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  • richardmitnick 11:50 am on June 9, 2016 Permalink | Reply
    Tags: , , , Tarantula Toxins Offer Key Insights Into Neuroscience of Pain   

    From Kavli: “Tarantula Toxins Offer Key Insights Into Neuroscience of Pain” 

    KavliFoundation

    The Kavli Foundation

    06/08/2016
    Nicholas Weiler, UCSF June 06, 2016

    Toxins Extracted from Ornamental Baboon Tarantula May Be Used as Tools to Study Disorders Ranging from Irritable Bowel Syndrome to Epilepsy.

    1
    A Heteroscodra maculata, a West African tarantula.

    When your dentist injects lidocaine into your gums, the drug blocks the pain of the oncoming drill, but it also blocks all other sensation – leaving your mouth feeling numb and swollen. What if there were a drug that could specifically block pain, but leave the rest of your sensations alone? In order to do this, you would need to find a way to control the cohort of nerve fibers that transmit the specific type of pain you would like to block.

    A research team led by UC San Francisco scientists has discovered molecules that may help researchers do just that: two toxins isolated from the venom of Heteroscodra maculata, a West African tarantula the size of your hand (commonly referred to as the “ornamental baboon” or “Togo starburst” tarantula). This spider’s massive fangs deliver a poison that causes excruciating pain in part by triggering a specific kind of sodium channel within A-delta nerve fibers, according to the new research.

    The study was led by researchers in the lab of David Julius, PhD, Chair of the Department of Physiology at UCSF, and was published June 6, 2016 in the journal Nature.

    The researchers are excited about this finding for two equally important reasons: for opening a new chapter in our understanding of pain, and because the new toxins can now be used as a highly selective tool for manipulating this type of sodium channel, which also has been implicated in neurological disorders unrelated to pain, from epilepsy to autism to Alzheimer’s disease.

    “It’s a good problem to have,” said Jeremiah Osteen, PhD, the postdoctoral fellow in Julius’s group who led the research team. “We didn’t know which of the two findings we should be more excited about.”

    Poisonous Creatures Reveal Tools for Pain, Neurological Research

    Julius’s lab – which is renowned for the discovery and characterization of the so-called “wasabi receptor” – has recently been working to identify new pain pathways by screening more than a hundred different venoms from poisonous spiders, scorpions, and centipedes — sourced from the collection of co-author Glenn F. King, PhD, of the University of Queensland in Australia — all of which have evolved chemical defenses that target the biology of animals’ pain nerves.

    “There are dozens to hundreds of different active peptides in each animal’s venom,” said Julius, who is a member of the Kavli Institute for Fundamental Neuroscience at UCSF. “The deeper you look the more toxins there seem to be.”

    The Togo starburst tarantula’s venom struck them as being particularly interesting because it appeared to activate a particular type of sodium channel within sensory nerves that was not a part of known pain pathways.

    To identify which of the dozens of chemicals that made up the tarantula’s venom were specifically targeting these channels, the researchers separated the venom and applied the components one-by-one to rodent sensory neurons in a lab dish. They found two peptide molecules that specifically and powerfully activated these sensory nerves, and experiments with lab-synthesized versions of the same molecules confirmed that these chemicals could activate pain-sensing neurons on their own.

    Experiments with an array of different drugs that block candidate receptor molecules demonstrated that the two toxins specifically bind to and demonstrated that this particular receptor is indeed found on A-delta nerves in mice.

    The accepted notion is that A-delta fibers may convey the sharp, immediate shock of a burn or a cut, ahead of the burning throb conveyed by slower C fibers. The newly discovered tarantula peptides allowed the researchers to isolate A-delta fibers in mice, and show that they also appear to play a role in touch hypersensitivity – when normally innocuous light touch causes discomfort – a type of pain common to diseases like shingles and many chronic pain syndromes.

    Nine Subtly Different Voltage-Sensitive Sodium Channels

    Additional experiments also implicated heightened touch sensitivity of Nav1.1-expressing nerves in a mouse model of irritable bowel syndrome, suggesting these nerves, and this channel, may play a role in the chronic discomfort such patients experience.

    The pharmacological aspect of the research is also exciting for researchers because the nine subtly different voltage-sensitive sodium channels that are critical for nervous system function are extremely hard to manipulate individually. Researchers have been on a decades-long quest to find selective drugs for each subtype, so identifying two in one spider is a valuable find.

    “These channels are incredibly hard to identify drugs for because the different subtypes are closely related, making it difficult to identify drugs or other agents that act on one subtype and not another,” Julius said. “These toxins provide unique tools to start understanding exactly what this particular subtype, Nav1.1, does in terms of pain sensation.”

    The Nav1.1 subtype in particular has been implicated in the development of diseases including epilepsy, autism, and Alzheimer’s disease, and the researchers hope that in addition to helping scientists understand the biology of pain, the new discovery will lead to the development of new drugs to target these diseases.

    “These spiders had millions of years of evolution to come up with these potent and specific toxins,” Osteen said. “They’re tools one might be hard pressed to design as well in the lab.”

    Additional UCSF authors on the paper were Joshua J. Emrick, Chuchu Zhang, Xidao Wang, PhD, and Allan I. Basbaum, PhD. Please see the paper online for a full list of authors and their contributions.

    See the full article here .

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    The Kavli Foundation, based in Oxnard, California, is dedicated to the goals of advancing science for the benefit of humanity and promoting increased public understanding and support for scientists and their work.

    The Foundation’s mission is implemented through an international program of research institutes, professorships, and symposia in the fields of astrophysics, nanoscience, neuroscience, and theoretical physics as well as prizes in the fields of astrophysics, nanoscience, and neuroscience.

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  • richardmitnick 12:39 pm on June 8, 2016 Permalink | Reply
    Tags: , , , Rice study details stress-diabetes link   

    From Rice: “Rice study details stress-diabetes link” 

    Rice U bloc

    Rice University

    June 6, 2016
    Mike Williams

    Connection established between anxiety control, inflammation, Type 2 diabetes

    A Rice University study has found a link between emotional stress and diabetes, with roots in the brain’s ability to control anxiety.

    1
    Illustration by Andrea Lugo/Rice University

    That control lies with the brain’s executive functions, processes that handle attention, inhibition, working memory and cognitive flexibility and are also involved in reasoning, problem-solving and planning.

    The study published in Psychoneuroendocrinology establishes a metabolic chain reaction that starts with low inhibition, aka attention control, which leaves a person vulnerable to tempting or distracting information, objects, thoughts or activities. Previous studies have shown that such vulnerability can lead to more frequent anxiety, and anxiety is known to activate a metabolic pathway responsible for the production of pro-inflammatory cytokines, signaling proteins that include interleukin-6 (IL-6).

    Along with cognitive tests that measured attention control, the Rice study measured levels of both blood glucose and IL-6 in more than 800 adults. IL-6 is a protein the body produces to stimulate immune response and healing. It is a biomarker of acute and chronic stress that also has been associated with a greater likelihood of diabetes and high blood glucose.

    The research showed individuals with low inhibition were more likely to have diabetes than those with high inhibition due to the pathway from high anxiety to IL-6. The results were the same no matter how subjects performed on other cognitive tests, like those for memory and problem-solving.

    Researchers have suspected a link between anxiety and poor health, including diabetes, for many years but none have detailed the biological pathway responsible, said lead author Kyle Murdock, a postdoctoral research fellow in psychology. He said the Rice study takes a deeper look at how inflammation bridges the two.

    “The literature shows individuals with poor inhibition are more likely to experience stressful thoughts and have a harder time breaking their attention away from them,” Murdock said. “That made me wonder if there’s a stress-induced pathway that could link inhibition with inflammation and the diseases we’re interested in, such as diabetes.

    “Plenty of research shows that when individuals are stressed or anxious or depressed, inflammation goes up,” he said. “The novel part of our study was establishing the pathway from inhibition to anxiety to inflammation to diabetes.”

    Murdock works in the Rice lab of Christopher Fagundes, assistant professor of psychology. The Fagundes lab investigates processes that happen along the border of psychology and physiology, and how those processes affect overall health and potential treatments.

    The data came from a Midlife Development in the United States study of 1,255 middle-aged adults whose cognitive abilities were tested two years apart. More than 800 of those also underwent blood tests to check IL-6 and glucose levels. The Rice researchers found not only the positive link between inhibition and diabetes, but the absence of a link between other cognitive functions and the disease. They also determined that the pathway only went in one direction: Inflammation never appeared to affect inhibition.

    Murdock said a year as a clinical psychology intern at the Oregon Health and Science University, where he studied with co-author and psychologist Danny Duke, led the researchers to think there could also be a feedback loop at play in those with diabetes. “Individuals who are anxious are more likely to avoid treatment and use maladaptive strategies (like smoking or unhealthy diets) that enhance their blood glucose, which is problematic. It’s a snowball effect: The further they go, the worse it gets,” he said.

    “We also know that extremely high blood glucose can impact cognition as well. We talked about how, if we’re going to treat these individuals appropriately, it won’t be by sitting them down in a room and saying, ‘Hey, you need to eat better,’ or ‘You need to use your insulin on time.’”

    The researchers listed several possible interventions, including mindfulness therapy, stimulant or anti-inflammatory medications and cognitive behavioral therapy. “Research shows that people who practice mindfulness do better on the inhibition tests over time,” Murdock said, suggesting that shifting one’s attention away from stressful thoughts may affect physiological responses.

    “I’m a firm believer that mindfulness-based approaches to treatment are a great idea, for a lot of reasons,” Fagundes said. “That doesn’t mean medicines that promote inhibition, such as stimulants, shouldn’t be considered, but a combination of the two could be really helpful.”

    Co-authors of the paper are Angie LeRoy, a Rice staff member and a graduate student at the University of Houston; and Tamara Lacourt, a postdoctoral researcher, and Cobi Heijnen, a professor of symptom research at the University of Texas MD Anderson Cancer Center.

    The National Institute on Aging and the National Heart, Lung and Blood Institute supported the research.

    See the full article here .

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    In his 1912 inaugural address, Rice University president Edgar Odell Lovett set forth an ambitious vision for a great research university in Houston, Texas; one dedicated to excellence across the range of human endeavor. With this bold beginning in mind, and with Rice’s centennial approaching, it is time to ask again what we aspire to in a dynamic and shrinking world in which education and the production of knowledge will play an even greater role. What shall our vision be for Rice as we prepare for its second century, and how ought we to advance over the next decade?

    This was the fundamental question posed in the Call to Conversation, a document released to the Rice community in summer 2005. The Call to Conversation asked us to reexamine many aspects of our enterprise, from our fundamental mission and aspirations to the manner in which we define and achieve excellence. It identified the pressures of a constantly changing and increasingly competitive landscape; it asked us to assess honestly Rice’s comparative strengths and weaknesses; and it called on us to define strategic priorities for the future, an effort that will be a focus of the next phase of this process.

     
  • richardmitnick 8:39 am on June 8, 2016 Permalink | Reply
    Tags: , ,   

    From Rutgers: “Quality Challenges Persist in Antipsychotic Medication for Foster Care and Other Medicaid-Covered Children” 

    Rutgers University
    Rutgers University

    June 6, 2016
    Media Contact:
    Steve Manas
    848-932-0559
    smanas@ucm.rutgers.edu

    Some signs of progress: rapid growth in prescribing has ceased, Rutgers study finds

    1
    Photo: Ray Natos

    Significant quality challenges persist in antipsychotic medication use for children in foster care and other Medicaid-insured children, according to a new Rutgers University-New Brunswick study published in Health Affairs. Overall prescribing rates for children in foster care and other Medicaid-insured children have leveled off since a period of rapid growth in the early and mid-2000s. However, guideline-recommended practices such as use of nonpharmacological mental health services as first-line treatment, and monitoring of blood sugar and cholesterol for metabolic side effects of the medication, are frequently not followed, the research found.

    Children in foster care, whose treatment receives closer oversight than other Medicaid children, were more likely than others to receive these guideline-recommended practices, said lead author Stephen Crystal, board of governors professor and associate director for health services research at Rutgers’ Institute for Health, Health Care Policy and Aging Research. However, among children treated with antipsychotics, more than one-third of foster children, and more than two-thirds of other Medicaid children, failed to receive psychosocial mental health interventions during the three months preceding and the month following the start of antipsychotic treatment, he observed.

    “Only 28 percent of foster children, and 18 percent of other children, received metabolic monitoring for both blood glucose and serum cholesterol,” Crystal said, adding that children in foster care continue to receive antipsychotic treatment at much higher rates than other Medicaid-insured children (8.92 percent versus 1.51 percent among 0-17-year-olds in 2010).

    In their article, “Rapid Growth of Antipsychotic Prescriptions for Children Who Are Publicly Insured, But Concerns Remain,” the authors found that antipsychotic medication use peaked in 2008 among Medicaid children and 2009 among privately insured children, but levels have not returned to the pre-2000 rates.

    “The ‘new normal’ levels of prescribing represent a substantially higher rate than was seen prior to the sharp expansion of the early 2000s,” Crystal said. “Given safety concerns and uncertainties about long-term effects on brain development, encouraging judicious prescribing of antipsychotic medications for children remains a policy challenge and a priority.”

    The study used national and state-level Medicaid data, in addition to data from private health insurance. Co-authors on the paper included Thomas Mackie, Miriam Fenton, Shahla Amin, Sheree Neese-Todd, Mark Olfson and Scott Bilder.

    One of his team’s key findings was the need to continue to address antipsychotic use among children in foster care, Crystal noted. “Levels of use of antipsychotics among children in foster care were almost six times higher than in nonfoster care children in 2010. The state serves in loco parentis (“in place of the parent”) for these children. Therefore, we have additional responsibility to ensure they are receiving the most appropriate treatment,” he said.

    The study found that antipsychotics continue to be prescribed for mental disorders not indicated by the Food and Drug Administration, particularly among children in foster care. For example, in 2010, 34 percent of antipsychotic prescriptions among foster care children were for Attention Deficit Hyperactivity Disorder (ADHD), anxiety or depression, compared to 18 percent among children not in foster care. “Doctors should consider other first-line treatments for children with these diagnoses,” Crystal said.

    An encouraging finding from the study is that higher rates of psychosocial interventions and metabolic monitoring have been achieved for children in foster care than for other Medicaid-insured children. “While these findings do suggest more careful monitoring of children in foster care who are prescribed antipsychotic medication, challenges remain in increasing safety monitoring and access to psychosocial treatment,” Crystal said.

    The study identifies several promising developments that have the potential to be important tools in improving prescribing quality for antipsychotics and other psychotropic drugs for children. These include the development in specialized managed care plans for children in foster care and new national quality measures for safe and judicious prescription of antipsychotic medication.

    “Progress in a number of states that have implemented programs for oversight and quality improvement in children’s psychotropic medication use is encouraging,” said Crystal. “However, persistently high rates of antipsychotic treatment, particularly among foster children, alongside gaps in metabolic monitoring, over-reliance on use of multiple concurrent antipsychotic medications and underuse of psychosocial interventions, underscore enduring behavioral health care challenges.

    “State and federal health care policymakers have opportunities to promote meaningful improvements that bear directly on the symptoms, social function and quality of life of foster children with mental health problems, by seizing opportunities such as emerging managed care models and new treatment guidelines,” he concluded.

    See the full article here .

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    Rutgers, The State University of New Jersey, is a leading national research university and the state’s preeminent, comprehensive public institution of higher education. Rutgers is dedicated to teaching that meets the highest standards of excellence; to conducting research that breaks new ground; and to providing services, solutions, and clinical care that help individuals and the local, national, and global communities where they live.

    Founded in 1766, Rutgers teaches across the full educational spectrum: preschool to precollege; undergraduate to graduate; postdoctoral fellowships to residencies; and continuing education for professional and personal advancement.
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  • richardmitnick 8:15 pm on June 6, 2016 Permalink | Reply
    Tags: , , Observational Health Data Sciences and Informatics program,   

    From Stanford: “Gigantic datasets reveal unexpected insights into global medical treatments” 

    Stanford University Name
    Stanford University

    In a first demonstration of the power of really big data, bioinformatician Nigam Shah, MBBS, PhD, and an international team asked some simple questions about health using the electronic medical records of 250 million patients.

    The team — a multi-institution collaboration called the Observational Health Data Sciences and Informatics program, which is centered at Columbia University — came up with surprising results and likely set a record for studying the largest medical dataset ever.

    “These kinds of numbers are going to become increasingly common,” Shah told me. “Most networks like this are already in the 100-million range.”

    The current 250-million-patient, four-country study, publishing today in PNAS [Proceedings of the National Academy of Sciences], combined data from 11 sites, including the Stanford Translational Research Integrated Database Environment (2 million patients), Columbia University Medical Center (4 million patients), MarketScan Commercial Claims and Encounters (119 million patients) and General Electric Centricity (33 million patients).

    The researchers directed each of the 11 sites to pull out the treatment protocols — the ordered sequence of medications a patient was prescribed — for each patient diagnosed with hypertension, Type 2 diabetes and depression so they could map the different ways patients were being treated.

    Amazingly, 24 percent of hypertension patients received a sequence of medications that was unique. That is, thousands of patients were given a combination of medications received by no other patient.

    When I asked Shah, “How is that even possible?” he answered, “There are that many different kinds of drugs!” He was quick to add that differences in the order in which drugs were prescribed helped drive up the number of unique treatments. Still, exactly why so many hypertension patients received seemingly idiosyncratic treatment is not yet clear. The high figure might indicate a lack of agreement on the most effective treatment.

    Among the diabetes and depression patients, only 10 percent of patients received unique treatments.

    A major hurdle the team had to tackle was standardizing the way the data in different databases is handled. Shah credited the paper’s second author Patrick Ryan, PhD, with creating a way to uniformly handle data that had been generated by so many different entities. Shah compared the approach, called the common data model, to a form used for a tax return. “Everybody uses a standard form and you can have all sorts of activities going on — you know, wages, and rental properties and businesses — but you report it all in one format.”

    Since 2010, Ryan, an adjunct assistant professor at Columbia and director of epidemiology at Janssen R&D, and others have refined the common data model to the point where the team can now rapidly write computer code to querying data from hundreds of millions of patient records, Shah said.

    In their next study, Shah and the OHDSI team will examine which treatments resulted in the best outcomes for patients. And this time they hope to be looking at the full set of 650 million patient records available in the common data model.

    Assembling the data in the electronic health records of virtually everyone in the world, the researchers write, is now technically feasible.

    See the full article here .

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    Leland and Jane Stanford founded the University to “promote the public welfare by exercising an influence on behalf of humanity and civilization.” Stanford opened its doors in 1891, and more than a century later, it remains dedicated to finding solutions to the great challenges of the day and to preparing our students for leadership in today’s complex world. Stanford, is an American private research university located in Stanford, California on an 8,180-acre (3,310 ha) campus near Palo Alto. Since 1952, more than 54 Stanford faculty, staff, and alumni have won the Nobel Prize, including 19 current faculty members

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  • richardmitnick 2:05 pm on June 3, 2016 Permalink | Reply
    Tags: , , , Venom based therapies   

    From Scripps: “Harnessing Nature’s Vast Array of Venoms for Drug Discovery” 

    Scripps
    Scripps Research Institute

    June 06, 2016
    No writer credit found

    There are lessons to be learned from venoms.

    Scorpions, snakes, snails, frogs and other creatures are thought to produce tens or even hundreds of millions of distinct venoms. These venoms have been honed to strike specific targets in the body.

    For victims of a scorpion’s sting, that spells doom. For scientists, however, the potent molecules in venoms hold the potential to be adapted into medicines. But venoms are difficult to isolate and analyze using traditional methods, so only a handful have been turned into drugs.

    Now a team led by scientists at The Scripps Research Institute (TSRI) has invented a method for rapidly identifying venoms that strike a specific target in the body—and optimizing such venoms for therapeutic use.

    The researchers demonstrated the new method by using it to identify venoms that block a certain protein on T cells—a protein implicated in multiple sclerosis, rheumatoid arthritis and other inflammatory disorders. The researchers then used their method to find an optimized, long-acting variant of a venom that blocks this protein and showed that the new molecule powerfully reduces inflammation in mice.

    “Until now we haven’t had a way to seriously harness venoms’ vast therapeutic potential,” said principal investigator Richard A. Lerner, Lita Annenberg Hazen Professor of Immunochemistry at TSRI.

    The report on the advance by Lerner and his colleagues was selected as a “Hot Paper”* and cover story by the journal Angewandte Chemie.

    Choose Your Poison

    The use of venoms as therapies may seem paradoxical, since these molecules generally evolved to harm and kill other organisms. But a low dose delivered to the right place can sometimes have highly beneficial effects. The pain-killing drug ziconotide (Prialt®), for example, is derived from one of the venoms used by cone-snails to immobilize their fishy prey. Venoms also are attractive from a drug development perspective because they tend to hit their targets on cells with very high potency and selectivity.

    Drug companies would have adapted far more venoms into therapies by now, but the traditional method of determining the biological target of a venom is slow, difficult and expensive. It involves the extraction of relatively large quantities of venom from the animal species in question, followed by purification of the molecules and laborious lab-dish tests to see how they affect cells.

    The new method is geared for speed and involves the extraction only of information—with little direct involvement of venomous creatures. To start, the TSRI-led team, including first author Hongkai Zhang, a senior scientist in the Lerner laboratory, consulted animal toxin databases and assembled a list of 589 venoms whose protein sequences have features of interest. They then synthesized the venoms’ genes and inserted them into special viruses that deliver genes into cells.

    The aim in this initial, proof-of-principle project was to find venoms that block a potassium ion-channel protein known as Kv1.3. Ion channels allow charged molecules to flow in and out of cells, and are involved in a variety of essential biological functions—which makes them common targets of venoms. Kv1.3 is of special interest to the pharmaceutical industry because it appears to facilitate the proliferation and migration of T-cells that drive inflammatory disorders such as multiple sclerosis. Drugs that block Kv1.3 are already under development.

    To screen their library of venoms for those that block Kv1.3, the researchers, including a team of collaborating biologists at the Institute for Advanced Immunochemical Studies at ShanghaiTech University, used a cell-based selection system of a type developed by Lerner, Zhang and colleagues in 2012. They created a culture of special Kv1.3-containing test cells in which a strong interaction between a venom and a Kv1.3 ion channel would switch on a red fluorescence gene. The researchers distributed the venom-gene-carrying viruses among the cells and used a fast, automated system to select the cells that showed strong fluorescence. Standard molecular biology techniques were then used to identify and quantify the venom genes these cells contained. The researchers repeated this selection process for three rounds to see which venom genes became most abundant in the cells.

    In this way, the team soon identified 27 likely Kv1.3-blocking venoms. All but two turned out to be known blockers of the ion channel. Another had been reported in the literature as a suspected potassium-channel blocker, and the last, an uncharacterized scorpion venom called CllTx1, proved in subsequent traditional-method testing—using actual venom extracted from a scorpion—to be a potent Kv1.3 blocker.

    Optimal Pharmaceutical Properties

    The team realized that their selection system could be useful not only for screening libraries of natural venoms but also for screening artificial variants or “analogs” of a given venom to find those with optimal pharmaceutical properties. To demonstrate, they generated about a million analogs of a long-acting protein based on ShK, a sea anemone toxin that blocks Kv1.3, and put the analogs through three rounds of selection to find the best one. The resulting candidate, S1-2, showed a strong effect not only for blocking Kv1.3 but also for reducing inflammation in a standard rodent model.

    “This analog appears to be very potent against Kv1.3 and has no off-target effects on closely related ion channels,” said Zhang.

    Zhang, Lerner and their colleagues now plan to use their method with much larger venom datasets to find more drug candidates. “We’re particularly interested in finding venoms that block sodium ion channels involved in pain,” Lerner said.

    In addition to Lerner and Zhang, co-authors of the paper, Autocrine-Based Selection of Drugs that Target Ion Channels from Combinatorial Venom Peptide Libraries, were Mingjuan Du, Xiao Liu, Jingying Sun, Wei Wang and Xiu Xin of ShanghaiTech University; Lourival D. Possani of the National Autonomous University of Mexico, who purified the scorpion toxin CllTx1 for analysis; and Jia Xie and Kyungmoo Yea of TSRI.

    Funding for the research was provided by the JPB foundation, Zebra Biologics and ShanghaiTech University.

    See the full article here .

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    The Scripps Research Institute (TSRI), one of the world’s largest, private, non-profit research organizations, stands at the forefront of basic biomedical science, a vital segment of medical research that seeks to comprehend the most fundamental processes of life. Over the last decades, the institute has established a lengthy track record of major contributions to the betterment of health and the human condition.

    The institute — which is located on campuses in La Jolla, California, and Jupiter, Florida — has become internationally recognized for its research into immunology, molecular and cellular biology, chemistry, neurosciences, autoimmune diseases, cardiovascular diseases, virology, and synthetic vaccine development. Particularly significant is the institute’s study of the basic structure and design of biological molecules; in this arena TSRI is among a handful of the world’s leading centers.

    The institute’s educational programs are also first rate. TSRI’s Graduate Program is consistently ranked among the best in the nation in its fields of biology and chemistry.

     
  • richardmitnick 8:29 am on May 27, 2016 Permalink | Reply
    Tags: , , , Superbug resistant to last resort antibiotic   

    From COSMOS: “Superbug resistant to last resort antibiotic” 

    Cosmos Magazine bloc

    COSMOS

    27 May 2016
    Bill Condie

    The emergence of the first strain of bacteria resistant to colistin is causing alarm among health professionals. Bill Condie reports.

    1
    A coloured scanning electron micrograph shows E. coli bacteria, a new strain of which is resistant to all known antibiotics.Credit: PASIEKA

    A patient has become the first in the US with an infection resistant to colistin – the antibiotic of last resort used to treat infections that have not responded to anything else.

    The so-called “superbug” is a strain of E. coli that could be the harbinger of pathogens resistant to all treatment.

    The case – a urinary tract infection of a 49-year-old Pennsylvania woman – was reported* in Antimicrobial Agents and Chemotherapy, a publication of the American Society for Microbiology.

    The study by the Walter Reed National Military Medical Center has alarmed health officials.

    “We risk being in a post-antibiotic world,” Thomas Frieden, director of the US Centers for Disease Control and Prevention, told Reuters.

    “The more we look at drug resistance, the more concerned we are. The medicine cabinet is empty for some patients. It is the end of the road for antibiotics unless we act urgently.”

    The study explains that the superbug itself had first been infected with a tiny piece of DNA called a plasmid, which passed along a gene called mcr-1 that confers resistance to colistin.

    “This heralds the emergence of truly pan-drug resistant bacteria,” said the study.

    “To the best of our knowledge, this is the first report of mcr-1 in the USA.”

    The mcr-1 gene was found last year in people and pigs in China and doctors are worried about the potential for the superbug to spread from animals to people.

    “It is dangerous and we would assume it can be spread quickly, even in a hospital environment if it is not well contained,” Gail Cassell, a microbiologist and senior lecturer at Harvard Medical School, told Reuters.

    Experts have warned of this potential problem since the 1990s thanks, in part, to the overprescribing of antibiotics and their extensive use in food livestock.

    2
    Extensive use of antibiotics in intensive farming is partly to blame for increased drug resistance in humans. Credit: Martin Harvey

    How did we come to this?

    In 1948, an American biochemist, Thomas H. Jukes, discovered that the addition of a cheap antibiotic to the diet of chickens made them gain weight much faster than normal.

    His company, Lederle, lost no time in rolling out the product as an agricultural supplement, effectively setting in train a vast uncontrolled experiment to transform the food chain.

    Now, nearly 70 years later, about 80% of antibiotic sales in the US go to livestock production rather than to human health care, despite the mounting evidence that drug resistance spills over from livestock to people.

    To read more about how this came about and the risks it poses, see How did antibiotics become part of the food chain?

    Some of the biggest effects of multi drug resistance are being felt by patients with tuberculosis. The problem is particularly acute in countries such as South Africa, where patients carrying drug-resistant TB strains are routinely returned to their communities.

    TB is the leading cause of death in South Africa thanks to the large number of people co-infected with HIV.

    For Extreme Drug Resistant TB, cure rates are now just 20% nationally.

    *Science paper:
    Escherichia coli Harboring mcr-1 and blaCTX-M on a Novel IncF Plasmid: First report of mcr-1 in the USA

    See the full article here .

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  • richardmitnick 9:00 pm on May 24, 2016 Permalink | Reply
    Tags: 'Kidney on a chip', , ,   

    From U Michigan: ” ‘Kidney on a chip’ could lead to safer drug dosing” 

    U Michigan bloc

    University of Michigan

    5/4/2016
    Gabe Cherry, Michigan Engineering

    1
    No image caption, no image credit

    University of Michigan researchers have used a “kidney on a chip” device to mimic the flow of medication through human kidneys and measure its effect on kidney cells. The new technique could lead to more precise dosing of drugs, including some potentially toxic medicines often delivered in intensive care units.

    Precise dosing in intensive care units is critical, as up to two-thirds of patients in the ICU experience serious kidney injury. Medications contribute to this injury in more than 20 percent of cases, largely because many intensive care drugs are potentially dangerous to the kidneys.

    Determining a safe dosage, however, can be surprisingly difficult. Today, doctors and drug developers rely mainly on animal testing to measure the toxicity of drugs and determine safe doses. But animals process medications more quickly than humans, making it difficult to interpret test results and sometimes leading researchers to underestimate toxicity.

    2
    No image caption, no image credit

    The new technique offers a more accurate way to test medications, closely replicating the environment inside a human kidney. It uses a microfluidic chip device to deliver a precise flow of medication across cultured kidney cells. This is believed to be the first time such a device has been used to study how a medication behaves in the body over time, called its “pharmacokinetic profile.”

    “When you administer a drug, its concentration goes up quickly and it’s gradually filtered out as it flows through the kidneys,” said University of Michigan Biomedical Engineering professor Shuichi Takayama, an author on the paper. “A kidney on a chip enables us to simulate that filtering process, providing a much more accurate way to study how medications behave in the body.”

    Takayama said the use of an artificial device provides the opportunity to run test after test in a controlled environment. It also enables researchers to alter the flow through the device to simulate varying levels of kidney function.

    “Even the same dose of the same drug can have very different effects on the kidneys and other organs, depending on how it’s administered,” said Sejoong Kim, an associate professor at Korea’s Seoul national University Budang Hospital, former U-M researcher and author on the paper. “This device provides a uniform, inexpensive way to capture data that more accurately reflects actual human patients.”

    In the study, the team tested their approach by comparing two different dosing regimens for gentamicin, an antibiotic that’s commonly used in intensive care units. They used a microfluidic device that sandwiches a thin, permeable polyester membrane and a layer of cultured kidney cells between top and bottom compartments.

    3
    No image caption, no image credit

    They then pumped a gentamicin solution into the top compartment, where it gradually filtered through the cells and the membrane, simulating the flow of medication through a human kidney. One test started with a high concentration that quickly tapered off, mimicking a once-daily drug dose. The other test simulated a slow infusion of the drug, using a lower concentration that stayed constant. Takayama’s team then measured damage to the kidney cells inside the device.

    They found that a once-daily dose of the medication is significantly less harmful than a continuous infusion—even though both cases ultimately delivered the same dose of medication. The results of the test could help doctors better optimize dosing regimens for gentamicin in the future. Perhaps most importantly, they showed that a kidney on a chip device can be used to study the flow of medication through human organs.

    “We were able to get results that better relate to human physiology, at least in terms of dosing effects, than what’s currently possible to obtain from common animal tests,” Takayama said. “The goal for the future is to improve these devices to the point where we’re able to see exactly how a medication affects the body from moment to moment, in real time.”

    Takayama said the techniques used in the study should be generalizable to a wide variety of other organs and medications, enabling researchers to gather detailed information on how medications affect the heart, liver and other organs. In addition to helping researchers fine-tune drug dosing regimens, he believes the technique could also help drug makers test drugs more efficiently, bringing new medications to market faster.

    Within a few years, Takayama envisions the creation of integrated devices that can quickly test multiple medication regimens and deliver a wide variety of information on how they affect human organs. PHASIQ, an Ann Arbor-based spinoff company founded by Takayama is commercializing the biomarker readout aspect of this type of technology in conjunction with the University of Michigan Office of Technology Transfer, where Takayama serves as a Faculty Innovation Ambassador.


    Access mp4 video here .
    University of Michigan researchers used a “kidney on a chip” to mimic the flow of medication through human kidneys. This enabled them to study the dosing regimen for a common intensive care drug. No video credit

    The paper, published in the journal Biofabrication, is titled Pharmacokinetic profile that reduces nephrotoxicity of gentamicin in a perfused kidney-on-a-chip. Funding and assistance for the project was provided by the National Institutes of Health (grant number GM096040), the University of Michigan Center for Integrative Research in Critical Care (MCIRCC), the University of Michigan Biointerfaces Institute, the National Research Foundation of Korea and the Korean Association of Internal Medicine Research Grant 2015.

    See the full article here .

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    U MIchigan Campus

    The University of Michigan (U-M, UM, UMich, or U of M), frequently referred to simply as Michigan, is a public research university located in Ann Arbor, Michigan, United States. Originally, founded in 1817 in Detroit as the Catholepistemiad, or University of Michigania, 20 years before the Michigan Territory officially became a state, the University of Michigan is the state’s oldest university. The university moved to Ann Arbor in 1837 onto 40 acres (16 ha) of what is now known as Central Campus. Since its establishment in Ann Arbor, the university campus has expanded to include more than 584 major buildings with a combined area of more than 34 million gross square feet (781 acres or 3.16 km²), and has two satellite campuses located in Flint and Dearborn. The University was one of the founding members of the Association of American Universities.

    Considered one of the foremost research universities in the United States,[7] the university has very high research activity and its comprehensive graduate program offers doctoral degrees in the humanities, social sciences, and STEM fields (Science, Technology, Engineering and Mathematics) as well as professional degrees in business, medicine, law, pharmacy, nursing, social work and dentistry. Michigan’s body of living alumni (as of 2012) comprises more than 500,000. Besides academic life, Michigan’s athletic teams compete in Division I of the NCAA and are collectively known as the Wolverines. They are members of the Big Ten Conference.

     
  • richardmitnick 12:14 pm on May 23, 2016 Permalink | Reply
    Tags: , , , UW Medical Center ready to deploy tiniest pacemaker ever   

    From U Washington: “UW Medical Center ready to deploy tiniest pacemaker ever” 

    U Washington

    University of Washington

    05.20.2016
    Brian Donohue

    1
    The old and the new: a conventional pacemaker, left, and the Medtronic Micra are displayed by UW Medicine electrophysiologists Jordan Prutkin and Kristen Patton.

    The world’s smallest pacemaker will debut soon at UW Medical Center – one of two Washington state hospitals that will offer the device for the next several months.

    Drs. Jordan Prutkin and Kristen Patton, cardiac electrophysiologists with the UW Medicine Regional Heart Center, received final training this week from representatives of Medtronic, the manufacturer of the device, named Micra.

    About as tall and wide as a AAA battery, the device is threaded up through the femoral vein to the heart, where it is attached to the right ventricle to deliver impuses when a patient’s heartbeat is too slow. The unit’s direct placement takes advantage of another advance: Its battery is inside, so there are no wires connected to a separate power source.

    For decades, pacemakers have comprised a generator, usually implanted under the skin in the patient’s left chest, and leads, which carry impulses from the generator into the heart. The wires are these devices’ main vulnerability, wearing out over time and heightening risk of infections. Removing broken leads years after implant can be problematic because they often have become enmeshed within the tissue of blood vessels.

    “That’s why this miniature technology is so important and transformative – because it really does reduce risks associated with these devices,” Patton said.

    On April 6, the U.S. Food and Drug Administration approved the Micra for patients with slow or irregular heart rhythms. The FDA based its decision on a clinical trial of 719 patients implanted with the device. In the study, 98 percent of patients experienced adequate heart pacing and fewer than 7 percent had complications such as blood clots, heart injury and device dislocation.

    The risk of dislodgement is low, Patton said. “Its tiny hooks deploy straight into the muscle and grab and it is very hard to detach.”

    The Micra will have limited applicability, at least initially, because it paces only one chamber. About 75 percent of conventional pacemakers pace at least two of the heart’s chambers.

    “This is good for people who only need pacing in the ventricle because they have atrial fibrillation in the top chamber, and for people who only need pacing a small percentage of the time,” Prutkin said.

    2
    Illustration of the Micra being deployed into a right ventricle. Medtronic

    Similar to other single-chamber devices on the market, the Micra’s battery is projected to last 10 to 14 years, depending on how much pacing a patient requires.

    At the Micra training, Patton said, she heard something that she hadn’t expected.

    “The two physicians leading the session have a lot of experience with this device, and they said it makes a difference psychologically to patients; it removes the visible bump under the skin of the generator and that persistent reminder that ‘something is wrong with my heart.’

    “We hear from patients all the time, wondering whether they should move less to protect against lead fracture. Patients ask, ‘What if I wear a backpack? Can I still do pushups or play golf?’ This device seems to be a positive step in that way,” Patton said.

    Prutkin sees this device as the beginning of the next generation of pacemakers.

    “Right now this can only go in the ventricle, but in time this will be available for both the atria and ventricles, and multiple devices in one person will be able to talk to one another to regulate a heartbeat. That’s down the road, but that’s where this technology is heading.”

    The device also will be available at Sacred Heart Medical Center in Spokane.

    See the full article here .

    Please help promote STEM in your local schools.

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    The University of Washington is one of the world’s preeminent public universities. Our impact on individuals, on our region, and on the world is profound — whether we are launching young people into a boundless future or confronting the grand challenges of our time through undaunted research and scholarship. Ranked number 10 in the world in Shanghai Jiao Tong University rankings and educating more than 54,000 students annually, our students and faculty work together to turn ideas into impact and in the process transform lives and our world. For more about our impact on the world, every day.

    So what defines us — the students, faculty and community members at the University of Washington? Above all, it’s our belief in possibility and our unshakable optimism. It’s a connection to others, both near and far. It’s a hunger that pushes us to tackle challenges and pursue progress. It’s the conviction that together we can create a world of good. Join us on the journey.

     
  • richardmitnick 4:13 pm on May 21, 2016 Permalink | Reply
    Tags: , Heart disease and stroke risk predicted by new tools, ,   

    From ICL: “Heart disease and stroke risk predicted by new tools” 

    Imperial College London
    Imperial College London

    21 May 2016
    Kate Wighton

    1
    Damage to blood vessels in eyes, kidneys and nerve cells may cause two-fold increased risk of heart attack or stroke in people with type 2 diabetes.

    Individuals with diabetes are susceptible to damage to small blood vessels in the eyes, kidneys and nerve cells that can, in turn, lead to blindness, kidney failure and leg amputation. In 2004, routine screening for this damage, known as microvascular disease, was introduced in the UK.

    The team, which included scientists from Imperial College London, St George’s, University of London, and St George’s University Hospitals NHS Foundation Trust, looked at data for 49,027 individuals with type 2 diabetes in the UK. They used this data to assess whether screening information on microvascular disease could also predict damage to the large blood vessels that causes heart attacks and stroke (cardiovascular disease).

    The researchers found any single sign of microvascular disease resulted in around a 30% increased risk of cardiovascular disease. Risk increased with each additional factor present such that the risk was increased two fold when all three were present. Researchers found that damage to small blood vessels in the eyes, kidneys and nerve cells were at least as strong an indication of the likelihood of later cardiovascular disease as many conventionally accepted risk factors – such as high blood pressure and cholesterol.

    Professor Kausik Ray, co-senior author from School of Public Health at Imperial said: “We found the presence of damage to the eyes, kidneys and nerves in combination incrementally doubled risk of cardiovascular disease, mortality and hospitalisation for heart failure. Our findings suggest that incorporating commonly available screening tests – that are already routinely assessed in those with diabetes – can significantly improve risk prediction. If applied globally, these findings have the potentially to improve therapeutic decision making in several millions of patients, simply by looking in the back of the eye, testing the feet with a microfilament and taking a dip stick test of the urine. It’s easy and cheap.”

    The data, published* in the journal Lancet Diabetes, suggests that continuing the screening programme for microvascular disease in GP practices is needed. Not only does this predict the risk of blindness, kidney failure and leg amputations, but it also provides a clear indication of whether an individual is likely to go on to develop cardiovascular disease.

    In the UK, NICE guidelines recommend that any individual who is 10% or more likely to experience cardiovascular disease in the next 10-years should be offered a statin prescription with the aim of preventing future heart attacks and strokes. When data on microvascular disease is included in the assessment of an individual patient’s risk of cardiovascular disease, an extra 135,000 people in the UK could be offered a statin prescription appropriately as their risk would cross this predicted threshold. Furthermore, 200,000 individuals would fall below the threshold for statin treatment and consequently these lower risk groups would not be offered a statin.

    The team argues this may mean earlier treatment for patients at higher risk of developing cardiovascular disease – in particular younger patients and women, who often are believed to be at low risk on the basis of age and gender. There are also potential cost benefits to the health service, by preventing more cardiovascular disease in higher risk patients. In addition to this, there would be fewer statin prescriptions – and so potentially fewer side effects – in low risk individuals.

    Co-Lead author, Jack Brownrigg, of St George’s University, added: “The study has identified a very high risk group of patients with diabetes. The number of people with diabetes in the UK is rising, driven largely by obesity. These results will help us to focus preventive treatments on those patients who are at most risk of developing cardiovascular disease and should reduce the number of people with diabetes who experience a heart disease or stroke”.

    *Science paper:
    Microvascular disease and risk of cardiovascular events among individuals with type 2 diabetes: a population-level cohort study

    See the full article here .

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    Imperial College London

    Imperial College London is a science-based university with an international reputation for excellence in teaching and research. Consistently rated amongst the world’s best universities, Imperial is committed to developing the next generation of researchers, scientists and academics through collaboration across disciplines. Located in the heart of London, Imperial is a multidisciplinary space for education, research, translation and commercialisation, harnessing science and innovation to tackle global challenges.

     
  • richardmitnick 5:23 pm on May 19, 2016 Permalink | Reply
    Tags: , , , ,   

    From World Community Grid and Rutgers University: “Fighting the Zika Virus with the Power of Supercomputing” 

    Rutgers University

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    WCGLarge

    From Rutgers

    Thursday, May 19, 2016

    Rutgers Open Zika

    Rutgers is taking a leading role in an IBM-sponsored World Community Grid project that will use supercomputing power to identify potential drug candidates to cure the Zika virus.

    The project, known as OpenZika, employs a global team of scientists who will perform “virtual” experiments in a search of treatments for the fast-spreading virus that the World Health Organization has declared a global public health emergency.

    OpenZika will screen current drugs and millions of drug-like compounds from existing databases against models of Zika protein structures (and also against structures of proteins from related viruses, including West Nile Virus and Dengue). These computational results will be shared quickly with the research community and general public, with compounds showing the most promise then tested in laboratory settings.

    “Instead of having to wait a number of years, even decades potentially, to test all these compounds in order to find a few that could form the basis of antiviral drugs to cure Zika, we will perform these initial tests in a matter of months, just by using idle computing power that would otherwise go to waste,” says Alex Perryman, a research teaching specialist at Rutgers’ New Jersey Medical School, in Professor Joel Freundlich’s lab.

    2
    OpenZika co-principal investigator Alex Perryman, researcher at Rutgers’ New Jersey Medical School, also managed the World Community Grid’s first biomedical computing project, FightAIDS@Home, and its Global Online Fight Against Malaria (GO FAM). Perryman was selected as co-principal investigator of the OpenZika project, while Freundlich serves as a key consultant.

    Perryman was selected as co-principal investigator of the OpenZika project, while Freundlich serves as a key consultant.

    Rutgers’ Perryman has had deep experience working with IBM’s World Community Grid. From 2007 to 2013, he managed and performed the day-to-day duties required for FightAIDS@Home, the first biomedical computing project on World Community Grid. In 2011, Perryman designed, developed and ran the grid’s Global Online Fight Against Malaria (GO FAM) project, which has resulted in identifying promising tool compounds for treating malaria and drug-resistant tuberculosis.

    In less than two years, GO FAM volunteers on the grid performed more than a billion docking jobs, which, Perryman estimates, would have taken at least 100 years using the computer capacity found at most universities. The Freundlich lab has leveraged GO FAM data against tuberculosis drug targets, along with novel machine learning techniques they have developed, to seed novel therapeutic strategies.

    For the OpenZika project IBM is working with an international team of researchers, led by Federal University of Goias in Brazil; with scientists from the Oswaldo Cruz Foundation (Fiocruz) in Brazil; Rutgers University’s New Jersey Medical School (NJMS); and the University of California, San Diego (UCSD). Carolina Horta Andrade, professor at Federal University of Goias, is the principal investigator. Joining Perryman as co-PI is Sean Ekins, CEO, Collaborations Pharmaceuticals.

    Volunteers can support the OpenZika search for a cure by joining World Community Grid. IBM also invites researchers to submit research project proposals to receive this free resource. For more information about IBM’s philanthropic efforts, visit http://www.citizenIBM.com or follow @CitizenIBM on Twitter.

    From World Community Grid

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    WCG Logo New

    Help an International Research Team Fight the Zika Virus

    19 May 2016
    By: Dr. Carolina Horta Andrade
    Universidade Federal de Goiás, Brazil

    Summary
    The Zika virus was relatively unknown until 2015, when it made headlines due its rapid spread and its link to severe brain-related deficiencies in newborns born to mothers who contracted the virus while pregnant. Dr. Carolina Horta Andrade, the principal investigator for the new OpenZika project, discusses how she and an international team of researchers are using World Community Grid to accelerate the search for an effective anti-Zika treatment.

    3
    Dr. Carolina Horta Andrade, principal investigator for OpenZika

    Introduction

    Few people had heard of the Zika virus before 2015, when it began rapidly spreading in the Americas, particularly in Brazil. The virus is mostly spread by Aedes aegypti mosquitoes, although sexual and blood transmission are also possible. A currently unknown percentage of pregnant women who have contracted the Zika virus have given birth to infants with a condition called microcephaly, which results in severe brain development issues. In other cases, adults and children who contract the Zika virus have suffered paralysis and other neurological problems.

    Currently, there is no treatment for the Zika virus and no vaccine. Given that Zika has quickly become an international public health concern, my team and I are working with researchers here in Brazil as well as in the United States to look for possible treatments, and we are using World Community Grid to accelerate our project.

    Background

    The world has become increasingly alarmed about the Zika virus, and with good reason. Until recently there has been little research on this disease, but in the past few months it has been linked to severe brain deficiencies in some infants as well as potential neurological issues in children and adults. As a scientist and a citizen of Brazil, which has been greatly affected by Zika, I am committed to the fight against the virus, but my team and I will need the help of World Community Grid volunteers to provide the massive computational power required for our search for a Zika treatment.

    I am a professor at the Universidade Federal de Goiás (UFG) in Brazil, and the director of LabMol, a university laboratory which searches for treatments for neglected diseases and cancer. My field is medicinal and computational chemistry, with an emphasis on drug design and discovery for neglected diseases. I first became interested in working in this area because these are diseases that do not interest pharmaceutical companies, since they mainly affect marginalized populations in underdeveloped and developing countries. However, these diseases are highly debilitating and, for most of them, there is no adequate drug treatment. Brazil is vulnerable to a number of neglected diseases, such as dengue, malaria, leishmaniasis, schistosomiasis, and others. My greatest desire is to find treatments to improve the lives of thousands of people throughout the world who suffer from these diseases.

    In 2015, I started a project in collaboration with Dr. Sean Ekins, a pharmacologist with extensive research experience, to focus on the development of computational models to identify active compounds against the dengue virus, which is a serious mosquito-borne disease found throughout the world. These active compounds could become candidates for antiviral drugs. We are now at the stage of selecting compounds to start laboratory tests. In January of 2016, when the Zika virus outbreak in Brazil became alarming, Sean and I decided to expand our dengue research, and we included the Zika virus in our work, since these two diseases are from the same family of viruses.

    4
    Dr. Sean Ekins, CEO, Collaborations Pharmaceuticals, Inc.

    Sean invited me and other collaborators to write a perspective paper that was published*in the beginning of 2016, about the need for open drug discovery for the Zika virus. This work grabbed the attention of scientific illustrator John Liebler, who wanted to produce a picture of the complete Zika virion. We are using the illustration he created (shown below) as a visual for the OpenZika project.

    4
    Image copyright John Liebler, http://www.ArtoftheCell.com. All rights reserved. Used by permission.

    John’s interest inspired us to try to model every protein in the Zika virus, which directly led to writing a groundbreaking paper** with homology models of all the proteins of the Zika virus. (Homology models, which are computational, three-dimensional renderings of proteins within an organism, are useful when the structure of a protein is not experimentally known, which is the case with the Zika virus.)

    The OpenZika Research Team

    After Sean and I began our work on the Zika virus, he introduced me to World Community Grid. Sean has also collaborated with Dr. Alexander Perryman of Rutgers University, New Jersey Medical School, who was previously at The Scripps Research Institute where he played a key role in two World Community Grid projects: Fight AIDS@Home and GO Fight Against Malaria. Sean and Alex are both co-principal investigators with me on the OpenZika project.

    5
    Dr. Alexander Perryman, co-primary investigator, and Dr. Joel Freundlich, collaborator, Rutgers University New Jersey Medical School

    The research team also includes my colleagues at UFG, Dr. Rodolpho Braga, Dr. Melina Mottin and Dr. Roosevelt Silva; Dr. Jair L. Siqueira-Neto from University of California, San Diego; and Dr. Wim Degrave of the Oswaldo Cruz Foundation in Brazil, who is already working with World Community Grid on the Uncovering Genome Mysteries project, among others.

    6
    The UFG team includes Dr. Rodolpho Braga, Dr. Carolina Horta Andrade, Dr. Melina Mottin and Dr. Roosevelt Silva (not pictured).

    This large group of collaborators means that the team has every set of skills and experience necessary to conduct this research end-to-end, as some of the researchers are computational modeling experts while others have extensive laboratory experience.

    Our Goals

    The OpenZika project on World Community Grid aims to identify drug candidates to treat the Zika virus in people who have been infected. The project will use software to screen millions of chemical compounds against the target proteins that the Zika virus likely uses to survive and spread in the human body, based on what is known from similar diseases such as dengue virus and yellow fever. As science’s knowledge of the Zika virus increases in the coming months and key proteins are identified, the OpenZika team will use the new knowledge to refine our search.

    Our work on World Community Grid is only the first step in the larger project of discovering a new drug to fight the Zika virus. Next, we will analyze the data obtained from World Community Grid’s virtual screening to choose the compounds that show the most promise. After we have selected and tested compounds that could be effective in killing the Zika virus, we will publish our results. As soon as we have proven that some of the candidate compounds can actually kill or disable the virus in cell-based tests, we and other labs can then modify the molecules to increase their potency against the virus, while ensuring that these modified compounds are safe and non-toxic.

    We are committed to releasing all the results to the public as soon as they are completed, so other scientists can help advance the development of some of these active compounds into new drugs. We hope that OpenZika will include a second stage, where we can perform virtual screenings on many more compounds.

    Without this research–and other projects that are studying the Zika virus–this disease could become an even bigger threat due to the rapid spread of the virus by mosquitoes, blood and sexual transmission. The link between the Zika virus in pregnant women and severe brain-based disorders in children could impact a generation with larger than usual numbers of members who have serious neurological difficulties.

    And without the resources of World Community Grid, using only the resources of our lab, we would only be able to screen a few thousand compounds against some of the Zika proteins, or it would take years to screen millions of compounds against all Zika proteins. This would severely limit our potential for drug discovery.

    Enlisting the help of World Community Grid volunteers will enable us to computationally evaluate over 20 million compounds in just the initial phase (and potentially up to 90 million compounds in future phases). Thus, running the OpenZika project on World Community Grid will allow us to greatly expand the scale of our project, and it will accelerate the rate at which we can obtain the results toward an antiviral drug for the Zika virus.

    By working together and sharing our work with the scientific community, many other researchers in the world will also be able to take promising molecular candidates forward, to accelerate progress towards defeating the Zika outbreak.

    *Science paper:
    Open drug discovery for the Zika virus [version 1; referees: 3 approved]

    **Science paper:
    Illustrating and homology modeling the proteins of the Zika virus [version 1; referees: 1 approved with reservations]

    See the full articles here and here.

    Please help promote STEM in your local schools.
    STEM Icon

    Stem Education Coalition

    World Community Grid (WCG) brings people together from across the globe to create the largest non-profit computing grid benefiting humanity. It does this by pooling surplus computer processing power. We believe that innovation combined with visionary scientific research and large-scale volunteerism can help make the planet smarter. Our success depends on like-minded individuals – like you.”

    WCG projects run on BOINC software from UC Berkeley.

    BOINC is a leader in the field(s) of Distributed Computing, Grid Computing and Citizen Cyberscience.BOINC is more properly the Berkeley Open Infrastructure for Network Computing.

    BOINC WallPaper

    CAN ONE PERSON MAKE A DIFFERENCE? YOU BET!!

    “Download and install secure, free software that captures your computer’s spare power when it is on, but idle. You will then be a World Community Grid volunteer. It’s that simple!” You can download the software at either WCG or BOINC.

    Please visit the project pages-

    OpenZika

    Rutgers Open Zika
    Zika

    Help Stop TB
    WCG Help Stop TB
    Outsmart Ebola together

    Outsmart Ebola Together

    Mapping Cancer Markers
    mappingcancermarkers2

    Uncovering Genome Mysteries
    Uncovering Genome Mysteries

    Say No to Schistosoma

    GO Fight Against Malaria

    Drug Search for Leishmaniasis

    Computing for Clean Water

    The Clean Energy Project

    Discovering Dengue Drugs – Together

    Help Cure Muscular Dystrophy

    Help Fight Childhood Cancer

    Help Conquer Cancer

    Human Proteome Folding

    FightAIDS@Home

    World Community Grid is a social initiative of IBM Corporation
    IBM Corporation
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