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News Article | May 2, 2017
Site: www.eurekalert.org

Donnelly Centre researchers have developed a deep learning algorithm that can track proteins, to help reveal what makes cells healthy and what goes wrong in disease Donnelly Centre researchers have developed a deep learning algorithm that can track proteins, to help reveal what makes cells healthy and what goes wrong in disease. "We can learn so much by looking at images of cells: how does the protein look under normal conditions and do they look different in cells that carry genetic mutations or when we expose cells to drugs or other chemical reagents? People have tried to manually assess what's going on with their data but that takes a lot of time," says Benjamin Grys, a graduate student in molecular genetics and a co-author on the study. Dubbed DeepLoc, the algorithm can recognize patterns in the cell made by proteins better and much faster than the human eye or previous computer vision-based approaches. In the cover story of the latest issue of Molecular Systems Biology , teams led by Professors Brenda Andrews and Charles Boone of the Donnelly Centre and the Department of Molecular Genetics, also describe DeepLoc's ability to process images from other labs, illustrating its potential for wider use. From self-driving cars to computers that can diagnose cancer, artificial intelligence (AI) is shaping the world in ways that are hard to predict, but for cell biologists, the change could not come soon enough. Thanks to new and fully automated microscopes, scientists can collect reams of data faster than they can analyze it. "Right now, it only takes days to weeks to acquire images of cells and months to years to analyze them. Deep learning will ultimately bring the timescale of this analysis down to the same timescale as the experiments," says Oren Kraus, a lead co-author on the paper and a graduate student co-supervised by Andrews and Professor Brendan Frey of the Donnelly Centre and the Department of Electrical and Computer Engineering. Andrews, Boone and Frey are also Senior Fellows at the Canadian Institute for Advanced Research. Similar to other types of AI, in which computers learn to recognize patterns in data, DeepLoc was trained to recognize diverse shapes made by glowing proteins -- labeled a fluorescent tag that makes them visible--in cells. But unlike computer vision that requires detailed instructions, DeepLoc learns directly from image pixel data, making it more accurate and faster. Grys and Kraus trained DeepLoc on the teams' previously published data that shows an area in the cell occupied by more than 4,000 yeast proteins--three quarters of all proteins in yeast. This dataset remains the most complete map showing exact position for a vast majority of proteins in any cell. When it was first released in 2015, the analysis was done with a complex computer vision and machine learning pipeline that took months to complete. DeepLoc crunched the data in a matter of hours. DeepLoc was able to spot subtle differences between similar images. The initial analysis identified 15 different classes of proteins, each representing distinct neighbourhoods in the cell; DeepLoc identified 22 classes. It was also able to sort cells whose shape changed due to a hormone treatment, a task that the previous pipeline couldn't complete. Grys and Kraus were able to quickly retrain DeepLoc with images that differed from the original training set, showing that it can be used to process data from other labs. They hope that others in the field, where looking at images by eye is still the norm, will adopt their method. "Someone with some coding experience could implement our method. All they would have to do is feed in the image training set that we've provided and supplement this with their own data. It takes only an hour or less to retrain DeepLoc and then begin your analysis," says Grys. In addition to sharing DeepLoc with the research community, Kraus is working with Jimmy Ba to commercialize the method through a new start-up, Phenomic AI. Ba is a graduate student of AI pioneer Geoffrey Hinton, a retired U of T professor and Chief Scientific Adviser of the newly established Vector Institute. Their goal is to analyse cell image-based data for pharmaceutical companies. "In an image based drug screen, you can actually figure out how the drugs are affecting different cells based on how they look rather than some simplified parameters such as live/dead or cell size. This way you can extract a lot more information about cell state form these screens. We hope to make the early drug discovery process all the more accurate by finding more subtle effects of chemical compounds," says Kraus.


News Article | April 26, 2017
Site: www.eurekalert.org

Scientists believe that schizophrenia, a disorder caused by an imbalance in the brain's chemical reactions, is triggered by a genetic interaction with environmental factors. A new Tel Aviv University study published in Human Molecular Genetics now points to cannabis as a trigger for schizophrenia. The research, conducted by Dr. Ran Barzilay and led by Prof. Dani Offen, both of TAU's Sackler School of Medicine, finds that smoking pot or using cannabis in other ways during adolescence may serve as a catalyst for schizophrenia in individuals already susceptible to the disorder. "Our research demonstrates that cannabis has a differential risk on susceptible versus non-susceptible individuals," said Dr. Barzilay, principal investigator of the study. "In other words, young people with a genetic susceptibility to schizophrenia -- those who have psychiatric disorders in their families -- should bear in mind that they're playing with fire if they smoke pot during adolescence." The research team included Prof. Inna Slutsky and Hadar Segal-Gavish, both of TAU's Sackler School of Medicine, and Prof. Abraham Weizman of Geha Medical Health Center and Prof. Akira Sawa of Johns Hopkins Medical Center. Researchers exposed mouse models with a genetic susceptibility to schizophrenia -- the mutant DISC-1 gene -- to THC, the psychoactive compound in cannabis. During a time period similar to that of human adolescence, the susceptible mice were found to be at a far higher risk for lasting brain defects associated with the onset of schizophrenia. Four categories of mice were used in the experiment: Genetically susceptible and exposed to cannabis; genetically susceptible and not exposed to cannabis; genetically intact and exposed to cannabis; and, finally, genetically intact and not exposed to cannabis. Only the genetically susceptible mice developed behavioral and biochemical brain pathologies related to schizophrenia after being exposed to cannabis, behavioral tests and neurological biochemical analyses revealed. "The study was conducted on mice but it mimics a clinical picture of 'first episode' schizophrenia, which presents during adolescence in proximity to robust cannabis use," said Dr. Barzilay, a child and adolescent psychiatrist. The researchers also discovered the mechanism through which the cannabis and the specific gene interact. "A protective mechanism was observed in the non-susceptible mice," said Prof. Offen. "This mechanism involves the upregulation of a protective neurotrophic factor, BDNF, in the hippocampus. We showed in the study that if we artificially deliver BDNF to the genetically susceptible mice, they could be protected from the deleterious effect of THC during adolescence. "This research clearly has implications in terms of public health," Prof. Offen concluded. "The novel protective mechanism identified in the study may serve as a basis for the future development of compounds capable of attenuating the deleterious effect of cannabis on brain development. However, until that time, it is important that young people at risk for psychiatric disorders (i.e., have psychiatric disorders in their family or have reacted strongly to drugs in the past) should be particularly cautious with cannabis use during adolescence." American Friends of Tel Aviv University supports Israel's most influential, comprehensive, and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. For three years in a row, TAU ranked 9th in the world, and first in Israel, for alumni going on to become successful entrepreneurs backed by significant venture capital, a ranking that surpassed several Ivy League universities. To date, 2,400 patents have been filed out of the University, making TAU 29th in the world for patents among academic institutions.


News Article | May 2, 2017
Site: phys.org

"We can learn so much by looking at images of cells: how does the protein look under normal conditions and do they look different in cells that carry genetic mutations or when we expose cells to drugs or other chemical reagents? People have tried to manually assess what's going on with their data but that takes a lot of time," says Benjamin Grys, a graduate student in molecular genetics and a co-author on the study. Dubbed DeepLoc, the algorithm can recognize patterns in the cell made by proteins better and much faster than the human eye or previous computer vision-based approaches. In the cover story of the latest issue of Molecular Systems Biology , teams led by Professors Brenda Andrews and Charles Boone of the Donnelly Centre and the Department of Molecular Genetics, also describe DeepLoc's ability to process images from other labs, illustrating its potential for wider use. From self-driving cars to computers that can diagnose cancer, artificial intelligence (AI) is shaping the world in ways that are hard to predict, but for cell biologists, the change could not come soon enough. Thanks to new and fully automated microscopes, scientists can collect reams of data faster than they can analyze it. "Right now, it only takes days to weeks to acquire images of cells and months to years to analyze them. Deep learning will ultimately bring the timescale of this analysis down to the same timescale as the experiments," says Oren Kraus, a lead co-author on the paper and a graduate student co-supervised by Andrews and Professor Brendan Frey of the Donnelly Centre and the Department of Electrical and Computer Engineering. Andrews, Boone and Frey are also Senior Fellows at the Canadian Institute for Advanced Research. Similar to other types of AI, in which computers learn to recognize patterns in data, DeepLoc was trained to recognize diverse shapes made by glowing proteins—labeled a fluorescent tag that makes them visible—in cells. But unlike computer vision that requires detailed instructions, DeepLoc learns directly from image pixel data, making it more accurate and faster. Grys and Kraus trained DeepLoc on the teams' previously published data that shows an area in the cell occupied by more than 4,000 yeast proteins—three quarters of all proteins in yeast. This dataset remains the most complete map showing exact position for a vast majority of proteins in any cell. When it was first released in 2015, the analysis was done with a complex computer vision and machine learning pipeline that took months to complete. DeepLoc crunched the data in a matter of hours. DeepLoc was able to spot subtle differences between similar images. The initial analysis identified 15 different classes of proteins, each representing distinct neighbourhoods in the cell; DeepLoc identified 22 classes. It was also able to sort cells whose shape changed due to a hormone treatment, a task that the previous pipeline couldn't complete. Grys and Kraus were able to quickly retrain DeepLoc with images that differed from the original training set, showing that it can be used to process data from other labs. They hope that others in the field, where looking at images by eye is still the norm, will adopt their method. "Someone with some coding experience could implement our method. All they would have to do is feed in the image training set that we've provided and supplement this with their own data. It takes only an hour or less to retrain DeepLoc and then begin your analysis," says Grys. In addition to sharing DeepLoc with the research community, Kraus is working with Jimmy Ba to commercialize the method through a new start-up, Phenomic AI. Ba is a graduate student of AI pioneer Geoffrey Hinton, a retired U of T professor and Chief Scientific Adviser of the newly established Vector Institute. Their goal is to analyse cell image-based data for pharmaceutical companies. "In an image based drug screen, you can actually figure out how the drugs are affecting different cells based on how they look rather than some simplified parameters such as live/dead or cell size. This way you can extract a lot more information about cell state form these screens. We hope to make the early drug discovery process all the more accurate by finding more subtle effects of chemical compounds," says Kraus. Explore further: New map uncovers the traffic of life in a cell More information: Oren Z Kraus et al. Automated analysis of high‐content microscopy data with deep learning, Molecular Systems Biology (2017). DOI: 10.15252/msb.20177551


News Article | April 20, 2017
Site: www.eurekalert.org

Colonization by the human and animal parasite, Giardia, changed the species composition of the mouse microbiome in a way that might be harmful. The research is published in Infection and Immunity, a journal of the American Society for Microbiology. "This shift is generally characterized by more aerobic bacteria and less diversity of anaerobic species in the gastrointestinal tract," said coauthor Scott C. Dawson, Associate Professor of Microbiology and Molecular Genetics, the University of California, Davis. "This suggests that Giardia infection could--at least in part--be an ecological disease, with parasite colonization disrupting the previously stable ecology of the gut." Indeed, "We found changes in the host microbial community throughout the entire gastrointestinal tract," said Dawson. These findings challenge the conventional wisdom that Giardia is a disease of the small intestine. "We infected mice with Giardia, sacrificed them at different times post-infection, and sequenced specific regions throughout the entire gastrointestinal tract using high-throughput 16S ribosomal RNA sequencing," said Dawson. This enabled the investigators to quantify the shifts in microbial diversity in each part of the GI tract, following infection. They also pre-treated one cohort of mice with antibiotics, to determine if that pretreatment resulted in different shifts in the microbiome as compared to those in mice not receiving antibiotics (it did so). The various investigators had different motives for their interest in conducting this research, said Dawson. Steven M. Singer, of Georgetown University, Washington, DC, had previously noted that when mice were infected with a human Giardia, they had to be pre-treated with antibiotics in order for a robust infection to develop. "That suggested that the gut microbiome had a protective effect in limiting giardiasis," said Dawson. Furthermore, giardiasis is a major cause of sickness and malnutrition in developing nations, said Dawson, infecting an estimated 200 million in Africa, Asia, and Latin America, "often infecting children in communities without access to clean water. In the US, more than 15,000 cases were reported in 2012. "While symptoms can be severe or even debilitating, the mechanism by which Giardia infection causes the disease symptoms remains unclear," said Dawson. "As an anaerobic, fermenting, eukaryotic parasite, we reasoned that Giardia's unique anaerobic metabolism may disturb host gut ecology." (Eukaryotes are all organisms with cells that contain a nucleus, from microbes to plants to vertebrates. Prokaryotes, mostly bacteria, have much simpler cells, which lack a nucleus.) Partly as a result of the unknown mechanism, there are few novel therapeutics, said Dawson. Moreover, even when treatment eradicates the parasite, GI symptoms may persist. The American Society for Microbiology is the largest single life science society, composed of over 48,000 scientists and health professionals. ASM's mission is to promote and advance the microbial sciences. ASM advances the microbial sciences through conferences, publications, certifications and educational opportunities. It enhances laboratory capacity around the globe through training and resources. It provides a network for scientists in academia, industry and clinical settings. Additionally, ASM promotes a deeper understanding of the microbial sciences to diverse audiences.


News Article | May 1, 2017
Site: www.eurekalert.org

EAST LANSING, Mich. - Mice have been and will continue to be good base models for human medicinal advances. However, their size and some of their physiological differences leave them lacking in important areas of human medicine, including neurological and reproductive research. In a study led by Michigan State University, scientists have shown that gene editing using CRISPR/Cas9 technology can be quite effective in rhesus monkey embryos ¬- the first time this has been demonstrated in the U.S. The results, published in the current issue of Human Molecular Genetics, open the door for pursuing gene editing in nonhuman primates as models for new therapies, including pharmacological, gene- and stem cell-based therapies, said Keith Latham, MSU animal science professor and lead author of the study. "Our paper is the first in the U.S. to publish on the use of this technology in nonhuman primate embryos," he said. "Using nonhuman primate embryos is important because the closer we can approximate the human condition in the animal model, the better the chances of developing successful treatments as well as limiting risks that may be encountered in clinical trials." While mice are mammals, they bear litters rather than individual offspring. Their anatomy and physiology differ in many respects from humans. While many advances in understanding diseases have been made first using mouse models, making the leap from a successful mouse study to clinical trials can be difficult or impossible for some areas of research. "If scientists want to test drugs for dementia, Alzheimer's or autism, ideal models would react similarly to humans in regards to the reduction of symptoms, outbreak of side effects, such as enduring the same lesions as humans do, or exhibiting similar behavioral characteristics," said Latham, who's with the College of Agriculture and Natural Resources and an MSU AgBioResearch scientist. "Nonhuman primates are much better models for such diseases. And in terms of some surgical procedures, implants, developing prosthetics, or other therapies, nonhuman primates can prove better suited than rodents." CRISPR has opened the door to do gene editing in many species other than mice. Developing this technology in nonhuman primates in the U.S. would allow more scientists in this country to incorporate these models into their research, he added. The advances will allow scientists to move forward and tackle some of the technical barriers related to the research. Other issues that may be later resolved are the commitment to increased costs and longer waiting times when using nonhuman primates. Fruit flies, often used in genetic studies, reproduce in two weeks. Rodents, with pre-disposed genetic characteristics, can be easily ordered and shipped to laboratories within days. Committing to raising nonhuman primates can cost around $15,000 and can take as long as 4-6 years to have a mature monkey with the desired genetic characteristics. The high-efficiency of gene editing that scientists are now able to achieve makes it worth the cost and the wait, Latham said. To conduct the research, Latham partnered with the California National Primate Research Center, where the monkey embryos were produced, in collaboration with his co-investigator Dr. Catherine VandeVoort, an expert in nonhuman primate reproduction. Dr. Daniel Bauer, at Harvard Medical School, Boston Children's Hospital and Dana-Farber Cancer Institute also collaborated on the study. The resources offered by the CNPRC were crucial for this work, Latham said. "Extreme amounts of care go into maintaining the well-being of the monkeys," he said. "They follow strict protocols to ensure this is a priority. So being able to conduct the science here at Michigan State while partnering with the center is the best combination of science and animal welfare." Additional MSU scientists contributing to the study include Uros Midic, Kailey Vincent and Benjamin Goheen. This research was funded by the National Institutes of Health, MSU AgBioResearch, MSU, the National Institute of Diabetes and Digestive and Kidney Disease, the Burroughs Wellcome Fund, American Society of Hematology, Charles H. Hood Foundation and Cooley's Anemia Foundation. Michigan State University has been working to advance the common good in uncommon ways for more than 150 years. One of the top research universities in the world, MSU focuses its vast resources on creating solutions to some of the world's most pressing challenges, while providing life-changing opportunities to a diverse and inclusive academic community through more than 200 programs of study in 17 degree-granting colleges. For MSU news on the Web, go to MSUToday. Follow MSU News on Twitter at twitter.com/MSUnews.


The International Association of HealthCare Professionals is pleased to welcome Dr. Jerrod Hendry, BS, MS, MD, CCFP(EM) to their prestigious organization with his upcoming publication in The Leading Physicians of the World. Dr. Jerrod Hendry is a highly trained and qualified physician with a vast expertise in all facets of his work, especially family medicine and emergency medicine. Dr. Jerrod Hendry has been in practice for more than 15 years, and is currently serving patients as an Emergency Room Physician at Peace Arch Hospital in White Rock, British Columbia. Dr. Jerrod Hendry’s career in medicine began in 2001 when he graduated with his Medical Degree from the University of British Columbia, where he earlier gained a Master of Science Degree in Molecular Genetics. He then went on to serve his Emergency Medicine residency at McGill University. Dr. Hendry is double board certified by the American Board of Emergency Medicine and the American Board of Family Medicine. To keep up to date with the latest advances and developments in his field, he remains a distinguished member of the Canadian Association of Emergency Physicians, and the College of Family Physicians of Canada. Dr. Hendry attributes his success to his love for emergency medicine, as well as his drive to make a difference. When he is not assisting his patients, Dr. Hendry enjoys traveling, swimming, and hockey. Learn more about Dr. Hendry by reading his upcoming publication in The Leading Physicians of the World. FindaTopDoc.com is a hub for all things medicine, featuring detailed descriptions of medical professionals across all areas of expertise, and information on thousands of healthcare topics.  Each month, millions of patients use FindaTopDoc to find a doctor nearby and instantly book an appointment online or create a review.  FindaTopDoc.com features each doctor’s full professional biography highlighting their achievements, experience, patient reviews and areas of expertise.  A leading provider of valuable health information that helps empower patient and doctor alike, FindaTopDoc enables readers to live a happier and healthier life.  For more information about FindaTopDoc, visit http://www.findatopdoc.com


News Article | February 23, 2017
Site: phys.org

The discovery, published on February 23, 2017 in the journal Cell, reveals new details about the evolution of sex. The protein acts as a nearly universal, biochemical "key" that enables two cell membranes to become one, resulting in the combination of genetic material—a necessary step for sexual reproduction. New details about the protein's function could help fight parasitic diseases, such as malaria, and boost efforts to control insect pests. "Our findings show that nature has a limited number of ways it can cause cells to fuse together into a single cell," said William Snell, a senior author of the study and a research professor in the University of Maryland Department of Cell Biology and Molecular Genetics. Snell joined UMD in June 2016, but performed the majority of the work at his previous institution, the University of Texas Southwestern Medical Center. "A protein that first made sex possible—and is still used for sexual reproduction in many of Earth's organisms—is identical to the protein used by dengue and Zika viruses to enter human cells," Snell said. "This protein must have really put the spice in the primordial soup." Snell and his colleagues studied the protein, called HAP2, in the single-celled green alga Chlamydomonas reinhardtii. HAP2 is common among single-celled protozoans, plants and arthropods—although it is not found in fungi or vertebrates such as humans. Prior results from Snell and his collaborators, as well as other research groups, indicated that HAP2 is necessary for sex cell fusion in the organisms that possess the protein. But the precise mechanism remained unclear. For the current study, Snell and his colleagues at UT Southwestern used sophisticated computer analysis tools to compare the amino acid sequence of Chlamydomonas HAP2 with that of known viral fusion proteins. The results suggested a striking degree of similarity, especially in a region called the "fusion loop" that enables the viral proteins to successfully invade a cell. If HAP2 functioned like a viral fusion protein, Snell reasoned, then disrupting HAP2's fusion loop should block its ability to fuse sex cells. Sure enough, when Snell's team changed just a single amino acid in the fusion loop of Chlamydomonas HAP2, the protein entirely lost its function. The sex cells were able to stick together—a process that depends on other proteins—but they were not able to complete the final fusion of their cell membranes. Similarly, the cells could not fuse when the researchers introduced an antibody that covered up the HAP2 fusion loop. "We were thrilled with these results, because they supported our new model of HAP2 function," Snell said. "But we needed to visualize the three-dimensional structure of the HAP2 protein to be sure it was similar to viral fusion proteins." Snell reached out to Felix Rey, a structural biologist at the Pasteur Institute in Paris who specializes in viruses. Coincidentally, Rey and his colleagues had just determined the structure of Chlamydomonas HAP2 using X-ray crystallography. Rey's results demonstrated that, indeed, HAP2 was functionally identical to dengue and Zika viral fusion proteins. "The HAP2 protein from Chlamydomonas is folded in an identical fashion to the viral proteins," Rey said, referring to the molecular folding that creates the three-dimensional structure of all proteins from a simple chain of amino acids. "The resemblance is unmistakable." HAP2 appears to be necessary for cell fusion in a wide variety of organisms, including disease-causing protozoans, invasive plants and destructive insect pests. So far, every known version of HAP2 shares the one critical amino acid in the fusion loop region. As such, HAP2 could provide a promising target for vaccines, therapies and other control methods. Snell is particularly encouraged by the possibility of controlling malaria, which is caused by the single-celled protozoan Plasmodium falciparum. "Developing a vaccine that blocks the fusion of Plasmodium sex cells would be a huge step forward," Snell said, noting that Plasmodium has a complex life cycle that depends on both mosquito and human hosts. "Our findings strongly suggest new strategies to target Plasmodium HAP2 that could disrupt the mosquito-borne stage of the Plasmodium life cycle." Explore further: Sperm-egg fusion proteins have same structure as those used by Zika and other viruses More information: The research paper, "The ancient gamete fusogen HAP2 is a eukaryotic class II fusion protein," Juliette Fedry, Yanjie Liu, Gerard Péhau-Arnaudet, Jimin Pei, Wenhao Li, M. Alejandra Tortorici, Francois Traincard, Annalisa Meola, Gerard Bricogne, Nick Grishin, William J. Snell, Félix A. Rey and Thomas Krey, was published February 23, 2017 in the journal Cell.


News Article | February 23, 2017
Site: www.eurekalert.org

Researchers determine that a protein required for sperm-egg fusion is identical to a protein viruses use to invade host cells; discovery could help fight parasitic diseases like malaria Sexual reproduction and viral infections actually have a lot in common. According to new research, both processes rely on a single protein that enables the seamless fusion of two cells, such as a sperm cell and egg cell, or the fusion of a virus with a cell membrane. The protein is widespread among viruses, single-celled protozoans, and many plants and arthropods, suggesting that the protein evolved very early in the history of life on Earth. The discovery, published on February 23, 2017 in the journal Cell, reveals new details about the evolution of sex. The protein acts as a nearly universal, biochemical "key" that enables two cell membranes to become one, resulting in the combination of genetic material--a necessary step for sexual reproduction. New details about the protein's function could help fight parasitic diseases, such as malaria, and boost efforts to control insect pests. "Our findings show that nature has a limited number of ways it can cause cells to fuse together into a single cell," said William Snell, a senior author of the study and a research professor in the University of Maryland Department of Cell Biology and Molecular Genetics. Snell joined UMD in June 2016, but performed the majority of the work at his previous institution, the University of Texas Southwestern Medical Center. "A protein that first made sex possible -- and is still used for sexual reproduction in many of Earth's organisms -- is identical to the protein used by dengue and Zika viruses to enter human cells," Snell said. "This protein must have really put the spice in the primordial soup." Snell and his colleagues studied the protein, called HAP2, in the single-celled green alga Chlamydomonas reinhardtii. HAP2 is common among single-celled protozoans, plants and arthropods -- although it is not found in fungi or vertebrates such as humans. Prior results from Snell and his collaborators, as well as other research groups, indicated that HAP2 is necessary for sex cell fusion in the organisms that possess the protein. But the precise mechanism remained unclear. For the current study, Snell and his colleagues at UT Southwestern used sophisticated computer analysis tools to compare the amino acid sequence of Chlamydomonas HAP2 with that of known viral fusion proteins. The results suggested a striking degree of similarity, especially in a region called the "fusion loop" that enables the viral proteins to successfully invade a cell. If HAP2 functioned like a viral fusion protein, Snell reasoned, then disrupting HAP2's fusion loop should block its ability to fuse sex cells. Sure enough, when Snell's team changed just a single amino acid in the fusion loop of Chlamydomonas HAP2, the protein entirely lost its function. The sex cells were able to stick together -- a process that depends on other proteins--but they were not able to complete the final fusion of their cell membranes. Similarly, the cells could not fuse when the researchers introduced an antibody that covered up the HAP2 fusion loop. "We were thrilled with these results, because they supported our new model of HAP2 function," Snell said. "But we needed to visualize the three-dimensional structure of the HAP2 protein to be sure it was similar to viral fusion proteins." Snell reached out to Felix Rey, a structural biologist at the Pasteur Institute in Paris who specializes in viruses. Coincidentally, Rey and his colleagues had just determined the structure of Chlamydomonas HAP2 using X-ray crystallography. Rey's results demonstrated that, indeed, HAP2 was functionally identical to dengue and Zika viral fusion proteins. "The HAP2 protein from Chlamydomonas is folded in an identical fashion to the viral proteins," Rey said, referring to the molecular folding that creates the three-dimensional structure of all proteins from a simple chain of amino acids. "The resemblance is unmistakable." HAP2 appears to be necessary for cell fusion in a wide variety of organisms, including disease-causing protozoans, invasive plants and destructive insect pests. So far, every known version of HAP2 shares the one critical amino acid in the fusion loop region. As such, HAP2 could provide a promising target for vaccines, therapies and other control methods. Snell is particularly encouraged by the possibility of controlling malaria, which is caused by the single-celled protozoan Plasmodium falciparum. "Developing a vaccine that blocks the fusion of Plasmodium sex cells would be a huge step forward," Snell said, noting that Plasmodium has a complex life cycle that depends on both mosquito and human hosts. "Our findings strongly suggest new strategies to target Plasmodium HAP2 that could disrupt the mosquito-borne stage of the Plasmodium life cycle." In addition to Snell and Rey, co-authors of the study include: Juliette Fedry, Gerard Péhau-Arnaudet, M. Alejandra Tortorici, Francois Traincard and Annalisa Meola (Pasteur Institute); Yanjie Liu, Jimin Pei, Wenhao Li and Nick Grishin (UT Southwestern); Gerard Bricogne (Global Phasing, Ltd.); and Thomas Krey (Pasteur Institute, Hannover Medical School and German Center for Infection Research). The research paper, "The ancient gamete fusogen HAP2 is a eukaryotic class II fusion protein," Juliette Fedry, Yanjie Liu, Gerard Péhau-Arnaudet, Jimin Pei, Wenhao Li, M. Alejandra Tortorici, Francois Traincard, Annalisa Meola, Gerard Bricogne, Nick Grishin, William J. Snell, Félix A. Rey and Thomas Krey, was published February 23, 2017 in the journal Cell. This work was supported by the United States National Institutes of Health (Award Nos. GM56778 and GM094575), the Welch Foundation (Award No. I-1505), the European Research Council, the Pasteur Institute and the French National Center for Scientific Research. The content of this article does not necessarily reflect the views of these organizations. University of Maryland College of Computer, Mathematical, and Natural Sciences 2300 Symons Hall College Park, MD 20742 http://www. @UMDscience About the College of Computer, Mathematical, and Natural Sciences The College of Computer, Mathematical, and Natural Sciences at the University of Maryland educates more than 7,000 future scientific leaders in its undergraduate and graduate programs each year. The college's 10 departments and more than a dozen interdisciplinary research centers foster scientific discovery with annual sponsored research funding exceeding $150 million.


TORONTO, ON--(Marketwired - February 08, 2017) - Next generation sequencing (NGS) based clinical genomics assays are increasingly being offered by laboratories worldwide across a wide range of disease areas, including cancer, reproductive health, inherited disease and infectious disease. Developing, optimizing, and monitoring such assays however can be a time consuming and challenging task. Scientists and clinicians can build and implement robust and accurate clinical genomics assays with the help of highly multiplexed and patient-like reference materials. Join industry expert Sandi Deans, Consultant Clinical Scientist and Director of UK National External Quality Assessment Service (UK NEQAS) for Molecular Genetics as she discusses a case study of how a global external quality assessment (EQA) organization is using these reference materials to ensure the accuracy and consistency of one such clinical genomics application in non-invasive prenatal testing (NIPT). The live broadcast takes place on Wednesday, March 1, 2017 at 1pm EST. For more information or to register for this complimentary event, visit: Enabling Precision Medicine with Highly Multiplexed and Patient-like Reference Materials Xtalks, powered by Honeycomb Worldwide Inc., is a leading provider of educational webinars to the global Life Sciences community. Every year thousands of industry practitioners (from pharmaceutical & biotech companies, private & academic research institutions, healthcare centers, etc.) turn to Xtalks for access to quality content. Xtalks helps Life Science professionals stay current with industry developments, trends and regulations. Xtalks webinars also provide perspectives on key issues from top industry thought leaders and service providers. To learn more about Xtalks visit http://xtalks.com For information about hosting a webinar visit http://xtalks.com/sponsorship.ashx


Researchers from University of Southern California, Interventional Pain Institute, and Proove Biosciences Publish Clinical Utility Study Supporting Precision Medicine in Pain Perception IRVINE, CA--(Marketwired - Feb 13, 2017) -  Proove Biosciences, Inc., the Healthcare Decision Company™, is pleased to announce the publication of a clinical study supporting the clinical utility of Proove Pain Perception® Profile in the latest edition of the peer-reviewed Journal of Psychiatric Research. In the study entitled, An observational study of the impact of genetic testing for pain perception in the clinical management of chronic non-cancer pain, researchers from the University of Southern California Keck School of Medicine in Los Angeles, Interventional Pain Institute in Baltimore, and Proove Biosciences published findings which demonstrate how clinicians use Proove Pain Perception to improve clinical outcomes for patients. Adding to the voluminous clinical validity evidence supporting Proove Pain Perception that is published in marquee peer-reviewed journals such as Human Molecular Genetics, Science, and Pain, this clinical utility study demonstrates the impact of physician decision-making and patient outcomes using this technology. "It is gratifying to see Proove's collaborative efforts gain acceptance among our vast community of discerning peers," says Dr. Maneesh Sharma, lead author of the study, Medical Director of the Interventional Pain Institute and member of Proove's Medical Advisory Board. "Proove is committed to uncovering the best treatment options for pain patients, and through this study, we hope to advance the adoption of precision medicine solutions in clinical settings to reduce the burden of chronic pain and prescription opioid abuse. We are grateful to our colleagues and to the Journal of Psychiatric Research for their recognition of our findings." Proove Pain Perception® Profile provides an objective measure of pain perception based, in part, on genetic markers in the catechol-O-methyltransferase (COMT) gene. The proprietary haplotype algorithm characterizing this gene was invented by NIH-funded scientists at the University of North Carolina at Chapel Hill, and the exclusive rights to this intellectual property was licensed to Proove Biosciences. In this study, authors found that using Proove Pain Perception substantially affected physician clinical decision-making and that the availability and utilization of this information was a contributing factor in clinical improvement. These findings demonstrate the clinical utility and actionability of the already clinically-validated algorithm behind the Proove Pain Perception Profile. "With opioid abuse and deaths from overdose at an all-time high as a result of mismanaged or misunderstood chronic pain, we have no doubt that these innovative treatment solutions may soon be the go-to option for thousands of doctors, surgeons and hospitals," adds Sharma. Since launching in 2009, Proove Biosciences has become the commercial and educational leader in the research, investigation and development of patent-protected tests that combine genetic and clinical data into reports to help physicians individualize -- and optimize -- medicine selection and dosing. Proove is backed by science, driven by data and supported by an advisory board of the world's leading medical experts. Its patented bioinformatics platform for collecting, storing, analyzing and integrating biological and genetic information, is changing the future of healthcare. "Over the past 5 years, Proove has been conducting a number of multi-center studies involving prospective outcomes of thousands of patients," explained Dr. Svetlana Kantorovich, Director of Research & Development at Proove. "Through these large studies, we look forward to many more publications in peer-reviewed journals providing continued evidence of the accuracy and positive impact of Proove's precision medicine technology." To learn more about Proove Biosciences, visit www.proove.com. With media inquiries, please contact Leslie Licano at leslie@beyondfifteen.com or (949)-733-8679. About Proove Biosciences: Proove Biosciences -- the Healthcare Decision Company™ -- is the commercial and educational leader in the research, investigation and development of patent-protected tests that combine genetic and clinical data into reports to help physicians to individualize -- and optimize -- medicine selection and dosing. Supported by leading medical experts and institutions across the globe, the reports facilitate objective decision-making to improve outcomes for patients, providers and insurers. Backed by science and driven by data, Proove is revolutionizing individualized medicine. With a patented bioinformatics platform that delivers therapy-defining information that allows prescribers to evaluate pain tolerance, assess patient drug metabolism, predict response and immunity to opioid and non-opioid pain medication, and identify risk for dependence and addiction, Proove provides the most technologically advanced solutions to enable accurate and evidence-based medical decision-making rather than "trial-and-error" approaches. Proove helps reduce the risk of treatment failure, decrease costs to insurers and relieve society of the emotional and financial burdens associated with addiction and other avoidable consequences. For more information, please visit www.proove.com or call toll free 855-PROOVE-BIO (855-776-6832).

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