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  • richardmitnick 7:12 pm on March 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From SN: “Clean-up gene gone awry can cause Lou Gehrig’s disease” 

    ScienceNews bloc

    ScienceNews

    March 24, 2015
    Kate Baggaley

    Mutations on a gene necessary for keeping cells clean can cause Lou Gehrig’s disease, scientists report online March 24 in Nature Neuroscience. The gene is one of many that have been connected to the condition.

    In amyotrophic lateral sclerosis, also known as Lou Gehrig’s disease, nerve cells that control voluntary movement die, leading to paralysis. Scientists have previously identified mutations in 29 genes that are linked with ALS, but these genes account for less than one-third of all cases.

    To track down more genes, a team of European researchers looked at the protein-coding DNA of 252 ALS patients with a family history of the disease, as well as of 827 healthy people. The team discovered eight mutations on a gene called TBK1 that were associated with ALS.

    TBK1 normally codes for a protein that controls inflammation and cleans out damaged proteins from cells. “We do not know which of these two principle functions of TBK1 is the more relevant one” to ALS, says coauthor Jochen Weishaupt, a neurologist at Ulm University in Germany. In cells with one of the eight TBK1 mutations, the protein either is missing or lacks components that it needs to interact with other proteins, the researchers found.

    TBK1 mutations may explain 2 percent of ALS cases that run in families, which make up about 10 percent of all incidences of the disease, Weishaupt says.

    See the full article here.

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  • richardmitnick 12:18 pm on March 28, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From Scripps: “Team Breaks Imaging Barrier” 

    Scripps

    Scripps Research Institute

    March 30, 2015
    Madeline McCurry-Schmidt

    Advances in Electron Microscopy Could Aid Drug Design

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    A team from the Carragher lab has imaged a protein complex at the highest resolution ever achieved with single particle cryo-electron microscopy. The image reveals individual molecules at 2.8 Å and is, to the researchers’ knowledge, the first published research using this technique that shows individual water molecules.

    Scientists at The Scripps Research Institute (TSRI) have broken a major barrier in structural imaging. Their study, published recently in the journal eLife, shows a protein complex at the highest resolution ever achieved with a standard technique called single particle cryo-electron microscopy.

    “The instruments and software are now so good that we do not know what the barriers are any more,” said Bridget Carragher, a professor at TSRI with a joint appointment at the New York Structural Biology Center.

    With single particle cryo-electron microscopy, scientists freeze a sample and then expose it to a beam of high-energy electrons. This excites electrons in the sample, allowing scientists to capture an image.

    While the technique has many practical advantages over other structural biology methods, scientists have so far not been able to reach resolutions more detailed than 3 Angstroms (one ten-billionth of a meter, marked with the symbol Å). At this resolution, some of the details of the structure that are important for guiding drug design are not discernable.

    The new study shows that reaching resolutions greater than 3 Å is possible using single particle cryo-electron microscopy. The imaged protein complex reveals individual molecules at 2.8 Å and is, to the researchers’ knowledge, the first time a paper has been published showing individual water molecules using this technique.

    Better Imaging, Better Drugs

    The scientists used a new type of electron microscope, called the FEI Titan Krios, and a new-generation camera, called a Gatan K2 Summit, to break the 3 Å barrier.

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    Titan Krios

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    Gatan K2 Summit

    The FEI Titan Krios is housed on TSRI’s La Jolla, California, campus. It has a higher energy electron source and a more stable platform than other types of electron microscopes. It also operates with software developed at TSRI through the National Resource for Automated Molecular Microscopy to find the best parts of a sample for imaging.

    The Gatan K2 Summit camera improves imaging by directly detecting electrons, instead of losing resolution by converting electrons to light. The camera can also capture a series of images, essentially a movie, giving scientists the ability to correct for movements in the specimen and make the images as sharp as possible.

    Revealing high-resolution details in a structure helps researchers develop new drugs to treat disease. Structures seen at greater than 3 Å might show vulnerabilities in a virus where drugs could bind, for example.

    “By seeing everything in more detail, you can design more effective drugs,” said Melody Campbell, a TSRI graduate student and co-first author of the new paper with David Veesler, previously a post-doctoral fellow at TSRI and now an assistant professor at the University of Washington.

    The advances in single particle cryo-electron microscopy also allow scientists to image more kinds of structures, more quickly. For many years, scientists have relied on a high-resolution imaging technique called X-ray crystallography. Although X-ray crystallography has led to many advances in drug design, figuring out how to grow a crystal can take years and not all structures can be crystallized.

    Electron microscopy does not require a crystal, however, and many projects take only weeks or months.

    In the new study, the researchers imaged a protein complex from a microbe called Thermoplasma acidophilum. This protein complex, called a proteasome, is also found in humans and is an important target for treating many types of cancer.

    The team spent several months setting up the instruments—since the FEI Titan Krios was new to the institute—and then they captured all the raw data over a single weekend. They then used computational programs to select the clearest images and refine them over several months to build a 3D model of the proteasome.

    “It was a relief to know we had finally done it,” said Campbell. “Now we hope other people can just hop on the microscope, use similar strategies and also get high-resolution structures.”

    In addition to Carragher, Campbell and Veesler, authors of the study, “2.8 Å resolution reconstruction of the Thermoplasma acidophilum 20 S proteasome using cryo-electron microscopy,” were Anchi Cheng and Clinton S. Potter of the New York Structural Biology Center. For more information on the paper, see http://elifesciences.org/content/4/e06380.

    This research was supported by the National Institutes of Health’s National Institute of General Medical Sciences (grant GM103310), a FP7 Marie Curie IOF fellowship (273427) and an American Heart Association fellowship (14PRE18870036).

    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 1:52 pm on March 27, 2015 Permalink | Reply
    Tags: Albuquerque Journal, Applied Research & Technology, ,   

    From Albuquerque Journal via LANL: “LANL takes on deadly bugs” 

    LANL bloc

    LANL Sign
    Los Alamos National Laboratory

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    March 27, 2015
    D’Val Westphal

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    Team members who discovered a treatment for resistant infections are, from left, Aimee Newsham, Dixie State University student; Rico Del Sesto, Dixie State University professor; David Fox, Los Alamos National Laboratory; Andrew Koppisch, Northern Arizona University professor; and Mattie Jones, Dixie State University student. (Courtesy of David Fox)

    This column is for everyone who has ever had to deal with a horrible infection – from the Streptococcus sp. that rots teeth, to the Pseudomonas aeruginosa that attacks diabetic patients’ feet, to the Methicillin-resistant Staphylococcus aureus (MRSA, i.e. flesh-eating bacteria) that makes any original medical problem much worse. And it’s for everyone who ever will.

    Considering a surgeon recently told me MRSA is our generation’s staph, in that it’s everywhere and on everything, that could be everybody.

    Treating these infections, known in the scientific world as biofilms, is expensive, time consuming, sickening and often unsuccessful when it comes to killing them before they kill their host. That’s because while they are responsible for up to 80 percent of all bacterial infections, they have their own protection that makes them 50 to 1,000 times more resistant to antibiotics.

    And that’s why a discovery at Los Alamos National Laboratory – a treatment with what amounts to fancy water – is beyond exciting. It could be life-changing and life-saving.

    Full disclosure: My mother contracted a biofilm infection after having a back surgery and spent years unsuccessfully fighting it with stronger and stronger oral and intravenous antibiotics that ultimately caused a serious reaction of their own. The drugs simply could not penetrate the infection to kill it. Doctors finally decided to remove the hardware (and its virulent bacteria) rather than continue a fruitless and damaging battle.

    In David Fox’s world, my mother would have had an antibiotic delivered via ionized liquid that could penetrate her skin, the biofilm, and kill the bug.

    Fox is a staff scientist in LANL’s Bioscience Division. For several years he and a team of fellow chemists and microbiologists have been working with ionic liquids – known as molten salts. Originally their work was for forensic applications, like how to pull certain molecules out of fabrics. The team then figured out they could also use the ionic liquids to deliver molecules: like antibiotics to an until-then impenetrable bacteria.

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    So these scientists – Fox, Tari Kern, Katherine Lovejoy, Rico Del Sesto (now at Dixie State University), Rashi Iyer, Amber Nagy, Andrew Goumas, Tarryn Miller and Andrew Koppisch (now at Northern Arizona University) – started working with the University of California-Santa Barbara on using their ionized water for transdermal drug delivery.

    Instead of infection treatments that range from irritating to painful – organic solvents, injections and debridement – the team focused on using 12 ionic liquids “generally recognized as safe” (GRAS in science-speak). They grew opportunistic gram negative bacteria, then added individual ionic liquids and incubated, then rinsed.

    And what they found was a greater than 99.9999 percent bacteria cell death, with some of the ionic liquids “more effective than a 10 percent bleach solution.”

    And that was before adding antibiotics.

    The team then moved on to ensuring the liquids with dissolved antibiotics could penetrate pig skin and the bacteria’s protective layer – and got equally stunning results. “Ninety-five and 98 percent reduction in cell viability” with one of the ionic liquids and that liquid plus an antibiotic.

    By comparison, antibiotics alone had a 20 percent kill rate.

    So why should someone who’s never had a cavity or a diabetic ulcer or a MRSA infection care? Fox points out the “economic burden of skin disease is over $100 billion.” That MRSA-type infections acquired in hospitals account for an estimated “$10 billion in extra patient costs and over 10,000 deaths per year.” That “wounds from infected surgical incisions account for over 1 million additional hospital days.” And that 10 to 20 percent of diabetic ulcers – a function of the Pseudomonas aeruginosa infection – require amputation.

    In other words, we are all paying for it, in terms of money, health and life.

    The discovery is now moving into clinical studies with live subjects – mice – Fox says, and if those go as well, on to human clinical trials. Funding for the years of required additional research could come from energy companies that want to extract high-energy density molecules like biofuels from an organism (the research’s first application), from corporations that could use it to more efficiently deliver their drugs to patients, and/or from the military that wants to protect/treat its soldiers.

    “Thousands of people die from, and billions is spent on treating, these secondary infections,” Fox says. The LANL team could be “providing a new weapon to combat flesh-eating bacteria and other microbes. We hope we have found a new silver bullet to treat these infections. We hope that’s where we’re at.”

    And so does everyone who has had, or will get, one of these very nasty infections.

    See the full article here.

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    Los Alamos National Laboratory’s mission is to solve national security challenges through scientific excellence.

    LANL Campus

    Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is operated by Los Alamos National Security, LLC, a team composed of Bechtel National, the University of California, The Babcock & Wilcox Company, and URS for the Department of Energy’s National Nuclear Security Administration.

    Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.

    Operated by Los Alamos National Security, LLC for the U.S. Dept. of Energy’s NNSA

    DOE Main

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  • richardmitnick 1:11 pm on March 27, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , , ,   

    From BNL: “Physicists Solve Low-Temperature Magnetic Mystery” 

    Brookhaven Lab

    March 27, 2015
    Chelsea Whyte, (631) 344-8671 or Peter Genzer, (631) 344-3174

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    Ignace Jarrige shown with the sample used in the experiment.

    Researchers have made an experimental breakthrough in explaining a rare property of an exotic magnetic material, potentially opening a path to a host of new technologies. From information storage to magnetic refrigeration, many of tomorrow’s most promising innovations rely on sophisticated magnetic materials, and this discovery opens the door to harnessing the physics that governs those materials.

    The work, led by Brookhaven National Laboratory physicist Ignace Jarrige, and University of Connecticut professor Jason Hancock, together with collaborators from Japan and Argonne National Laboratory, marks a major advance in the search for practical materials that will enable several types of next-generation technology. A paper describing the team’s results was published this week in the journal Physical Review Letters.

    The work is related to the Kondo Effect, a physical phenomenon that explains how magnetic impurities affect the electrical resistance of materials. The researchers were looking at a material called ytterbium-indium-copper-four (usually written using its chemical formula: YbInCu4).

    YbInCu4 has long been known to undergo a unique transition as a result of changing temperature. Below a certain temperature, the material’s magnetism disappears, while above that temperature, it is strongly magnetic. This transition, which has puzzled physicists for decades, has recently revealed its secret. “We detected a gap in the electronic spectrum, similar to that found in semiconductors like silicon, whose energy shift at the transition causes the Kondo Effect to strengthen sharply,” said Jarrige

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    From Left to Right: Jason Hancock, Diego Casa, and Jung-ho Kim, shown with one of the instruments used in the experiment.

    Electronic energy gaps define how electrons move (or don’t move) within the material, and are the critical component in understanding the electrical and magnetic properties of materials. “Our discovery goes to show that tailored semiconductor gaps can be used as a convenient knob to finely control the Kondo Effect and hence magnetism in technological materials,” said Jarrige.

    To uncover the energy gap, the team used a process called Resonant Inelastic X-Ray Scattering (RIXS), a new experimental technique that is made possible by an intense X-ray beam produced at a synchrotron operated by the Department of Energy and located at Argonne National Laboratory outside of Chicago. By placing materials in the focused X-ray beam and sensitively measuring and analyzing how the X-rays are scattered, the team was able to uncover elusive properties such as the energy gap and connect them to the enigmatic magnetic behavior.

    The new physics identified through this work suggest a roadmap to the development of materials with strong “magnetocaloric” properties, the tendency of a material to change temperature in the presence of a magnetic field. “The Kondo Effect in YbInCu4 turns on at a very low temperature of 42 Kelvin (-384F),” said Hancock, “but we now understand why it happens, which suggests that it could happen in other materials near room temperature.” If that material is discovered, according to Hancock, it would revolutionize cooling technology.

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    During the RIXS experiment, an X-ray beam is used to excite electrons inside the sample. The X-ray loses energy during the process and then is scattered out of the sample. A fine analysis of the scattered X-rays yields insight into the mechanism that controls the strength of the Kondo Effect.

    Household use of air conditioners in the US accounts for over $11 billion in energy costs and releases 100 million tons of carbon dioxide annually. Use of the magnetocaloric effect for magnetic refrigeration as an alternative to the mechanical fans and pumps in widespread use today could significantly reduce those numbers.

    In addition to its potential applications to technology, the work has advanced the state of the art in research. “The RIXS technique we have developed can be applied in other areas of basic energy science,” said Hancock, noting that the development is very timely, and that it may be useful in the search for “topological Kondo insulators,” materials which have been predicted in theory, but have yet to be discovered.

    See the full article here.

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    BNL Campus

    One of ten national laboratories overseen and primarily funded by the Office of Science of the U.S. Department of Energy (DOE), Brookhaven National Laboratory conducts research in the physical, biomedical, and environmental sciences, as well as in energy technologies and national security. Brookhaven Lab also builds and operates major scientific facilities available to university, industry and government researchers. The Laboratory’s almost 3,000 scientists, engineers, and support staff are joined each year by more than 5,000 visiting researchers from around the world.Brookhaven is operated and managed for DOE’s Office of Science by Brookhaven Science Associates, a limited-liability company founded by Stony Brook University, the largest academic user of Laboratory facilities, and Battelle, a nonprofit, applied science and technology organization.
    i1

     
  • richardmitnick 12:38 pm on March 27, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , Johns-Hopkins U,   

    From Hopkins: “New genetic variant that causes autism identified by Johns Hopkins-led team” 

    Johns Hopkins
    Johns Hopkins University

    Mar 25, 2015
    Shawna Williams

    Using a novel approach that focuses on rare families severely affected by autism, a Johns Hopkins-led team of researchers has identified a new genetic cause of the disease.

    The rare genetic variant offers important insights into the root causes of autism, the researchers say. And, they suggest, their unconventional method can be used to identify other genetic causes of autism and other complex genetic conditions.

    A report on the study was published today in the journal Nature.

    In recent years, falling costs for genetic testing, together with powerful new means of storing and analyzing massive amounts of data, have ushered in the era of the genome-wide association and sequencing studies. These studies typically compare genetic sequencing data from thousands of people with and without a given disease to map the locations of genetic variants that contribute to the disease. While genome-wide association studies have linked many genes to particular diseases, their results have so far failed to lead to predictive genetic tests for common conditions, such as Alzheimer’s, autism, or schizophrenia.

    “In genetics, we all believe that you have to sequence endlessly before you can find anything,” says Aravinda Chakravarti, a professor in the Johns Hopkins University School of Medicine’s McKusick-Nathans Institute of Genetic Medicine. “I think whom you sequence is as important—if not more so—than how many people are sequenced.”

    With that idea, Chakravarti and his collaborators identified families in which more than one female has autism spectrum disorder, a condition first described at Johns Hopkins in 1943. For reasons that are not understood, girls are far less likely than boys to have autism. When girls do have the condition, however, their symptoms tend to be severe. Chakravarti reasoned that females with autism, particularly those with a close female relative who is also affected, must carry very potent genetic variants for the disease, and he wanted to find out what those were.

    The research team compared the gene sequences of autistic members of 13 such families to the gene sequences of people from a public database. They found four potential culprit genes and focused on one, called CTNND2, because it fell in a region of the genome known to be associated with another intellectual disability. When they studied the gene’s effects in zebrafish, mice, and cadaveric human brains, the research group found that the protein it makes affects how many other genes are regulated. The CTNND2 protein was found at far higher levels in fetal brains than in adult brains or other tissues, Chakravarti says, so it likely plays a key role in brain development.

    While autism-causing variants in CTNND2 are very rare, Chakravarti says, the finding provides a window into the general biology of autism.

    “To devise new therapies, we need to have a good understanding of how the disease comes about in the first place,” he says. “Genetics is a crucial way of doing that.”

    Chakravarti’s research group is now working to find the functions of the other three genes identified as possibly associated with autism. They plan to use the same principle to look for disease genes in future studies of 100 similar autism-affected families, as well as other illnesses.

    “We’ve shown that even for genetically complicated diseases, families that have an extreme presentation are very informative in identifying culprit genes and their functions—or, as geneticists are taught, ‘treasure your exceptions.'” Chakravarti says.

    Other authors on the paper are Tychele N. Turner, Kamal Sharma, Maria X. Sosa, Dallas R. Auer, Stephan J. Sanders, Daniel Moreno-De-Luca, Vasyl Pihur, Christa Lese Martin, Matthew W. State, and Richard Huganir of The Johns Hopkins University; Edwin C. Oh, Yangfan P. Liu, and Nicholas Katsanis of Duke University; Ryan L. Collins, Harrison Brand, and Michael E. Talkowski of Massachusetts General Hospital and Harvard Medical School; Teri Plona, Kristen Pike, and Daniel R. Soppet of Leidos Biomedical Research; Michael W. Smith of the National Human Genome Research Institute; SauWai Cheung of Baylor College of Medicine; and Edwin Cook of the University of Illinois at Chicago.

    This work was funded by grants from the Simons Foundation, the National Institute of Mental Health, and an Autism Speaks Dennis Weatherstone Predoctoral Fellowship.

    See the full article here.

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    Johns Hopkins Campus

    The Johns Hopkins University opened in 1876, with the inauguration of its first president, Daniel Coit Gilman. “What are we aiming at?” Gilman asked in his installation address. “The encouragement of research … and the advancement of individual scholars, who by their excellence will advance the sciences they pursue, and the society where they dwell.”

    The mission laid out by Gilman remains the university’s mission today, summed up in a simple but powerful restatement of Gilman’s own words: “Knowledge for the world.”

    What Gilman created was a research university, dedicated to advancing both students’ knowledge and the state of human knowledge through research and scholarship. Gilman believed that teaching and research are interdependent, that success in one depends on success in the other. A modern university, he believed, must do both well. The realization of Gilman’s philosophy at Johns Hopkins, and at other institutions that later attracted Johns Hopkins-trained scholars, revolutionized higher education in America, leading to the research university system as it exists today.

     
  • richardmitnick 7:48 am on March 27, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From New Scientist: “Keeping warming to 2 °C is not enough to save species” 

    NewScientist

    New Scientist

    27 March 2015
    Fred Pearce

    1
    A warmer climate would raise sea levels and swamp islands (Image: Wolfgang Kaehler/Getty)

    Is the world’s target of limiting global warming to 2 °C too high, or too low? Does it even make scientific sense? The consensus around the target, which was agreed at climate talks in Copenhagen in 2009, seems to be coming unstuck.

    Back in October, US climate analysts David Victor and Charles Kennel called it scientifically meaningless and politically unachievable. We should get used to the idea of something warmer, they said.

    Now the target has been denounced as “utterly inadequate”, by Petra Tschakert of Penn State University in University Park, who has been involved in a UN review of the target. She wants a 1.5 °C target instead. Writing in the journal Climate Change Responses, she says this lower limit is necessary if we want sea levels to rise less than a metre, to protect half of all coral reefs, and to still have some ice during Arctic summers.

    Tschakert is not alone. There was a groundswell of support for a revised 1.5 °C target at an expert meeting during the climate conference in Lima, Peru, last December, as part of the UN’s target review. The review is set for publication in June and could be adopted at the Paris climate negotiations this December, where new emissions limits for after 2020 will be agreed.

    Knowledge gap

    In a summary of that meeting, Hans-Otto Pörtner ofthe Alfred Wegener Institute in Bremen, Germany, an author of the Intergovernmental Panel on Climate Change’s Fifth Assessment Report, warned that some species would struggle to cope with the speed of 2 °C warming, but that most organisms should be able to move to a different place under 1.5 °C.

    Tschakert, herself an author on the same IPCC report, says its officials have in the past vetoed discussion of a 1.5 °C target because they were mandated by the UN to look specifically at the effects of 2 °C.

    Nigel Arnell, another IPCC author and a climate scientist at Reading University, UK, says there is simply much less research into 1.5 °C. “The extra benefits are tricky to establish. The science isn’t there yet. Nobody says 2 °C is safe. It is an arbitrary threshold, but so too would be 1.5 °C.”

    Is a cap on warming at 1.5 °C achievable? Many think that, with the world already warmed by 0.85 °C, it is now all but impossible. But even so, it could shape the blame game, said Tschakert. The Paris agreement is likely to include a clause entitling the poorest countries to compensation for “loss and damage” resulting from climate change. If a 1.5 °C target were set – and then exceeded – their case for a payout in the event of climate disaster would be that much stronger. “The stakes,” she writes, “are enormous.”

    See the full article here.

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  • richardmitnick 7:23 am on March 27, 2015 Permalink | Reply
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    From Rockefeller: “Genetic mutation helps explain why, in rare cases, flu can kill” 

    Rockefeller U bloc

    Rockefeller University

    March 26, 2015
    Zach Veilleux | 212-327-8982

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    A small number of children who catch the influenza virus fall so ill they end up in the hospital even while their family and friends recover easily. New research from Rockefeller helps explain why: a rare genetic mutation that prevents the production of a critical protein, interferon, that is needed to fight off the virus.

    Nobody likes getting the flu, but for some people, fluids and rest aren’t enough. A small number of children who catch the influenza virus fall so ill they end up in the hospital — perhaps needing ventilators to breathe — even while their family and friends recover easily. New research by Rockefeller University scientists, published March 26 in Science, helps explain why: a rare genetic mutation.

    The researchers scrutinized blood and tissue samples from a young girl who, at the age of two-and-a-half, developed acute respiratory distress syndrome after catching the flu, and ended up fighting for her life in the hospital. Years after her ordeal, which she survived, scientists led by Jean-Laurent Casanova discovered that it could be explained by a rare mutation she carries that prevented her from producing a protein, interferon, that helps fight off the virus.

    “This is the first example of a common, isolated and life-threatening infection of childhood that is shown to be also a genetic disease,” says Casanova. The good news from these results, however, is that clinicians have a new treatment option for children who mysteriously develop severe cases of the flu. “This finding suggests that one could treat severe flu of childhood with interferon, which is commercially available,” says Casanova, who is professor and head of the St. Giles Laboratory of Human Genetics of Infectious Disease at Rockefeller, as well as a Howard Hughes Medical Institute investigator.

    The fact that a child’s genes could affect the severity of her illness wasn’t a surprise to the members of Casanova’s lab, who have been studying this phenomenon for decades. For instance, they have discovered genetic differences that help explain why the herpes simplex virus — which causes innocuous cold sores in most people — can, in rare cases, lead to potentially fatal infections that spread to the brain.

    Turning their attention to influenza, Michael J. Ciancanelli, a research associate and senior member of Casanova’s lab, and his colleagues sequenced all genes in the genomes of the young girl who survived her dangerous bout of the flu and her parents, looking for mutations that might explain her vulnerability. Knowing how rare her reaction to the flu was, they narrowed their search to mutations that were unique to her, then focused only on those that affected the immune system.

    What emerged from their work was the finding that the girl had inherited two differently mutated copies of the gene IRF7, which encodes a protein that amplifies the production of interferon, a critical part of the body’s response to viral infections. “No other mutations could have explained her reaction to the influenza virus,” says Ciancanelli. “Each mutation is very uncommon and thus the likelihood of carrying two damaged copies of the gene is extremely rare.”

    Indeed, when they infected a sample of her blood cells that normally produce interferon —plasmacytoid dendritic cells — the researchers measured no interferon. In contrast, blood cells from her parents, who each carried only one mutated version of the gene, produced healthy amounts of interferon when exposed to influenza. “That really was definitive proof that a single, non-mutated copy of this gene is enough to allow people to mount a response to the virus,” says Ciancanelli.

    The researchers also employed a cutting-edge technology developed by their collaborators at Columbia University to reprogram the child’s skin cells into early progenitor cells, then differentiate those into lung cells, the front lines of influenza infections. Not surprisingly, the virus replicated more in the patient’s cells than in the same cells from healthy people.

    Although the patient remains susceptible to severe reactions to new influenza viruses, annual vaccination against seasonal flu has, so far, prevented the occurrence of severe symptoms, indiciating that IRF7 is not needed for adaptive immunity to secondary infection by a flu virus.

    Moreover, she hasn’t fallen nearly as ill from other viruses, suggesting her lack of IRF7-dependent interferon production may not leave her vulnerable to viruses overall — a situation the researchers say they have also noted with other mutations that underlie infectious disease.

    See the full article here.

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    Rockefeller U Campus

    The Rockefeller University is a world-renowned center for research and graduate education in the biomedical sciences, chemistry, bioinformatics and physics. The university’s 76 laboratories conduct both clinical and basic research and study a diverse range of biological and biomedical problems with the mission of improving the understanding of life for the benefit of humanity.

    Founded in 1901 by John D. Rockefeller, the Rockefeller Institute for Medical Research was the country’s first institution devoted exclusively to biomedical research. The Rockefeller University Hospital was founded in 1910 as the first hospital devoted exclusively to clinical research. In the 1950s, the institute expanded its mission to include graduate education and began training new generations of scientists to become research leaders around the world. In 1965, it was renamed The Rockefeller University.

     
  • richardmitnick 4:36 pm on March 26, 2015 Permalink | Reply
    Tags: Applied Research & Technology, ,   

    From LANL: “Using magnetic fields to understand high-temperature superconductivity “ 

    LANL bloc

    LANL Sign
    Los Alamos National Laboratory

    March 26, 2015
    Nancy Ambrosiano

    Los Alamos explores experimental path to potential ‘next theory of superconductivity’

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    Los Alamos National Laboratory scientist Brad Ramshaw conducts an experiment at the Pulsed Field Facility of the National High Magnetic Field Lab, exposing high-temperature superconductors to very high magnetic fields, changing the temperature at which the materials become perfectly conducting and revealing unique properties of these substances.

    Taking our understanding of quantum matter to new levels, scientists at Los Alamos National Laboratory are exposing high-temperature superconductors to very high magnetic fields, changing the temperature at which the materials become perfectly conducting and revealing unique properties of these substances.

    “High magnetic-field measurements of doped copper-oxide superconductors are paving the way to a new theory of superconductivity,” said Brad Ramshaw, a Los Alamos scientist and lead researcher on the project. Using world-record high magnetic fields available at the National High Magnetic Field Laboratory (NHMFL) Pulsed Field Facility, based in Los Alamos, Ramshaw and his coworkers are pushing the boundaries of how matter can conduct electricity without the resistance that plagues normal materials carrying an electrical current.

    LANL National High Magnetic Field Lab
    NHMFL

    The eventual goal of the research would be to create a superconductor that operates at room temperature and needs no cooling at all. At this point, all devices that make use of superconductors, such as the MRI magnets found in hospitals, must be cooled to temperatures far below zero with liquid nitrogen or helium, adding to the cost and complexity of the enterprise.

    “This is a truly landmark experiment that illuminates a problem of central importance to condensed matter physics,” said MagLab Director Gregory Boebinger, who is also chief scientist for Condensed Matter Science at the National High Magnetic Field Laboratory’s headquarters in Florida. “The success of this quintessential MagLab work relied on having the best samples, the highest magnetic fields, the most sensitive techniques, and the inspired creativity of a multi-institutional research team.”

    High-temperature superconductors have been a thriving field of research for almost 30 years, not just because they can conduct electricity with no losses—one hundred degrees higher than any other material—but also because they represent a very difficult and interesting “correlated-electron” physics problem in their own right.

    The theory of traditional, low-temperature superconductors was constructed by Bardeen, Cooper, and Schrieffer in 1957, winning them the Nobel prize; this theory (known as the BCS theory) had a far-reaching impact, laying the foundation for the Higgs mechanism in particle physics, and it represents one of the greatest triumphs of 20th century physics.

    On the other hand, high-temperature superconductors, such as yttrium barium copper oxide (YBa2Cu3O6+x), cannot be explained with BCS theory, and so researchers need a new theory for these materials. One particularly interesting aspect of high-temperature superconductors, such as YBa2Cu3O6+x, is that one can change the superconducting transition temperature (Tc, where the material becomes perfectly conducting) by “doping” it, : changing the number of electrons that participate in superconductivity.

    The Los Alamos team’s research in the 100-T magnet found that if one dopes YBa2Cu3O6+x to the point where Tc is highest (“optimal doping”), the electrons become very heavy and move around in a correlated way.

    “This tells us that the electrons are interacting very strongly when the material is an optimal superconductor,” said Ramshaw. “This is a vital piece of information for building the next theory of superconductivity.”

    “An outstanding problem in the field of high-transition-temperature (high-Tc) superconductivity has been the issue as to whether a quantum critical point—a special doping value where quantum fluctuations lead to strong electron-electron interactions—is driving the remarkably high Tc’s in these materials,” he said.

    Proof of its existence has previously not been found due to the robust nature of the superconductivity in the copper oxide materials, yet if scientists can show that there is a quantum critical point, it would constitute a significant milestone toward resolving the superconducting pairing mechanism, Ramshaw explained.

    “Assembling the pieces of this complex superconductivity puzzle is a daunting task that has involved scientists from around the world for decades,” said Charles H. Mielke, NHMFL-Pulsed Field Facility director at Los Alamos. “Though the puzzle is unfinished, this essential piece links unquestionable experimental results to fundamental condensed matter physics — a connection made possible by an exceptional team, strong partner support and unsurpassed capabilities.”

    In a paper this week in the journal Science, the team addresses this longstanding problem by measuring magnetic quantum oscillations as a function of hole doping in very strong magnetic fields in excess of 90 tesla.

    Strong magnetic fields such as the world-record field accessible at the NHMFL site at Los Alamos enable the normal metallic state to be accessed by suppressing superconductivity. Fields approaching 100 tesla, in particular, enable quantum oscillations to be measured very close to the maximum in the transition temperature Tc ~ 94 kelvin. These quantum oscillations give scientists a picture of how the electrons are interacting with each other before they become superconducting.

    By accessing a very broad range of dopings, the authors show that there is a strong enhancement of the effective mass at optimal doping. A strong enhancement of the effective mass is the signature of increasing electron interaction strength, and the signature of a quantum critical point. The broken symmetry responsible for this point has yet to be pinned down, although a connection with charge ordering appears to be likely, Ramshaw notes.

    Funding: Work carried out at the National High Magnetic Field Laboratory—Pulsed Field Facility at Los Alamos National Laboratory was provided through funding from the National Science Foundation Division of Materials Research through Grant No. DMR-1157490 and from the US Department of Energy’s Office of Science, Florida State University, the State of Florida, and Los Alamos National Laboratory through the LDRD program.

    See the full article here.

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    Los Alamos National Laboratory’s mission is to solve national security challenges through scientific excellence.

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    Los Alamos National Laboratory, a multidisciplinary research institution engaged in strategic science on behalf of national security, is operated by Los Alamos National Security, LLC, a team composed of Bechtel National, the University of California, The Babcock & Wilcox Company, and URS for the Department of Energy’s National Nuclear Security Administration.

    Los Alamos enhances national security by ensuring the safety and reliability of the U.S. nuclear stockpile, developing technologies to reduce threats from weapons of mass destruction, and solving problems related to energy, environment, infrastructure, health, and global security concerns.

    Operated by Los Alamos National Security, LLC for the U.S. Dept. of Energy’s NNSA

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  • richardmitnick 2:47 pm on March 26, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , ,   

    From Wisconsin: “Ebola whole virus vaccine shown effective, safe in primates” 

    U Wisconsin

    University of Wisconsin

    March 26, 2015
    Terry Devitt

    1
    Ebola virus swarms the surface of a host cell in this electron micrograph. Like most viruses, Ebola requires the help of a host cell to survive and replicate. Photo: Takeshi Noda, University of Tokyo

    An Ebola whole virus vaccine, constructed using a novel experimental platform, has been shown to effectively protect monkeys exposed to the often fatal virus.

    The vaccine, described today (March 26, 2015) in the journal Science, was developed by a group led by Yoshihiro Kawaoka, a University of Wisconsin-Madison expert on avian influenza, Ebola and other viruses of medical importance. It differs from other Ebola vaccines because as an inactivated whole virus vaccine, it primes the host immune system with the full complement of Ebola viral proteins and genes, potentially conferring greater protection.

    “In terms of efficacy, this affords excellent protection,” explains Kawaoka, a professor of pathobiological sciences in the UW-Madison School of Veterinary Medicine and who also holds a faculty appointment at the University of Tokyo. “It is also a very safe vaccine.”

    The vaccine was constructed on an experimental platform first devised in 2008 by Peter Halfmann, a research scientist in Kawaoka’s lab. The system allows researchers to safely work with the virus thanks to the deletion of a key gene known as VP30, which the Ebola virus uses to make a protein required for it to reproduce in host cells. Ebola virus has only eight genes and, like most viruses, depends on the molecular machinery of host cells to grow and become infectious.

    By engineering monkey kidney cells to express the VP30 protein, the virus can be safely studied in the lab and be used as a basis for devising countermeasures like a whole virus vaccine. The vaccine reported by Kawaoka and his colleagues was additionally chemically inactivated using hydrogen peroxide, according to the new Science report.

    Ebola first emerged in 1976 in Sudan and Zaire. The current outbreak in West Africa has so far claimed more than 10,000 lives. There are no proven treatments or vaccines, although several vaccine platforms have been devised in recent years, four of which recently advanced to the clinical trial stage in humans.

    2
    Yoshihiro Kawaoka

    The new vaccine reported by Kawaoka has not been tested in people. However, the successful tests in nonhuman primates conducted at the National Institutes of Health (NIH) Rocky Mountain Laboratories, a biosafety level 4 facility in Hamilton, Montana, may prompt further tests and possibly clinical trials of the new vaccine. The work at Rocky Mountain Laboratories was conducted in collaboration with a group led by Heinz Feldmann of NIH.

    Those studies were conducted with cynomolgus macaques, which are very susceptible to Ebola. “It’s the best model,” Kawaoka says. “If you get protection with this model, it’s working.”

    Ebola vaccines currently in trials include:

    A DNA-based plasmid vaccine that primes host cells with some of the Ebola proteins.
    A vaccine based on a replication incompetent chimpanzee respiratory virus engineered to express a key Ebola protein.
    A live attenuated virus from the same family of viruses that causes rabies, also engineered to express a critical Ebola protein.
    A vaccine based on a vaccinia virus and engineered to express a critical Ebola protein.

    Each of those strategies, Kawaoka notes, has drawbacks in terms of safety and delivery.

    Whole virus vaccines have long been used to successfully prevent serious human diseases, including polio, influenza, hepatitis and human papillomavirus-mediated cervical cancer.

    The advantage conferred by inactivated whole virus vaccines such as the one devised by Halfmann, Kawaoka and their colleagues is that they present the complete range of proteins and genetic material to the host immune system, which is then more likely to trigger a broader and more robust immune response.

    Early attempts to devise an inactivated whole virus Ebola vaccine through irradiation and the preservative formalin failed to protect monkeys exposed to the Ebola virus and were abandoned.

    Although the new vaccine has surpassed that hurdle, human trials are expensive and complex, costing millions of dollars.

    The Ebola vaccine study conducted by Kawaoka was supported by the National Institutes of Health and by the Japanese Health and Labour Sciences Research Grants.

    In addition to Kawaoka, co-authors of the new Science report include Halfmann, Lindsay Hill-Batorski and Gabriele Neumann of UW-Madison and Andrea Marzi, W. Lesley Shupert and Feldmann of the National Institute of Allergy and Infectious Diseases.

    See the full article here.

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    In achievement and prestige, the University of Wisconsin–Madison has long been recognized as one of America’s great universities. A public, land-grant institution, UW–Madison offers a complete spectrum of liberal arts studies, professional programs and student activities. Spanning 936 acres along the southern shore of Lake Mendota, the campus is located in the city of Madison.

     
  • richardmitnick 1:19 pm on March 26, 2015 Permalink | Reply
    Tags: Applied Research & Technology, , Horizon 2020, Ukraine   

    From AAAS: “Ukraine joins E.U. research club—at a steep discount” 

    AAAS

    AAAS

    24 March 2015
    Tania Rabesandratana

    1
    European Commissioner Carlos Moedas (left) and Ukrainian education and science minister Serhii Myronovych Kvit exchange signatures in Kiev.

    Ukraine has earned privileged access to competitive research funds from the European Union, bringing its science closer to the Western bloc. Under a deal signed in Kiev on 20 March with the European Commission, Ukraine becomes an “associated country” to Horizon 2020, the European Union’s €80 billion, 7-year research program. That means researchers and businesses in Ukraine may apply for any Horizon 2020 grant.

    The commission has given Ukraine a sweet deal: It receives a 95% rebate on its association fee and a 1-year deferment to pay the first year’s installment. The agreement is a testament to the European Union’s will to build closer economic and political ties with its former Soviet neighbor, a process that has sped up after the conflict in Eastern Ukraine erupted last year. Researchers in the Crimean Peninsula, annexed by Russia, are excluded from the agreement.

    “Ukraine will now have access to the full spectrum of activities funded under Horizon 2020, helping spur its economy,” said E.U. research commissioner Carlos Moedas in a statement.

    Ukraine-based researchers did receive about €24 million of E.U. research money under the previous program, between 2007 and 2013. But until now, Russia’s neighbor had the status of a “third country,” meaning that researchers there were excluded from parts of the program, including coveted grants from the European Research Council (ERC). The upgrade puts Ukraine on par with 12 other non-E.U. countries including Iceland, Norway, and Turkey.

    Ukrainian applicants are encouraged to submit research proposals under this year’s calls, says a Horizon 2020 document issued last month, but formal grant agreements will be signed only when the Horizon 2020 agreement enters into force—that is, after the Ukrainian parliament ratifies it.

    The conflict in Ukraine has had a major impact on the country’s science. Entire universities have been relocated from war-torn Eastern Ukraine, along with an estimated 1500 scientists and 10,000 students; meanwhile, the country lost several important research assets when Russia annexed the Crimean Peninsula in March 2014. The European Union strongly rejects the annexation, and the Horizon 2020 association rules reflect that. “Given that the EU does not recognise the illegal annexation … legal persons established in the Autonomous Republic of Crimea or the city of Sevastopol are not eligible to participate,” says the document.

    The European Union has tried to build bridges with Ukraine in other ways as well; last year, it offered a package of aid and loans worth more than €11 billion to boost recovery and reform.

    See the full article here..

    The American Association for the Advancement of Science is an international non-profit organization dedicated to advancing science for the benefit of all people.

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