the Type III-A CRISPR-Cas system only destroyed the target in the presence of this chemical."This discovery of a transcription requirement is likely to surprise many who work with these systems," Marraffini says. "Although we do not yet understand the mechanism behind it, we can say that the Type -III-A system is quite different from other CRISPR-Cas systems, of which there is a mysteriously large variety. Our discovery hints at the possibility that each CRISPR type and subtype recognizes and destroys its targets in different ways, each in tune with a particular bacterium's needs. If these different targeting mechanisms do exist, they could have important implications for biotechnology." | Genetically Modified | 2,014 |
August 28, 2014 | https://www.sciencedaily.com/releases/2014/08/140828184743.htm | Mouse model provides window into working brain | University of Utah scientists have developed a genetically engineered line of mice that is expected to open the door to new research on epilepsy, Alzheimer's and other diseases. | The mice carry a protein marker, which changes in degree of fluorescence in response to different calcium levels. This will allow many cell types, including cells called astrocytes and microglia, to be studied in a new way."This is opening up the possibility to decipher how the brain works," said Petr Tvrdik, Ph.D., a research fellow in human genetics and a senior author on the study.The research was published Aug. 14, 2014, in "We're really in the era of team science," said John White, Ph.D., professor of bioengineering, executive director of the Brain Institute and the study's corresponding author.With the new mouse line, scientists can use a laser-based fluorescence microscope to study the calcium indicator in the glial cells of the living mouse, either when the mouse is anesthetized or awake. Calcium is studied because it is an important signaling molecule in the body and it can reveal how well the brain is functioning.Using this method, the scientists are essentially creating a window into the working brain to study the interactions between neurons, astrocytes and microglia."We believe this will give us new insights for treatments of epilepsy and for new views of how the immune system of the brain works," White said.About one-third of the 3 million Americans estimated to have epilepsy lack adequate treatment to manage the disease.Describing a long-standing collaboration with fellow university researcher and professor of pharmacology and toxicology Karen Wilcox, Ph.D., White said, "We believe the glial cells are malfunctioning in epilepsy. What we're trying to do is find out in what ways astrocytes participate in the disease."This research is expected to lead to new classes of drugs.The ability to track calcium changes in microglial cells will also open up the possibility of studying inflammatory diseases of the brain. Every neurological disease, including Multiple Sclerosis and Alzheimer's, appears to include components of inflammation, the scientists said."Live imaging and monitoring microglial activity in response to inflammation was not possible before," said Tvrdik. In the past, researchers studied post-mortem tissue or relied on invasive approaches using synthetic dyes. | Genetically Modified | 2,014 |
August 21, 2014 | https://www.sciencedaily.com/releases/2014/08/140821124823.htm | Mouse model for epilepsy, Alzheimer's gives window into working brain | University of Utah scientists have developed a genetically engineered line of mice that is expected to open the door to new research on epilepsy, Alzheimer's and other diseases. | The mice carry a protein marker, which changes in degree of fluorescence in response to different calcium levels. This will allow many cell types, including cells called astrocytes and microglia, to be studied in a new way."This is opening up the possibility to decipher how the brain works," said Petr Tvrdik, Ph.D., a research fellow in human genetics and a senior author on the study.The research was published Aug. 14, 2014, in "We're really in the era of team science," said John White, Ph.D., professor of bioengineering, executive director of the Brain Institute and the study's corresponding author.With the new mouse line, scientists can use a laser-based fluorescence microscope to study the calcium indicator in the glial cells of the living mouse, either when the mouse is anesthetized or awake. Calcium is studied because it is an important signaling molecule in the body and it can reveal how well the brain is functioning.Using this method, the scientists are essentially creating a window into the working brain to study the interactions between neurons, astrocytes and microglia."We believe this will give us new insights for treatments of epilepsy and for new views of how the immune system of the brain works," White said.About one-third of the 3 million Americans estimated to have epilepsy lack adequate treatment to manage the disease.Describing a long-standing collaboration with fellow university researcher and professor of pharmacology and toxicology Karen Wilcox, Ph.D., White said, "We believe the glial cells are malfunctioning in epilepsy. What we're trying to do is find out in what ways astrocytes participate in the disease."This research is expected to lead to new classes of drugs.The ability to track calcium changes in microglial cells will also open up the possibility of studying inflammatory diseases of the brain. Every neurological disease, including Multiple Sclerosis and Alzheimer's, appears to include components of inflammation, the scientists said."Live imaging and monitoring microglial activity and responses to inflammation was not possible before," said Tvrdik, particularly in living animals. In the past, researchers studied post-mortem tissue or relied on invasive approaches using synthetic dyes. | Genetically Modified | 2,014 |
August 19, 2014 | https://www.sciencedaily.com/releases/2014/08/140819155222.htm | New vaccine shows promise as stronger weapon against both tuberculosis, leprosy | In many parts of the world, leprosy and tuberculosis live side-by-side. Worldwide there are approximately 233,000 new cases of leprosy per year, with nearly all of them occurring where tuberculosis is endemic. | The currently available century-old vaccine Bacille Calmette-Guerin, or BCG, provides only partial protection against both tuberculosis and leprosy, so a more potent vaccine is needed to combat both diseases. UCLA-led research may have found a stronger weapon against both diseases.In a study published in the September issue of the peer-reviewed journal "This is the first study demonstrating that an improved vaccine against tuberculosis also offers cross-protection against Mycobacterium leprae, the causative agent of leprosy," said Dr. Marcus A. Horwitz, professor of medicine and microbiology, immunology and molecular genetics, and the study's senior author. "That means that this vaccine has promise for better protecting against both major diseases at the same time."It is also the first study demonstrating that boosting a recombinant BCG vaccine further improves cross-protection against leprosy," he added.In one experiment, mice were immunized with either rBCG30 or the old BCG vaccine, or they were given a salt solution. Ten weeks later, the mice were injected with live leprosy bacteria into their footpads and seven months after that, the number of leprosy bacteria in their footpads was measured. The researchers found that the mice given BCG or rBCG30 had much fewer leprosy bacteria in their footpads than the mice given the salt solution. Additionally, mice immunized with rBCG30 had significantly fewer leprosy bacteria than those vaccinated with BCG.In a second experiment, the mice were first immunized with BCG or rBCG30, and then immunized with a booster vaccine (r30) consisting of the TB bacterium's 30-kDa Antigen 85B protein in adjuvant -- that is, in a chemical formulation that enhances the immune response. The group of mice immunized with rBCG30 and boosted with r30 had no detectable leprosy bacteria in their footpads, in contrast to groups of mice immunized with all other vaccines tested, including BCG and rBCG30 alone and BCG boosted with r30.In other experiments, the immune responses of the mice were measured after vaccination. Mice immunized with rBCG30 and boosted with r30 had markedly enhanced immune responses to the leprosy bacterium's version of the Antigen 85B protein, which is very similar to the one expressed by the tuberculosis bacillus, compared with mice immunized with the other vaccines and vaccine combinations.A Phase 1 human trial for rBCG30 has proven that it is safe and significantly more effective than BCG, and it is the only candidate replacement vaccine for BCG tested thus far to satisfy both of these key clinical criteria. Horwitz noted that this most recent study, however, was conducted in an animal model of leprosy, so further study is needed to gauge the effectiveness of the rBCG30 vaccine in protecting against leprosy in humans. The next step in the research will be to test the rBCG30 vaccine for efficacy in humans against TB. If it's effective against TB, then the next step would be to test its effectiveness in humans against leprosy. | Genetically Modified | 2,014 |
August 18, 2014 | https://www.sciencedaily.com/releases/2014/08/140818113430.htm | Pigs' hearts transplanted into baboon hosts remain viable more than a year | Investigators from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) have successfully transplanted hearts from genetically engineered piglets into baboons' abdomens and had the hearts survive for more than one year, twice as long as previously reported. This was achieved by using genetically engineered porcine donors and a more focused immunosuppression regimen in the baboon recipients, according to a study published in | Cardiac transplantation is the treatment of choice for end stage heart failure. According to the NHLBI, approximately 3,000 people in the US are on the waiting list for a heart transplant, while only 2,000 donor hearts become available each year. For cardiac patients currently waiting for organs, mechanical assist devices are the only options available. These devices, however, are imperfect and experience issues with power supplies, infection, and problems with blood clots and bleeding.Transplantation using an animal organ, or xenotransplantation, has been proposed as a valid option to save human lives. "Until we learn to grow organs via tissue engineering, which is unlikely in the near future, xenotransplantation seems to be a valid approach to supplement human organ availability. Despite many setbacks over the years, recent genetic and immunologic advancements have helped revitalized progress in the xenotransplantation field," comments lead investigator Muhammad M. Mohiuddin, MD, of the Cardiothoracic Surgery Research Program at the NHLBI.Dr. Mohiuddin's group and other investigators have developed techniques on two fronts to overcome some of the roadblocks that previously hindered successful xenotransplantation. The first advance was the ability to produce genetically engineered pigs as a source of donor organs by NHLBI's collaborator, Revivicor, Inc. The pigs had the genes that cause adverse immunologic reactions in humans "knocked out" and human genes that make the organ more compatible with human physiology were inserted. The second advance was the use of target-specific immunosuppression, which limits rejection of the transplanted organ rather than the usual generalized immunosuppression, which is more toxic.Pigs were chosen because their anatomy is compatible with that of humans and they have a rapid breeding cycle, among other reasons. They are also widely available as a source of organs.In this study, researchers compared the survival of hearts from genetically engineered piglets that were organized into different experimental groups based on the genetic modifications introduced. The gene that synthesizes the enzyme alpha 1-3 galactosidase transferase was "knocked out" in all piglets, thus eliminating one immunologic rejection target. The pig hearts also expressed one or two human transgenes to prevent blood from clotting. The transplanted hearts were attached to the circulatory systems of the host baboons, but placed in the baboons' abdomens. The baboons' own hearts, which were left in place, maintained circulatory function, and allowed the baboons to live despite the risk of organ rejection.The researchers found that in one group (with a human gene), the average transplant survival was more than 200 days, dramatically surpassing the survival times of the other three groups (average survival 70 days, 21 days, and 80 days, respectively). Two of the five grafts in the long-surviving group stopped contracting on postoperative days 146 and 150, but the other three grafts were still contracting at more than 200 to 500 days at the time of the study's submission for publication.Prolonged survival was attributed to several modifications. This longest-surviving group was the only one that had the human thrombomodulin gene added to the pigs' genome. Dr. Mohiuddin explains that thrombomodulin expression helps avoid some of the microvascular clotting problems that were previously associated with organ transplantation.Another difference was the type, strength, and duration of antibody used for costimulation blockade to suppress T and B cell immune response in the hosts. In several groups, longer survival of transplants was observed with the use of anti-CD40 monoclonal antibodies but the longest-surviving group was treated specifically with a high dose of recombinant mouse-rhesus chimeric antibody (clone 2C10R4). In contrast, use of an anti-CD40 monoclonal antibody generated in a mouse (clone 3A8) did not extend survival. Anti-CD40 monoclonal antibodies also allow for faster recovery, says Dr. Mohiuddin.No complications, including infections, were seen in the longest-survival group. The researchers used surveillance video and telemetric monitoring to identify any symptoms of complications in all groups, such as abdominal bleeding, gastrointestinal bleeding, aspiration pneumonia, seizures, or blood disorders.The goal of the current study was to evaluate the viability of the transplants. The researchers' next step is to use hearts from the genetically-engineered pigs with the most effective immunosuppression in the current experiments to test whether the pig hearts can sustain full life support when replacing the original baboon hearts."Xenotransplantation could help to compensate for the shortage of human organs available for transplant. Our study has demonstrated that by using hearts from genetically engineered pigs in combination with target-specific immunosuppression of recipient baboons, organ survival can be significantly prolonged. Based on the data from long-term surviving grafts, we are hopeful that we will be able to repeat our results in the life-supporting model. This has potential for paving the way for the use of animal organs for transplantation into humans," concludes Dr. Mohiuddin. | Genetically Modified | 2,014 |
August 14, 2014 | https://www.sciencedaily.com/releases/2014/08/140812235300.htm | Genetically engineered fruit flies could save crops | Releasing genetically engineered fruit flies into the wild could prove to be a cheap, effective and environmentally friendly way of pest control, according to scientists at the University of East Anglia and Oxitec Ltd. | New research published today reveals how the release of genetically engineered male flies could be used as an effective population suppression method – saving crops around the world.The Mediterranean fruit fly is a serious agricultural pest which causes extensive damage to crops. It is currently controlled by a combination of insecticides, baited traps, biological control and releasing sterilised insects to produce non-viable matings, known as the Sterile Insect Technique (SIT).Lead researcher Dr Philip Leftwich, from UEA’s school of Biological Sciences and Oxitec, said: “The Mediterranean Fruit Fly infests more than 300 types of cultivated and wild fruits, vegetables and nuts. It is a real pest to agriculture and causes extreme damage to crops all around the world.“Of all of the current techniques used to control these flies, SIT is considered the most environmentally friendly as it uses sterile males to interrupt matings between wild males and females. The down side is that these males don’t tend to mate as well in the wild because the irradiation method used for sterilisation weakens them.“Our research looked at whether releasing Oxitec flies, which are genetically engineered so that only male fly offspring survive, could provide a better alternative.“We simulated a wild environment within secure eight-meter greenhouses containing lemon trees at the University of Crete. When we tested the release of the genetically modified male flies, we found that they were capable of producing rapid population collapse in our closed system.“This method presents a cheap and effective alternative to irradiation. We believe this is a promising new tool to deal with insects which is both environmentally friendly and effective.”The Oxitec method works by introducing a female-specific gene into the insects that interrupts development before females reach a reproductive stage. Populations of healthy males and females can be produced in controlled environments by the addition of a chemical repressor. If the chemical repressor is absent in the genetically engineered flies’ diet, only males survive. The surviving males are released, mate with local wild pest females and pass the female specific self-limiting trait onto the progeny resulting in no viable female offspring.The next stage of the research will be to gain approval for open-field studies.‘Genetic elimination of field-cage populations of Mediterranean Fruit Flies’ is published in the journal | Genetically Modified | 2,014 |
August 13, 2014 | https://www.sciencedaily.com/releases/2014/08/140813131044.htm | Coming soon: Genetically edited 'super bananas' and other fruit? | Recent advances that allow the precise editing of genomes now raise the possibility that fruit and other crops might be genetically improved without the need to introduce foreign genes, according to researchers writing in the Cell Press publication | With awareness of what makes these biotechnologies new and different, genetically edited fruits might be met with greater acceptance by society at large than genetically modified organisms (GMOs) so far have been, especially in Europe, they say. This could mean that genetically edited versions of GMOs such as "super bananas" that produce more vitamin A and apples that don't brown when cut, among other novelties, could be making an appearance on grocery shelves."The simple avoidance of introducing foreign genes makes genetically edited crops more "natural" than transgenic crops obtained by inserting foreign genes," said Chidananda Nagamangala Kanchiswamy of Istituto Agrario San Michele in Italy.For instance, changes to the characteristics of fruit might be made via small genetic tweaks designed to increase or decrease the amounts of natural ingredients that their plant cells already make. Genome editing of fruit has become possible today due to the advent of new tools -- CRISPR, TALEN, and the like -- and also because of the extensive and growing knowledge of fruit genomes.So far, editing tools have not been applied to the genetic modification of fruit crops. Most transgenic fruit crop plants have been developed using a plant bacterium to introduce foreign genes, and only papaya has been commercialized in part because of stringent regulation in the European Union (EU). The researchers say that genetically edited plants, modified through the insertion, deletion, or altering of existing genes of interest, might even be deemed as nongenetically modified, depending on the interpretation of the EU commission and member state regulators.Fruit crops are but one example of dozens of possible future applications for genetically edited organisms (GEOs), Kanchiswamy and his colleagues say. That would open the door to the development of crops with superior qualities and perhaps allow their commercialization even in countries in which GMOs have so far met with harsh criticism and controversy."We would like people to understand that crop breeding through biotechnology is not restricted only to GMOs," he said. "Transfer of foreign genes was the first step to improve our crops, but GEOs will surge as a "natural" strategy to use biotechnology for a sustainable agricultural future." | Genetically Modified | 2,014 |
August 6, 2014 | https://www.sciencedaily.com/releases/2014/08/140806142213.htm | Gene-editing technique offers new way to model cancer | Sequencing the genomes of tumor cells has revealed thousands of mutations associated with cancer. One way to discover the role of these mutations is to breed a strain of mice that carry the genetic flaw -- but breeding such mice is an expensive, time-consuming process. | Now, MIT researchers have found an alternative: They have shown that a gene-editing system called CRISPR can introduce cancer-causing mutations into the livers of adult mice, enabling scientists to screen these mutations much more quickly.In a study appearing in the Aug. 6 issue of "The sequencing of human tumors has revealed hundreds of oncogenes and tumor suppressor genes in different combinations. The flexibility of this technology, as delivery gets better in the future, will give you a way to pretty rapidly test those combinations," says Institute Professor Phillip Sharp, an author of the paper.Tyler Jacks, director of MIT's Koch Institute for Integrative Cancer Research and the David H. Koch Professor of Biology, is the paper's senior author. The lead authors are Koch Institute postdocs Wen Xue, Sidi Chen, and Hao Yin.CRISPR relies on cellular machinery that bacteria use to defend themselves from viral infection. Researchers have copied this bacterial system to create gene-editing complexes that include a DNA-cutting enzyme called Cas9 bound to a short RNA guide strand that is programmed to bind to a specific genome sequence, telling Cas9 where to make its cut.In some cases, the researchers simply snip out part of a gene to disrupt its function; in others, they also introduce a DNA template strand that encodes a new sequence to replace the deleted DNA.To investigate the potential usefulness of CRISPR for creating mouse models of cancer, the researchers first used it to knock out p53 and pten, which protect cells from becoming cancerous by regulating cell growth. Previous studies have shown that genetically engineered mice with mutations in both of those genes will develop cancer within a few months.Studies of such genetically engineered mice have yielded many important discoveries, but the process, which requires introducing mutations into embryonic stem cells, can take more than a year and costs hundreds of thousands of dollars. "It's a very long process, and the more genes you're working with, the longer and more complicated it becomes," Jacks says.Using Cas enzymes targeted to cut snippets of p53 and pten, the researchers were able to disrupt those two genes in about 3 percent of liver cells, enough to produce liver tumors within three months.The researchers also used CRISPR to create a mouse model with an oncogene called beta catenin, which makes cells more likely to become cancerous if additional mutations occur later on. To create this model, the researchers had to cut out the normal version of the gene and replace it with an overactive form, which was successful in about 0.5 percent of hepatocytes (the cells that make up most of the liver).The ability to not only delete genes, but also to replace them with altered versions "really opens up all sorts of new possibilities when you think about the kinds of genes that you would want to mutate in the future," Jacks says. "Both loss of function and gain of function are possible."Using CRISPR to generate tumors should allow scientists to more rapidly study how different genetic mutations interact to produce cancers, as well as the effects of potential drugs on tumors with a specific genetic profile."This is a game-changer for the production of engineered strains of human cancer," says Ronald DePinho, director of the University of Texas MD Anderson Cancer Center, who was not part of the research team. "CRISPR/Cas9 offers the ability to totally ablate gene function in adult mice. Enhanced potential of this powerful technology will be realized with improved delivery methods, the testing of CRISPR/Cas9 efficiency in other organs and tissues, and the use of CRISPR/Cas9 in tumor-prone backgrounds."In this study, the researchers delivered the genes necessary for CRISPR through injections into veins in the tails of the mice. While this is an effective way to get genetic material to the liver, it would not work for other organs of interest. However, nanoparticles and other delivery methods now being developed for DNA and RNA could prove more effective in targeting other organs, Sharp says. | Genetically Modified | 2,014 |
August 1, 2014 | https://www.sciencedaily.com/releases/2014/08/140801213521.htm | Clues to curbing obesity found in neuronal 'sweet spot' | Preventing weight gain, obesity, and ultimately diabetes could be as simple as keeping a nuclear receptor from being activated in a small part of the brain, according to a new study by Yale School of Medicine researchers. | Published in the Aug. 1 issue of "These animals ate fat and sugar, and did not gain weight, while their control littermates did," said lead author Sabrina Diano, professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine. "We showed that the PPARgamma receptor in neurons that produce POMC could control responses to a high-fat diet without resulting in obesity."POMC neurons are found in the hypothalamus and regulate food intake. They are the neurons that when activated make you feel full and curb appetite. PPARgamma regulates the activation of these neurons.Diano and her team studied transgenic mice that were genetically engineered to delete the PPARgamma receptor from POMC neurons. They wanted to see if they could prevent the obesity associated with a high-fat, high-sugar diet."When we blocked PPARgamma in these hypothalamic cells, we found an increased level of free radical formation in POMC neurons, and they were more active," said Diano, who is also professor of comparative medicine and neurobiology at Yale and director of the Reproductive Neurosciences Group.The findings also have key implications in diabetes. PPARgamma is a target of thiazolidinedione (TZD), a class of drugs used to treat type 2 diabetes. They lower blood-glucose levels, however, patients gain weight on these medications."Our study suggests that the increased weight gain in diabetic patients treated with TZD could be due to the effect of this drug in the brain, therefore, targeting peripheral PPARgamma to treat type 2 diabetes should be done by developing TZD compounds that can't penetrate the brain," said Diano. "We could keep the benefits of TZD without the side-effects of weight gain. Our next steps in this research are to test this theory in diabetes mouse models."Other Yale authors on the study included Lihong Long, Chitoku Toda, Jin Kwon Jeong, and Tamas Horvath.The study was funded by the National Institutes of Health (RO1DK097566) | Genetically Modified | 2,014 |
July 29, 2014 | https://www.sciencedaily.com/releases/2014/07/140729093116.htm | New method provides researchers with efficient tool for tagging proteins | DNA linked to proteins -- including antibodies -- provides a strong partnership that can be used in diagnostic techniques, nanotechnology and other disciplines. DNA-protein conjugates -- which tag proteins with DNA -- can be used for purposes such as the sensitive detection and visualisation of biological material. The method also provides easier access to handling proteins in nanotechnology, where the DNA acts as a handle on the protein. | Controlling the conjugation of macromolecules such as DNA and proteins can be quite a challenge when scientists want to join them in particular ways and places. Researchers at Aarhus University have now developed a new and efficient method to tag proteins with DNA, making it much simpler to control the process than previously. The new method was developed at the Danish National Research Foundation's Centre for DNA Nanotechnology (CDNA) in collaboration between researchers at Aarhus University's Interdisciplinary Nanoscience Centre (iNANO), Department of Chemistry and Department of Molecular Biology and Genetics. The work is described in the highly scientific journal "Maintaining the protein's function and activity often requires the attachment of only a single DNA strand to the protein. At the same time, it can be important to know where the DNA strand is attached to the protein. You can normally only achieve this if you are working with genetically engineered proteins. This is a time-consuming and technically challenging process," explains PhD student Christian B. Rosen, CDNA, Aarhus University -- one of the researchers behind the new method.The new method makes it possible to direct the tagging of proteins with DNA to a particular site on the protein, without genetically modifying the protein beforehand. In other words, it is possible to tag natural proteins, including antibodies.The researchers use a piece of DNA that is engineered to bind to metal ions. Using this 'control stick', they direct another piece of DNA to a metal binding site on the protein, where it reacts. A considerable number of proteins bind metal ions, which makes them suitable for this method. A significant point in using this method is that the tagged proteins retain their functionality after being bound to DNA.The researchers are applying for a patent for the new method, which has potential in a number of areas."Of greatest importance is the fact that we can use our technique for tagging antibodies. Antibodies that are chemically bound (conjugated) to chemotherapeutics represent an entirely new class of medicine in which the antibody part is used to recognise specific tissue and the chemotherapeutic part is used to kill the cell. When you tag antibodies, it's important that you keep the recognition element of the antibody intact. With our method, we strike the constant part of the antibody and not the variable part, which contains its recognition element. Our technique is therefore general for a major class of proteins," explains Anne Louise Bank Kodal, CDNA, another author of the article.The researchers are working on further developing the method so they can attach chemotherapeutics to antibodies and not just DNA. | Genetically Modified | 2,014 |
July 22, 2014 | https://www.sciencedaily.com/releases/2014/07/140722142521.htm | Therapeutic bacteria prevent obesity in mice, study finds | A probiotic that prevents obesity could be on the horizon. | Bacteria that produce a therapeutic compound in the gut inhibit weight gain, insulin resistance and other adverse effects of a high-fat diet in mice, Vanderbilt University investigators have discovered."Of course it's hard to speculate from mouse to human," said senior investigator Sean Davies, Ph.D., assistant professor of Pharmacology. "But essentially, we've prevented most of the negative consequences of obesity in mice, even though they're eating a high-fat diet."Regulatory issues must be addressed before moving to human studies, Davies said, but the findings published in the August issue of the Davies has a long-standing interest in using probiotic bacteria -- "friendly" bacteria like those in yogurt -- to deliver drugs to the gut in a sustained manner, in order to eliminate the daily drug regimens associated with chronic diseases.In 2007, he received a National Institutes of Health Director's New Innovator Award to develop and test the idea."The NIH basically said, 'we like this idea, now make it work,'" Davies said. "The New Innovator Award was critical to our success."Other studies have demonstrated that the natural gut microbiota plays a role in obesity, diabetes and cardiovascular disease."The types of bacteria you have in your gut influence your risk for chronic diseases," Davies said. "We wondered if we could manipulate the gut microbiota in a way that would promote health."To start, the team needed a safe bacterial strain that colonizes the human gut. They selected They genetically modified the "NAPE seemed like a great compound to try -- since it's something that the host normally produces," Davies said.The investigators added the NAPE-producing bacteria to the drinking water of mice eating a high-fat diet for eight weeks. Mice that received the modified bacteria had dramatically lower food intake, body fat, insulin resistance and fatty liver compared to mice receiving control bacteria.They found that these protective effects persisted for at least four weeks after the NAPE-producing bacteria were removed from the drinking water. And even 12 weeks after the modified bacteria were removed, the treated mice still had much lower body weight and body fat compared to the control mice. Active bacteria no longer persisted after about six weeks."We still haven't achieved our ultimate goal, which would be to do one treatment and then never have to administer the bacteria again," Davies said. "Six weeks is pretty long to have active bacteria, and the animals are still less obese 12 weeks out."This paper provides a proof of concept," he said. "Clearly, we can get enough bacteria to persist in the gut and have a sustained effect. We would like for that effect to last longer."Davies noted that the researchers also observed effects of the compounds in the liver, suggesting that it may be possible to use modified bacteria to deliver therapeutics beyond the gut.The investigators are currently working on strategies to address regulatory issues related to containing the bacteria, for example by knocking out genes required for the bacteria to live outside the treated host. | Genetically Modified | 2,014 |
July 22, 2014 | https://www.sciencedaily.com/releases/2014/07/140722091559.htm | Viral therapy could boost limb-saving cancer treatment | Viruses designed to target and kill cancer cells could boost the effectiveness of chemotherapy to the arms and legs and help avoid amputation, a new study reports. | Scientists at The Institute of Cancer Research, London, tested the effectiveness of a genetically engineered version of the virus used to vaccinate against smallpox.They found use of the virus alongside isolated limb perfusion chemotherapy -- given directly to blood vessels supplying the affected arm or leg as an alternative to amputation -- was more effective in rats than either treatment on its own.The study, published in the Researchers at the ICR, in collaboration with colleagues at The Royal Marsden, used a vaccinia virus known as GLV-1h68. This virus had been modified to infect and kill cancer cells.The study suggests that the combination, if successful in the clinic, could help some skin cancer and sarcoma patients avoid radical surgery or amputation, greatly improving their quality of life. A clinical trial to test the combination in cancer patients has now been approved and is expected to take place in the near future.Isolated limb perfusion uses a heart and lung bypass machine connected to the arm or leg to separate its blood supply from the rest of the body. This allows a high dose of a chemotherapy drug (in this case melphalan) to be given directly and specifically to the diseased limb without causing toxic side-effects to the rest of the body.Chemotherapy is given alongside a drug called tumour necrosis factor-alpha (TNF-α) which helps make blood vessels more leaky, allowing melphalan to get to the tumour more effectively. In this study, researchers found that TNF- α also helped the virus get to the tumour more easily.Researchers first tested the treatments on rat sarcoma cells in tissue culture, and found combining modified vaccinia virus and melphalan killed more cells than either treatment on its own.They tested the combination in rats with advanced sarcoma and found it slowed tumour growth and prolonged survival by 50% compared to standard ILP therapy (melphalan and TNF-α). Rats given the combined therapy survived a median of 24 days, compared to 16 days for rats who received standard limb perfusion treatment, 15 days with the modified virus alone, and 11 days with no treatment. They saw the modified virus had no adverse effects on the rats, adding to existing evidence that the virus has a good safety profile.Isolated limb perfusion allows drugs to be given in much higher doses than could be tolerated by the whole body. It is used by doctors as a last line of treatment for advanced skin cancer or sarcomas in the hope of avoiding amputation. However, the technique is not always successful and researchers have been searching for ways to make the approach more effective.Professor Kevin Harrington, Professor of Biological Cancer Therapies at The Institute of Cancer Research, London, and Honorary Consultant at The Royal Marsden NHS Foundation Trust, said: "Our research shows that a virus that targets and kills cancer cells could significantly improve an existing treatment for advanced skin cancer and sarcoma in the arms and legs. Combining modified virus and isolated limb chemotherapy doubled survival times in the laboratory, which gives us hope that it might be effective in the clinic. We have approval to start clinical trials on the combination therapy and hope to begin testing in patients in the near future."The beauty of this technique is that the arm or leg is isolated, making it harder for the virus to be destroyed by the immune system -- something that has been a stumbling block for virus treatments in the past. The study also showed that the virus didn't cause any adverse effects, adding to evidence that it should be safe to use as a cancer treatment.Professor Paul Workman, Deputy Chief Executive of The Institute of Cancer Research, London, said: "Viral therapies have been suggested as a possible treatment for cancer for a number of years, but trials of cancer-killing viruses alone have not proved effective enough. Combining cancer-killing viruses with chemotherapy gives the tumour a double hit that could offer an improvement over existing treatment, and might help cancer patients avoid amputation." | Genetically Modified | 2,014 |
July 15, 2014 | https://www.sciencedaily.com/releases/2014/07/140715214301.htm | Dodos and spotted green pigeons are descendants of an island hopping bird | The mysterious spotted green pigeon ( | The only known example of the spotted green pigeon is the Liverpool pigeon, which is currently in the World Museum, Liverpool. The only other known specimen has been lost, and there are no records of the bird in the wild. There is no record of where the pigeon was found, and it wasn't even known if the spotted green pigeon was a species, or just an unusual form of the Nicobar pigeon from around Indonesia.The scientists took DNA from two feathers of the spotted green pigeon. Because of its age, the DNA was highly fragmented, so they focused in on three DNA 'mini barcodes' -- small sections of DNA which are unique for most bird species. They looked at these sections of the pigeon's DNA, and compared it to other species.This showed that the spotted green pigeon is indeed a separate species, showing a unique DNA barcode compared to other pigeons. The pigeon is genetically most closely related to the Nicobar pigeon and the dodo and Rodrigues solitaire, both extinct birds from islands near Madagascar. The spotted green pigeon shows signs of a semi-terrestrial island lifestyle and the ability to fly. The closely related Nicobar pigeon shows similar habits and has a preference for travelling between small islands.The scientists say this lifestyle, together with the relationship of both pigeons to the dodo and Rodrigues solitaire supports an evolutionary theory that the ancestors of these birds were 'island hoppers', moving between islands around India and Southeast Asia. The birds that settled on particular islands then evolved into the individual species. The dodo's ancestor managed to hop as far as the island of Mauritius near Madagascar where it then lost the ability to fly.Dr Tim Heupink, Griffith University Australia says: "This study improves our ability to identify novel species from historic remains, and also those that are not novel after all. Ultimately this will help us to measure and understand the extinction of local populations and entire species."Clemency Fisher, Curator of Vertebrate Zoology at the World Museum says: "We are very pleased that the extinct spotted green pigeon has its correct place in the world of birds after more than 230 years. Tim Heupink's groundbreaking genetic research, analysing small fragments of DNA from tiny pieces of feather, proves the spotted green pigeon is unique and a distant relation to the Nicobar pigeon, the Rodrigues solitaire and the dodo of Mauritius." | Genetically Modified | 2,014 |
July 14, 2014 | https://www.sciencedaily.com/releases/2014/07/140714152435.htm | CRISPR system can promote antibiotic resistance | CRISPR, a system of genes that bacteria use to fend off viruses, is involved in promoting antibiotic resistance in | The results are scheduled for publication in The CRISPR system has attracted considerable attention for its potential uses in genetic engineering and biotechnology, but its roles in bacterial gene regulation are still surprising scientists. It was discovered by dairy industry researchers seeking to prevent phages, viruses that infect bacteria, from ruining the cultures used to make cheese and yogurt.Bacteria incorporate small bits of DNA from phages into their CRISPR region and use that information to fight off the phages by chewing up their DNA. Cas9, an essential part of the CRISPR system, is a DNA-chewing enzyme that has been customized for use in biotechnology.Researchers at the Division of Infectious Diseases of the Emory University School of Medicine and the Emory Vaccine Center were surprised to find that when the gene encoding Cas9 is mutated in "The mutant bacteria are more permeable to certain chemicals from the outside," says David Weiss, PhD, assistant professor of medicine (infectious diseases) at Emory University School of Medicine and Yerkes National Primate Research Center. "That increased permeability also seems to make them more likely to set off alarms when they are infecting mammalian cells."Graduate student Timothy Sampson, working with Weiss, found that Cas9 mutant bacteria may be more likely to leak bits of their DNA, a trigger for immune cells to get excited. This is a large reason why Cas9 is necessary for The regulatory role for Cas9 does not appear to be restricted to The findings add to recent discoveries where Cas9 has been found to be involved in virulence -- the ability to cause disease in a living animal or human -- in various pathogenic bacteria such as | Genetically Modified | 2,014 |
July 10, 2014 | https://www.sciencedaily.com/releases/2014/07/140710141632.htm | Technology developed to redirect proteins towards specific areas of genome | The Spanish National Cancer Research Centre (CNIO) Macromolecular Crystallography Group has managed to reprogramme the binding of a protein called BuD to DNA in order to redirect it towards specific DNA regions. Guillermo Montoya, the researcher who led the study, says the discovery: "will allow us to modify and edit the instructions contained in the genome to treat genetic diseases or to develop genetically-modified organisms." The study is published in the journal | The possibility of making à la carte modifications to the genome of living organisms could have a wide variety of applications, not only in the field of synthetic biology -- the science that seeks to create new living beings or improve existing ones for their biotechnological use -- but also for the treatment of human illnesses.To achieve this, several researchers from around the world have focused on the proteins that bind to the DNA in very specific ways: their manipulation to direct them towards specific places in the genome, linked to their binding to genetic effectors (DNA repair or activator proteins, among others), could serve to modify DNA messages or to redesign genetic circuits as needed.The CNIO team has deciphered the DNA binding code of BurrH, a new protein that was identified in Burkholderia rhizoxinica bacteria whose BuD domain specifically binds to the genome. To get there, the researchers have resolved the complete three-dimensional structure of the protein using the biophysical technique known as X-ray crystallography.The main advantage of BuDs lies in their high specificity: they are able to distinguish DNA sequences that differ only in two nucleotides (the letters that make up the DNA). "This high specificity acts as a GPS that allows them to find their destinations within the intricate genome map," says Montoya, adding that: "They are very versatile and easy to reprogram in comparison with other proteins used to the same end."Montoya's group has redesigned BuDs that are capable of recognizing the areas of the genome close to mutations responsible for sickle-cell disease, a pathology caused by modifications in the beta globin gene that produce alterations in red blood cells. "The linking of DNA repair proteins to these redesigned BuDs could serve to correct genetic alterations in patients with this disease," say the researchers.Montoya says that several companies are already interested in this new technology: "Our tool, as well as being used to treat genetic disease, could be used to genetically modify micro-organisms targeting metabolite synthesis needed to produce biofuels, for example." | Genetically Modified | 2,014 |
July 9, 2014 | https://www.sciencedaily.com/releases/2014/07/140709115507.htm | Tiny DNA pyramids enter bacteria easily -- and deliver a deadly payload | Bacterial infections usually announce themselves with pain and fever but often can be defeated with antibiotics -- and then there are those that are sneaky and hard to beat. Now, scientists have built a new weapon against such pathogens in the form of tiny DNA pyramids. Published in the journal | David Leong, Jianping Xie and colleagues note that some infectious pathogens can lie in wait, undetectable in the human body or in places that antibiotics have a hard time accessing. Engineered nanomedicine offers a new way to deliver drugs directly into bacterial cells, but the carriers developed so far pose problems such as toxicity. So Leong's team decided to use DNA to build a better, safer drug-delivery tool.They made little pyramids out of DNA that were so small that thousands could fit in the period at the end of this sentence. Then, they attached gold nanomaterials as fluorescent tags and also packaged the drug actinomycin D (AMD) into the struts of the DNA pyramids. In tests on the common bacteria | Genetically Modified | 2,014 |
July 8, 2014 | https://www.sciencedaily.com/releases/2014/07/140708111243.htm | When faced with some sugars, bacteria can be picky eaters | Researchers from North Carolina State University and the University of Minnesota have found for the first time that genetically identical strains of bacteria can respond very differently to the presence of sugars and other organic molecules in the environment, with some individual bacteria devouring the sugars and others ignoring it. | "This highlights the complexity of bacterial behaviors and their response to environmental conditions, and how much we still need to learn," says Dr. Chase Beisel, an assistant professor of chemical and biomolecular engineering at NC State and senior author of a paper describing the work. "This is one additional piece of the puzzle that could help us understand the behaviors of bacterial pathogens or the population dynamics of the micro-organisms that live in our guts."The researchers grew a non-pathogenic strain of To explore how individual bacteria respond to different sugars, the research team genetically modified the bacteria to create fluorescent proteins whenever they produced the pumps or enzymes. These fluorescent proteins acted as visual cues that the researchers could use to see how individual bacteria responded to the presence of a particular sugar.The researchers tested the But the bacteria responded differently to the other four molecules, exhibiting a wide range of behaviors."The behaviors were all over the place," Beisel says."While this is the first time we've seen such divergent behavior from bacteria regarding sugars, it's consistent with 'bet-hedging' behaviors that have been reported for bacteria in other contexts," he adds. "Bet hedging means that at least some of the bacteria will survive when faced with new environments."The researchers also performed mathematical modeling, which found that the bacteria's diverse behaviors could be traced to the production of pumps and enzymes in the presence of sugar.One question this study raises is whether this bet-hedging behavior is exhibited by bacteria used to convert sugars into biofuels. If it is, that would mean that a percentage of the bacteria aren't converting the sugar -- which would mean the system wasn't working at peak efficiency."But this work raises a lot of other questions as well," Beisel says. Why does this happen in the presence of some sugars but not others? What are the circumstances in which this bet-hedging behavior actually helps the bacteria? What happens in the presence of multiple sugars? And what does this mean for bacteria in real-world conditions? For example, how would this behavior impact the introduction of probiotics -- or pathogens -- into the human gut?"These are all questions we'd love to answer," Beisel says. | Genetically Modified | 2,014 |
July 7, 2014 | https://www.sciencedaily.com/releases/2014/07/140707152251.htm | Restored immunity shown for cancer-related fungal infections | Sleeping Beauty and fungal infections -- not two items one would normally associate together, but for immunocompromised cancer patients they may prove to be a helpful combination. | A study at The University of Texas MD Anderson Cancer Center used the Sleeping Beauty gene transfer system to modify T cells in hopes of fighting major life-threatening infections caused by invasive Aspergillus fungus. Results of the study appear in This type of gene therapy is already being used to recognize antigens associated with tumors. Clinical trials at MD Anderson were the first to use Sleeping Beauty to customize immune system T cells to attack specific types of leukemia and lymphoma.The Aspergillus study, led by Laurence Cooper, M.D., Ph.D., professor in Pediatrics at MD Anderson, shows that it may also be effective for combatting fungal infections that can be deadly for immunosuppressed patients such as those receiving hematopoietic stem cell transplants. The transplants are used to treat cancers of the blood or bone marrow such as leukemia, lymphoma, and multiple myeloma.Cooper's study, which included collaboration with Dimitrios Kontoyiannis, M.D., Sc.D., professor in the Department of Infectious Diseases, employed a novel method for inhibiting growth of fungus. The Sleeping Beauty system, developed at the University of Minnesota, offered a fresh approach to genetically modifying T cells for human use which is being piloted at MD Anderson for immunotherapy.The team harnessed Sleeping Beauty to engineer human T cells to express receptors known as chimeric antigen receptors (CARs) which redirected the killing machinery of the T cells. T cells displaying CAR targeted sugar molecules in the Aspergillus cell walls, killing the fungus."Mortality associated with invasive Aspergillus remains unacceptably high, especially in hematopoietic stem cell transplant recipients," said Kontoyiannis. "While antifungal therapies are available, the patient's own weakened immune system and emerging resistance to antifungals compromise the drugs' effectiveness. There is a dire need for effective immune enhancements strategies for the treatment of opportunistic fungal infections in patients with profound and persistent immune defects."Cooper said that new approaches for treating invasive Aspergillus are urgently needed. Since use of CARs has resulted in successful treatment of patients with B-cell malignancies, his team sought to determine if a CAR could be developed to redirect T-cell specificity to fungus.The Sleeping Beauty gene transfer system earned its name by its ability to "awaken" certain DNA sequences known as transposon. Researchers find transposon useful as a means to alter DNA inside human cells. Sleeping Beauty uses transposon in a "cut and paste" approach to relocating genetic material."We demonstrated a new approach for Aspergillus immunotherapy based on redirecting T-cell specificity through a CAR that recognizes carbohydrate antigen on the fungal cell wall," said Cooper. "The T cells expressing the CAR can be manipulated in a manner suitable for human application, enabling this immunology to be translated into immunotherapy."The approach has implications for genetically modifying T cells to target carbohydrate, and thus broadening their application in the investigational treatment of pathogens as well as malignancies. | Genetically Modified | 2,014 |
July 1, 2014 | https://www.sciencedaily.com/releases/2014/07/140701193259.htm | How does your garden grow? 3-D root imaging in real time | Growing plants in a microscope is helping scientists to view roots developing in 3D and in real time. "With the growth conditions under our control, we can explore how roots respond to different environmental conditions", says Professor Ernst Stelzer (Goethe Universität Frankfurt am Main, Germany). "This could help plant breeders to select crops which are more resistant to drought or flooding." | Scientists already know that lateral roots in plants develop from cells deep within the main root, so that the emerging roots must force through multiple layers of tissue to reach the soil. Until now, capturing the cell-division events behind this process has proved exceptionally difficult.The researchers grew Arabidopsis thaliana (a model organism for plant scientists) in miniature chambers placed inside fluorescence microscopes. This new technique allows root production to be observed without damaging these delicate structures.The top of the chamber, containing the leaves, was illuminated by a timed light source to mimic the natural day / night cycle. The roots, meanwhile, were grown in a special transparent gel to resemble soil. The plants had been genetically engineered to contain special proteins (called "fluorophores") that fluoresce when exposed to specific wavelengths of light. A focused sheet of light was used to illuminate the fluorophores in a single cross section of the root, which was then photographed. Images taken at different levels of the root axis were combined to form a 3D reconstruction. The scientists were able to track the movements of the cells over more than three days, capturing the formation of new roots.This research was presented at the Society for Experimental Biology Annual Meeting 2014 held at Manchester University, UK, from the 1st - 4th of July. | Genetically Modified | 2,014 |
June 30, 2014 | https://www.sciencedaily.com/releases/2014/06/140630164057.htm | 'Microbe sniffer' could point way to next-generation bio-refining | A new biosensor invented at the University of British Columbia could help optimize bio-refining processes that produce fuels, fine chemicals and advanced materials. | It works by sniffing out naturally occurring bacterial networks that are genetically wired to break down wood polymer."Nature has already invented microbial processes to degrade lignin--the tough polymer in wood and plant biomass that currently stymies industrial bio-refining," says UBC microbiologist Steven Hallam. "We needed to do the detective work, and develop the right toolkit, to isolate these processes in naturally occurring microbial communities from coal beds."Developed by Hallam and his team, the biosensor screens DNA from environmental samples to isolate the lignin-busting genetic machinery encoded in the samples' resident microbes." "We've found that bacteria harness adaptive genetic circuits to break down lignin and that these circuits can be mobilized in nature via horizontal gene transfer," says Hallam. "Our biosensor and screening enables us to uncover this genetic network, and then further optimize it in the laboratory."The improved understanding of adaptive, eco-engineered lignin transformation could also lead to more tunable industrial processes."We need to remain sensitive to the complexity of natural processes that act on lignin, but this project has unearthed some basic organizing principles that will also enable us to exploit microbial processes more quickly for any number of engineering applications," says UBC researcher Cameron Strachan. "It's a biological search function for biologists interested in harnessing naturally assembled genetic machinery."The sensor, screening and adaptive genetic circuitry discovered with them have been licensed through the University Industry Liaison Office. A spin-off company, guided by the e@UBC program, is looking into ways to increase the scale of production of this technology.The findings validating the screening were published in the Most bio-refining agents are based on enzymes engineered from fungi. In this case, UBC researchers used the innovative screening approach to source and test genetic arrays from bacteria inhabiting coal beds. The biosensor reacts to a set of small molecules that are the residue of lignin's natural degradation process. The researchers surmised that coal -- ancient wood and plant biomass deposited before the evolution of fungal lignin degradation pathways -- might contain bacterial pathways involved in the transformation process. | Genetically Modified | 2,014 |
June 26, 2014 | https://www.sciencedaily.com/releases/2014/06/140626172846.htm | A mini-antibody with broad antiviral activity chews up viral DNA and RNA | Antibodies and their derivatives can protect plants and animals -- including humans -- against viruses. Members of this class of drugs are usually highly specific against components of a particular virus, and mutations in the virus that change these components can make them ineffective. An article published on June 26th in | Sukchan Lee, from Sungkyunkwan University, Suwon, Korea, and colleagues had previously discovered that 3D8 has both DNase and RNase activity (that is, it can degrade both), and that it can inhibit viruses under certain circumstances. In this study, they genetically manipulated cells and mice to produce 3D8.They show that when the right amount of 3D8 is produced, the cells and the animals become resistant to two different and normally deadly viruses, namely herpes simplex virus and pseudorabies virus. To protect the animals, it appears critical that the right dose of 3D8 is present in the tissues initially infected by the viruses; once the virus has started to multiply and spread, it seems that 3D8 can no longer contain it efficiently.When the researchers examined the mechanisms underlying the protective activity, they found that 3D8 fights viruses at two different places and stages of the viral life cycle. In the cell nucleus, it degrades viral DNA to prevent it from getting copied. In the cytoplasm (the area outside of the nucleus), it destroys RNA destined to be used for the production of virus components.As the researchers discuss, the correct 3D8 dose is critical to destroy only viral DNA and RNA (but not their host genetic material), and additional research is needed to understand the basis for this selective activity. Moreover, to protect the host, 3D8 needs to be present at the time of viral infection and in the right tissues. That said, they conclude that "3D8 scFv is a candidate antiviral protein that can potentially confer resistance to a broad spectrum of animal and plant viruses." They also suggest that "this strategy may facilitate control of...viruses uncharacterized at the molecular level, regardless of their genome type or variations in gene products." | Genetically Modified | 2,014 |
June 26, 2014 | https://www.sciencedaily.com/releases/2014/06/140626132019.htm | Sequencing efforts miss DNA crucial to bacteria's disease causing power | Genomic sequencing is supposed to reveal the entire genetic makeup of an organism. For infectious disease specialists, the technology can be used to analyze a disease-causing bacterium to determine how much harm it is capable of causing and whether or not it will be resistant to antibiotics. But new research at Rockefeller University suggests that current sequencing protocols overlook crucial bits of information: isolated pieces of DNA floating outside the bacterial chromosome, the core of a cell's genetic material. | "Extensive sequencing of chromosomal DNA has been performed for a variety of pathogenic organisms, but these sequences fail to uncover the presence of DNA elements in the cell's cytoplasm. As a result, the DNA profile of a pathogenic bacteria may be incomplete," says Vincent Fischetti, head of the Laboratory of Bacterial Pathogenesis and Immunology. "We have now devised a way to identify these elements."Extrachromosomal DNA can include bacteria-infecting viruses, known as phages, and strands of self-replicating DNA, known as plasmids, often picked up from other bacteria. These phages and plasmids can easily move between bacterial cells, and scientists have known for some time that, as a result, these so-called mobile genetic elements can play important roles in virulence and antibiotic resistance.This study focused on phages. Their activity outside the chromosomes has been poorly studied; most research has focused on phages integrated into bacterial chromosomes. Meanwhile, plasmids, which allow bacteria to share genes among themselves, are well studied."So far, no one has looked across a variety of strains of bacteria, as we have done with Until now, an analysis of this scope wasn't possible, because chromosomal DNA easily fragments and contaminates the sample during the process by which researchers prepare the extrachromosomal DNA, making them virtually impossible to identify and sequence."To solve this problem, we borrowed a tool from phages themselves: the enzymes these viruses use to break apart a phage-infected cell to release their progeny," says Douglas Deutsch, a graduate student in the lab. These enzymes, a focus of research in the lab in the development of novel anti-infectives, are now being harnessed to gently extract the chromosomal DNA, while leaving behind any other genetic elements for analysis. Using this technique, they looked for extrachromosomal phages across 24 medically important strains of Not only did extrachromosomal phages appear widespread among these strains, but the researchers found evidence that these phages encode genes that can make the bacteria more dangerous.For example, when the researchers decoded the complete sequence of one extrachromosomal circular phage from a disease-causing The implications go beyond pathogenicity. Phage elements, including those not integrated into chromosomes, are part of a bacterial system for regulating genes. For instance, some of these phage elements can activate or silence bacterial genes by moving into or out of the chromosome. Within the "By examining the DNA outside the bacterial chromosomes, you may get a better understanding of the dynamics by which these elements may mobilize thereby controlling microbial genes," Fischetti says. | Genetically Modified | 2,014 |
June 19, 2014 | https://www.sciencedaily.com/releases/2014/06/140619125032.htm | Genetic control mechanism for major livestock pest developed | Researchers from North Carolina State University have developed a technique to control populations of the Australian sheep blowfly -- a major livestock pest in Australia and New Zealand -- by making female flies dependent upon a common antibiotic to survive. | Dr. Max Scott, professor of entomology at NC State, and his research team genetically modified lines of female Australian sheep blowflies (Lucilia cuprina) so that they required doses of tetracycline in order to live. Female blowflies that did not receive the antibiotic died in the late larval or pupal stages, before reaching adulthood. Several genetically modified lines lacking tetracycline showed 100 percent female deaths.Scott says that the gene construct responsible for lethality in antibiotic-free diets is female-specific. Interestingly and unexpectedly, the genetically modified female larvae containing the tetracycline lethality genes also took on a crimson color due to overexpression of the linked red fluorescent protein "marker gene." This allows scientists to tell which larvae will be females and which will be males."Overexpression of the gene responsible for the reliance on tetracycline also seems to overexpress this marker gene," Scott says.Since the females will die when not provided tetracycline in their diets, the males can be separated out in the larval stage. This is essential for a "male-only" genetic control program to reduce blowfly populations, Scott says, as fertile males would pass the lethality construct on to female offspring, which would die in the absence of tetracycline. Male larval offspring, however, would still be dangerous to livestock.In the study, the researchers showed that the tetracycline gene construct also works in Drosophila, the fruit fly "lab rat" of the insect world that is a distant cousin of the sheep blowfly. This holds promise that the genetic system will function in the New World and Old World screwworm, two major livestock pests that are close relatives of the sheep blowfly. Scott is working with the U.S. Department of Agriculture to make "male-only" strains of the New World screwworm ("The New World screwworm is a devastating pest of livestock that was eradicated from North and Central America by releasing sterilized male and female flies," Scott says. However, a male-only strain offers several advantages, including potentially more efficient population suppression for the ongoing program. "Efficient genetic control systems have the potential to help eradicate some of the biggest problem pests across the globe," he said. | Genetically Modified | 2,014 |
June 16, 2014 | https://www.sciencedaily.com/releases/2014/06/140616093032.htm | How sperm get into the zona | Before it can fertilize an egg, a sperm has to bind to and bore through an outer egg layer known as the zona pellucida. Despite decades of research, some of the biological mechanisms behind this process remain unclear. A study in | The zona pellucida protects the egg and the early embryo before implantation. Its structure seems simple -- in humans it contains four kinds of glycoproteins, and in mice it only contains three. But researchers haven't been able to identify the sperm's binding partner in the layer, although their suspicions have fallen on two of the glycoproteins, ZP2 and ZP3.To find out more, Jurrien Dean and colleagues from the National Institute of Diabetes and Digestive and Kidney Diseases engineered mice to produce various combinations of human and mouse zona pellucida glycoproteins. Mouse sperm didn't bind to the zona pellucida if it was missing ZP2, and female mice lacking the protein were sterile. The researchers also found that sperm couldn't latch onto eggs if ZP2 was missing a key region at the beginning of the protein. This result jibes with a previous finding that fertilization triggers the release of an enzyme that severs ZP2 in this region, thus preventing additional sperm from attaching to the zona pellucida.The team also tested the binding of human sperm to mouse eggs surrounded by a zona pellucida harboring human glycoproteins. Human sperm adhered to the mouse zona pellucida if it contained human ZP2 but not if it carried human ZP3, confirming the importance of ZP2. | Genetically Modified | 2,014 |
June 11, 2014 | https://www.sciencedaily.com/releases/2014/06/140611170901.htm | Famine fear won't sway minds on GM crops | A sack-hauling time traveler from the 21st century lands in an Irish potato field in 1849, just before a terrible famine, and asks: If you thought genetically modified potatoes could avert late blight disease, spare a million countrymen from starvation and keep another million from emigrating off the Emerald Isle, would you plant these newfangled spuds? | Fast forward to the Internet Age, when communication researchers ran 859 U.S. grocery shoppers through a similar thought experiment: Half the subjects in an online survey read the story of the 1850s Irish Potato Famine, learning the potential impact of fungal Phytophthora infestans on potato and tomato crops today. The other 400-plus pondered generic plant disease, with no mention of specific crops or historic famines."Stories of the Irish Potato Famine were no more likely to boost support for disease-resistant genetically modified crops than were our generic crop-disease descriptions," said Katherine A. McComas, professor and chair of Cornell's Department of Communication in the College of Agriculture and Life Sciences."Preconceived views about risks and benefits of agricultural genetic engineering -- and perceptions about the fairness and legitimacy of the decision-making process -- these things matter most," McComas said.With co-authors John C. Besley (Michigan State University) and Joseph Steinhardt (Cornell), McComas will publish study results as "Factors influencing U.S. consumer support for genetic modification to prevent crop disease" in the July 2014 journal "If you think genetically modified crops are dangerous 'frankenfoods' and/or that crop disease is best controlled with chemicals -- if you suspect federal regulators care more about Big Ag's interests than your family's, thus the whole game is rigged -- plaintive tales of historical famines won't change your mind about genetic modification for disease resistance," McComas said. | Genetically Modified | 2,014 |
June 10, 2014 | https://www.sciencedaily.com/releases/2014/06/140610112455.htm | Malaria-carrying mosquitoes wiped out in lab with genetic method that creates male-only offspring | Scientists have modified mosquitoes to produce sperm that will only create males, pioneering a fresh approach to eradicating malaria. | In a study published in the journal In the first laboratory tests, the method created a fully fertile mosquito strain that produced 95 per cent male offspring.The scientists introduced the genetically modified mosquitoes to five caged wild-type mosquito populations. In four of the five cages, this eliminated the entire population within six generations, because of the lack of females. The hope is that if this could be replicated in the wild, this would ultimately cause the malaria-carrying mosquito population to crash.This is the first time that scientists have been able to manipulate the sex ratios of mosquito populations. The researchers believe the work paves the way for a pioneering approach to controlling malaria.Since 2000, increased prevention and control measures have reduced global malaria mortality rates by 42 per cent, but the disease remains a prevalent killer especially in vulnerable sub-Saharan African regions. Malaria control has also been threatened by the spread of insecticide resistant mosquitoes and malaria parasites resistant to drugs. According to latest estimates by the World Health Organization, over 3.4 billion people are at risk from contracting malaria and an estimated 627,000 people die each year from the disease.Lead researcher Professor Andrea Crisanti from the Department of Life Sciences at Imperial College London said: "Malaria is debilitating and often fatal and we need to find new ways of tackling it. We think our innovative approach is a huge step forward. For the very first time, we have been able to inhibit the production of female offspring in the laboratory and this provides a new means to eliminate the disease."Dr Nikolai Windbichler, also a lead researcher from the Department of Life Sciences at Imperial College London, said: "What is most promising about our results is that they are self-sustaining. Once modified mosquitoes are introduced, males will start to produce mainly sons, and their sons will do the same, so essentially the mosquitoes carry out the work for us."In this new experiment the scientists inserted a DNA cutting enzyme called I-PpoI into Anopheles gambiae mosquitoes. In normal reproduction, half of the sperm bear the X chromosome and will produce female offspring, and the other half bear the Y chromosome and produce male offspring.The enzyme that the researchers used works by cutting the DNA of the X chromosome during production of sperm, so that almost no functioning sperm carry the female X chromosome. As a result the offspring of the genetically modified mosquitoes was almost exclusively male.It took the researchers six years to produce an effective variant of the enzyme."The research is still in its early days, but I am really hopeful that this new approach could ultimately lead to a cheap and effective way to eliminate malaria from entire regions. Our goal is to enable people to live freely without the threat of this deadly disease," concluded Dr Roberto Galizi from the Department of Life Sciences at Imperial College London. | Genetically Modified | 2,014 |
June 5, 2014 | https://www.sciencedaily.com/releases/2014/06/140605093151.htm | Protecting mainland Europe from an invasion of grey squirrels | The first genotyping of grey squirrels sampled from Italy and the UK shows a direct link between their genetic diversity and their ability to invade new environments. | In this new study, published in Diversity and Distributions, an international team of scientists from Imperial College London and the Zoological Society of London compared 12 DNA markers from grey squirrels (Sciurus carolinensis) in Piedmont in Northern Italy with the same markers from squirrel populations in Northern Ireland, Northumberland and East Anglia.After correlating genetic diversity against size of founding populations, the scientists have shown that if the number of squirrels in a founding group is low, then their genetic diversity is reduced, which in turn reduces their ability to invade new environments.Grey squirrels are an invasive species introduced from North America. While they are common throughout most of the UK and Ireland, on mainland Europe they are currently only found in Italy, where they mostly exist in discrete, but slowly expanding, populations. This new research has implications for preventing the spread of grey squirrels across the Alps into the rest of Europe where they would threaten native populations of red squirrels (Sciurus vulgaris).Several of the grey squirrel introductions have been well documented, making it possible to correlate their spread today against the size of their original founding populations. For example, one of today's Italian populations has spread from a deliberate introduction in 1948 by diplomat Giuseppe Casimiro Simonis Vallario. He took a shine to the 'exotic' animals while in Washington DC for meetings following the end of World War Two and brought back just four squirrels, which he released in the park of near his Turin villa.The small size of founding populations in Italy means that the spread of grey squirrels there has, until recently, been slow. But genetically distinct populations have now expanded to the point of merging, which would increase diversity and accelerate their ability to invade new environments.Lead researcher Dr Lisa Signorile from the Department of Life Sciences at Imperial College London said: "Italian grey squirrels are edging closer to the northern border and are perilously close to crossing the Alps. If the Italian populations interbreed, they will increase in genetic diversity, which will increase their chances of invading the rest of Europe. To stop the spread, we need to understand what makes some populations such successful invaders. Our new study, which is the first to specifically examine grey squirrel population genetics at a large scale, helps us uncover some of those reasons."Grey squirrels are twice as heavy as red ones. They outcompete for food and have spread the deadly parapoxvirus, decimating native populations. These crippling colonisers are also changing the composition of British forests. By debarking trees, such as Garry Oaks, these invaders are a pesky problem for forest plantations, which take hundreds of years to cultivate and flourish.Until now, scientists have focused on ecological and physical traits of grey squirrels, rather than investigating the genetics behind their invasive 'triumphs'. In this study, scientists examined the genetic variation of 315 squirrels from 14 locations across Piedmont, Northern Ireland, Northumberland and East Anglia, and compared this against the original numbers of animals that were deliberately introduced.Results showed arrivals of bigger grey squirrel groups, which were ten times as large in the East Anglia region as Italy, generated greater genetic diversity, allowing the population to adapt more easily to new environments and expand faster. By contrast, descendants from Vallario's original population of four animals had the lowest genetic variability amongst all groups studied."The fact that today's grey squirrel populations depend on the size of their founding population has important management implications," says Lisa Signorile: "We need to find ways of helping Italian managers prevent breeding between genetically distinct populations." | Genetically Modified | 2,014 |
June 4, 2014 | https://www.sciencedaily.com/releases/2014/06/140604203056.htm | Habitat loss on breeding grounds cause of monarch decline, study finds | Habitat loss on breeding grounds in the United States -- not on wintering grounds in Mexico -- is the main cause of recent and projected population declines of migratory monarch butterflies in eastern North America, according to new research from the University of Guelph. | The groundbreaking study was published in the "Our work provides the first evidence that monarch butterfly numbers in eastern North America are most sensitive to changes in the availability of milkweed on breeding grounds, particularly in the Corn Belt region of the United States," said Ryan Norris, a professor in Guelph's Department of Integrative Biology.He conducted the study with lead author and current Guelph post-doc Tyler Flockhart, as well as scientists from the Commonwealth Scientific and Industrial Research Organisation (Australia's national science agency).These results contradict the long-held belief that monarch butterflies are most vulnerable to disturbances on wintering grounds in Mexico. They also confirm suspicions that recent declines have actually been driven by breeding events.During the winter months, monarch butterflies congregate in a small area at high densities in Mexico. Scientists thought factors on those wintering grounds, such as climate change or deforestation, were the greatest threat to the population.That led to multiple Mexican presidential decrees to protect butterfly overwintering habitats and efforts to curb illegal deforestation."The protection of overwintering habitat has no doubt gone a long way towards conserving monarchs that breed throughout eastern North America. However, our results provide evidence that there is now another imminent threat," said Flockhart.Milkweed is the only group of plants that monarch caterpillars feed upon before they develop into butterflies. Industrial farming contributed to a 21-per-cent decline in milkweed plants between 1995 and 2013, and much of this loss occurred in the central breeding region, the study said.More than 70 per cent of milkweed in this region is located in agricultural-intensive landscapes where genetically modified crops are increasing, as opposed to 16 per cent in conservation lands and 10 per cent in public areas such as roadways, the study said.Changes in milkweed abundance can affect everything from larval competition for food to egg-laying in adults."The rapid loss of milkweed projected for this region, attributable to land cover changes and shifts in agricultural practices, is a very large concern," said Flockhart. Left unchecked, milkweed loss will cause the monarch population to decline by at least another 14 per cent, the study said.The researchers developed a model to predict effects of habitat loss on both breeding and wintering grounds and the effects of climate change. They aimed to explain the observed population decline and make predictions for the next 100 years.Their results connect an increase in genetically modified, herbicide-resistant crops and the current population decline of monarch butterflies in eastern North America."Reducing the negative effects of milkweed loss in the breeding grounds should be the top conservation priority to slow or halt future population declines of the monarch in North America," Flockhart said.Norris added:"Planting milkweed in the south and central United States would provide the largest immediate benefit."Earlier pioneering studies from Norris's research lab have tracked year-round migration patterns of this iconic species using chemical markers and have looked at how monarchs migrate to their Mexican wintering grounds. | Genetically Modified | 2,014 |
June 2, 2014 | https://www.sciencedaily.com/releases/2014/06/140602155855.htm | Microbes engineered for direct conversion of biomass to fuel | The promise of affordable transportation fuels from biomass -- a sustainable, carbon neutral route to American energy independence -- has been left perpetually on hold by the economics of the conversion process. New research from the University of Georgia has overcome this hurdle allowing the direct conversion of switchgrass to fuel. | The study, published in the Pre-treatment of the biomass feedstock -- non-food crops such as switchgrass and miscanthus -- is the step of breaking down plant cell walls before fermentation into ethanol. This pre-treatment step has long been the economic bottleneck hindering fuel production from lignocellulosic biomass feedstocks.Janet Westpheling, a professor in the Franklin College of Arts and Sciences department of genetics, and her team of researchers -- all members of U.S. Department of Energy-funded BioEnergy Science Center in which UGA is a key partner -- succeeded in genetically engineering the organism C. bescii to deconstruct un-pretreated plant biomass."Given a choice between teaching an organism how to deconstruct biomass or teaching it how to make ethanol, the more difficult part is deconstructing biomass," said Westpheling, who spent two and a half years developing genetic methods for manipulating the C. bescii bacterium to make the current work possible.The UGA research group engineered a synthetic pathway into the organism, introducing genes from other anaerobic bacterium that produce ethanol, and constructed a pathway in the organism to produce ethanol directly."Now, without any pretreatment, we can simply take switchgrass, grind it up, add a low-cost, minimal salts medium and get ethanol out the other end," Westpheling said. "This is the first step toward an industrial process that is economically feasible."The recalcitrance of plant biomass for the production of fuels, a resistance to microbial degradation evolved in plants over millions of years, results from their rigid cell walls that have been the key to their survival and the major impediment to biofuel production. Understanding the scientific basis of, and ultimately eliminating recalcitrance as a barrier has been the core mission of the BioEnergy Science Center."To take a virtually unknown and uncharacterized organism and engineer it to produce a biofuel of choice within the space of a few years is a towering scientific achievement for Dr. Westpheling's group and for BESC," said Paul Gilna, director of the BioEnergy Science Center, headquartered at Oak Ridge National Laboratory. "It is a true reflection of the highly collaborative research we have built within BESC, which, in turn, has led to accelerated accomplishments such as this."Caldicellulosiruptor bacteria have been isolated around the world-from a hot spring in Russia to Yellowstone National Park. Westpheling explained that many microbes in nature demonstrate prized capabilities in chemistry and biology but that developing the genetic systems to use them is the most significant challenge."Systems biology allows for the engineering of artificial pathways into organisms that allow them to do things they cannot do otherwise," she said.Ethanol is but one of the products the bacterium can be taught to produce. Others include butanol and isobutanol (transportation fuels comparable to ethanol), as well as other fuels and chemicals-using biomass as an alternative to petroleum."This is really the beginning of a platform for manipulating organisms to make many products that are truly sustainable," she said. | Genetically Modified | 2,014 |
May 29, 2014 | https://www.sciencedaily.com/releases/2014/05/140529142544.htm | New approach to HIV vaccine explored by scientists | Using a genetically modified form of the HIV virus, a team of University of Nebraska-Lincoln scientists has developed a promising new approach that could someday lead to a more effective HIV vaccine. | The team, led by chemist Jiantao Guo, virologist Qingsheng Li and synthetic biologist Wei Niu, has successfully tested the novel approach for vaccine development in vitro and has published findings in the international edition of the German journal With the new approach, the UNL team is able to use an attenuated -- or weakened -- HIV virus in the vaccine. The new method involves manipulating the virus' codons -- a sequence of three nucleotides that form genetic code -- to rely on an unnatural amino acid for proper protein translation, which allows it to replicate. Because this amino acid is foreign to the human body, the virus cannot continue to reproduce, Guo said.Adaptive immunity is developed when the body's immune system develops antibodies that attack the virus. The virus is then shut off from replicating by removing the amino acid."Since the unnatural amino acid is not present in humans, the virus cannot further replicate and cause disease once a desirable protection is achieved," Guo said.On June 1, they will begin the next phase of development through a four-year, $1.9 million grant from the National Institutes of Healthand the National Institute of Allergy and Infectious Diseases. The grant will allow further research involving the genetically modified virus and lead to animal trials of the vaccine.Since the HIV/AIDS pandemic began in the 1980s, an estimated 36 million people have died from the disease. Today, more than 35 million people live with the virus and 2.5 million new infections are recorded each year. No universal cure or vaccine exists, mainly because of the virus' persistent replication and evolution.The most successful vaccination attempt in humans -- a trial in Thailand in the middle of the last decade -- had a roughly 31 percent efficacy rate. But that vaccine used engineered versions of HIV genes and proteins, rather than the actual virus."The science tells us a live-attenuated vaccine would work best to stop the pandemic and possibly eradicate the disease," Li said. "But, using a live virus in a human trial has safety concerns."Using an attenuated virus in a vaccine has not been accomplished before because HIV -- even a weakened form of the virus -- replicates rapidly, which allows it to evolve quickly and regain is virulence and disease-causing ability.With the funds from the grant, Guo, assistant professor of chemistry, and Li, associate professor of biology, along with Niu, research assistant professor in chemistry, will perfect the technology and begin new trials. | Genetically Modified | 2,014 |
May 29, 2014 | https://www.sciencedaily.com/releases/2014/05/140529092221.htm | Vaccine candidate using genetically engineered malaria parasite developed | Seattle BioMed researchers today announced they have developed a next generation genetically attenuated parasite (GAP) that might constitute the path to a highly protective malaria vaccine. The study was published online in the journal | Malaria is caused by The manuscript describes the development of genetically engineered malaria parasites that are weakened by the precise removal of genes and designed to effectively prevent the parasite from inducing an infection in humans. These genetically attenuated parasites, or "GAPs," are incapable of multiplying, but are alive and able to effectively stimulate the immune system to build up defenses to prevent pathogenic infection. While this vaccine strategy has proven very successful in providing protection against viruses and bacteria, it remains a novel approach in combating parasites."While vaccination with live-attenuated parasites is capable of providing complete protection from malaria infection, it is imperative that we permanently cripple the very complex malaria parasite so that it cannot cause disease, and instead, effectively primes the immune system," said Stefan Kappe, Ph.D., corresponding author and professor, Seattle BioMed."This most recent publication builds on our previous work," said Sebastian Mikolajczak, PhD., Seattle BioMed senior scientist and GAP project leader. "The first generation GAP strain had two genes removed from the malaria parasite, but this new 'triple punch', developed in collaboration with scientists at the Walter and Eliza Hall Institute in Australia, removes three separate genes associated with the pathogenicity of the parasite, effectively abrogating its ability to establish an infection in humans.""The next step is to test the safety and efficacy of this attenuated parasite in clinical trials in a highly efficient manner," said Alan Aderem, Ph.D., president, Seattle BioMed. "Seattle BioMed's Malaria Clinical Trials Center is one of only four centers in the world approved to safely and effectively test new malaria treatments and vaccines in humans by the malaria human challenge model. We are committed better understanding and eventually eradicate this deadly pathogen." | Genetically Modified | 2,014 |
May 28, 2014 | https://www.sciencedaily.com/releases/2014/05/140528114116.htm | Some consumers confuse 'local' with 'organic' food | With more people buying local and organic food, consumers should know the difference between the two so they recognize what they're buying, but nearly one in five still confuse the terms, a University of Florida researcher says. | Newly published research, done in partnership with three other universities, aims to help local and organic food producers and sellers target their marketing messages to reinforce or dispel consumers' perceptions. The organic-food industry has spent millions of dollars building brand awareness, only to see some consumers confuse "organic" food with "local" food products, said Ben Campbell, a University of Connecticut extension economist and the study's lead author.Hayk Khachatryan, a UF food and resource economics assistant professor, worked with Campbell and others to survey 2,511 people online in the U.S. and Canada in 2011 and found 17 percent thought the terms were interchangeable, the study said."If consumers can distinguish between local and organic, then by buying organic, they will be able to reduce their exposure to synthetic pesticides," said Khachatryan, with the Mid-Florida Research and Education Center in Apopka, part of the Institute of Food and Agricultural Sciences. "However, there is no guarantee that organic is grown locally. Before reaching the consumer, organic produce may travel long distances, which involves some level of environmental footprint."By the same token, he noted that locally produced food may not be the most sustainable choice, if same or better quality produce can be grown and transported less expensively from elsewhere.Another finding showed 22 percent incorrectly thought "local" means non-genetically modified. Now that several states have, or are now debating GMO regulations, it's essential that consumers know that a locally labeled product does not imply non-GMO, Campbell said."We are not saying GMO is bad or good, but rather that local does not imply GMO-free," he said.Local and organic products have seen increasing consumer demand over the last decade, with sales of organic products reaching $26.7 billion in the U.S. and $2.6 billion in Canada in 2010, according to the Organic Trade Association, a group that promotes organic food producers and related industries.Exact figures for locally grown food are tougher to come by, but recent estimates indicate sales of local products were $4.8 billion in the U.S. in 2008, according to a U.S. Department of Agriculture study.One factor clouding consumers' understanding is that Canada is changing its definition of "local" food, and the definition of "local" food varies by jurisdiction in the U.S.U.S. and Canadian governments both mandate organic production to mean grown without synthetic pesticides, among other things. The USDA organic seal verifies that irradiation, sewage sludge and genetically modified organisms were not used. | Genetically Modified | 2,014 |
May 28, 2014 | https://www.sciencedaily.com/releases/2014/05/140528105410.htm | What can plants reveal about gene flow? That it's an important evolutionary force | A plant breeder discovers his experimental crops have been "contaminated" with genes from a neighboring field. New nasty weeds sometimes evolve directly from natural crosses between domesticated species and their wild relatives. A rare plant is threatened due to its small population size and restricted range. What do all these situations have in common? They illustrate the important role of gene flow among populations and its potential consequences. Although gene flow was recognized by a few scientists as a significant evolutionary force as early as the 1940s, its relative role in maintaining a species' genetic integrity and/or its diversity has been debated over the decades, vacillating from trivial to critical. | So how much gene flow is there between plant populations? How important is gene flow for maintaining a species' identity and diversity, and what are the implications of these processes for evolution, conservation of endangered species, invasiveness, or unintentional gene flow from domesticated crops to wild relatives?Norman Ellstrand, a plant geneticist at the University of California, Riverside, is interested in many aspects regarding gene flow, especially in applied plant biology, and has spent more than 25 years considering the possibility and potential impacts of unintended gene flow from genetically engineered crops. As part of the Selection, mutation, gene flow, and genetic drift, are the four mechanisms that lead to biological evolution, or a change in allele frequencies in a population over time. Just how important are each of these forces relative to each other?Interestingly, Ellstrand points out that evolutionary biologists' view on the importance of gene flow has waxed and waned over the last century. Although it was first seen in the 1940s to be the evolutionary glue that held species together, and thus a significant evolutionary force, a few decades later when quantitative data on gene flow in plant populations began being collected, this view changed as evidence seemed to indicate that gene flow was not all that significant.Not only was intra-specific gene flow among populations seen to be minimal at that time, but, somewhat incongruously, inter-specific hybridization, or the movement of genes among species, was seen to be a much larger force in evolution than intra-specific allele movement. At the time the main concern for plant breeders was pollen movement between different strains of crops -- if a variety of sweet corn was contaminated by pollen from a popcorn variety, then the resulting hybrid offspring would produce seeds that were unusable for market purposes or for selecting new varieties. Increasing the distance between plots of different varieties was seen to be the best solution to this problem.However, beginning in the 1980s the tide turned again due to mounting evidence from new approaches: parentage and spatial population genetic structure studies."When I first started doing plant paternity studies in the 1980s," Ellstrand comments, "our lab assumed that gene flow was limited. But we kept identifying 'impossible fathers' that could not be assigned to our study population. Surely, these couldn't be fathers from outside of our wild radish populations -- hundreds of meters away? But after excluding all other possibilities, the improbable turned out to be the answer. And the paradigm of limited gene flow in plants began to crumble."Indeed, one of the amazing things that parentage studies revealed is just how far genes could flow -- from hundreds to thousands of meters in some cases. In one extraordinary case, a study found that the nearest possible paternal sire of an individual fig tree was 85 km away!With the advent of more and more sophisticated ways to measure genetic variation and relatedness using molecular markers, such as allozyme polymorphisms and DNA-based markers, not only can individuals be tracked as to their parentage, but changes in allele patterns over time and thus the effects of evolution on populations can be "seen" in the genetic information.As it turns out, despite the initial skepticism about the importance of gene flow, modern empirical and theoretical research using up-to-date molecular and DNA techniques have shown us not only how surprisingly far the flow of genes between distant plant populations can be, but also that the flow of alleles among populations is just as important, if not more so in some cases, as natural selection. Indeed, even just a low level of gene flow between populations can counter opposing forces of mutation, genetic drift, and selection."Just like selection, gene flow is one of the evolutionary forces -- and a potentially important one," notes Ellstrand. And plants are very well suited for studies on gene flow because individuals are stationary yet pollen and seeds are mobile.However, an important caveat that Ellstrand reports in his review is that the relative importance of gene flow can vary tremendously among species and among populations, and can be as low as no gene flow at all to very high rates of gene flow."This review paper tells the story of gene flow's rise to respect among plant evolutionary biologists," he concludes, "a fact that hasn't yet penetrated biology in general that is still mired in selection/adaptation-only thinking." | Genetically Modified | 2,014 |
May 27, 2014 | https://www.sciencedaily.com/releases/2014/05/140527085443.htm | New jigsaw piece for the repair of DNA crosslinks | Environmental influences such as ionizing radiation, intense heat or various chemical substances damage the DNA constantly. Only thanks to efficient repair systems can mutations -- changes in the DNA -- largely be prevented. DNA crosslinks that covalently link both strands of the DNA double helix are among the most dangerous DNA lesions. Crosslinks block DNA replication and can thus cause cell death. Moreover, their faulty repair can trigger the development of tumors. | Crosslink repair is highly complex and only vaguely understood today. A team of cancer researchers headed by Alessandro Sartori from the University of Zurich now reveals interesting details as to how cells recognize crosslink damage. In their study recently published inFor their study, the researchers examined the Fanconi anemia signal pathway, which coordinates the complex repair of crosslinks, with the aid of genetically modified and unchanged cells. Sartori and his team wanted to find out whether and how the signal pathway and the repair protein CtIP interact with one another. "We are able to show that CtIP recognizes and repairs crosslinks efficiently with the aid of the Fanconi anemia signal pathway, or FANCD2 to be more precise," explains Sartori. The scientists also discovered the point where CtIP attaches itself to the FANCD2 protein. According to the researchers, the interplay between the two proteins is necessary for the flawless and smooth repair of crosslink damage as it prevents the relocation of entire chromosome sections to another position (see figure). Referred to as chromosomal translocation, the process is one of the main causes of the development of cancer.These days, substances that specifically trigger crosslink damage are used in cancer chemotherapy. The new findings are therefore important for both our understanding of the development of cancer and the further development of improved drugs.Fanconi anemia (FA) is a rare congenital disorder that was first described in 1927 by Guido Fanconi (1892-1979), Professor of Pediatrics at the University of Zurich. Fanconi anemia is triggered by mutations in genes that regulate the repair of DNA crosslinks. Patients who suffer from Fanconi anemia display bone marrow failure already during childhood and have a risk of developing cancer that is about 1,000 times higher compared to healthy individuals. Only around a third of Fanconi anemia patients live beyond the age of 30. | Genetically Modified | 2,014 |
May 26, 2014 | https://www.sciencedaily.com/releases/2014/05/140526182755.htm | How DNA is 'edited' to correct genetic diseases | An international team of scientists has made a major step forward in our understanding of how enzymes 'edit' genes, paving the way for correcting genetic diseases in patients. | Researchers at the Universities of Bristol, Münster and the Lithuanian Institute of Biotechnology have observed the process by which a class of enzymes called CRISPR -- pronounced 'crisper' -- bind and alter the structure of DNA.The results, published in the CRISPR enzymes were first discovered in bacteria in the 1980s as an immune defence used by bacteria against invading viruses. Scientists have more recently shown that one type of CRISPR enzyme -- Cas9 -- can be used to edit the human genome -- the complete set of genetic information for humans.These enzymes have been tailored to accurately target a single combination of letters within the three billion base pairs of the DNA molecule. This is the equivalent of correcting a single misspelt word in a 23-volume encyclopaedia.To find this needle in a haystack, CRISPR enzymes use a molecule of RNA -- a nucleic acid similar in structure to DNA. The targeting process requires the CRISPR enzymes to pull apart the DNA strands and insert the RNA to form a sequence-specific structure called an 'R-loop'.The global team tested the R-loop model using specially modified microscopes in which single DNA molecules are stretched in a magnetic field. By altering the twisting force on the DNA, the researchers could directly monitor R-loop formation events by individual CRISPR enzymes.This allowed them to reveal previously hidden steps in the process and to probe the influence of the sequence of DNA bases.Professor Mark Szczelkun, from Bristol University's School of Biochemistry, said: "An important challenge in exploiting these exciting genome editing tools is ensuring that only one specific location in a genome is targeted."Our single molecule assays have led to a greater understanding of the influence of DNA sequence on R-loop formation. In the future this will help in the rational re-engineering of CRISPR enzymes to increase their accuracy and minimise off-target effects. This will be vital if we are to ultimately apply these tools to correct genetic diseases in patients."The work was funded at the University of Bristol by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Wellcome Trust. | Genetically Modified | 2,014 |
May 26, 2014 | https://www.sciencedaily.com/releases/2014/05/140526101700.htm | Insights into genetics of cleft lip | Scientists at the European Molecular Biology Laboratory (EMBL) in Heidelberg, have identified how a specific stretch of DNA controls far-off genes to influence the formation of the face. The study, published today in Nature Genetics, helps understand the genetic causes of cleft lip and cleft palate, which are among the most common congenital malformations in humans. | "This genomic region ultimately controls genes which determine how to build a face and genes which produce the basic materials needed to execute this plan," says François Spitz from EMBL, who led the work. "We think that this dual action explains why this region is linked to susceptibility to cleft lip or palate in humans."Previous studies had shown that variations in a large stretch of DNA are more frequent in people with cleft lip or cleft palate. But there are no genes in or around this DNA stretch, so it was unclear what its role might be. To answer this question, Spitz and colleagues genetically engineered mice to lack that stretch of DNA, as the mouse and human versions are very similar, and are therefore likely to have the same role in both species. They found that these genetically engineered mice had slight changes to the face -- such as a shorter snout -- and a few had cleft lips. The scientists also used this mouse model to look at what happened during embryonic development to lead to those changes."We found that this stretch of DNA contains regulatory elements that control the activity of a gene called Myc, which sits far away on the same chromosome," Spitz explains, "and it exerts that control specifically in the cells that will form the upper lip."The researchers discovered that, in the face of mouse embryos that lack this stretch of DNA, Myc becomes largely inactive. This in turn affects two groups of genes: genes directly involved in building the face, and genes that make ribosomes, the cell's protein-producing factories. The latter effect could make the developing upper lip more sensitive to other genetic conditions and to environmental factors -- like smoking or drinking during pregnancy -- that can influence cell growth. This is because making the face in general, and the upper lip in particular, are very complex processes, requiring different groups of cells in the embryo to grow and fuse with each other at the right time. If the cells involved have their protein production impaired -- due to reduced Myc activity -- any additional burden could disrupt that growth, increasing the likelihood of a malformation like cleft palate. This increased susceptibility to a wide range of factors -- both genetic and environmental -- could the link between variations in this stretch of DNA and the incidence of cleft lip.The EMBL scientists would now like to use their genetically engineered mice to untangle the interplay between genetic and environmental factors. They would also like to investigate how this stretch of DNA can control Myc across such a long distance, and determine the exact role of the genetic variants found in humans. | Genetically Modified | 2,014 |
May 25, 2014 | https://www.sciencedaily.com/releases/2014/05/140525154744.htm | Mind alteration device makes flies sing and dance | In a joint effort with collaboration partners from the Vienna University of Technology and a lab in the USA, the team of Andrew Straw at the IMP developed a special device for the thermogenetic control of flies. This tool, called FlyMAD, enabled the scientists to target light or heat to specific body regions of flies in motion and to analyse the animals' brain cells. Compared to other techniques, FlyMAD allows highly improved temporal resolution. Using the new technology, Straw and his colleagues got new insight into the role of two neuronal cell types in courtship behavior of flies. | The fruit fly Straw and his co-workers are interested in the mechanisms underlying cell circuits in the fly brain. Straw's group concentrates on the control of complex behaviors such as courtship. In order to better understand how different neuronal circuits work together, Straw and his team developed FlyMAD ("Fly Mind Altering Device"), an apparatus using a video camera to track the flies' motion in a box. FlyMAD allows simultaneous observation of several flies and targeted irradiation of specific body regions of these animals. By combining the sensitive methods of optogenetics and thermogenetics, the researchers were able to specifically alter neural pathways in the fly brain with FlyMAD.The novel technology of thermogenetics uses genetically modified, temperature-sensitive flies. Upon irradiation with infrared light and the concomitant rise in temperature to 30 degrees Celsius, these animals change certain aspects of their behavior. This does not happen at a control temperature of 24 degrees Celsius. Compared to other commonly used methods, FlyMAD applies a highly improved temporal resolution. Infrared-induced activation or repression of specific neurons and the following change in the animals' behavior occur within the fraction of a second.The application of visible light to certain genetically engineered flies can also induce alterations of their brain. FlyMAD thus represents an absolute novelty for fly research, as optogenetics has been restricted to mice so far.Straw and his co-workers tested FlyMAD by analyzing already known reactions of genetically modified flies to light and heat. As this proof-of-principle showed that FlyMAD worked reliably -- for example by making the flies "moonwalk" -- the researchers went on to use their method to tackle new scientific questions. In a thermogenetic set up, they investigated a certain type of neurons that had been linked to the flies' courtship song in earlier experiments. Taking advantage of the better temporal resolution of FlyMAD, the scientists were able to characterize the role of two neuronal cell types in the brain in more detail. They could show that activity of one type of neurons correlated with a persistent state of courtship, whereas the other cell type was important for the action of "singing." In the experiment this became obvious when males tried to mate with a ball of wax, circled it and started vibrating their wings after stimulation with the laser beamIn the future, Straw wants to combine the activation of flies both by light and by heat in one experiment -- that is feasible with FlyMAD. This would allow the activation or repression of different genetic elements in one fly. "FlyMAD offers the fantastic opportunity to address many of our questions. We could, for example, analyze how single neurons function in a cascade within the neuronal circuit," Straw emphasizes the potential of his work. Ultimately, new insight into the function of the fly brain can also be applied to the network of cells in the mammalian brain. | Genetically Modified | 2,014 |
May 23, 2014 | https://www.sciencedaily.com/releases/2014/05/140523094259.htm | Rapid evolution aids spread of exotic plant species | A team of Belgian biologists led by researchers at KU Leuven has provided the first genetic evidence that rapid evolution can help non-native plant species spread in new environments. Using samples of centuries-old herbaria and DNA analysis, the researchers reconstructed the genetic adaptations undergone by the Pyrenean rocket prior to its rapid spread in Belgium. | The Pyrenean rocket (The colonization history of the Pyrenean rocket is well documented, explains postdoctoral researcher and corresponding author Katrien Vandepitte (Plant Conservation and Population Biology Research Group): "We found dried specimens of the Pyrenean rocket in herbaria from the 19th and 20th centuries and were able to isolate DNA from these samples. We then compared this DNA with the genetic profile of contemporary samples from Belgium and the Pyrenees. This gave us a unique opportunity to reconstruct when and how an exotic plant species genetically adapted to a new environment.""When we looked at the genetic evolution of the Pyrenean rocket, we found the greatest divergences in a set of genes that regulate flowering time, an important plant fitness trait. When we compared current individuals taken from our region and the Pyrenees, both grown under Belgian conditions, the Belgian variant bloomed later.""Our DNA analysis shows that the Belgian variant genetically adapted quite rapidly -- in about 20 generations. This very likely helped the plant to survive and spread here.""Our findings are important because until now evidence supporting the hypothesis that exotic plants can spread after a period of rapid genetic adaptation has been very scant," says Dr. Vandepitte.The results also suggest that we should be wary of 'latent' non-native plant species. "These plants can be present in small numbers for years before spreading as a result of genetic adaptation. The Pyrenean rocket is a harmless plant, but some exotics can become a real plague. And this can occur even after a period of unproblematic presence in a non-native environment." | Genetically Modified | 2,014 |
May 19, 2014 | https://www.sciencedaily.com/releases/2014/05/140519184550.htm | Genetic basis of pest resistance to biotech cotton discovered | An international team led by scientists at the University of Arizona and the U.S. Department of Agriculture has discovered what happens on a molecular basis in insects that evolved resistance to genetically engineered cotton plants. Their findings, reported in the May 19 issue of the journal | "Bt crops have had major benefits for society," said Jeffrey Fabrick, the lead author of the study and a research entomologist at the USDA Agricultural Research Service in Maricopa, Arizona. "By understanding how insects adapt to Bt crops we can devise better strategies to delay the evolution of resistance and extend these benefits.""Many mechanisms of resistance to Bt proteins have been proposed and studied in the lab, but this is the first analysis of the molecular genetic basis of severe pest resistance to a Bt crop in the field," said Bruce Tabashnik, one of the paper's authors and the head of the Department of Entomology in the UA College of Agriculture and Life Sciences. He also is a member of the UA's BIO5 Institute.Based on laboratory experiments aimed at determining the molecular mechanisms involved, scientists knew that pink bollworm can evolve resistance against the Bt toxin, but they had to go all the way to India to observe this happening in the field.Farmers in the U.S., but not in India, adopted tactics designed to slow evolution of resistance in pink bollworm. Scientists from the UA and the U.S. Department of Agriculture worked closely with cotton growers in Arizona to develop and implement resistance management strategies such as providing "refuges" of standard cotton plants that do not produce Bt proteins and releasing sterile pink bollworm moths. Planting refuges near Bt crops allows susceptible insects to survive and reproduce and thus reduces the chances that two resistant insects will mate with each other and produce resistant offspring. Similarly, mass release of sterile moths also makes it less likely for two resistant individuals to encounter each other and mate.As a result, pink bollworm has been all but eradicated in the southwestern U.S. Suppression of this pest with Bt cotton is the cornerstone of an integrated pest management program that has allowed Arizona cotton growers to reduce broad spectrum insecticide use by 80 percent, saving them over $10 million annually. In the U.S., pink bollworm populations have not evolved resistance to Bt toxins in the wild. However, resistant pink bollworm populations have emerged in India, which grows the most Bt cotton of any country in the world.Crops genetically engineered to produce proteins from the bacterium Bacillus thuringiensis -- or Bt -- were introduced in 1996 and planted on more than 180 million acres worldwide during 2013. Organic growers have used Bt proteins in sprays for decades because they kill certain pests but are not toxic to people and most other organisms. Pest control with Bt proteins -- either in sprays or genetically engineered crops -- reduces reliance on chemical insecticides. Although Bt proteins provide environmental and economic benefits, these benefits are cut short when pests evolve resistance.The emergence of resistant pink bollworm in India provided the researchers an opportunity to test the hypothesis that insects in the field would evolve resistance to Bt toxin by the same genetic mechanism found previously in the lab. In the lab strains, the scientists had identified mutations in a gene encoding a protein called cadherin. Binding of Bt toxin to cadherin is an essential step in the intoxication process. Mutations that disrupt cadherin block this binding, which leaves the insect unscathed by the Bt toxin."We wanted to see if field-resistant pink bollworm from India harbored these same changes in the cadherin gene," Fabrick said. He said that by collaborating with Indian scientists, "we discovered that the same cadherin gene is associated with the resistance in India, but the mutations are different and much more numerous than the ones we found in lab-selected pink bollworm from Arizona."Tabashnik added: "In 17 years of research and screening more than 10,000 individuals from Arizona, we identified four cadherin-based resistance mutations. And in just eight individuals from India, we found 19 different cadherin variants that confer resistance. It blew our minds."Sequencing the DNA of resistant pink bollworm collected from the field in India, the team found that the insects produce remarkably diverse disrupted variants of cadherin. The researchers learned that the astonishing diversity of cadherin in pink bollworm from India is caused by alternative splicing, a novel mechanism of resistance that allows a single DNA sequence to code for many variants of a protein. "Our findings represent the first example of alternative splicing associated with Bt resistance that evolved in the field," said Fabrick, who is also an adjunct scientist in the Department of Entomology at UA.Mario Soberón, a Bt expert at the Universidad Nacional Autónoma de México in Cuernavaca who was not an author of the study, commented, "This is a neat example of the diverse mechanisms insect possess to evolve resistance. An important implication is that DNA screening would not be efficient for monitoring resistance of pink bollworm to Bt toxins." | Genetically Modified | 2,014 |
May 19, 2014 | https://www.sciencedaily.com/releases/2014/05/140519160712.htm | Why you need olive oil on your salad | A diet that combines unsaturated fats with nitrite-rich vegetables, such as olive oil and lettuce, can protect you from hypertension, suggests a new study led by King's College London. The findings, published in the journal | The Mediterranean diet typically includes unsaturated fats found in olive oil, nuts and avocados, along with vegetables like spinach, celery and carrots that are rich in nitrites and nitrates.When these two food groups are combined, the reaction of unsaturated fatty acids with nitrogen compounds in the vegetables results in the formation of nitro fatty acids.The study, supported by the British Heart Foundation, used mice to investigate the process by which these nitro fatty acids lower blood pressure, looking at whether they inhibited an enzyme known as soluble Epoxide Hydrolase which regulates blood pressure.Mice genetically engineered to be resistant to this inhibitory process were found to maintain their high blood pressure despite being fed the type of nitro fatty acids that normally form when a Mediterranean diet is consumed. However, nitro fatty acids were found to lower the blood pressure of normal mice following the same diets.Thus, the study concludes that the protective effect of the Mediterranean diet, combining unsaturated fats and vegetables abundant in nitrite and nitrate, comes at least in part from the nitro fatty acids generated which inhibit soluble Epoxide Hydrolase to lower blood pressure.Professor Philip Eaton, Professor of Cardiovascular Biochemistry at King's College London, said: "The findings of our study help to explain why previous research has shown that a Mediterranean diet supplemented with extra-virgin olive oil or nuts can reduce the incidence of cardiovascular problems like stroke, heart failure and heart attacks." | Genetically Modified | 2,014 |
May 15, 2014 | https://www.sciencedaily.com/releases/2014/05/140515142706.htm | Roadmap Shows How to Improve Lignocellulosic Biofuel Biorefining | When making cellulosic ethanol from plants, one problem is what to do with a woody agricultural waste product called lignin. The old adage in the pulp industry has been that one can make anything from lignin except money. | A new review article in the journal "We've developed a roadmap for integrating genetic engineering with analytical chemistry tools to tailor the structure of lignin and its isolation so it can be used for materials, chemicals and fuels," said Arthur Ragauskas, a professor in the School of Chemistry and Biochemistry at the Georgia Institute of Technology. Ragauskas is also part of the Institute for Paper Science and Technology at Georgia Tech.The roadmap was published May 15 in the journal The growth of the cellulosic fuel industry has created a stream of lignin that the industry needs to find valuable ways to use. At the same time, federal agencies and industry are funding research to simplify the process of taking biomass to fuels."One of the very promising approaches to doing that is to genetically engineer plants so they have more reactive polysaccharides suitable for commercial applications, but also to change lignin's structural features so that it'll become more attractive for materials applications, chemicals and fuels." Ragauskas said.Research highlighted in the review has shown it's theoretically possible to genetically alter lignin pathways to reduce undesirable byproducts and more efficiently capture the desired polysaccharides -- which are sugars that can be converted to other products -- and enhance lignin's commercial value."There are sufficient publications and data points out there to say that say, 'Yes, we can do this,'" Ragauskas said.Through work on transgenic plants and wild plants that naturally have fewer undesirable constituents, biologists, engineers and chemists have recently improved the biorefinery field's understanding of the chemistry and structure of lignin, which provides a better idea of the theoretical chemistry that lignin can do, Ragauskas said."We should be able to alter the structure of lignin and isolate it in such a manner that we can use it for green-based materials or use it in a blend for a variety of synthetic polymers," Ragauskas said.Doing so would create a stream of polysaccharides for use as ethanol fuels, with lignin waste that has structural features that would make it attractive for commercial applications such as polymers or carbon fibers.The science could be applied to a variety of plants currently used for cellulosic biofuel production, such as switchgrass and poplar.Today, lignin is mostly burned for energy to fulfill a small amount of the power requirements of the ethanol biorefineries. But the new roadmap emphasizes how, through genetic engineering tools that currently exist, lignin could become much more valuable to industry."Our primary mission is to reduce the cost of taking biomass to biofuels," Ragauskas said, "But in the process we've learned a lot about lignin, and we might be able to do more than just reduce cost. We might be able to tailor lignin's structure for commercial applications." | Genetically Modified | 2,014 |
May 14, 2014 | https://www.sciencedaily.com/releases/2014/05/140514100308.htm | New Zealand sea lion is a relative newcomer | The modern New Zealand sea lion is a relative newcomer to our mainland, replacing a now-extinct, unique prehistoric New Zealand sea-lion that once lived here, according to a new study led by University of Otago researchers. | A team of biologists from the University of Otago estimates that this prehistoric mainland sea-lion population became extinct as recently as 600 years ago, and was then replaced by a lineage previously limited to the waters of the cold subantarctic.The Marsden-funded study, carried out by Otago Zoology PhD student Catherine Collins, and led by Professor Jon Waters, set out to investigate changes in the New Zealand sea-lion population since human settlement.Ms Collins says they were startled to identify a previously unknown sea-lion lineage that dominated South Island shores until just a few hundred years ago."It is estimated that the mainland sea-lions became extinct between 1300 and 1500AD, soon after Polynesian settlement, and midden remains suggest they were hunted extensively. The extinction apparently created an opportunity for the subantarctic lineage to colonise New Zealand's mainland," she says.The team identified the extinct mainland sea-lion lineage using ancient DNA from prehistoric bones."We found that the extinct mainland population was clearly genetically distinct from the modern subantarctic population that arrived more recently," she says.The unexpected finding closely mirrors a prehistoric extinction-replacement event for yellow-eyed penguins, recently detected by the same team led by Professor Waters."Our findings demonstrate that our current sea-lion population is not a declining remnant of an original mainland population, but rather represents a new arrival from the subantarctic," he says."Competition between the two lineages may have previously prevented the subantarctic lineage from expanding northwards to the mainland of New Zealand."Professor Waters adds that all they know for certain about the attributes of this prehistoric sea-lion is that it was genetically distinct from the modern sea-lion lineage. He anticipates that future study of the prehistoric remains will lead to a greater understanding of its biology.The team's findings have been published today in the international biological research journal | Genetically Modified | 2,014 |
May 13, 2014 | https://www.sciencedaily.com/releases/2014/05/140513092533.htm | Humans and companion animals harbor the same types of MRSA infections | shared population of methicillin-resistant | "Our study demonstrates that humans and companion animals readily exchange and share MRSA bacteria from the same population," says senior author Mark Holmes, senior lecturer in preventive veterinary medicine at the University of Cambridge in England. MRSA naturally lives on the skin and also causes difficult-to-treat infections in humans and animals. "It also furthers the 'one health' view of infectious diseases that the pathogens infecting both humans and animals are intrinsically linked, and provides evidence that antibiotic usage in animal medicine is shaping the population of a major human pathogen."Holmes and colleagues sequenced the genomes of 46 MRSA samples from cats and dogs, collected between August 2003 and August 2007 from two large veterinary hospitals and several smaller veterinary practices throughout the United Kingdom. The samples were found to be similar to those associated with MRSA strains in humans, with most coming from wound infections or skin and soft tissue infections. Additional samples were from the animals' urine; cerebrospinal fluid; nasal wash or discharge; and bloodstream, heart valve or joint infections.Comparing the samples to a global collection of human MRSA samples sequenced as part of other studies and evaluating the evolution of the bacteria, the investigators found that all animal infections fell in the same family: Epidemic MRSA 15 (EMRSA-15) (sequence type ST22), a common strain of MRSA first detected in the United Kingdom in the 1990s that spread throughout Europe. The bacteria were interspersed throughout the EMRSA-15 genetic family tree. Nearly all samples were genetically similar to human bacteria, and their place in the family tree showed that the companion animal bacteria most likely originated in humans.Researchers also observed that samples from the same veterinary hospitals clustered together genetically, suggesting that as in human hospitals, MRSA can be readily transmitted in veterinary hospital settings."It's a reminder that constant vigilance and high levels of hygiene are just as important when treating cats and dogs as with humans," Holmes says.Analysis of the genomes showed very little genetic discrimination between bacteria samples from humans and animals, indicating that the MRSA from cats and dogs had not undergone extensive adaptation to the companion animals, suggesting this type of MRSA has a broad host range. But the animal MRSA were significantly less likely than those from humans to have resistance to the antibiotic erythromycin, used rarely in English veterinary practices. Instead, these MRSA from animals were more likely to contain mutations making them resistant to the antibiotic clindamycin, used widely in veterinary medicine in the United Kingdom.Holmes says pet owners don't need to worry."MRSA infection in cats and dogs is still extremely rare," Holmes says. "There is very little risk of owners getting ill from their pets." In addition, he says, healthy pets are not likely to pick up MRSA from their human companions but if a pet already is ill or its health is severely compromised, MRSA patients should inform their pets' veterinarians. | Genetically Modified | 2,014 |
May 12, 2014 | https://www.sciencedaily.com/releases/2014/05/140512155029.htm | Corn dwarfed by temperature dip suitable for growing in mines, caves | Lowering temperatures for two hours each day reduces the height of corn without affecting its seed yield, a Purdue study shows, a technique that could be used to grow crops in controlled-environment facilities in caves and former mines. | Raising the crops in isolated and enclosed environments would help prevent genetically modified pollen and seed from escaping into the ecosystem and crossing with wild plants.Cary Mitchell, professor of horticulture, said the technique could be particularly useful for growing transgenic crops to produce high-value medicinal products such as antibodies for the budding plant-derived industrial and pharmaceutical compounds industry."Grains of corn could be engineered to produce proteins that could be extracted and processed into medicine, pharmaceuticals and nutraceuticals such as essential vitamins," he said. "This is a young industry, but what we've done is show that you can successfully grow these high-value crops in contained environments."Mitchell described corn as a "good candidate crop" for the industry because of the plant's bounty of seeds and well-characterized genome, which can be modified in many ways. Using plants as "factories" to generate bioactive medicines would be far cheaper than the current methods that rely on cell cultures from mammals, he said.But raising corn -- a towering crop that needs bright light and heat -- in a dark, cool, underground mine presented a challenge to Mitchell and then-postdoctoral researchers, Yang Yang and Gioia Massa. They installed a growth chamber with insulation and yellow and blue high-intensity discharge lamps in a former limestone mine in Marengo, Indiana, to test how corn would react to an environment in which its growing conditions -- light, temperature, humidity and carbon dioxide -- were tightly controlled. To their surprise, the hybrid corn responded by growing "too well," said Yang."We coddled the plants with such luxurious conditions that the corn was touching the lamps before it had even tasseled," he said.To reduce the corn's height, the researchers borrowed a trick used by the greenhouse industry to dwarf Christmas poinsettias. Using a growth chamber that mimicked the temperature conditions and carbon dioxide levels of the Marengo mine, they dropped the temperature to 60 degrees Fahrenheit for the first two hours of each photoperiod, the time in which the corn received light. The temperature was restored to 80 degrees for 14 hours and then lowered to 65 degrees for eight hours of darkness.The temperature dip dwarfed stalk height by 9 to 10 percent and reduced stalk diameter by 8 to 9 percent without significantly affecting the number and weight of the seeds."This is a technique you could easily do in a mine or cave," Mitchell said. "It is an affordable, non-chemical means of taking genetically modified crops to harvest maturity without getting any kind of pollen or seed into the ecosystem."He said that former mines could be prime locations to grow high-value, transgenic plants because their natural coolness lessens the need to ventilate the heat produced by lamps. The high levels of carbon dioxide in mines also promote plant growth."Productivity in a controlled environment is superior to that in the field, and you can raise more than one crop per year," Mitchell said. "Controlled environment agriculture is going to be one of the big movements of the 21st century." | Genetically Modified | 2,014 |
May 5, 2014 | https://www.sciencedaily.com/releases/2014/05/140505155343.htm | Groovy turtles' genes to aid in their rescue | The diverse patterns on the diamondback terrapins' intricately grooved shell may be their claim to fame, but a newly published U.S. Geological Survey study of the genetic variation underneath their shell holds one key to rescuing these coastal turtles. | Listed as an endangered species in Rhode Island and deemed threatened in Massachusetts, the terrapin is the only turtle in North America that spends its entire life in coastal marshes and mangroves. Seven different subspecies of terrapins are currently recognized by scientists based on external traits, such as their skin color and the shape of their shells. Each subspecies occupies a strip of the eastern seaboard or Gulf of Mexico coastline, from as far north as Massachusetts to as far west as Texas.Many of the coastal states where terrapins are found have designated it a species of special concern, and the states are looking to address the issues the terrapins face due to fragmentation of their coastal habitats. An increasingly patchy swath of isolated coastal marshes makes it harder for terrapins to find each other and continue interbreeding as they have in the past."Before now, it was not clear how terrapin genetics varied across the range," said Kristen Hart, a USGS research ecologist and lead author of the study. "Understanding this variation across the landscape helps land managers develop conservation plans. For example, they may pinpoint areas where habitat protection can be supplemented with migration corridors."Agencies often maintain migration corridors to help wildlife continue to breed based on their historic patterns. These are areas where habitat restoration, regulatory policies, or other means are used to ensure animals can pass safely between two or more prime areas of habitat. Well-placed corridors could maintain the terrapins' existing natural diversity and keep their overall population numbers robust, explained Hart."Diversity loss can be a silent threat to many species," explained Maggie Hunter, a USGS research geneticist and co-author of the study. "The threat to long-term survival of terrapins occurs if they become separated into isolated groups. Isolation can affect their overall survival several generations down the line."To support a healthy mix of genetic diversity, however, managers must first understand the existing genetic variation."Healthy interbreeding doesn't mean that turtles from Maine have to interbreed with those from Texas," explained Hunter. "Once managers know where 'natural breaks' in populations occur, they can focus on keeping terrapin populations healthy by enabling reproduction within each of those distinct groups."To identify those natural genetic breaks, Hart teamed up with Hunter and USGS research geneticist Tim King to study their breeding patterns using DNA from the blood samples of nearly a thousand terrapins. Based on their variation in 12 genetic markers -- strands of DNA that King had decoded for comparative purposes -- the terrapins were assigned into genetically similar groups.They found only 4 genetically distinct populations, which came as a surprise, given there are 7 recognized terrapin subspecies. This means the 'natural breaks' in breeding don't correspond to the ranges of those subspecies.The results of the genetic study offer one more benefit. During the 1920s, terrapins were considered a delicacy and hunted for their meat, and they still occasionally turn up as food in markets around the country. Now, wildlife agencies can use a DNA test to determine where these turtles came from, so they can return rescued turtles back to their original habitat. | Genetically Modified | 2,014 |
May 5, 2014 | https://www.sciencedaily.com/releases/2014/05/140505093925.htm | Journey between XX, XY: Getting closer to unravelling mystery of sexual ambiguity | In both humans and mammals, sexual development is a long process. In most cases, the genetic sex (XX or XY) results in the development of the corresponding gonadal sex (ovaries or testes), which in turn secretes hormones that will masculinize or feminize the fetus. But throughout gonadal development, various accidents may occur, giving rise to a wide range of alterations and ambiguities. Disorders of gonadal development represent a heterogeneous class of sexual ambiguities caused by defects in gonadal development or a failure of testis differentiation. | Sexual ambiguities are relatively frequent congenital conditions. In many cases, despite considerable progress in understanding the genetic factors involved in gonadal differentiation, the causative mutation remains unknown. Identifying them is therefore crucial to carry out genetic testing, reason why, for many years, researchers have been collecting as much data as possible on the genome of patients affected by various forms of disorder of sex development.Within this context, geneticists at UNIGE have had the opportunity to focus on the case of a child, a genetically XY little girl presenting a disorder of sex development, with testicular dysgenesis and chondrodysplasia, an illness which disrupts skeletal growth and alters its structure and shape. In this child, they were able to determine the cellular elements at work in gonadal formation, and in turn to identify the genetics involved.Using the patient's DNA sequencing data, the researchers identified a mutation in the HHAT gene, a gene largely expressed in human organs during fetal development, including in the testes and ovaries during sexual development. HHAT function is to encode an enzyme essential to the proper functioning of a family of signalling molecules known as Hedgehog, which play a key role in embryonic development. Reduced Hedgehog functional performance results in the disorders suffered by the patient, which affect not only sexual development, but also growth and skeletal development.To confirm their discovery, geneticists then developed in vitro tests to show that the mutation interferes with a specific activity of the HHAT gene. They also found that mutant mice with the non-functioning HHAT gene presented testicular dysgenesis and other skeletal, neuronal and growth development problems which were very similar to those identified in the young patient.In developing testes, the HHAT gene plays a role in the formation of the testis cords itself and in the differentiation of fetal Leydig cells; the latter, which produce androgens which contribute to the masculinzation of the fetus, and later of the individual, were absent in the testes of mutant mice. Generally speaking, these results shed new light on the mechanisms of action of the Hedgehog proteins and provide the first clinical evidence of the essential role played by these proteins in human testicular organogenesis and embryonic development."Using this patient's case as a starting point, we were able to trace the genetic course up to the cause of this sexual and other development disorders," stresses Serge Nef. "Identifying the gene and mechanism at stake allows us to pinpoint the exact diagnosis, develop genetic tests and provide better treatment to patients suffering from this syndrome." If, for the time being, we cannot cure patients suffering from a disorder of sex development and its consequences, an early diagnosis in a child's life will enable us to predict how they will develop later and to propose appropriate therapeutic strategies. | Genetically Modified | 2,014 |
May 4, 2014 | https://www.sciencedaily.com/releases/2014/05/140504211035.htm | Tracking proteins in single HIV particle | An interdisciplinary team of scientists from KU Leuven in Belgium has developed a new technique to examine how proteins interact with each other at the level of a single HIV viral particle. The technique allows scientists to study the life-threatening virus in detail and makes screening potential anti-HIV drugs quicker and more efficient. The technique can also be used to study other diseases. | Understanding how the human immunodeficiency virus (HIV) reproduces itself is crucial in the effort to fight the disease. Upon entering the bloodstream, HIV viral particles, or virions, 'highjack' individual immune cells. The virion binds to and then penetrates the immune cell. Once inside, the virion reprograms the genetic material of the immune cell to produce more HIV virions. In this way, HIV disables the disease-fighting 'bodyguards' in our blood and turns them into breeding machines for new HIV virions.Integrase plays a key role throughout this whole process: "Integrase is the HIV protein that causes the genetic material of HIV to link to that of the hijacked cell. It ensures the programming of the human cell upon infection. In our study, we wanted to track integrase during the different stages of infection," explains postdoctoral researcher Jelle Hendrix (Department of Chemistry). The challenge is to do this at the level of a single virion: "HIV has multiple ways of doing the same thing. This is the case for cell penetration, for instance. So it is certainly useful to be able to see exactly how the individual HIV virions are behaving."To achieve this, the researchers used single-molecule fluorescence imaging. They engineered a genetically modified HIV virion that was capable of infecting the cell but incapable of reproducing inside it. The virion was programmed to produce a fluorescent form of integrase. "This allowed us to examine the interactions of the florescent integrase under the light microscope both in vitro in a single HIV virion as well as in a human cell infected with it.""We then used the technique to study both clinically approved and newly developed HIV inhibitors. Some of these drugs were thought to affect interaction between integrase particles. With our new technique, we were able to observe that this was indeed the case.""There are already a few dozen medications available for HIV, but further research is essential. Whenever HIV multiplies by hijacking an immune cell, there is a chance of mutation, and there is no guarantee that an HIV drug will be able to handle that mutation. A medication may not be as effective over the course of a patient's lifetime. Moreover, current HIV drugs are very expensive. Hence the importance of being able to test anti-HIV medications quickly and efficiently."The good news is that this new technique can be broadly applied: "It may seem surprising, but we can also use a genetically modified version of a dangerous virus to examine other pathogens. Essentially, we have created a nano test tube out of an HIV virion, inside of which protein interactions can be studied. In principle, we can make any protein fluorescent, be it from HIV, from another disease or from a human cell.""Researchers have been studying protein interactions for some time, but studying them at the level of a single viral particle was not possible until now," says Jelle Hendrix. Our technique allows scientists to quickly test many molecules -- potential medications -- for many diseases using minimal material. In future research, we will be using the technique to study integrase proteins of other viruses." | Genetically Modified | 2,014 |
April 30, 2014 | https://www.sciencedaily.com/releases/2014/04/140430133147.htm | Fattening gene discovered by researchers | The long-term consumption of too much high-energy and high-fat food leads to overweight. Behind this trivial statement lies the extremely complex regulation of lipid metabolism. Together with colleagues from Japan, scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now discovered that the Sirt7 gene plays a central role in energy metabolism. Despite consuming high-fat food, genetically modified mice that lack the gene maintain their normal weight. | Food was not always available to such excess as it is in western societies today. On the contrary, our metabolism was tailored to the optimum exploitation of energy, as humans, for millennia, had to budget their calories carefully. Thus, the formation and depletion of fat depots as energy stores is subject to complex regulation. A series of regulators is involved in lipid metabolism in the liver for the purpose of storing excess energy and making it available again when required.Working in cooperation with colleagues from the Sendai and Kumamoto Universities in Japan, scientists from the Max Planck Institute for Heart and Lung Research in Bad Nauheim have now identified a protein from the sirtuin group that plays a major role in the utilization of energy in the context of a high-fat diet and is responsible for the formation of fat depots. Sirtuins are known as a group of proteins with wide-ranging biological functions.The researchers carried out their tests on mice which lack a sirtuin known as SIRT7. These Sirt7-knockout mice and non-genetically-modified animals were fed particularly high-fat pellets for months. "We established that Sirt7-knockout mice put on significantly less weight than the control group. On the contrary, they maintained their normal weight," says Eva Bober, a scientist at the MPI. Moreover, compared with the non-genetically-modified mice, these animals tended to have lower triglyceride and cholesterol levels in their livers and normal insulin levels. "Everything pointed to the fact that the animals which lacked SIRT7 were able to process the excess energy in the food better and did not build up any pathological fat depots," says Bober.To investigate the molecular processes behind this observation, the scientists studied the gene activities of the liver cells. In the process, it emerged that SIRT7 activates the expression of a large number of genes for lipid metabolism. In the liver cells from mice without SIRT7, this gene remains largely unactivated and fewer fat depots are formed as a result."We discovered a second mechanism as well," says Bober. "SIRT7 also inhibits the degradation of certain proteins. Because they are then active for longer, these proteins also make a greater contribution to energy storage than is actually intended." Conversely, if SIRT7 is missing, these proteins are degraded and fewer fat depots are formed.The researchers hope that their study will provide the basis for new therapeutic approaches. "We would now like to examine substances with which the function of SIRT7 can be deliberately inhibited. We want to examine whether the same effects arise as observed in the mice that lack the Sirt7 gene," explains Bober. The long-term objective is the development of a drug that would reduce the efficiency of lipid metabolism. This would enable the avoidance of overweight. | Genetically Modified | 2,014 |
April 28, 2014 | https://www.sciencedaily.com/releases/2014/04/140428143128.htm | Technological advancements extend long-term survival of transplanted hearts across species | Cardiac transplantation is the treatment of choice for end stage heart failure. According to the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, approximately 3,000 people in the US are on the waiting list for a heart transplant, while only 2,000 donor hearts become available each year. Therefore for the cardiac patients currently waiting for organs, mechanical assist devices are the only options available. These devices, however, are not perfect and have issues with power supplies, infection, and both clotting and hemolysis. | Transplantation using an animal organ, or xenotransplantation, has been proposed as a valid option to save valuable human lives. Muhammad M. Mohiuddin, MD, of the Cardiothoracic Surgery Research Program at the NHLBI, and co-investigators have now developed techniques to overcome some of the immunologic roadblocks that hinder successful xenotransplantation using genetically engineered pigs as a source of donor organs. Pigs were chosen because their anatomy is compatible with that of humans and they have a rapid breeding cycle, among other reasons.As the result of recent improvements in technology for genetic modification of pigs, genes that are immunogenic for humans have been eliminated ('knocked out") and several human genes have been added to the pig genome. Grafts from these genetically engineered (GE) pigs are less likely to be seen as foreign, thus reducing the immune reaction against them. These modifications should also allow transplants utilizing lower amounts of toxic immunosuppressive drugs."These recent scientific developments in the field of genetic engineering, along with the generation of novel target specific immune suppression, and their favorable impact on organ and cellular transplantation, may instill a new ray of hope for thousands of patients waiting for human donor organs," comments Dr. Mohiuddin.The NHLBI group was fortunate to have access to GE pigs through close collaboration with Revivicor, Inc. Experiments using these GE pig hearts, transplanted in the abdomen of baboons along with their native hearts, were designed to study the usefulness of these GE pigs along with several new target-specific immunosuppressive agents in prolonging the graft survival. Through the combination of a pig heart with certain gene modifications, with drugs suppressing both T and B cell immune responses, investigators were able to prolong the graft survival in baboons to over one year. This unique achievement by the NIH laboratory is twice as long as previously reported.The long-term surviving grafts exhibit normal histology (cellular architecture) and contractility. The researchers' next step is to use hearts from the same GE pigs with the same immunosuppression utilized in the current experiments to test their ability to provide full life support by replacing the original baboon heart."Based on the data from long-term surviving grafts, we are hopeful that we will be able to repeat our results in the life-supporting model. If successful, this method could change the current transplant paradigm, eliminating the shortage of donor organs including hearts, livers, kidneys, intestine, as well as insulin producing cells for treatment of diabetes," concludes Dr. Mohiuddin. He is presenting the results of this research at the 94th AATS Annual Meeting in Toronto, ON, Canada on April 28, 2014. | Genetically Modified | 2,014 |
April 24, 2014 | https://www.sciencedaily.com/releases/2014/04/140424125138.htm | Surprising new insights into the PTEN tumor suppressor gene | Ever since it was first identified more than 15 years ago, the PTEN gene has been known to play an integral role in preventing the onset and progression of numerous cancers. Consequently, when PTEN is either lost or mutated, malignant cells can grow unchecked and cancer can develop. | Now a team led by investigators at Beth Israel Deaconess Medical Center (BIDMC) helps explain more precisely how PTEN exerts its anti-cancer effects and how its loss or alteration can set cells on a cancerous course. The new study, which reveals that PTEN loss and PTEN mutations are not synonymous, not only provides key insights into basic tumor biology but also offers a potential new direction in the pursuit of new cancer therapies.The findings are reported online in the April 24 issue of the journal "By characterizing the ways that two specific PTEN mutations regulate the tumor suppressor function of the normal PTEN protein, our findings suggest that different PTEN mutations contribute to tumorigenesis by regulating different aspects of PTEN biology," explains senior author Pier Paolo Pandolfi, MD, PhD, Director of the Cancer Center at BIDMC and George C. Reisman Professor of Medicine at Harvard Medical School. "It has been suggested that cancer patients harboring mutations in PTEN had poorer outcomes than cancer patients with PTEN loss. Now, using mouse modeling, we are able to demonstrate that this is indeed the case. Because PTEN mutations are extremely frequent in various types of tumors, this discovery could help pave the way for a new level of personalized cancer treatment."The PTEN gene encodes a protein, which acts as a phosphatase, an enzyme that removes phosphates from other substrates. Several of the proteins that PTEN acts upon, both lipids and proteins, are known to promote cancer when bound to a phosphate. Consequently, when PTEN removes their phosphates, it is acting as a tumor suppressor to prevent cancer. When PTEN is mutated, it loses this suppressive ability, and the cancer-promoting proteins are left intact and uninhibited. This new study unexpectedly shows that the PTEN mutant protein is not only functionally impaired (losing its enzymatic function) it additionally acquires the ability to affect the function of the normal PTEN proteins, thereby gaining a "pro-tumorigenic" function."We sought to compare PTEN loss with PTEN mutations," explains first author Antonella Papa, PhD, an investigator in the Pandolfi laboratory. "We wanted to know, would outcomes differ in cases when PTEN was not expressed compared with cases when PTEN was expressed, but encoded a mutation within its sequence? It turned out the answer was yes."The scientific team created several genetically modified strains of mice to mimic the PTEN mutations found in human cancer patients. "All mice [and humans] have two copies of the PTEN gene," Papa explains. "The genetically modified mice in our study had one copy of the PTEN gene that contained a cancer-associated mutation [either PTENC124S or PTENG129E] and one normal copy of PTEN. Other mice in the study had only one copy of the normal PTEN gene, and the second copy was removed."The researchers found that the mice with a single mutated copy of PTEN were more tumor-prone than the mice with a deleted copy of PTEN. They also discovered that the mutated protein that was produced by PTENC124S or PTENG129E was binding to and inhibiting the PTEN protein made from the normal copy of the PTEN gene."This was very surprising, as we were expecting a reduction in tumorigenesis,," says Papa. "Instead, mechanistically, we found that PTEN exists as a dimer [two-protein complex] and in this new conformation, the mutated protein prevents the normal protein from functioning." At the molecular level, she adds, this generates an increased activation of a PTEN target -- a protein called Akt -- which is what leads to the augmented tumorigenesis in the mice. Akt is part of a signaling pathway that regulates cell growth, division and metabolism; when PTEN is prevented from inhibiting Akt, the pathway becomes overactive. As a result, say the authors, targeting Akt and its pathway may be an effective treatment strategy for patients with PTEN mutations, adding that inhibitors to affect this pathway are currently being tested and developed."This defines a new working model for the function and regulation of PTEN and tells us that PTEN mutational status can be used to determine which cancer patients might benefit from earlier and more radical therapeutic interventions and, ultimately, better prognosis," notes Pandolfi. "Our findings may help to better identify and stratify patients and their response to treatment based on the different genetic alterations found in the PTEN gene. Importantly, our study shows that cancer therapy should be tailored on the basis of the very specific type of mutations that the tumor harbors. This adds a new layer of complexity but also a new opportunity for precision medicine. I would say that, based on these thorough genetic analyses, this story represents the ultimate example of why personalized cancer medicine is so urgently needed." | Genetically Modified | 2,014 |
April 24, 2014 | https://www.sciencedaily.com/releases/2014/04/140424124650.htm | Protein crucial for development of biological rhythms in mice identified by researchers | Johns Hopkins researchers report that they have identified a protein essential to the formation of the tiny brain region in mice that coordinates sleep-wake cycles and other so-called circadian rhythms. | By disabling the gene for that key protein in test animals, the scientists were able to home in on the mechanism by which that brain region, known as the suprachiasmatic nucleus or SCN, becomes the body's master clock while the embryo is developing.The results of their experiments, reported in the April 24 issue of "Shift workers tend to have higher rates of diabetes, obesity, depression and cancer. Many researchers think that's somehow connected to their irregular circadian rhythms, and thus to the SCN," says Seth Blackshaw, Ph.D., an associate professor in the Department of Neuroscience and the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. "Our new research will help us and other researchers isolate the specific impacts of the SCN on mammalian health."Blackshaw explains that every cell in the body has its own "clock" that regulates aspects such as its rate of energy use. The SCN is the master clock that synchronizes these individual timekeepers so that, for example, people feel sleepy at night and alert during the day, are hungry at mealtimes, and are prepared for the energy influx that hits fat cells after eating. "A unique property of the SCN is that if its cells are grown in a dish, they quickly synchronize their clocks with each another," Blackshaw says.But while evidence like this gave researchers an idea of the SCN's importance, they hadn't completely teased its role apart from that of the body's other clocks, or from other parts of the brain.The Johns Hopkins team looked for ways to knock down SCN function by targeting and disabling certain genes that disrupt only the formation of the SCN clock. They analyzed which genes were active in different areas of developing mouse brains to identify those that were "turned on" only in the SCN. One of the "hits" was Lhx1, a member of a family of genes whose protein products affect development by controlling the activity of other genes. When the researchers turned off Lhx1 in the SCN of mouse embryos, the grown mice lacked distinctive biochemical signatures seen in the SCN of normal mice.The genetically modified mice behaved differently, too. Some fell into a pattern of two to three separate cycles of sleep and activity per day, in contrast to the single daily cycle found in normal mice, while others' rhythms were completely disorganized, Blackshaw says. Though an SCN is present in mutant mice, it communicates poorly with clocks elsewhere in the body.Blackshaw says he expects that the mutant mice will prove a useful tool in finding whether disrupted signaling from the SCN actually leads to the health problems that shift workers experience, and if so, how this might happen. Although mouse models do not correlate fully to human disease, their biochemical and genetic makeup is closely aligned.Blackshaw's team also plans to continue studying the biochemical chain of events surrounding the Lhx1 protein to determine which proteins turn the Lhx1 gene on and which genes it, in turn, directly switches on or off. Those genes could be at the root of inherited sleep disorders, Blackshaw says, and the proteins they make could prove useful as starting points for the development of new drugs to treat insomnia and even jet lag. | Genetically Modified | 2,014 |
April 15, 2014 | https://www.sciencedaily.com/releases/2014/04/140415203819.htm | Modified stem cells offer potential pathway to treat Alzheimer's disease | UC Irvine neurobiologists have found that genetically modified neural stem cells show positive results when transplanted into the brains of mice with the symptoms and pathology of Alzheimer's disease. The pre-clinical trial is published in the journal | Alzheimer's disease, one of the most common forms of dementia, is associated with accumulation of the protein amyloid-beta in the brain in the form of plaques. While the search continues for a viable treatment, scientists are now looking into non-pharmaceutical ways to slow onset of this disease.One option being considered is increasing the production of the enzyme neprilysin, which breaks down amyloid-beta, and shows lower activity in the brains of people with Alzheimer's disease. Researchers from UC Irvine investigated the potential of decreasing amyloid-beta by delivering neprilysin to mice brains."Studies suggest that neprilysin decreases with age and may therefore influence the risk of Alzheimer's disease," said Mathew Blurton-Jones, an assistant professor of neurobiology & behavior. "If amyloid accumulation is the driving cause of Alzheimer's disease, then therapies that either decrease amyloid-beta production or increase its degradation could be beneficial, especially if they are started early enough."The brain is protected by a system called the blood-brain-barrier that restricts access of cells, proteins, and drugs to the brain. While the blood-brain-barrier is important for brain health, it also makes it challenging to deliver therapeutic proteins or drugs to the brain. To overcome this, the researchers hypothesized that stem cells could act as an effective delivery vehicle. To test this hypothesis the brains of two different mouse models (3xTg-AD and Thy1-APP) were injected with genetically modified neural stem cells that over-expressed neprilysin. Most studies up to now have only looked into a single model, and there has been found to be variation in results between models.These genetically modified stem cells were found to produce 25-times more neprilysin than control neural stem cells, but were otherwise equivalent to the control cells. The genetically modified and control stem cells were then transplanted into the hippocampus or subiculum of the mice brains -- two areas of the brain that are greatly affected by Alzheimer's disease. The mice transplanted with genetically modified stem cells were found to have a significant reduction in amyloid-beta plaques within their brains compared to the controls. The effect remained even one month after stem cell transplantation. This new approach could provide a significant advantage over unmodified neural stem cells because neprilysin-expressing cells could not only promote the growth of brain connections but could also target and reduce amyloid-beta pathology.Before this can be investigated in humans, more work needs to be done to see if this affects the accumulation of soluble forms of amyloid-beta. Further investigation is also needed to determine whether this new approach improves cognition more than the transplantation of un-modified neural stem cells."Every mouse model of Alzheimer's disease is different and develops varying amounts, distribution, and types of amyloid-beta pathology," Blurton-Jones said. "By studying the same question in two independent transgenic models, we can increase our confidence that these results are meaningful and broadly applicable to Alzheimer's disease. But there is clearly a great deal more research needed to determine whether this kind of approach could eventually be translated to the clinic." | Genetically Modified | 2,014 |
April 10, 2014 | https://www.sciencedaily.com/releases/2014/04/140410194644.htm | Scientists grow cartilage to reconstruct nose | Scientists at the University of Basel report first ever successful nose reconstruction surgery using cartilage grown in the laboratory. Cartilage cells were extracted from the patient's nasal septum, multiplied and expanded onto a collagen membrane. The so-called engineered cartilage was then shaped according to the defect and implanted. The results will be published in the current edition of the academic journal | A research team from the University of Basel in Switzerland has reported that nasal reconstruction using engineered cartilage is possible. They used a method called tissue engineering where cartilage is grown from patients' own cells. This new technique was applied on five patients, aged 76 to 88 years, with severe defects on their nose after skin cancer surgery. One year after the reconstruction, all five patients were satisfied with their ability to breathe as well as with the cosmetic appearance of their nose. None of them reported any side effects.The type of non-melanoma skin cancer investigated in this study is most common on the nose, specifically the alar wing of the nose, because of its cumulative exposure to sunlight. To remove the tumor completely, surgeons often have to cut away parts of cartilage as well. Usually, grafts for reconstruction are taken from the nasal septum, the ear or the ribs and used to functionally reconstruct the nose. However, this procedure is very invasive, painful and can, due to the additional surgery, lead to complications at the site of the excision.Together with colleagues from the University Hospital, the research team from the Department of Biomedicine at the University of Basel has now developed an alternative approach using engineered cartilage tissue grown from cells of the patients' nasal septum. They extracted a small biopsy, isolated the cartilage cells (chondrocytes) and multiplied them. The expanded cells were seeded onto a collagen membrane and cultured for two additional weeks, generating cartilage 40 times the size of the original biopsy. The engineered grafts were then shaped according to the defect on the nostril and implanted.According to Ivan Martin, Professor for Tissue Engineering at the Department of Biomedicine at the University and University Hospital of Basel, "The engineered cartilage had clinical results comparable to the current standard surgery. This new technique could help the body to accept the new tissue better and to improve the stability and functionality of the nostril. Our success is based on the long-standing, effective integration in Basel between our experimental group at the Department of Biomedicine and the surgical disciplines at the University Hospital. The method opens the way to using engineered cartilage for more challenging reconstructions in facial surgery such as the complete nose, eyelid or ear."The same engineered grafts are currently being tested in a parallel study for articular cartilage repair in the knee. Despite the optimistic perspectives, the use of these procedures in the clinical practice is still rather distant. "We need rigorous assessment of efficacy on larger cohorts of patients and the development of business models and manufacturing paradigms that will guarantee cost-effectiveness," says Martin. | Genetically Modified | 2,014 |
April 10, 2014 | https://www.sciencedaily.com/releases/2014/04/140410194326.htm | Laboratory-grown vaginas implanted in patients | Scientists reported today the first human recipients of laboratory-grown vaginal organs. A research team led by Anthony Atala, M.D., director of Wake Forest Baptist Medical Center's Institute for Regenerative Medicine, describes in the | "This pilot study is the first to demonstrate that vaginal organs can be constructed in the lab and used successfully in humans," said Atala. "This may represent a new option for patients who require vaginal reconstructive surgeries. In addition, this study is one more example of how regenerative medicine strategies can be applied to a variety of tissues and organs."The girls in the study were born with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, a rare genetic condition in which the vagina and uterus are underdeveloped or absent. The treatment could also potentially be applied to patients with vaginal cancer or injuries, according to the researchers.The girls were between 13 and 18 years old at the time of the surgeries, which were performed between June 2005 and October 2008. Data from annual follow-up visits show that even up to eight years after the surgeries, the organs had normal function."Tissue biopsies, MRI scans and internal exams using magnification all showed that the engineered vaginas were similar in makeup and function to native tissue, said Atlantida-Raya Rivera, lead author and director of the HIMFG Tissue Engineering Laboratory at the Metropolitan Autonomous University in Mexico City, where the surgeries were performed.In addition, the patients' responses to a Female Sexual Function Index questionnaire showed they had normal sexual function after the treatment, including desire and pain-free intercourse.The organ structures were engineered using muscle and epithelial cells (the cells that line the body's cavities) from a small biopsy of each patient's external genitals. In a Good Manufacturing Practices facility, the cells were extracted from the tissues, expanded and then placed on a biodegradable material that was hand-sewn into a vagina-like shape. These scaffolds were tailor-made to fit each patient.About five to six weeks after the biopsy, surgeons created a canal in the patient's pelvis and sutured the scaffold to reproductive structures. Previous laboratory and clinical research in Atala's lab has shown that once cell-seeded scaffolds are implanted in the body, nerves and blood vessels form and the cells expand and form tissue. At the same time the scaffolding material is being absorbed by the body, the cells lay down materials to form a permanent support structure -- gradually replacing the engineered scaffold with a new organ.Followup testing on the lab-engineered vaginas showed the margin between native tissue and the engineered segments was indistinguishable and that the scaffold had developed into tri-layer vaginal tissue.Current treatments for MRHK syndrome include dilation of existing tissue or reconstructive surgery to create new vaginal tissue. A variety of materials can be used to surgically construct a new vagina -- from skin grafts to tissue that lines the abdominal cavity. However, these substitutes often lack a normal muscle layer and some patients can develop a narrowing or contracting of the vagina.The researchers say that with conventional treatments, the overall complication rate is as high as 75 percent in pediatric patients, with the need for vaginal dilation due to narrowing being the most common complication.Before beginning the pilot clinical study, Atala's team evaluated lab-built vaginas in mice and rabbits beginning in the early 1990s. In these studies, scientists discovered the importance of using cells on the scaffolds. Atala's team used a similar approach to engineer replacement bladders that were implanted in nine children beginning in 1998, becoming the first in the world to implant laboratory-grown organs in humans. The team has also successfully implanted lab-engineered urine tubes (urethras) into young boys.The team said the current study is limited because of its size, and that it will be important to gain further clinical experience with the technique and to compare it with established surgical procedures.Co-researchers were James J. Yoo, M.D., Ph.D., and Shay Soker, Ph.D., Wake Forest Baptist, and Diego R. Esquiliano M.D., Reyna Fierro-Pastrana P.hD., Esther Lopez-Bayghen Ph.D., Pedro Valencia M.D., and Ricardo Ordorica-Flores, M.D.,Children's Hospital Mexico Federico Gomez Metropolitan Autonomous University, Mexico. | Genetically Modified | 2,014 |
April 10, 2014 | https://www.sciencedaily.com/releases/2014/04/140410122108.htm | Too much protein may kill brain cells as Parkinson's progresses | Scientists may have discovered how the most common genetic cause of Parkinson's disease destroys brain cells and devastates many patients worldwide. The study was partially funded by the National Institutes of Health's National Institute of Neurological Disorders and Stroke (NINDS); the results may help scientists develop new therapies. | "This may be a major discovery for Parkinson's disease patients," said Ted Dawson, M.D., Ph.D., director of the Johns Hopkins University (JHU) Morris K. Udall Center of Excellence for Parkinson's Disease, Baltimore, MD. Dr. Dawson and his wife Valina Dawson, Ph.D., director of the JHU Stem Cell and Neurodegeneration Programs at the Institute for Cell Engineering, led the study published in The investigators found that mutations in a gene called leucine-rich repeat kinase 2 (LRRK2; pronounced "lark two" or "lurk two") may increase the rate at which LRRK2 tags ribosomal proteins, which are key components of protein-making machinery inside cells. This could cause the machinery to manufacture too many proteins, leading to cell death."For nearly a decade, scientists have been trying to figure out how mutations in LRRK2 cause Parkinson's disease," said Margaret Sutherland, Ph.D., a program director at NINDS. "This study represents a clear link between LRRK2 and a pathogenic mechanism linked to Parkinson's disease."Affecting more than half a million people in the United States, Parkinson's disease is a degenerative disorder that attacks nerve cells in many parts of the nervous system, most notably in a brain region called the substantia nigra, which releases dopamine, a chemical messenger important for movement. Initially, Parkinson's disease causes uncontrolled movements; including trembling of the hands, arms, or legs. As the disease gradually worsens, patients lose ability to walk, talk or complete simple tasks.For the majority of cases of Parkinson's disease, a cause remains unknown. Mutations in the LRRK2 gene are a leading genetic cause. They have been implicated in as many as 10 percent of inherited forms of the disease and in about 4 percent of patients who have no family history. One study showed that the most common LRRK2 mutation, called G2019S, may be the cause of 30-40 percent of all Parkinson's cases in people of North African Arabic descent.LRRK2 is a kinase enzyme, a type of protein found in cells that tags molecules with chemicals called phosphate groups. The process of phosphorylation helps regulate basic nerve cell function and health. Previous studies suggest that disease-causing mutations, like the G2019S mutation, increase the rate at which LRRK2 tags molecules. Identifying the molecules that LRRK2 tags provides clues as to how nerve cells may die during Parkinson's disease.In this study, the researchers used LRRK2 as bait to fish out the proteins that it normally tags. Multiple experiments performed on human kidney cells suggested that LRRK2 tags ribosomal proteins. These proteins combine with other molecules, called ribonucleic acids, to form ribosomes, which are the cell's protein-making factories.Further experiments suggested that disease-causing mutations in LRRK2 increase the rate at which it tags two ribosomal proteins, called s11 and s15. Moreover, brain tissue samples from patients with LRRK2 mutations had greater levels of phosphorylated s15 than seen in controls.Next, the researchers investigated whether phosphorylation could be linked to cell death, by studying nerve cells derived from rats or from human embryonic stem cells. Genetically engineering the cells to have a LRRK2 mutant gene increased the amount of cell death and phosphorylated s15. In contrast, the researchers prevented cell death when they engineered the cells to also make a mutant s15 protein that could not be tagged by LRRK2."These results suggest that s15 ribosome protein may play a critical role in the development of Parkinson's disease," said Dr. Dawson.How might phosphorylation of s15 kill nerve cells? To investigate this, Dr. Dawson and his colleagues performed experiments on fruit flies.Previous studies on flies showed that genetically engineering dopamine-releasing nerve cells to overproduce the LRRK2 mutant protein induced nerve cell damage and movement disorders. Dr. Dawson's team found that the brains of these flies had increased levels of phosphorylated s15 and that engineering the flies so that s15 could not be tagged by LRRK2 prevented cell damage and restored normal movement.Interestingly, the brains of the LRRK2 mutant flies also had abnormally high levels of all proteins, suggesting that increased s15 tagging caused ribosomes to make too much protein. Treating the flies with low doses of anisomycin, a drug that blocks protein production, prevented nerve cell damage and restored the flies' movement even though levels of s15 phosphorylation remained high."Our results support the idea that changes in the way cells make proteins might be a common cause of Parkinson's disease and possibly other neurodegenerative disorders," said Dr. Dawson.Dr. Dawson and his colleagues think that blocking the phosphorylation of s15 ribosomal proteins could lead to future therapies as might other strategies which decrease bulk protein synthesis or increase the cells' ability to cope with increased protein metabolism. They also think that a means to measure s15 phosphorylation could also act as a biomarker of LRRK2 activity in treatment trials of LRRK2 inhibitors.This work was supported by grants from the NINDS (NS038377, NS072187), the JPB Foundation, the Maryland Stem Cell Research Fund (2007-MSCRFI-0420-00, 2009-MSCRFII-0125-00, 2013-MSCRFII-0105-00), and the New York Stem Cell Foundation. | Genetically Modified | 2,014 |
April 10, 2014 | https://www.sciencedaily.com/releases/2014/04/140410121943.htm | Influenza has an Achilles' Heel: New drug reduces flu mortality | Flu epidemics cause up to half a million deaths worldwide each year, and emerging strains continually threaten to spread to humans and cause even deadlier pandemics. A study by McGill University professor Maziar Divangahi published by Cell Press on April 10 in the journal | "Drugs that specifically target PGE2 pathways have already been developed and tested in animals, so our results have excellent potential for clinical translation, not only for the treatment of influenza, but other viral respiratory infections that interact with similar host immune pathways," says senior study author Divangahi, who is also a member of the Infectious and Immunity Axis at the Research Institute of the McGill University Health Centre (RI-MUHC).Persistent threat to human health Despite the worldwide use of vaccination and other antiviral interventions, the flu virus remains a persistent threat to human health. To investigate molecular pathways that could be targeted by new interventions, Divangahi, an assistant professor in the Faculty of Medicine (Department of Microbiology and Immunology), and his team focussed on drugs such as aspirin and ibuprofen, commonly used to manage flu-like symptoms. By inhibiting a molecule called cyclooxygenase (COX), ibuprofen and other nonsteroidal anti-inflammatory drugs (NSAIDs) lower the production of five major prostanoids -- immune molecules that contribute to pain and fever."But since these drugs inhibit all prostanoids, each may contribute differently towards the immunity against influenza virus," says Francois Coulombe, a McGill Ph.D. student and the study's first author. "Understanding their individual role is crucial in developing a new therapy."Enhanced antiviral immunity Divangahi's research team found that mice genetically engineered to lack a member of the prostanoid family, PGE2, showed remarkably enhanced immunity to flu infection. Most importantly, the vast majority of these mice infected with a lethal dose of the H1N1 flu virus survived. Similarly, mice treated with a compound that inhibits PGE2 showed enhanced antiviral immunity and produced better survival rates following infection with a lethal dose of the flu virus compared with untreated mice."Previous studies produced conflicting results due to the inhibition of all prostanoids, not just PGE2," Divangahi says. "Our findings suggest that different prostaglandins have different roles in antiviral immunity and that specific inhibition of PGE2 will be an effective therapy against influenza viral infection by boosting immune responses." | Genetically Modified | 2,014 |
April 8, 2014 | https://www.sciencedaily.com/releases/2014/04/140408111226.htm | Viral therapy shows promise against brain tumors | Researchers at the University of Alabama at Birmingham report a genetically engineered herpes simplex viral therapy is safe when used in conjunction with radiation in the treatment of malignant gliomas, one of the most deadly forms of brain cancer. | The virus, G207, is a modified herpes simplex virus that in two previous UAB studies has been shown to be safe when used as a sole therapy. The new findings, published online April 8, 2014 in The study examined nine patients with malignant glioma, and all nine tolerated the therapy well. None developed encephalitis, the brain inflammation often associated with herpes simplex; the gene responsible for causing encephalitis has been removed from G207. Some patients also showed evidence of tumor reduction, and survival rates were increased for others."This was a phase one study designed foremost to see whether the therapy was safe," said James M. Markert, M.D., Ph.D., professor and chair of the Department of Neurosurgery at UAB and the study's first author. "While this study, with a limited number of patients and no controls, prevents any conclusions about the efficacy of this treatment, the decrease in tumor size seen on MRI's in some patients, as well as an increase in survival in some patients without other proven treatment options, is highly encouraging."G207 was administered directly to glioma cells in the brain, followed the next day by a low-dose radiation treatment.The virus works by infecting tumor cells and replicating until it overwhelms the cell's machinery and causes the cell to rupture and die, releasing new viral particles. The virus has been genetically modified so that it can reproduce only in tumor cells, which lack the stronger antiviral defense mechanisms of healthy brain cells. After destroying a tumor cell, the virus moves on, looking for new tumor cells to infect.While the study was designed for each patient to receive one dose of G207, two of the nine patients received a second dose as part of a compassionate-use protocol."While we cannot draw any firm conclusions from just two study subjects, we are encouraged to note that both of the compassionate-use patients tolerated the second dose extremely well, indicating that the drug may be suitable for multiple use," said Markert.UAB is gearing up for another study with a new modified version of herpes simplex virus called M032. Preliminary studies have indicated M032 could be an even more effective therapy. It includes a genetically engineered protein called IL12, which the researchers believe will induce a stronger immune response and will contribute to increased anti-angiogenesis, the process of shutting off the blood supply to tumor cells, denying oxygen and essential nutrients."This study showed the safety and the potential for clinical response of single-dose HSV therapy augmented with radiation in the treatment of malignant glioma patients," said Markert. "Additional studies with modified viruses such as G207 in the treatment of human glioma are certainly warranted from the results of this trial."Gliomas account for about a third of brain tumors, and survival rates are poor; only about half of the 10,000 Americans diagnosed with malignant glioma survive the first year, and only about one-quarter survive for two years. | Genetically Modified | 2,014 |
April 7, 2014 | https://www.sciencedaily.com/releases/2014/04/140407164725.htm | Potential Combination Therapy for Aggressive Thyroid Cancer | Researchers from the Jacks Laboratory at MIT's Koch Institute for Integrative Cancer Research (KI) have developed and characterized a genetically engineered mouse that successfully models progression from papillary thyroid cancer, which has an excellent prognosis, to anaplastic thyroid cancer (ATC), a highly lethal disease. The model, described in the | Most patients diagnosed with thyroid cancer do very well, but in a small fraction of patients it evolves into aggressive forms of thyroid cancer. Among these, the extremely aggressive human ATC is associated with one of the worst prognoses of any kind of human cancer. To complicate matters more, ATC is extremely rare. The combination of aggressiveness and low incidence has hindered research efforts to learn more about this cancer and systematic clinical trials, and there has been little progress in developing effective therapies for ATC. "There have been very few successful clinical trials in ATC in part because it is hard to get patients recruited, and, when these patients present with ATC, the disease may be so aggressive that they are too sick to participate in the trial," says Koch Institute postdoctoral research David McFadden, lead author of this work. McFadden has witnessed these roadblocks first hand: he is also a thyroid cancer endocrinologist at the MGH Center for Endocrine Tumors. "My clinical training has allowed me to identify the real areas of need in thyroid cancer," he explains. It is McFadden's clinical practice that drove him to join the laboratory of KI Director and David H. Koch Professor of Biology, Tyler Jacks, with one goal of engineering a mouse model of ATC to better understand what causes these tumors to form and resist treatments, otherwise so hard to study in human trials.Mutations affecting the tumor suppressor p53 are the most common genetic mutation in human ATC. BRAF mutations occur in a subset of these tumors as well. McFadden hypothesized that if they could build a mouse with these mutations in the thyroid gland maybe they would observe development of ATC. Taking advantage of genetically engineered mice generated by the Jacks Laboratory as well as models shared by other investigators in the scientific community, the group engineered a mouse where BRAF and p53 can be conditionally mutated specifically in the thyroid gland.In this model, expression of mutant BRAF V600E was sufficient to initiate tumor formation in adult animals, but only its combination with p53 loss enabled progression from papillary thyroid cancer to ATC. This study demonstrates that combined BRAF mutation and loss of p53 cooperate In the model, thyroid tumors develop and progress in the natural tissue environment, including an intact immune system, and the tumors recapitulate the hallmarks of human ATC, including rapid progression once disease presents, gene expression programs, and intrinsic resistance to BRAF inhibitors. Of note, it takes months between the initiation of BRAF and p53 mutation in the mouse's thyroid gland and the actual development of ATC. What causes these tumors to convert from a low-grade papillary cancer to the very aggressive ATC? The team hypothesizes that other genetic or epigenetic changes may occur in these tumors and that these may facilitate the progression from papillary to anaplastic cancer. They now plan to use this mouse model to identify and study the molecular events that may be driving this transition.Small molecule inhibitors of BRAF have been developed to target BRAF mutations that are common in a variety of human tumors, including melanomas, colon cancers, and thyroid cancers. However, BRAF-mutant tumors in the ATC mice did not respond to BRAF inhibitors. Based on promising clinical results in BRAF-mutant melanoma and mechanistic models of BRAF-resistance in several cancer types, the team predicted that addition of another drug, called a MEK inhibitor, that targets the same pathway activated by BRAF mutation, could improve the response to treatment. Indeed, in this preclinical model, the combination of these inhibitors shrunk ATC tumors dramatically. The combination was also effective slowing down cell proliferation and inhibiting BRAF signaling in a human ATC cell line that carries both BRAF mutation and loss of p53. "In spite of the aggressiveness of the tumors, blocking this pathway very effectively may allow us to improve the initial responses of patients with ATC and provide an entry point to improve ATC treatments," McFadden points out."Despite our efforts to maximize ATC treatment approaches by integrating surgery, radiation, and chemotherapy, we have made little to no headway with these standard therapeutic tools. A more sophisticated targeted approach will likely be required to improve ATC treatment options and offer some hope for improving survival," says Dr. Lori Wirth, the Medical Director of MGH's Center for Head and Neck Cancers and a leading expert in new treatments for advanced thyroid cancers. "The greatest promise for this new ATC mouse model is, perhaps, its utility in studying new treatment approaches for this rare and devastating disease. McFadden and colleagues' data are readily applicable to ATCs in humans that harbor mutant BRAF V600E, and will hopefully be translated directly to clinical trial development soon," Wirth adds.Regardless of the initial responses to the MEK-BRAF combination treatment, however, tumors in these animals do come back after a few months on this regimen. The group plans to look at these resistant tumors to dissect the molecular drivers of the acquired resistance to this drug combination. They also intend to use this new preclinical model to study whether the MEK and BRAF inhibitors work in combination with standard chemotherapy used to treat human ATC. "The goal is to stay one step ahead of the human clinical trials and be able to inform the design of these human trials with the mechanistic details learned from the mouse," says McFadden. | Genetically Modified | 2,014 |
April 7, 2014 | https://www.sciencedaily.com/releases/2014/04/140407090611.htm | Freshwater turtle crosses the Aegean Sea | Scientists at the Senckenberg Research Institute in Dresden, together with an international team of researchers, have studied the widely distributed freshwater turtle, | The wide range of the species led the research team of Prof Dr Uwe Fritz, Managing Director at Senckenberg Dresden to study this species of turtle genetically."Because of the many geographical barriers in the range of this freshwater turtle -- especially the Aegean Sea -- we assumed that there would be many genetically different populations. This was based on the consideration that there was no gene flow between the isolated distribution patches, as the sea divides the populations," says Fritz.The story that emerged, however, was quite a different one: Using different genetic methods, the scientists examined 340 turtle samples from a total of 63 localities across the entire region of distribution. "The astonishing thing is that even turtles living at great distances from each other display an almost identical genetic pattern, for instance, in southeast Europe and Asian Turkey" explains Fritz. This means that the turtles must have found a means to exchange their genes across large distances -- and indeed over hundreds of kilometres of sea.But how do the animals manage to live on both sides of the Aegean without developing into an individual species over time? "One idea is that the turtles were brought to the different regions by humans, which meant that the gene pool could mix constantly," explains Melita Vamberger, lead author of the study, and adds: "Yet in contrast to other turtles, Thus, only one other -- unexpected -- possibility remained for the researchers: "We assume that this freshwater turtle is dispersed across the sea. It is likely that turtles are swept repeatedly from their habitats in coastal swamps into the sea by storms. They can obviously survive for a long time in the sea, long enough until they are washed onto some shoreline somewhere. And this occasional exchange is sufficient!"In fact, some time ago a And whatever a turtle can do might also be a feasible option for others. "It might well be possible," says Fritz, "that other turtle species take the route across the sea. For instance, this could also explain the weak genetic structure found throughout the widely distributed and endangered North American diamond terrapin ( | Genetically Modified | 2,014 |
April 3, 2014 | https://www.sciencedaily.com/releases/2014/04/140403142031.htm | Researchers design trees that make it easier to produce paper | Researchers have genetically engineered trees that will be easier to break down to produce paper and biofuel, a breakthrough that will mean using fewer chemicals, less energy and creating fewer environmental pollutants. | "One of the largest impediments for the pulp and paper industry as well as the emerging biofuel industry is a polymer found in wood known as lignin," says Shawn Mansfield, a professor of Wood Science at the University of British Columbia.Lignin makes up a substantial portion of the cell wall of most plants and is a processing impediment for pulp, paper and biofuel. Currently the lignin must be removed, a process that requires significant chemicals and energy and causes undesirable waste.Researchers used genetic engineering to modify the lignin to make it easier to break down without adversely affecting the tree's strength."We're designing trees to be processed with less energy and fewer chemicals, and ultimately recovering more wood carbohydrate than is currently possible," says Mansfield.Researchers had previously tried to tackle this problem by reducing the quantity of lignin in trees by suppressing genes, which often resulted in trees that are stunted in growth or were susceptible to wind, snow, pests and pathogens."It is truly a unique achievement to design trees for deconstruction while maintaining their growth potential and strength."The study, a collaboration between researchers at the University of British Columbia, the University of Wisconsin-Madison, Michigan State University, is a collaboration funded by Great Lakes Bioenergy Research Center, was published today in The structure of lignin naturally contains ether bonds that are difficult to degrade. Researchers used genetic engineering to introduce ester bonds into the lignin backbone that are easier to break down chemically.The new technique means that the lignin may be recovered more effectively and used in other applications, such as adhesives, insolation, carbon fibres and paint additives.The genetic modification strategy employed in this study could also be used on other plants like grasses to be used as a new kind of fuel to replace petroleum.Genetic modification can be a contentious issue, but there are ways to ensure that the genes do not spread to the forest. These techniques include growing crops away from native stands so cross-pollination isn't possible; introducing genes to make both the male and female trees or plants sterile; and harvesting trees before they reach reproductive maturity.In the future, genetically modified trees could be planted like an agricultural crop, not in our native forests. Poplar is a potential energy crop for the biofuel industry because the tree grows quickly and on marginal farmland. Lignin makes up 20 to 25 per cent of the tree."We're a petroleum reliant society," says Mansfield. "We rely on the same resource for everything from smartphones to gasoline. We need to diversify and take the pressure off of fossil fuels. Trees and plants have enormous potential to contribute carbon to our society." | Genetically Modified | 2,014 |
April 3, 2014 | https://www.sciencedaily.com/releases/2014/04/140403131942.htm | New approach to detecting changes in GM foods | Does genetic manipulation causes unintended changes in food quality and composition? Are genetically modified (GM) foods less nutritious than their non-GM counterparts, or different in unknown ways? | Despite extensive cultivation and testing of GM foods, those questions still linger in the minds of many consumers. A new study in the March issue of In research led by Owen Hoekenga, a Cornell University adjunct assistant professor, scientists extracted roughly 1,000 biochemicals, or "metabolites," from the fruit of tomatoes. These tomatoes had been genetically engineered to delay fruit ripening -- a common technique to help keep fruits fresher longer. The researchers then compared this "metabolic profile" from the GM fruit to the profile of its non-GM variety.Extracting and analyzing hundreds metabolites at once gives researchers a snapshot of the fruit's physiology, which can be compared against others.When the scientists compared the biochemicals of the GM tomato and a wide assortment other non-GM tomatoes, including modern and heirloom varieties, they found no significant differences overall. Thus, although the GM tomato was distinct from its parent, its metabolic profile still fell within the "normal" range of biochemical diversity exhibited by the larger group of varieties. However, the biochemicals related to fruit ripening did show a significant difference -- no surprise because that was the intent of the genetic modification.The finding suggests little or no accidental biochemical change due to genetic modification in this case, as well as a "useful way to address consumer concerns about unintended effects" in general, Hoekenga says.He explains that the FDA already requires developers of GM crops to compare a handful of key nutritional compounds in GM varieties relative to their non-GM parents. The process is designed to catch instances where genetic manipulation may have affected nutritional quality, for example.Moreover, comparing a GM variety to diverse cultivars can help scientists and consumers put into context any biochemical changes that are observed. "We accept that there isn't just one kind of tomato at the farmer's market. We look for diverse food experiences," Hoekenga says. "So we think that establishing the range of acceptable metabolic variability [in food] can be useful for examining GM varieties."The process was expensive, and the chemistry methods can't yet be used in official safety assessments, Hoekenga acknowledges. Making statistical comparisons of metabolic "fingerprints" is no easy task. In their study, Hoekenga's group adapted a style of statistics used in other research.But the techniques don't apply only to tomato. "The method can be applied to any plant or crop," Hoekenga says. "We've made something fundamentally useful that anyone can use and improve on."When crossing parent plants, for example, breeders often like to track the genes underlying their trait of interest, such as resistance to a pathogen. That's because pinpointing offspring that carry the right genes is often faster and easier than examining plants for the trait itself.But sometimes, so many genes contribute to a single trait that figuring out which genes are involved in the first place becomes onerous. This is where Hoekenga thinks his style of research and analysis might one day help. "We're trying to describe at the biochemical level what might be responsible for a trait. And from that, you could extract genetic information to use in breeding." | Genetically Modified | 2,014 |
March 31, 2014 | https://www.sciencedaily.com/releases/2014/03/140331153606.htm | Self-healing engineered muscle grown in the laboratory | Biomedical engineers have grown living skeletal muscle that looks a lot like the real thing. It contracts powerfully and rapidly, integrates into mice quickly, and for the first time, demonstrates the ability to heal itself both inside the laboratory and inside an animal. | The study conducted at Duke University tested the bioengineered muscle by literally watching it through a window on the back of living mouse. The novel technique allowed for real-time monitoring of the muscle's integration and maturation inside a living, walking animal.Both the lab-grown muscle and experimental techniques are important steps toward growing viable muscle for studying diseases and treating injuries, said Nenad Bursac, associate professor of biomedical engineering at Duke.The results appear the week of March 25 in the "The muscle we have made represents an important advance for the field," Bursac said. "It's the first time engineered muscle has been created that contracts as strongly as native neonatal skeletal muscle."Through years of perfecting their techniques, a team led by Bursac and graduate student Mark Juhas discovered that preparing better muscle requires two things -- well-developed contractile muscle fibers and a pool of muscle stem cells, known as satellite cells.Every muscle has satellite cells on reserve, ready to activate upon injury and begin the regeneration process. The key to the team's success was successfully creating the microenvironments -- called niches -- where these stem cells await their call to duty."Simply implanting satellite cells or less-developed muscle doesn't work as well," said Juhas. "The well-developed muscle we made provides niches for satellite cells to live in, and, when needed, to restore the robust musculature and its function."To put their muscle to the test, the engineers ran it through a gauntlet of trials in the laboratory. By stimulating it with electric pulses, they measured its contractile strength, showing that it was more than 10 times stronger than any previous engineered muscles. They damaged it with a toxin found in snake venom to prove that the satellite cells could activate, multiply and successfully heal the injured muscle fibers.Then they moved it out of a dish and into a mouse.With the help of Greg Palmer, an assistant professor of radiation oncology in the Duke University School of Medicine, the team inserted their lab-grown muscle into a small chamber placed on the backs of live mice. The chamber was then covered by a glass panel. Every two days for two weeks, Juhas imaged the implanted muscles through the window to check on their progress.By genetically modifying the muscle fibers to produce fluorescent flashes during calcium spikes -- which cause muscle to contract -- the researchers could watch the flashes become brighter as the muscle grew stronger."We could see and measure in real time how blood vessels grew into the implanted muscle fibers, maturing toward equaling the strength of its native counterpart," said Juhas.The engineers are now beginning work to see if their biomimetic muscle can be used to repair actual muscle injuries and disease."Can it vascularize, innervate and repair the damaged muscle's function?" asked Bursac. "That is what we will be working on for the next several years." | Genetically Modified | 2,014 |
March 27, 2014 | https://www.sciencedaily.com/releases/2014/03/140327100610.htm | Increasing longevity of seeds with genetic engineering | A study developed by researchers of the Institute for Plant Molecular and Cell Biology (IBMCP), a joint center of the Universitat Politècnica de València and the Spanish National Research Council (CSIC), in collaboration with the Unit for Plant Genomics Research of Evry, France (URGV, in French) has discovered a new way of improving the longevity of plant seeds using genetic engineering. | The key is the overexpression of the ATHB25 gene. This gene encodes a protein that regulates gene expression, producing a new mutant that gives the seed new properties. Researchers have proven that this mutant has more gibberellin -the hormone that promotes plant growth-, which means the seed coat is reinforced as well. "The seed coat is responsible for preventing oxygen from entering the seed; the increase in gibberellin strengthens it and this leads to a more durable and longer lasting seed," explains Eduardo Bueso, researcher at the IBMCP (UPV-CSIC).This mechanism is new, as tolerance to stresses such as aging has always been associated with another hormone, abscisic acid, which regulates defenses based on proteins and small protective molecules, instead of producing the growth of structures like gibberellin does.The study has been made on the experimental model plant Arabidopsis thaliana, a species that presents great advantages for molecular biology research. Researchers of the IBMCP traced half a million seeds, related to one hundred thousand lines of Arabidopsis mutated by T-DNA insertion, using the natural system of Agrobacterium tumefaciens. "Finally, we analyzed four mutants in the study and we proved the impact on the seed longevity when the overexpression of the ATHB25 gene is introduced," states Ramón Serrano, researcher at the IBMCP.Researchers compared the longevity of genetically modified Arabidopsis seeds and seeds which were not modified. In order to do this, they preserved them for thirty months under specific conditions of room temperature and humidity. After thirty months, only 20% of the control plants germinated again, whereas almost the all of the modified plants (90%) began the germination process again.Researchers of the IBMCP are now trying to improve the longevity of different species that are of agronomical interest, such as tomatoes or wheat.Biodiversity and benefits for farmersThis discovery is particularly significant for the conservation of biodiversity, preserving seed species and, especially, for farmers."In the past, a lot of different plant species were cultivated, but many of them are dissapearing because high performance crops have now become a priority. Seed banks were created in order to guarantee the conservation of species, but they require a periodical regeneration of the seeds. With this mutant the regeneration periods could be extended," explains Eduardo Bueso.With regard to farmers, Serrano explains that "the increase of the lifespan of seeds would mean a reduction in their purchase price." | Genetically Modified | 2,014 |
March 26, 2014 | https://www.sciencedaily.com/releases/2014/03/140326092333.htm | Genetics can explain why infections can trigger onset of different types of rheumatoid arthritis | A new international study has revealed how genetics could explain why different environmental exposures can trigger the onset of different forms of rheumatoid arthritis. | A team at the Arthritis Research UK Centre for Genetics and Genomics at The University of Manchester, part of a large international consortium involving scientists from across 15 academic institutions, believe their findings could have important implications for the way that rheumatoid arthritis is diagnosed and treated.Publishing their findings in the journal Rheumatoid arthritis is a serious inflammatory form of arthritis, affecting almost 400,000 people in the UK, which causes painful, swollen joints, and in severe cases, considerable disability. It is known to have strong genetic and environmental components.It was already known that a proportion of rheumatoid arthritis patients test positive for autoantibodies, whilst about 30% remain sero-negative. In this study, the researchers have better defined the genetic distinction between these two disease subtypes: sero-positive and sero-negative rheumatoid arthritis.They have now established that different genetic variants of a protein that plays a vital role in how the body's immune system fights infection are associated with the two forms of rheumatoid arthritis. This provides clues to the theory that exposure to different infectious agents, such as bacteria or viruses, trigger the different forms of rheumatoid arthritis in susceptible individuals. Sero-negative rheumatoid is less well understood than sero-positive, and patients who have this type of arthritis can be misdiagnosed, leading to inappropriate treatment.Dr Steve Eyre from the genetics and genomics centre in Manchester commented: "We recognise that rheumatoid arthritis is a complex disease that can have variable presentation and outcomes for different people, in particular in the way they respond to treatment. These findings add to our ability to genetically define subtypes of rheumatoid arthritis, which is an important step towards selecting the best treatment for each patient."Centre director Professor Jane Worthington added: "Now that we have established a genetic basis for these two types of rheumatoid arthritis, we hope it will lead to patients receiving a swifter, accurate diagnosis and more appropriate, targeted treatment. These findings have opened the door to a better understanding of sero-negative rheumatoid arthritis." | Genetically Modified | 2,014 |
March 25, 2014 | https://www.sciencedaily.com/releases/2014/03/140325190712.htm | Unravelling nerve-cell death in rare children's disease | A team of scientists, led by Stuart Lipton, M.D., Ph.D., professor and director of the Neuroscience and Aging Research Center at Sanford-Burnham Medical Research Institute (Sanford-Burnham), recently discovered why cerebellar granule cell neurons in patients suffering from ataxia-telangiectasia (A-T) were unable to repair DNA damage and thus died. | A-T is a hereditary condition that begins early in childhood, and causes a gradual loss of certain nerve cells in the cerebellum of the brain. A-T occurs in about 1 in 40,000 births, with symptoms including severe loss of muscle control, dilated small blood vessels, repeated infections in the sinus and lungs, and it frequently leads to cancers such as lymphoma or leukemia. Today, thanks to improved treatment of infections and cancer, many patients live into their 30s or longer.His study, with Nobuki Nakanishi, Ph.D., associate professor in Sanford-Burnham's Degenerative Disease Program, was published March 25 in "This is the first time that a signal that regulates MEF2D-dependent survival in response to DNA damage has been identified," said Lipton. "Knowing that ATM-mediated activation of MEF2D promotes survival in cerebellar neurons in response to DNA damage may provide a therapeutic opportunity for A-T. For example, if we can confirm that defects in the ATM-MEF2D signal contribute to A-T, we can search for molecules that enhance MEF2D activity to 'revive' the DNA repair system.""As parents, we are excited that this research could lead to new ideas about how to slow the brain cell loss seen in our kids, improving their ability to walk, talk, and eat. This could lead to big improvements in their quality of life," said Brad Margus, voluntary president and founder of the A-T Children's Project.In general, DNA repair systems are essential for cellular integrity and stability. DNA can be damaged in many ways, including UV rays, tobacco, and oxidative damage from byproducts of metabolism, such as free radicals. Inherited defects of DNA repair systems can lead to many types of cancer, dwarfism, growth and mental retardation, deafness -- as well as A-T."Prior to this study, we knew that p53 -- a protein known as the guardian angel of the genome -- was a target of ATM activation and contributes to the control and efficacy of DNA repair. Now, we have shown another pathway whereby MEF2D participates in DNA damage repair in the cerebellum. The fact that there is an abundance of MEF2D in the cerebellum, and that ATM mutations are associated with A-T, adds support to the proposed ATM-MEF2D dysfunction as a cause of A-T," said Lipton."Moving forward, we will be interested to see if this mechanism contributes to other rare hereditary diseases with defects in DNA repair." | Genetically Modified | 2,014 |
March 25, 2014 | https://www.sciencedaily.com/releases/2014/03/140325113300.htm | MRI reveals genetic activity: Deciphering genes' roles in learning and memory | Doctors commonly use magnetic resonance imaging (MRI) to diagnose tumors, damage from stroke, and many other medical conditions. Neuroscientists also rely on it as a research tool for identifying parts of the brain that carry out different cognitive functions. | Now, a team of biological engineers at MIT is trying to adapt MRI to a much smaller scale, allowing researchers to visualize gene activity inside the brains of living animals. Tracking these genes with MRI would enable scientists to learn more about how the genes control processes such as forming memories and learning new skills, says Alan Jasanoff, an MIT associate professor of biological engineering and leader of the research team."The dream of molecular imaging is to provide information about the biology of intact organisms, at the molecule level," says Jasanoff, who is also an associate member of MIT's McGovern Institute for Brain Research. "The goal is to not have to chop up the brain, but instead to actually see things that are happening inside."To help reach that goal, Jasanoff and colleagues have developed a new way to image a "reporter gene" -- an artificial gene that turns on or off to signal events in the body, much like an indicator light on a car's dashboard. In the new study, the reporter gene encodes an enzyme that interacts with a magnetic contrast agent injected into the brain, making the agent visible with MRI. This approach, described in a recent issue of the journal MRI uses magnetic fields and radio waves that interact with protons in the body to produce detailed images of the body's interior. In brain studies, neuroscientists commonly use functional MRI to measure blood flow, which reveals which parts of the brain are active during a particular task. When scanning other organs, doctors sometimes use magnetic "contrast agents" to boost the visibility of certain tissues.The new MIT approach includes a contrast agent called a manganese porphyrin and the new reporter gene, which codes for a genetically engineered enzyme that alters the electric charge on the contrast agent. Jasanoff and colleagues designed the contrast agent so that it is soluble in water and readily eliminated from the body, making it difficult to detect by MRI. However, when the engineered enzyme, known as SEAP, slices phosphate molecules from the manganese porphyrin, the contrast agent becomes insoluble and starts to accumulate in brain tissues, allowing it to be seen.The natural version of SEAP is found in the placenta, but not in other tissues. By injecting a virus carrying the SEAP gene into the brain cells of mice, the researchers were able to incorporate the gene into the cells' own genome. Brain cells then started producing the SEAP protein, which is secreted from the cells and can be anchored to their outer surfaces. That's important, Jasanoff says, because it means that the contrast agent doesn't have to penetrate the cells to interact with the enzyme.Researchers can then find out where SEAP is active by injecting the MRI contrast agent, which spreads throughout the brain but accumulates only near cells producing the SEAP protein.In this study, which was designed to test this general approach, the detection system revealed only whether the SEAP gene had been successfully incorporated into brain cells. However, in future studies, the researchers intend to engineer the SEAP gene so it is only active when a particular gene of interest is turned on.Jasanoff first plans to link the SEAP gene with so-called "early immediate genes," which are necessary for brain plasticity -- the weakening and strengthening of connections between neurons, which is essential to learning and memory."As people who are interested in brain function, the top questions we want to address are about how brain function changes patterns of gene expression in the brain," Jasanoff says. "We also imagine a future where we might turn the reporter enzyme on and off when it binds to neurotransmitters, so we can detect changes in neurotransmitter levels as well."Assaf Gilad, an assistant professor of radiology at Johns Hopkins University, says the MIT team has taken a "very creative approach" to developing noninvasive, real-time imaging of gene activity. "These kinds of genetically engineered reporters have the potential to revolutionize our understanding of many biological processes," says Gilad, who was not involved in the study.The research was funded by the Raymond and Beverly Sackler Foundation, the National Institutes of Health, and an MIT-Germany Seed Fund grant. The paper's lead author is former MIT postdoc Gil Westmeyer; other authors are former MIT technical assistant Yelena Emer and Jutta Lintelmann of the German Research Center for Environmental Health. | Genetically Modified | 2,014 |
March 23, 2014 | https://www.sciencedaily.com/releases/2014/03/140323152144.htm | Engineers design 'living materials': Hybrid materials combine bacterial cells with nonliving elements that emit light | Inspired by natural materials such as bone -- a matrix of minerals and other substances, including living cells -- MIT engineers have coaxed bacterial cells to produce biofilms that can incorporate nonliving materials, such as gold nanoparticles and quantum dots. | These "living materials" combine the advantages of live cells, which respond to their environment, produce complex biological molecules, and span multiple length scales, with the benefits of nonliving materials, which add functions such as conducting electricity or emitting light.The new materials represent a simple demonstration of the power of this approach, which could one day be used to design more complex devices such as solar cells, self-healing materials, or diagnostic sensors, says Timothy Lu, an assistant professor of electrical engineering and biological engineering. Lu is the senior author of a paper describing the living functional materials in the March 23 issue of "Our idea is to put the living and the nonliving worlds together to make hybrid materials that have living cells in them and are functional," Lu says. "It's an interesting way of thinking about materials synthesis, which is very different from what people do now, which is usually a top-down approach."The paper's lead author is Allen Chen, an MIT-Harvard MD-PhD student. Other authors are postdocs Zhengtao Deng, Amanda Billings, Urartu Seker, and Bijan Zakeri; recent MIT graduate Michelle Lu; and graduate student Robert Citorik.Lu and his colleagues chose to work with the bacterium By programming cells to produce different types of curli fibers under certain conditions, the researchers were able to control the biofilms' properties and create gold nanowires, conducting biofilms, and films studded with quantum dots, or tiny crystals that exhibit quantum mechanical properties. They also engineered the cells so they could communicate with each other and change the composition of the biofilm over time.First, the MIT team disabled the bacterial cells' natural ability to produce CsgA, then replaced it with an engineered genetic circuit that produces CsgA but only under certain conditions -- specifically, when a molecule called AHL is present. This puts control of curli fiber production in the hands of the researchers, who can adjust the amount of AHL in the cells' environment. When AHL is present, the cells secrete CsgA, which forms curli fibers that coalesce into a biofilm, coating the surface where the bacteria are growing.The researchers then engineered The researchers also demonstrated that the cells can coordinate with each other to control the composition of the biofilm. They designed cells that produce untagged CsgA and also AHL, which then stimulates other cells to start producing histidine-tagged CsgA."It's a really simple system but what happens over time is you get curli that's increasingly labeled by gold particles. It shows that indeed you can make cells that talk to each other and they can change the composition of the material over time," Lu says. "Ultimately, we hope to emulate how natural systems, like bone, form. No one tells bone what to do, but it generates a material in response to environmental signals."To add quantum dots to the curli fibers, the researchers engineered cells that produce curli fibers along with a different peptide tag, called SpyTag, which binds to quantum dots that are coated with SpyCatcher, a protein that is SpyTag's partner. These cells can be grown along with the bacteria that produce histidine-tagged fibers, resulting in a material that contains both quantum dots and gold nanoparticles.These hybrid materials could be worth exploring for use in energy applications such as batteries and solar cells, Lu says. The researchers are also interested in coating the biofilms with enzymes that catalyze the breakdown of cellulose, which could be useful for converting agricultural waste to biofuels. Other potential applications include diagnostic devices and scaffolds for tissue engineering. | Genetically Modified | 2,014 |
March 18, 2014 | https://www.sciencedaily.com/releases/2014/03/140318190027.htm | Fried foods may interact with genes to influence body weight, say experts | The results of a new study show that eating fried food more than four times a week had twice as big an effect on body mass index (BMI) for those with the highest genetic risk scores compared with lower scores. In other words, genetic makeup can inflate the effects of bad diet, says an accompanying editorial. | It is well known that both fried food consumption and genetic variants are associated with adiposity (fatness). However, the interaction between these two risk factors in relation to BMI and obesity has not been examined.So a team of US researchers, led by Lu Qi, Assistant Professor at Harvard School of Public Health and Brigham and Women's Hospital and Harvard Medical School, analyzed interactions between fried food consumption and genetic risk associated with obesity in over 37,000 men and women taking part in three large US health trials.They used food frequency questionnaires to assess fried food consumption (both at home and away from home) and a genetic risk score based on 32 known genetic variants associated with BMI and obesity.Three categories of fried food consumption were identified: less than once a week, one to three times a week, and four or more times a week. Genetic risk scores ranged from 0 to 64 and those with a higher score had a higher BMI.Height and body weight were assessed at the start of the trials, and weight was requested at each follow-up questionnaire. Lifestyle information, such as physical activity and smoking, was also collected.The researchers found consistent interactions between fried food consumption and genetic risk scores on BMI.Among participants in the highest third of the genetic risk score, the differences in BMI between individuals who consumed fried foods four or more times a week and those who consumed less than once a week were 1.0 kg/m2 in women and 0.7 kg/m2 in men.For participants in the lowest third of the genetic risk score, the differences were 0.5 kg/m2 in women and 0.4 kg/m2 in men.The authors stress that their results may have been affected by other unmeasured or unknown factors, despite carefully adjusting for several diet and lifestyle factors.However, they say they indicate that the association between fried food consumption and adiposity may vary according to differences in genetic predisposition; and vice versa, the genetic influences on adiposity may be modified by fried food consumption.Professor Lu Qi said: "Our findings emphasize the importance of reducing fried food consumption in the prevention of obesity, particularly in individuals genetically predisposed to adiposity.""This work provides formal proof of interaction between a combined genetic risk score and environment in obesity," write Professor Alexandra Blakemore and Dr Jessica Buxton at Imperial College London in an editorial. However, the results "are unlikely to influence public health advice, since most of us should be eating fried food more sparingly anyway."In contrast, they stress that genetic information can be very valuable for treating 'monogenic' forms of obesity, caused by changes in a single gene. They say that it would therefore be "a great shame" to assume that genetics can be ignored in the management of obesity, and call for further studies "providing clinically useful predictions for individuals and enabling stratification of patients for appropriate care and treatment." | Genetically Modified | 2,014 |
March 17, 2014 | https://www.sciencedaily.com/releases/2014/03/140317155615.htm | Bacterial reporters that get the scoop: Engineered gut bacteria 'remembers' what it saw | It's a jungle in there. In the tightly woven ecosystem of the human gut, trillions of bacteria compete with each other on a daily basis while they sense and react to signals from the immune system, ingested food, and other bacteria. | Problems arise when bad gut bugs overtake friendly ones, or when the immune system is thrown off balance, as in Crohn's disease, celiac disease, and colorectal cancer. Doctors have struggled to diagnose these conditions early and accurately. But now a new engineered strain of The new strain non-destructively detected and recorded an environmental signal in the mouse gut, and remembered what it "saw." The advance, reported in the The key to turning "This achievement paves the way toward living monitors programmed using synthetic gene circuits," said Wyss Institute Core Faculty member Pamela Silver, Ph.D., senior author on the study who is also the Elliott T. and Onie H. Adams Professor of Biochemistry and Systems Biology at Harvard Medical School (HMS). Silver's team included James Collins, Ph.D., who is also a Wyss Core Faculty member and professor of bioengineering at Boston University, as well as other collaborators from the Wyss Institute, Harvard Medical School and Boston University. "It could lead to new diagnostics for all sorts of complex environments."The approach Silver's team took runs counter to the prevailing dogma in synthetic biology, which is to design genetic systems that drive cell behavior from scratch, said Wyss Institute Senior Staff Scientist Jeff Way, Ph.D., a coauthor on the paper. On the other hand, "Nature has a tried-and-true blueprint for memory systems if you know where to look," Way said. "Why not just accept Nature as it is, and develop the system from there?"The genetic switch the team inserted in After invading "This is a very stable system in Nature," said lead author Jonathan Kotula, Ph.D., a Postdoctoral Fellow at HMS who is also affiliated with the Wyss Institute. "We knew the lambda switch would be a great candidate for the memory element, and we simply tweaked it to meet our needs."The cells with the engineered lambda switch would not become lytic under any conditions. Kotula and the rest of Silver's team used standard molecular genetic tools to rig the switch such that it turned on only in the presence of an inactive form of the antibiotic tetracycline.In laboratory experiments, the switch turned on within a few hours of exposure to the antibiotic- and stayed in this 'ON' state inside "It was truly shocking how cleanly the experiments worked," said Jordan Kerns, Ph.D., a Wyss Institute Postdoctoral Fellow.But to function as a living diagnostic, the engineered The engineered strain worked fine in laboratory experiments, but gradually disappeared when the team introduced it into the gut of the mouse itself. It turned out that it had been outcompeted by the animal's native gut bacteria. The team did not fret in the face of this result because they knew that the classical strain of They tackled the problem by isolating a native strain of The team envisions a day when a doctor would give a patient a strain of engineered bacteria as a diagnostic, much as they give a probiotic today. The strain would be rigged to monitor the gut for any number of conditions from inflammation to disease markers. At a follow-up visit, the patient would submit a stool sample, and medical technicians would collect For now the team is focusing on genetically tweaking the memory element of their system so that the cells remember for even longer periods of time, and engineering it so the switch flips when it senses other chemical signatures as well, such as those of cancer or parasites. In the longer term, their engineered bacteria could sense a disease state and work with other engineered genetic circuits that can produce a specific drug on command, thus producing a dynamic therapy."Our increasing appreciation of the role of the microbiome in health and disease is transforming the entire medical field. The concept of using the power of synthetic biology to harness microbes that live in our gut to develop living diagnostic and therapeutic devices is a harbinger of things to come, and Pam's work provides the first proof-of-principle that this is a viable and exciting path to pursue," said Wyss Institute Founding Director Don Ingber, Ph.D., M.D. | Genetically Modified | 2,014 |
March 13, 2014 | https://www.sciencedaily.com/releases/2014/03/140313123235.htm | We must forget to avoid serious mental disorders, and forgetting is actively regulated | In order to function properly, the human brain requires the ability not only to store but also to forget: Through memory loss, unnecessary information is deleted and the nervous system retains its plasticity. A disruption of this process can lead to serious mental disorders. Basel scientists have now discovered a molecular mechanism that actively regulates the process of forgetting. | The scientific journal The human brain is build in such a way, that only necessary information is stored permanently -- the rest is forgotten over time. However, so far it was not clear if this process was active or passive. Scientists from the transfaculty research platform Molecular and Cognitive Neurosciences (MCN) at the University of Basel have now found a molecule that actively regulates memory loss. The so-called musashi protein is responsible for the structure and function of the synaptic connections of the brain, the place where information is communicated from one neuron to the next.Using olfactory conditioning, the researchers Attila Stetak and Nils Hadziselimovic first studied the learning abilities of genetically modified ringworms (Further experiments showed that the protein inhibits the synthesis of molecules responsible for the stabilization of synaptic connections. This stabilization seems to play an important role in the process of learning and forgetting. The researchers identified two parallel mechanisms: One the one hand, the protein adducin stimulates the growth of synapses and therefore also helps to retain memory; on the other hand, the musashi protein actively inhibits the stabilization of these synapses and thus facilitates memory loss. Therefore, it is the balance between these two proteins that is crucial for the retention of memories.Forgetting is thus not a passive but rather an active process and a disruption of this process may result in serious mental disorders. The musashi protein also has interesting implications for the development of drugs trying to prevent abnormal memory loss that occurs in diseases such as Alzheimer's. Further studies on the therapeutic possibilities of this discovery will be done. | Genetically Modified | 2,014 |
March 5, 2014 | https://www.sciencedaily.com/releases/2014/03/140305125154.htm | Synthetic spider silk strong enough for a superhero | Spider silk of fantastical, superhero strength is finally speeding toward commercial reality -- at least a synthetic version of it is. The material, which is five times stronger than steel, could be used in products from bulletproof vests to medical implants, according to an article in | Alex Scott, a senior editor at C&EN, notes that spider silk's impressive strength has been studied for years, and scientists have been trying to make a synthetic version of the super-strong protein in the lab. For other simpler proteins, scientists have been able to insert relevant genes into bacterial DNA, essentially turning the microorganisms into protein factories. But spider silk has not been so easy to churn out. In fact, the challenge has caused big name companies including DuPont and BASF to bow out after several years of investment.Now, small firms just might have found the right genetic tricks, the article states. They are coaxing not just genetically engineered bacteria but also goats, transgenic silkworms and even alfalfa to produce multiple different versions of synthetic spider and spider-silkworm silks. One company has even taken their iteration to the market -- though theirs is a non-fiber kind of spider silk for use in cosmetics. So far, commercialization has been on a modest scale. But the research pipeline for synthetic spider silk is very active, and scientists expect that production is right on the verge of scaling up. | Genetically Modified | 2,014 |
March 5, 2014 | https://www.sciencedaily.com/releases/2014/03/140305124939.htm | Newly engineered molecules doom proteins with kiss of death | Like mobsters following strict orders, newly engineered molecules called "ubiquibodies" can mark specific proteins inside a cell for destruction -- a molecular kiss of death that is paving the way for new drug therapies and powerful research tools. | Led by professor Matthew DeLisa, chemical engineers at Cornell University have developed a new type of antibody, called a "ubiquibody," which is an antibody fragment they have inserted into the natural process known as the ubiquitin-proteasome pathway (UPP). Their work appears in the March 16 issue of the The UPP is the natural cellular pathway, or process, by which a cell gets rid of proteins it doesn't want anymore. A doomed protein gets tagged with a chain of a protein called ubiquitin, which is like a molecular sign that reads, "destroy me." The ubiquitin-tagged protein gets sent to the cell's proteasome -- the cell's trash compactor -- which breaks the protein into component amino acids.DeLisa and colleagues hypothesized that this common process could be harnessed as a simple, tunable way to eliminate certain target proteins in a cell without having to mess with the genome to delete the protein using standard genetic engineering tools. They did it by taking advantage of the modular nature of the UPP, which involves three enzymes called E1, E2 and E3. They modified a particular E3 enzyme called CHIP, giving only that part of the pathway a makeover.They removed CHIP's natural binding domain, replacing it with an engineered binding protein -- in this case an antibody fragment -- that was created in the lab. The idea was to empower CHIP to put ubiquitin chains on any target, guided by the homing capabilities of the antibody fragment to seek out and bind to its specific target. They named the entire re-engineered molecule with the modified CHIP enzyme a ubiquibody.To prove their concept, the researchers modified CHIP with a binding protein that targets the enzyme beta-galactosidase. They introduced DNA that encoded for their beta-galactosidase target into a human cell line, along with DNA that encoded their ubiquibodies with a binding protein for the beta-galactosidase enzyme. Sure enough, beta-galactosidase levels went down in the presence of the corresponding ubiquibodies."Our ability to redirect whatever protein you want to the proteasome is now made possible simply by swapping out different binding proteins with specificity for targets of interest to the researcher," DeLisa said.Ubiquibodies could provide a powerful way to not only completely delete a protein from a cell to study that protein's effects, but to discover what happens if, say, only 50 percent of that protein is deleted. Current gene knockout technologies are all or nothing, DeLisa said. Ubiquibodies could fine-tune research around protein deletion or reduction.The technology could also prove useful for future drug therapies. In a cancer cell in which a certain protein has been identified as contributing to the disease, the ubiquibody could reduce or eliminate the protein from within by targeting that specific protein only, DeLisa said.The therapeutic potential for ubiquibodies is being explored further in DeLisa's lab, with experiments on target proteins known to be present in diseases including Alzheimer's, cancer and Parkinson's. | Genetically Modified | 2,014 |
March 4, 2014 | https://www.sciencedaily.com/releases/2014/03/140304125427.htm | Predators delay pest resistance to Bt crops | Crops genetically modified with the bacterium Bt ( | Cornell research shows that the combination of natural enemies, such as ladybeetles, with Bt crops delays a pest’s ability to evolve resistance to these insecticidal proteins.“This is the first demonstrated example of a predator being able to delay the evolution of resistance in an insect pest to a Bt crop,” said Anthony Shelton, a professor of entomology at Cornell University's New York State Agricultural Experiment Station in Geneva, N.Y., and a co-author of the paper. Xiaoxia Liu, a visiting scientist from China Agricultural University who worked in the Shelton lab, is the lead author on the paper published in the journal Bt is a soil bacterium that produces proteins that are toxic to some species of caterpillars and beetles when they are ingested, but have been proven safe to humans and many natural enemies, including predaceous ladybirds. Bt genes have been engineered into a variety of crops to control insect pests.Since farmers began planting Bt crops in 1996 with 70 million hectares planted in the United States in 2012, there have been only three clear-cut cases in agriculture of resistance in caterpillars, and one in a beetle. “Resistance to Bt crops is surprisingly uncommon,” said Shelton.To delay or prevent insect pests from evolving resistance to Bt crops, the U.S. Environmental Protection Agency promotes the use of multiple Bt genes in plants and the practice of growing refuges of non-Bt plants that serve as a reservoir for insects with Bt susceptible genes.“Our paper argues there is another factor involved: the conservation of natural enemies of the pest species,” said Shelton. These predators can reduce the number of potentially resistant individuals in a pest population and delay evolution of resistance to Bt.In the study, the researchers set up large cages in a greenhouse. Each cage contained Bt broccoli and refuges of non-Bt broccoli. They studied populations of diamondback moth (Plutella xylostella) larvae, a pest of broccoli, and their natural enemies, ladybird beetles (Coleomegilla maculata), for six generations.Cages contained different combinations of treatments with and without predators, and with and without sprayed insecticides on the non-Bt refuge plants. Farmers commonly spray insecticides on refuge plants to prevent loss by pests, but such sprays can kill predators and prey indiscriminately.The results showed that diamondback moth populations were reduced in the treatment containing ladybird beetles and unsprayed non-Bt refuge plants. Also, resistance to Bt plants evolved significantly slower in this treatment. In contrast, Bt plants with no refuge were completely defoliated in treatments without ladybirds after only four to five generations, showing rapid development of resistance in the pests. In the treatment with sprayed non-Bt refuge plants and predators, diamondback moth populations were reduced, but the larvae more quickly evolved resistance to the Bt plants.“These results demonstrate the effectiveness of Bt plants in controlling the pest population, the lack of effect of Bt on the predators and the role predators play in delaying resistance to Bt plants in the pest population,” said Shelton. | Genetically Modified | 2,014 |
March 3, 2014 | https://www.sciencedaily.com/releases/2014/03/140303135902.htm | Gut microbes spur development of bowel cancer | It is not only genetics that predispose to bowel cancer; microbes living in the gut help drive the development of intestinal tumors, according to new research in mice published in the March issue of | Bowel cancer, also called colorectal cancer, results from a series of genetic changes (mutations) that cause healthy cells to become progressively cancerous, first forming early tumors called polyps that can eventually become malignant. Although mutations can occur anywhere in the human intestine, certain types of colorectal cancer tend to develop in particular locations, suggesting that additional, nongenetic factors contribute to tumor growth and dictate where polyps appear.Dr. Sergio Lira and his team at the Icahn School of Medicine at Mount Sinai, New York, asked if gut microbes have a hand in tumor development. The researchers had noticed previously that mice carrying polyp-causing mutations develop polyps only in a limited section of the intestine, despite the mutations being present in all cells along the intestine. In the new study, they treated the mice with antibiotics to disrupt the populations of microbes living in their gut. This treatment prevented the formation of polyps, showing that bacteria are essential for early tumor development in this model. The authors propose that bacteria cross from the gut into the tissue of the intestinal wall, triggering inflammation that promotes tumor growth.While further research is needed to confirm the identity of the cancer-promoting bacteria, the findings suggest it may be possible to reduce the risk of colorectal cancer in genetically susceptible individuals by removing certain types of gut bacteria.The work may also help explain some of the nongenetic factors that have been implicated in colorectal cancer. "In addition to genetic changes, various lifestyle-related factors, such as obesity and diet, have been linked to colorectal cancer. Some of these lifestyle factors appear to affect the types of bacteria present in the gut," explains Dr Lira. "Ultimately, understanding the interplay between genetic mutations, gut microbes, and inflammation may lead to novel diagnostics and therapies for intestinal cancer." | Genetically Modified | 2,014 |
March 3, 2014 | https://www.sciencedaily.com/releases/2014/03/140303084414.htm | Entomologists update definitions to tackle resistance to biotech crops, pesticides | Resistance to pesticides has now been recorded in nearly a thousand pest species, including more than 500 insects, 218 weeds, and 190 fungi that attack plants. The recorded cases of resistance in insects, mites and other arthropods, which include resistance to multiple pesticides per species, more than doubled from 5,141 in 1990 to 11,254 in 2013. A first step in tackling this growing global problem is establishing a common vocabulary, because the current jumble of terms fosters confusion among scientists in academia, industry and government. To address this issue, five entomologists from the University of Arizona and Michigan State University updated definitions for 50 key terms related to resistance in a new article in the | "The lack of a modern glossary for resistance was recently brought to our attention by an initiative of the U.S. Environmental Protection Agency (EPA) seeking input on definitions of terms about resistance," said Dr. Mark Whalon, one of the co-authors from Michigan State University, who directs the online Arthropod Pesticide Resistance Database and who also serves as the Entomological Society of America's Liaison to the EPA Office of Pesticide Programs. "We provide a list of 50 key resistance terms and definitions aimed at facilitating understanding and management of resistance."The authors favor definitions that promote proactive detection and management of resistance, such as resistance defined as "a genetically based decrease in susceptibility to a pesticide." They contrast this with an alternative definition used by some industry scientists that requires "repeated failure of a product to achieve the expected level of control," which generally occurs only after it's too late to respond most effectively.The stakes are especially high for defining and managing insect resistance to corn and cotton plants genetically engineered to produce proteins from the bacterium Recognizing that resistance is not "all or none" and that intermediate levels of resistance can have a continuum of effects on pest control, the authors describe five categories of field-evolved resistance and use them to classify 13 cases of resistance to five Bt toxins in transgenic corn and cotton based on monitoring data from five continents for nine major pest species.Emerging resistance of the western corn rootworm to Bt corn exemplifies the urgent need for well-defined resistance terms. The cost of this insidious beetle to U.S. corn growers has been estimated at one billion dollars annually. In 2003, to reduce costs and cut back on soil insecticides, U.S. farmers began planting Bt corn that kills rootworms."The first evidence of rootworm resistance to Bt corn was discovered in Iowa in 2009," said Dr. Bruce Tabashnik, the study's lead author and head of the entomology department at the University of Arizona. "Nearly five years later, the resistance has spread but decisive regulatory action by the EPA is still stalled, in part because an effective definition of resistance is lacking in this case."Although some scientists have expressed concern that reports of pest resistance to Bt crops provide 'ammunition' to anti-biotech activists, Tabashnik said "Pests are remarkably adaptable. They usually evolve resistance to any tactic that's used repeatedly to control them, so this problem is not limited to transgenic crops." Noting that insects have been evolving resistance to natural plant defenses for millions of years and that this year marks the 100th anniversary of the first reported case of insecticide resistance, he concludes, "Finding ways to delay resistance is a never-ending challenge with any pest management approach." | Genetically Modified | 2,014 |
February 27, 2014 | https://www.sciencedaily.com/releases/2014/02/140227134656.htm | Manipulating heat, drought tolerance in cowpeas | Cowpeas, known as black-eyed peas in the U.S., are an important and versatile food legume grown in more than 80 countries. Texas A&M University scientists are working to map the genes controlling drought and heat tolerance in recent varieties. | New and improved varieties of cowpeas have numerous adaptive traits of agronomic importance, such as 60-70 day maturity, drought tolerance, heat tolerance, aphid resistance and low phosphorus tolerance, said Dr. Meiping Zhang, Texas A&M AgriLife Research associate research scientist in College Station.Under a National Institute for Food and Agriculture grant of $500,000, Zhang and other Texas A&M scientists will take advantage of the recently developed DNA sequencing technology to map and ultimately clone the genes controlling drought and heat tolerance for molecular studies and deployment of these genes in other crops, she said.Joining Zhang on the project are Dr. Hongbin Zhang, Texas A&M professor of plant genomics and systems biology and director of the Laboratory for Plant Genomics and Molecular Genetics; Dr. B.B. Singh, a visiting scholar and cowpea breeder with the Texas A&M soil and crop sciences department; and Dr. Dirk Hays, Texas A&M associate professor of physiological and molecular genetics, all in College Station.The goal of the study is to develop single nucleotide polymorphisms or SNP markers, the latest DNA marker technology, enabling efficient manipulation of heat and drought tolerances in cowpeas and related species, Zhang said.Cowpeas were chosen for the study because they are a high protein grain, vegetable, fodder and high nitrogen-fixing legume that can be intercropped with corn, cotton and other crops in many countries, including the U.S., Zhang said."We know it is highly tolerant to drought, heat and several other biotic and abiotic stresses," she said. "This research will use high-throughput site-associated DNA sequencing to map the genes controlling drought and heat tolerance and to develop SNP markers, enabling efficient manipulation of heat and drought tolerances in cowpea and related species."Zhang said they have already developed a mapping population of 110 recombinant inbred lines from a cross of two cowpea lines that are highly tolerant or susceptible to both drought and high temperature. This population is being augmented into more than 200 recombinant inbred lines for the new project."We will not only map drought and heat tolerant genes, but also develop a platform for mapping genes controlling several other biotic and abiotic stress tolerances such as aphid resistance and low phosphorus tolerance, both of which are also of extreme significance for agricultural production of many crops."The drought and heat tolerant genes, once defined and cloned, will significantly advance understanding of the molecular basis underlying plant tolerances to these stresses, Zhang said.This will help researchers design tools to effectively combine multiple traits into new cultivars adapted to the globally changing climate in this and related crops, thus supporting the long-term genetic improvement and sustainability of U.S. agriculture and food systems, she said. | Genetically Modified | 2,014 |
February 27, 2014 | https://www.sciencedaily.com/releases/2014/02/140227125514.htm | Math anxiety factors into understanding genetically modified food messages | People who feel intimidated by math may be less able to understand messages about genetically modified foods and other health-related information, according to researchers. | "Math anxiety, which happens when people are worried or are concerned about using math or statistics, leads to less effort and decreases the ability to do math," said Roxanne Parrott, Distinguished Professor of Communication Arts and Sciences and Health Policy and Administration. "Math anxiety also has been found to impair working memory."The researchers found that math anxiety led to a decrease in comprehension for people who read statistics in a message about genetically modified foods, while an increase in skills in math and a confidence in those skills led to better comprehension."This is the first study that we know of to take math anxiety to a health and risk setting," said Parrott. "Math skills have become a common element in many health and risk message studies, which addresses the skill component of math competence but ignores the cognitive and affective components."People who have lower levels of math skills and who have less confidence in their ability to do math had higher levels of math anxiety, said Parrott, who worked with Kami J. Silk, professor of communication, Michigan State University.However, math anxiety also increased for people who had high levels in both math skills and their belief in those math-solving skills when exposed to a message about genetically modified foods. The math anxiety in high-skilled individuals did not significantly affect the understanding of the message."Perhaps this is due to performance anxiety," Parrott said. "It's a sense of 'I know I can do it and I have the skills to do it, but it is making me anxious to apply my skills.'"Participants also reported they believed that statistics presented in messages were more important than those presented on a bar graph, according to the researchers. The perceived level of importance of the messages may make text more persuasive than graphics.The study underscores the need to not only improve math skills, but also confidence in one's skills.The study also emphasizes that anxiety about facing tasks that require math or statistics skills likely reduces efforts to understand consumer warnings and other health information that relies on numbers."This is one more piece of evidence about the importance of applied math education, in which students tackle real world messages and content when learning math skills," said Parrott. "We have to focus on teaching people math, but also we need to tell people that they do have the skills, and find strategic ways to communicate that ease anxiety and worry about understanding math."The researchers, who reported their findings in the online issue of the Researchers measured the participants' math skills, confidence and anxiety prior to reading the message. After the test, the researchers again measured the participants' levels of math anxiety, as well as other abilities, including their comprehension, sense of the message's importance and intentions.Parrott said that future research should determine whether math anxiety plays a similar role in other types of health risk messages. The researchers investigated genetically modified food messages because the topic is currently in the news and developing smart policies on food acquisition and safety is increasing."My goal is to help people make informed decisions and to do that, they need to understand and comprehend messages," said Parrott. "Food policy, in particular, interests me because having enough food to feed people is a really big issue that we're facing." | Genetically Modified | 2,014 |
February 27, 2014 | https://www.sciencedaily.com/releases/2014/02/140227092147.htm | Cancer vaccine could use immune system to fight tumors | Cincinnati Cancer Center (CCC) and UC Cancer Institute researchers have found that a vaccine, targeting tumors that produce a certain protein and receptor responsible for communication between cells and the body's immune system, could initiate the immune response to fight cancer. | These findings, published in the Feb. 27 online edition of the journal Principal Investigator John Morris, MD, clinical co-leader of the Molecular Therapeutics and Diagnosis Program for the CCC, co-leader of the UC Cancer Institute's Comprehensive Lung Cancer Program, professor in the division of hematology oncology at the UC College of Medicine and UC Health medical oncologist, says a number of antitumor vaccines have shown promise for causing immune responses against tumor antigens to improve patient outcomes."Recently, human Interleukin-15 (IL-15) has entered clinical trials for treatment of patients with melanoma, a type of skin cancer, and renal cancer. In this study, we examined the effectiveness of a vaccination targeting tumors that produced IL-15 and its cell surface receptor called IL-15R-alpha () and examined their ability to up-regulate (or increase) immune responses to tumor antigens," Morris says. "We showed that the presence of both IL-15 with its receptor IL-15Rα increased the cell-surface production and secretion of IL-15, and in turn, stopped tumor cells from reproducing."Researchers used IL-15 to develop a whole tumor cell vaccine to target breast (TS/A) and prostate (TRAMP-C2) cancer cells in animal models; results showed that tumor cells stopped growing after the vaccine was introduced and that beneficial effects were enhanced further when IL-15Rα was co-produced by the vaccine cells.Morris says vaccination with modified tumor cells producing IL-15 and IL-15Rα slowed tumor growth and led to increased survival for animal models. Furthermore, the cells that control the immune responses (CD8+ T-cells and NK cells) were elevated in these tumors, showing evidence of a true immune response."IL-15 is a powerful pro-inflammatory protein that can enhance immune responses," he says. "Our findings suggest that genetically altering tumor cells to produce IL-15 and IL-15Rα can cause and enhance immune responses to tumor antigens found in these tumor cells and can be used as a vaccine to target these antigens."Additionally, this provides evidence needed to begin investigating a vaccine in human cancer clinical trials to determine whether genetically modified tumor cells producing IL-15 and IL-15Rα may induce anti-cancer responses." | Genetically Modified | 2,014 |
February 26, 2014 | https://www.sciencedaily.com/releases/2014/02/140226125338.htm | New target for dengue virus vaccine found | Creating a vaccine that protects people from all four types of dengue virus has frustrated scientists for decades. But researchers at the University of North Carolina have discovered a new target for human antibodies that could hold the key to a vaccine for the world's most widespread mosquito-borne disease. | Using an experimental technique new to the dengue field, the labs of Ralph Baric, PhD, and Aravinda de Silva, PhD, showed that a molecular hinge where two regions of a protein connect is where natural human antibodies attach to dengue 3 to disable it. The finding, published in the It's the first study to demonstrate how these binding sites -- composed of just 25 amino acids -- can be genetically swapped out for amino acids from another dengue type without disrupting the integrity of the virus."This gives us a lot of insight into how human antibodies work," said de Silva, a professor of microbiology and immunology in the UNC School of Medicine. "And there could be a lot of translational aspects to this; it could lead to a new way to create vaccines for other diseases."De Silva and Baric, a professor with a dual appointment in the UNC School of Medicine and the UNC Gillings School of Global Public Health, are now working with vaccine developers at two pharmaceutical companies to test the effectiveness of potential dengue vaccines now in clinical trials. If these vaccines don't bind to their molecular hinge, then the vaccines will likely prove less effective than researchers would like, especially over time.Dengue, which infects approximately 390 million people each year, is common in tropical and subtropical regions around the world. There were 63 confirmed cases in the Florida Keys in 2010. The virus, widespread in the United States territory of Puerto Rico, has also been confirmed in mainland south Florida and Texas. "The mosquitos that can carry dengue exist throughout the southeastern United States," Baric said. "It's just a matter of time before dengue virus reemerges in the South, making vaccines and therapeutics a critical long-term public health priority."Making a truly effective dengue vaccine has proven difficult because of a phenomenon called antibody dependent enhancement. People infected with one type of dengue usually develop a natural immune response that rids the body of the virus and prevents a repeat infection of that same virus type. But if those people are infected with a second type of dengue, the virus is enhanced Consequently, a vaccine that offers immunity for only one type of dengue would make other types of dengue more virulent and dangerous. The first large clinical trial of a dengue vaccine, conducted in Thailand in 2011, contained a cocktail of all four types of dengue. But for reasons that remain unclear the vaccine was just partially protective. There was no evidence that the vaccine protected people during a dengue 2 outbreak that same year.To study dengue, de Silva and colleagues have collected samples from infected Sri Lankans and from Americans who had acquired the disease while abroad. Such samples allowed de Silva's team to find that human antibodies are not the same as mouse antibodies, which had served as the basis for vaccine development. De Silva saw that mouse antibodies latched onto a region of a protein that forms an outer shell of the virus. Human antibodies rarely recognize that region; instead human antibodies bind to a different region where two parts of the outer protein connect. De Silva calls this region an epitope hinge. An epitope is any part of a foreign substance that a human antibody binds to.To prove the importance of the hinge, de Silva recruited Baric, an expert in pioneering novel ways to manipulate genes in viruses using primarily noroviruses and coronaviruses as models. Using de Silva's dengue expertise and the structure of the dengue virus, Baric was able to pinpoint the structurally complex, nonlinear 25-amino-acid hinge domain and remove it from dengue 3 particles. His group, led by William Messer, PhD, then developed strategies to recover dengue viruses from DNA clones and replace the dengue 3 hinge with a replicated 25-amino-acid chain from dengue 4. Essentially, Baric turned dengue 3 into dengue 4.The genetically mutated virus survived and grew in cell cultures and in primates. Then the researchers exposed the mutant virus to dengue 3 antibodies, which typically bind to dengue 3. But they had no effect on the genetically modified dengue. They then showed in cell lines that the virus could be neutralized by antibodies directed against dengue 4. In collaboration with researchers at the University of Puerto Rico, de Silva and Baric's team was able to show that the new virus infected primates, which developed antibodies against dengue 4."These results amount to a paradigm shift," Baric said. De Silva added, "This told told us that the epitope we thought was important was indeed the De Silva and Baric are conducting similar experiments with dengue 1 and 3. If they can isolate the major epitopes for each dengue type, then they could potentially genetically modify a virus with all four epitopes. The result could become the basis for a vaccine against all four types.De Silva and Baric are using their results to study why antibodies bind to a specific epitope but not to other sites. Such information would lend even more insight into how to design effective vaccines.Also, de Silva and Baric's research could be translated into other fields in need of vaccines. "The general idea is that a complex protein-interaction site can now be moved from one virus to another," de Silva said. For instance, an epitope from a virus like hepatitis C could be moved onto the live virus used in the measles vaccine. This new chimeric virus would simultaneously offer people protection against hepatitis C and measles."We might not even need a virus," de Silva added. "We might just need to create the epitope that we know antibodies can bind to. And | Genetically Modified | 2,014 |
February 26, 2014 | https://www.sciencedaily.com/releases/2014/02/140226101817.htm | Different eggs in adolescent girls, adult women | Are the eggs produced by adolescent girls the same as the ones produced by adult women? A recent study published in | Professor Liu's team used two genetically modified mouse models to show that the first wave of eggs, which starts immediately after birth, contributes to the onset of puberty and provides fertilizable eggs into the transition from adolescence to adulthood. In contrast, the adult wave remains in a state of dormancy until activated during the adult life and then provides eggs throughout the entire reproductive lifespan.This is the first time that the developmental dynamics of two distinct populations of eggs have been clearly described in an animal model, and there is evidence that these two waves of eggs most likely also exist in the human ovary. The identification and characterization of the two waves of eggs will lead to new ways of thinking about how to obtain the best eggs when treating women for ovarian diseases that cause infertility. Such techniques will prove especially useful for women suffering from premature ovarian failure (POF), which affects 1%-4% of all women of childbearing age. The results may also lead to more effective treatments for ovarian diseases by specifically targeting the different egg populations. | Genetically Modified | 2,014 |
February 21, 2014 | https://www.sciencedaily.com/releases/2014/02/140221184758.htm | Seed-filled buoys may help restore diverse sea meadows in San Francisco Bay | A pearl net filled with seedpods, tethered by a rope anchored in the coastal mud but swaying with the tide, could be an especially effective way to restore disappearing marine meadows of eelgrass, according to a new study. | The resulting crop of eelgrass grown by SF State researchers is as genetically diverse as the natural eelgrass beds from which the seeds were harvested, said Sarah Cohen, an associate professor of biology at the Romberg Tiburon Center. As eelgrass meadows are threatened by a number of human activities, restoration plans that maintain diversity are more likely to succeed, she noted.The emphasis on genetic diversity is a relatively new concern in ecosystem restoration projects, where there has been an understandable urgency to move plants and animals back into an area as quickly as possible. "It's taken a little longer for people to say, 'we need to know who we're moving,'" Cohen said, "and to explore how successful different genotypes are in different settings, so we can more strategically design the movement of individuals for restoration."Eelgrass restoration projects are challenging because it's not easy to plant seedlings under the water, and seeds scattered over a large area could be washed away from the restoration site. Instead, RTC researchers tested the Buoy Deployed Seeding (BuDS) restoration technique. They first harvested eelgrass seedpods from several eelgrass beds in San Francisco Bay, then suspended the pods within floating nets over experimental tanks (called mesocosms) supplied with Bay water and with or without sediment from the original eelgrass areas. As the seeds inside each pod ripened, a few at a time, they dropped out of the nets and began to grow within the tanks.The researchers then examined "genetic fingerprints" called microsatellites from the plants to measure the genetic diversity in each new crop. Genetic diversity can be measured in a number of ways, by looking at the number of different variants in a gene in a population, for instance, or by examining how these variants are mixed in an individual.Based on these measurements and others, the new crops were nearly as genetically diverse as their parent grass beds, Cohen and colleagues found. "These offspring impressively maintained the genetic diversity and distinctiveness of their source beds in their new mesocosm environments at the RTC-SFSU lab," said Cohen."I think it's impressive how well it worked for a relatively small scale design," she added, "and that's one of the things we wanted to point out in the paper, since a lot of eelgrass restoration projects are so small, up to a few acres."Sea grass meadows are a key marine environment under siege. In their healthy state, they stabilize coastal sediment and provide a huge nursery for a variety of algae, fish, shellfish and birds. But a variety of human influences, from bridge building to runoff pollution to smothering loads of sediment, have threatened these grass beds globally.They're often overlooked and misunderstood, Cohen said. For instance, many of the eelgrass beds in the San Francisco Bay are submerged. "If you were out kayaking at low tide, you might see these grasses in places like Richardson Bay, which is full of a big meadow," she said.During low tides, beachcombers could walk to eelgrass beds at places like Crown Beach in Alameda or Keller Beach in Richmond. But for the most part, "people might see the green blades washed up on the beach, and not realize that these are flowering plants instead of a piece of algae."In classes at the RTC, students are learning how to combine genetics and ecology for projects that build better strategies to preserve the surprisingly distinct eelgrass meadows of San Francisco Bay. Cohen said that differences in water salinity, wind, sunlight, a sandy or silty bottom, and the kinds of organisms that live with the eelgrass all might play a role in creating such genetically different meadows. | Genetically Modified | 2,014 |
February 19, 2014 | https://www.sciencedaily.com/releases/2014/02/140219142556.htm | Cell therapy shows remarkable ability to eradicate cancer in clinical study | Investigators from Memorial Sloan Kettering Cancer Center have reported more encouraging news about one of the most exciting methods of cancer treatment today. The largest clinical study ever conducted to date of patients with advanced leukemia found that 88 percent achieved complete remissions after being treated with genetically modified versions of their own immune cells. The results were published today in | "These extraordinary results demonstrate that cell therapy is a powerful treatment for patients who have exhausted all conventional therapies," said Michel Sadelain, MD, PhD, Director of the Center for Cell Engineering at Memorial Sloan Kettering and one of the study's senior authors. "Our initial findings have held up in a larger cohort of patients, and we are already looking at new clinical studies to advance this novel therapeutic approach in fighting cancer."Adult B cell acute lymphoblastic leukemia (B-ALL), a type of blood cancer that develops in B cells, is difficult to treat because the majority of patients relapse. Patients with relapsed B-ALL have few treatment options; only 30 percent respond to salvage chemotherapy. Without a successful bone marrow transplant, few have any hope of long-term survival.In the current study, 16 patients with relapsed B-ALL were given an infusion of their own genetically modified immune cells, called T cells. The cells were "reeducated" to recognize and destroy cancer cells that contain the protein CD19. While the overall complete response rate for all patients was 88 percent, even those with detectable disease prior to treatment had a complete response rate of 78 percent, far exceeding the complete response rate of salvage chemotherapy alone.Dennis J. Billy, C.Ss.R, of Wynnewood, Pennsylvania, was one of the first patients to receive this treatment more than two years ago. He was able to successfully undergo a bone marrow transplant and has been cancer-free and back at work teaching theology since 2011. Paolo Cavalli, a restaurant owner from Oxford, Connecticut, remains in complete remission eight months after receiving his personalized T cell treatment.Cell-based, targeted immunotherapy is a new approach to treating cancer that harnesses the body's own immune system to attack and kill cancerous cells. Unlike with a common virus such as the flu, our immune system does not recognize cancer cells as foreign and is therefore at a disadvantage in eradicating the disease. For more than a decade, researchers at Memorial Sloan Kettering have been exploring ways to reengineer the body's own T cells to recognize and attack cancer. In 2003, they were the first to report that T cells engineered to recognize the protein CD19, which is found on B cells, could be used to treat B cell cancers in mice."Memorial Sloan Kettering was the first center to report successful outcomes using this CD19-targeted approach in B-ALL patients," said Renier Brentjens, MD, PhD, Director of Cellular Therapeutics at Memorial Sloan Kettering and one of the study's senior authors. "It's extremely gratifying to witness the astonishing results firsthand in my patients, having worked for more than a decade developing this technology from the ground up."In March 2013, the same team of researchers first reported the results of five patients with advanced B-ALL who were treated with cell therapy. Remarkably, all five patients achieved complete remissions.In the current study, seven of the 16 patients (44 percent) were able to successfully undergo bone marrow transplantation -- the standard of care and the only curative option for B-ALL patients -- following treatment. Three patients were ineligible due to failure to achieve a complete remission, three were ineligible due to preexisting medical conditions, two declined, and one is still being evaluated for a potential bone marrow transplant. Historically, only 5 percent of patients with relapsed B-ALL have been able to transition to bone marrow transplantation.The study also provides guidelines for managing side effects of cell therapy, which can include severe flu-like symptoms such as fever, muscle pain, low blood pressure, and difficulty breathing, referred to as cytokine release syndrome. The researchers developed diagnostic criteria and a laboratory test that can identify which patients are at greater risk for developing this syndrome.Additional studies to determine whether cell therapy can be applied to other types of cancer are already underway, and studies to test whether B-ALL patients would benefit from receiving targeted immunotherapy as frontline treatment are being planned. | Genetically Modified | 2,014 |
February 13, 2014 | https://www.sciencedaily.com/releases/2014/02/140213142223.htm | Cortical convolutions controlled in sections: Non-coding DNA sequence affects brain's characteristic folding, study shows | Researchers have tied a particular gene to the development of cortical convolutions -- the prominent but enigmatic folds covering the surface of the human brain. Their discovery should shed some light on these characteristic contours, which have been the subject of wild speculation for ages, and perhaps also provide a better understanding of how such brain ridges form, how they evolved from our pre-human ancestors and, ultimately, how they influence brain function. | The exact role of cortical convolutions remains unknown, but theories have abounded. (Some, for example, have suggested that the folds act as the body's cooling system and others have even proposed that Albert Einstein's genius could have been traced to a single cortical fold on his brain.)Now, leveraging advances that permit a closer look at how these folds develop, research published in the 14 February issue of "There is already a list of genetic mutations that cause abnormal neocortical folding, which can be used for prenatal testing," explained Byoung-il Bae from the Division of Genetics and Genomics at Boston Children's Hospital and Harvard Medical School in Boston, Massachusetts, one of the lead authors of the Bae and colleagues from around the world investigated the genomes of five individuals with abnormalities on Broca's area, or the language center of the brain. These study participants were from three different families -- one Turkish and two Irish-American -- and they suffered from refractory seizures as well as intellectual and language difficulties.The researchers found that all five patients harbored a mutation on a particular regulatory element that influences the They discovered that low expression of This particular "Our story tells us that the regional proliferation of progenitor cells is controlled by multiple promoters that enable the formation of distinct gyri (folds) in different parts of the brain," said Bae. "Such promoters introduce more switches for the same proteins, and they may have been among the genetic tools our pre-human ancestors relied upon to evolve."The human "By regulating populations of progenitor cells in different parts of the brain with such promoter elements, our pre-human ancestors may have controlled the regions that grew over evolutionary time," he said.But what purpose do cortical convolutions actually serve? Bae imagines them to represent a developmental strategy for packing enormous numbers of neurons and glial cells into the limited space of the skull. "Humans have 12 times the amount of neurons that chimpanzees have," he explained. "But the volume of our skull is only three times bigger."Regardless of their precise role, however, the identification of this novel regulatory element affecting "We need to compile all of the available data at one convenient place… and make them easily accessible to scientists," Bae said. "If the huge amount of the RNA sequencing data is hoarded in a web server in a format that only bioinformaticians can dig into, then the efforts of this massive RNA sequencing are wasted."The report by Bae | Genetically Modified | 2,014 |
February 11, 2014 | https://www.sciencedaily.com/releases/2014/02/140211141105.htm | Antibody treatment used by researchers to protect humanized mice from HIV | NIH-funded scientists have shown that boosting the production of certain broadly neutralizing antibodies can protect humanized mice from both intravenous and vaginal infection with HIV. Humanized mice have immune systems genetically modified to resemble those of humans, making it possible for them to become HIV-infected. | Led by David Baltimore, Ph.D., of the California Institute of Technology, the investigators inserted the genes encoding the NIH-discovered broadly HIV neutralizing antibody VRC01 into a vector, a virus that infects mice but does not cause disease. In a unique technique known as vectored immunoprophylaxis (VIP), the researchers infected laboratory mice with this altered virus, enabling certain of their cells to produce the antibodies for extended periods. To test the applicability of this approach to human infections, the researchers used a novel method of repeatedly exposing these mice to low doses of HIV in a manner that mimics human sexual intercourse. In two separate experiments, the investigators assessed protection from infection with two strains of HIV: a standard laboratory strain as well as one that is commonly transmitted among humans.Two of the 10 mice expressing VRC01 antibodies became infected with the laboratory strain of HIV after 13 to 15 exposures to the virus. In contrast, all nine mice without the antibodies were infected with HIV within six exposures. In the second experiment, researchers used a modified form of the VRC01 antibody, known as VRC07, and challenged the mice with an HIV strain known to be heterosexually transmitted among people. The mice expressing the VRC07 antibody were completely resistant to infection during repeated intravaginal challenge. Taken together, these results indicate that VIP can protect mice from infection with strains of HIV that cause human disease and suggest that a similar strategy could be developed to reduce transmission in people, the authors write. | Genetically Modified | 2,014 |
February 10, 2014 | https://www.sciencedaily.com/releases/2014/02/140210095406.htm | Chronic inflammation: Slowing down immune system when in overdrive | Many people suffer from chronic inflammation because their immune systems overreact to 'self' tissue. Sydney scientists believe that a small molecule known as Interleukin 21 is a promising therapeutic target in such cases. | Interleukin 21 (IL-21) is one of a group of chemical messengers known as 'cytokines', which affect the behavior of immune cells. IL-21 is already well known to play an important role in autoimmune diseases such as Sjögren's syndrome and type 1 diabetes.The current study shows how much IL-21 contributes to inflammation. It also shows how important it is to remove IL-21 to reduce inflammation, even where there are other severe immune defects present.Undertaken at Sydney's Garvan Institute of Medical Research, researchers used mice genetically deficient in another cytokine (IL-2), a well-established mouse model of autoimmunity. In some mice, the IL-21 cell surface receptor was also genetically removed. In these mice, inflammatory disease was much less severe, demonstrating that IL-21 contributes to fatal inflammatory disease.Immunologists Associate Professor Cecile King and Dr Alexis Vogelzang, in collaboration with bioinformatics experts Drs Marcel Dinger and Brian Gloss, combined cellular analysis and RNA sequencing to compare genes expressed in the disease model with those expressed in healthy immune cells. The study confirmed that IL-21 is one of the most highly expressed genes in autoimmune disease.The findings are published in the "RNA sequencing is an unbiased way of determining differential expression of genes, and this data revealed the proinflammatory gene signature of autoimmune disease and confirmed the extent to which IL-21 is elevated in the absence of IL-2," said Associate Professor King."When you remove the IL-2 gene, another group of very calming immune cells known as 'T regulatory cells' also disappear -- because T regulatory cells express high levels of the IL-2 receptor and are IL-2 dependent. Without T regulatory cells, the immune system goes haywire and the body starts attacking itself.""Under these conditions, IL-21 kicks in and make things much worse.""When IL-21 is blocked, the huge inflammatory response is greatly subdued, although not entirely eliminated.""There are many people with chronic inflammation caused by defective T cell regulation, and this research suggests that blocking IL-21 with drugs might help them." | Genetically Modified | 2,014 |
February 7, 2014 | https://www.sciencedaily.com/releases/2014/02/140207132911.htm | Surprising new clue to the roots of hunger, neurons that drive appetite | While the function of eating is to nourish the body, this is not what actually compels us to seek out food. Instead, it is hunger, with its stomach-growling sensations and gnawing pangs that propels us to the refrigerator – or the deli or the vending machine. Although hunger is essential for survival, abnormal hunger can lead to obesity and eating disorders, widespread problems now reaching near-epidemic proportions around the world. | Over the past 20 years, Beth Israel Deaconess Medical Center (BIDMC) neuroendocrinologist Bradford Lowell, MD, PhD, has been untangling the complicated jumble of neurocircuits in the brain that underlie hunger, working to create a wiring diagram to explain the origins of this intense motivational state. Key among his findings has been the discovery that Agouti-peptide (AgRP) expressing neurons – a group of nerve cells in the brain’s hypothalamus – are activated by caloric deficiency, and when either naturally or artificially stimulated in animal models, will cause mice to eat voraciously after conducting a relentless search for food.Now, in a new study published on-line this week in the journal “Our goal is to understand how the brain controls hunger,” explains Lowell, an investigator in BIDMC’s Division of Endocrinology, Diabetes and Metabolism and Professor of Medicine at Harvard Medical School. “Abnormal hunger can lead to obesity and eating disorders, but in order to understand what might be wrong – and how to treat it – you first need to know how it works. Otherwise, it’s like trying to fix a car without knowing how the engine operates.”Hunger is notoriously complicated and questions abound: Why do the fed and fasted states of your body increase or decrease hunger? And how do the brain’s reward pathways come into play – why, as we seek out food, especially after an otherwise complete meal, do we prefer ice cream to lettuce?“Psychologists have explained how cues from the environment and from the body interact, demonstrating that food and stimuli linked with food [such as a McDonald’s sign] are rewarding and therefore promote hunger,” explains Lowell. “It’s clear that fasting increases the gain on how rewarding we find food to be, while a full stomach decreases this reward. But while this model has been extremely important in understanding the general features of the ‘hunger system,’ it’s told us nothing about what’s inside the ‘black box’ – the brain’s neural circuits that actually control hunger.”To deal with this particularly complex brain region – a dense and daunting tangle of circuits resembling a wildly colorful Jackson Pollack painting – the Lowell team is taking a step-by-step approach to find out how the messages indicating whether the body is in a state of feeding or fasting enter this system. Their search has been aided by a number of extremely powerful technologies, including rabies circuit mapping and channelrhodopsin-assisted circuit mapping, which enable their highly specific, neuron-by-neuron analysis of the region.“By making use of these new technologies, we are able to follow the synapses, follow the axons, and see how it all works,” says Lowell. “While this sounds like a relatively straightforward concept, it’s actually been a huge challenge for the neuroscience field.”In this new paper, first authors Michael Krashes, PhD, and Bhavik Shah, PhD, postdoctoral fellows in the Lowell lab, employed rabies circuit mapping, a technology in which a modified version of the rabies virus is engineered to “infect” just one type of neuron – in this case, the AgRP neurons that drive hunger. The virus moves upstream one synapse and identifies all neurons that are providing input to AgRP starter neurons. Then, using a host of different neuron-specific cre-recombinase expressing mice (a group of genetically engineered animals originally developed in the Lowell lab) the investigators were able to map inputs to just these nerve cells, and then manipulate these upstream neurons so that they could be targeted for activation by an external stimulus.“We wanted to know, of all the millions of neurons in a mouse brain, which provided input to the AgRP neurons,” explains Lowell. “And the shocking result was that there were only two sites in the brain that were involved – the dorsal medial hypothalamus and the paraventricular nucleus, with the input from the paraventricular neurons shown to be extremely strong.”With this new information, the investigators now had a model to pursue. “We hypothesized that neurons in the paraventricular nucleus were communicating with and turning on the AgRP neurons. We developed mice that expressed cre-recombinase in many subsets of the paraventricular neurons and then, mapping the neurons one-by-one, we determined which was talking to which,” says Lowell. Their results revealed that subsets of neurons expressing thyrotropin-releasing hormone (TRH) and pituitary adenylate cylcase-activating polypeptide (PACAP) were in on the neuronal chatter.Finally, through a chemogenetic technique known as DREADDs – Designer Receptor Exclusively Activated by Designer Drug – the authors used chemicals to specifically and selectively stimulate or inhibit these upstream neurons in the animal models. The fed mice, which had already consumed their daily meal and otherwise had no interest in food, proceeded to search out and voraciously eat after DREADD stimulation. Conversely, the fasting mice – which should have been hungry after a period of no food – ate very little when these upstream neurons were turned off.“This has led us to the discovery of a novel, previously unknown means of activating AgRP neurons and producing hunger,” explains Lowell. “Surprisingly, these hunger-inducing neurons were found in a region of the brain which has long been thought to have the opposite effect – causing satiety. This unexpected discovery, made possible only through the use of the new wiring diagram-elucidating technologies, highlights the importance of following the labeled neuronal lines of information flow. We are getting closer and closer to completing our wiring diagram, and the nearer we come to understanding how it all works, the better our chances of being able to treat obesity and eating disorders, the consequences of abnormal hunger.” | Genetically Modified | 2,014 |
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