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  • richardmitnick 1:22 pm on June 30, 2017 Permalink | Reply
    Tags: , , , , Science   

    From Science: “Cancer studies pass reproducibility test” 

    AAAS
    Science Magazine

    Jun. 27, 2017
    Jocelyn Kaiser
    1
    Though researchers have had general success reproducing cancer results, studies involving mice have proven difficult to replicate.
    Adva/Flickr (CC BY-NC 2.0)

    A high-profile project aiming to test reproducibility in cancer biology has released a second batch of results, and this time the news is good: Most of the experiments from two key cancer papers could be repeated.

    The latest replication studies, which appear today in eLife, come on top of five published in January that delivered a mixed message about whether high-impact cancer research can be reproduced. Taken together, however, results from the completed studies are “encouraging,” says Sean Morrison of the University of Texas Southwestern Medical Center in Dallas, an eLife editor. Overall, he adds, independent labs have now “reproduced substantial aspects” of the original experiments in four of five replication efforts that have produced clear results.

    In the two new replication efforts, however, one key mouse experiment could not be repeated, suggesting ongoing problems with the reproducibility of animal studies, says one leader of the Reproducibility Project: Cancer Biology.

    The unusual initiative was inspired by reports from two drugs companies that up to 89% of preclinical biomedical studies didn’t hold up in their labs. The project is having contract labs repeat key experiments from about 30 high-impact cancer papers published between 2010 and 2012. Whereas some researchers laud the effort, others have worried that contract labs lack the expertise to perform certain experiments as well as cutting-edge academic research labs and that any failures will unfairly tarnish the field.

    In January, critics’ fears were realized when the first five replications came out. Only two studies could be reproduced; one result was negative, and two studies were ruled inconclusive because of problems with mouse tumor models. The findings have led some experts to conclude that biomedicine suffers from a replication crisis.

    Now, scientists’ track records seem to be improving. In one of the new studies [eLIFE], a contract lab confirmed a 2010 report in Cancer Cell that mutations in genes called IDH1 and IDH2, found in some leukemias and brain cancers, cause cells to produce a metabolite that spurs cancer growth. The replicators also verified that levels of the metabolite in leukemia cells indicate whether a cancer patient has the IDH mutations. (The original paper’s lead author, Craig Thompson of Memorial Sloan Kettering Cancer Center in New York City, who co-founded a company that is testing IDH drugs in clinical trials, was traveling and unable to comment.)

    The second replication study [eLIFE]looked at a 2011 Nature paper reporting that a compound called a BET inhibitor, which controls whether genes are activated—can stop a type of leukemia. As in the original study, the compound, I-BET151, killed human leukemia cells in a dish and reduced their numbers in mice that had been injected with the cells. However, unlike in the original paper, these mice did not survive any longer than untreated mice with leukemia.

    Several scientists say that result doesn’t invalidate the overall conclusions that I-BET151 works against leukemia. The replication team did the mouse experiment differently, using a lower dose of I-BET151, for example. Given such differences, “I think we should be careful not to make too much of the absence of statistically significant differences in survival as an endpoint,” says Harvard University molecular biologist Karen Adelman, an eLife editor who oversaw reviews of the replication paper.

    And cancer biologist Tony Kouzarides of the University of Cambridge in the United Kingdom, who led the original Nature study, says this one negative result “highlights the pitfalls of biological research, namely that different labs may vary conditions that affect the outcome of a given experiment.”

    But Tim Errington of the Center for Open Science in Charlottesville, Virginia, which is co-sponsoring the reproducibility project, counters that the fact that the mouse survival experiment worked only under certain conditions raises questions about whether the paper’s overall findings are “robust.” He adds, “You want this to be generalizable.”

    The cancer biology project hopes to finish experiments for another 22 replications by the end of this year, when the grant funding the effort runs out, Errington says.

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  • richardmitnick 8:22 am on June 29, 2017 Permalink | Reply
    Tags: , , , , Reproducibility Project: Cancer Biology, Science, Scientists’ track records seem to be improving   

    From Science: “Cancer studies pass reproducibility test” 

    AAAS
    Science

    Jun. 27, 2017
    Jocelyn Kaiser

    1
    Though researchers have had general success reproducing cancer results, studies involving mice have proven difficult to replicate.
    Adva/Flickr (CC BY-NC 2.0)

    A high-profile project aiming to test reproducibility in cancer biology has released a second batch of results, and this time the news is good: Most of the experiments from two key cancer papers could be repeated.

    The latest replication studies, which appear today in eLife, come on top of five published in January that delivered a mixed message about whether high-impact cancer research can be reproduced. Taken together, however, results from the completed studies are “encouraging,” says Sean Morrison of the University of Texas Southwestern Medical Center in Dallas, an eLife editor. Overall, he adds, independent labs have now “reproduced substantial aspects” of the original experiments in four of five replication efforts that have produced clear results.

    In the two new replication efforts, however, one key mouse experiment could not be repeated, suggesting ongoing problems with the reproducibility of animal studies, says one leader of the Reproducibility Project: Cancer Biology.

    The unusual initiative was inspired by reports from two drugs companies that up to 89% of preclinical biomedical studies didn’t hold up in their labs. The project is having contract labs repeat key experiments from about 30 high-impact cancer papers published between 2010 and 2012. Whereas some researchers laud the effort, others have worried that contract labs lack the expertise to perform certain experiments as well as cutting-edge academic research labs and that any failures will unfairly tarnish the field.

    In January, critics’ fears were realized when the first five replications came out. Only two studies could be reproduced; one result was negative, and two studies were ruled inconclusive because of problems with mouse tumor models. The findings have led some experts to conclude that biomedicine suffers from a replication crisis.

    Now, scientists’ track records seem to be improving. In one of the new studies, a contract lab confirmed a 2010 report in Cancer Cell that mutations in genes called IDH1 and IDH2, found in some leukemias and brain cancers, cause cells to produce a metabolite that spurs cancer growth. The replicators also verified that levels of the metabolite in leukemia cells indicate whether a cancer patient has the IDH mutations. (The original paper’s lead author, Craig Thompson of Memorial Sloan Kettering Cancer Center in New York City, who co-founded a company that is testing IDH drugs in clinical trials, was traveling and unable to comment.)

    The second replication study looked at a 2011 Nature paper reporting that a compound called a BET inhibitor, which controls whether genes are activated—can stop a type of leukemia. As in the original study, the compound, I-BET151, killed human leukemia cells in a dish and reduced their numbers in mice that had been injected with the cells. However, unlike in the original paper, these mice did not survive any longer than untreated mice with leukemia.

    Several scientists say that result doesn’t invalidate the overall conclusions that I-BET151 works against leukemia. The replication team did the mouse experiment differently, using a lower dose of I-BET151, for example. Given such differences, “I think we should be careful not to make too much of the absence of statistically significant differences in survival as an endpoint,” says Harvard University molecular biologist Karen Adelman, an eLife editor who oversaw reviews of the replication paper.

    And cancer biologist Tony Kouzarides of the University of Cambridge in the United Kingdom, who led the original Nature study, says this one negative result “highlights the pitfalls of biological research, namely that different labs may vary conditions that affect the outcome of a given experiment.”

    But Tim Errington of the Center for Open Science in Charlottesville, Virginia, which is co-sponsoring the reproducibility project, counters that the fact that the mouse survival experiment worked only under certain conditions raises questions about whether the paper’s overall findings are “robust.” He adds, “You want this to be generalizable.”

    The cancer biology project hopes to finish experiments for another 22 replications by the end of this year, when the grant funding the effort runs out, Errington says.

    See the full article here .

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  • richardmitnick 2:07 pm on June 16, 2017 Permalink | Reply
    Tags: , , , Science, The Baker Lab U Washington   

    From Science: “Designer protein halts flu” 

    AAAS
    Science Magazine

    June 12, 2017
    Robert Service

    1

    A designer protein (brown and orange) fits snugly on top of the influenza virus’s hemagglutinin protein (green), which helps the virus latch onto and infect cells.
    Eva-Maria Strauch

    There’s a new weapon taking shape in the war on flu, one of the globe’s most dangerous infectious diseases. Scientists have created a designer protein that stops the influenza virus from infecting cells in culture and protects mice from getting sick after being exposed to a heavy dose of the virus. It can also be used as a sensitive diagnostic. And although it isn’t ready as a treatment itself, the protein may point the way to future flu drugs, scientists say.

    “It’s impressive,” says James Crowe, an immunologist at Vanderbilt University in Nashville, who was not involved in the study. But because it hasn’t yet been tested in humans, “it [still] has a long way to go,” he says.

    Influenza severely sickens 3–5 million people each year, and it kills between 250,000 and 500,000, mostly the elderly and people with weakened immune systems. Every year, public health officials survey the three flu subtypes circulating in humans and design a vaccine for the next winter season that covers them all. But those vaccines are far from perfect: They don’t always exactly match the viruses actually going around, and in some people, the shots fail to trigger a vigorous immune response.

    Drugs are another line of defense. Most focus on the proteins on the virus’s outer coat, neuraminidase and hemagglutinin (HA). Some drugs that block neuraminidase, which helps the virus escape already infected cells, are starting to bump up against viral resistance. HA is scientists’ next target. The mushroom-shaped protein specializes in infecting cells, first by binding a trio of sites on its head to three separate sugar molecules on the surface of targeted cells. Once the virus latches on, parts of HA’s stem act as a grappling hook to pull the virus in close, allowing it to fuse with the cell membrane and release its contents inside.

    In 2011, researchers led by David Baker, a computational biologist at the University of Washington in Seattle, created a designer protein that binds HA’s stem, which prevented viral infection in cell cultures.

    Dr. David Baker, Baker Lab, U Washington

    But because the stem is often shrouded by additional protein, it can be hard for drugs to reach it.

    Now, Baker’s team has designed proteins to target HA’s more exposed head group. They started by analyzing x-ray crystal structures that show in atomic detail how flu-binding antibodies in people grab on to the three sugar-binding sites on HA’s head. They copied a small portion of the antibody that wedges itself into one of these binding sites. They then used protein design software called Rosetta to triple that head-binding section, creating a three-part, triangular protein, which the computer calculated would fit like a cap over the top of HA’s head group.

    Rosetta@home project, a project running on BOINC software from UC Berkeley

    My BOINC

    Next, they synthesized a gene for making the protein and inserted it into bacteria, which cranked out copies for them to test.

    In the test, Baker’s team immobilized copies of the protein on a paperlike material called nitrocellulose. They then exposed it to different strains of the virus, which it grabbed and held. “We call it flu glue, because it doesn’t let go,” Baker says. In other experiments, the protein blocked the virus from infecting cells in culture, and it even prevented mice from getting sick when administered either 1 day before or after viral exposure, they report today in Nature Biotechnology.

    Despite these early successes, Baker and Crowe caution that the newly designed protein isn’t likely to become a medicine itself. For starters, Baker says, the protein doesn’t bind all flu strains that commonly infect humans. That means a future drug may require either a cocktail of HA head group binding proteins or work in combination with stem-binding versions. Second, the safety of designer proteins will have to be studied carefully, Crowe says, because they are markedly different than natural HA-binding antibodies. “The further you get away from a natural antibody, the less you can predict what will happen,” Crowe says.

    But down the road, Baker says, the new designer protein could serve as the basis for a cheap diagnostic—akin to a pregnancy test—for detecting flu and possibly even medicines able to knock it out.

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  • richardmitnick 3:23 pm on April 15, 2017 Permalink | Reply
    Tags: , , Science, Teleocrater   

    From Science: “Curious fossil could rewrite early days of the dinosaurs” 

    AAAS
    Science Magazine

    Apr. 12, 2017
    Carolyn Gramling

    1
    In this artist’s rendition of life in the middle Triassic, carnivorous Teleocrater rhadinus, newly identified as a very early ancestor of dinosaurs and pterosaurs, feasts on mammallike reptile Cynognathus. Natural History Museum, London, artwork by Mark Witton

    How did the dinosaur become the dinosaur? Somewhere along the line, the ancestor of dinosaurs diverged from the ancestor of crocodiles, a momentous split in the evolution of vertebrates that ultimately set the stage for the age of dinos. But the details of that split remain mysterious, thanks to a dearth of fossils of early dinosaur relatives. Enter the newly identified 247-million- to 242-million-year-old Teleocrater rhadinus, a close relative of dinosaurs that also happened to walk on all fours and share some key features with the ancestors of crocodiles. These shared features, the authors say, suggest that it’s time to rethink what we thought we knew about dinosaurs’ earliest ancestors.

    “We’ve been waiting a long time to find fossils like this that fit in this part of the family tree,” says Randall Irmis, a paleontologist at the Natural History Museum of Utah in Salt Lake City, who was not involved in the work. “This has pretty big implications for how we understand the early evolution of dinosaurs.”

    Some 251 million years ago, at the end of the Permian period, a mass extinction wiped out most of life on Earth. In its wake arose a group of egg-laying reptile precursors called archosaurs, the common ancestors of dinosaurs, flying reptiles known as pterosaurs, and crocodiles. At some point during the next period, the Triassic, pterosaurs and dinosaurs split off from the crocodile lineage.

    Those two different lineages, avian versus crocodilian, have long been identified by their types of ankle joints. Dinosaurs and pterosaurs all have a version of a hinged, birdlike ankle, rather than the crocodilelike ankle with ball-and-socket joint.

    But exactly what early dinosaurs and their closest relatives looked like has been something of a mystery, because few fossils exist from the dawn of the dinosaurs. And many of the fossils that do exist, collected perhaps decades to a century ago, languish unidentified in museum drawers.

    Indeed, Teleocrater isn’t a completely new discovery. A specimen was first unearthed in what is now Tanzania in the 1930s and sat in London’s Natural History Museum until 1956, when Ph.D. candidate Alan Charig (later a paleontologist at the museum) dubbed it T. rhadinus (referring to the shape of the animal’s hip and its slender body). Charig, who died in 1997 but is included as an author on the new paper, speculated that it was some sort of early dinosaur relative. But the fossil was in pieces, just bits of vertebrae and pelvis and limb, and difficult to place on the family tree.

    Then in 2015, Sterling Nesbitt, a paleontologist at Virginia Polytechnic Institute and State University in Blacksburg, and a team of researchers headed back to southern Tanzania to take another look at the middle Triassic rocks where Teleocrater was first discovered. This time, the rocks—estimated to be about 247 million to 242 million years old—yielded several individuals of the same species. With that new bounty, the researchers were able to catalog many more of the creature’s features—enough to place it on the vertebrate family tree.

    Teleocrater, Nesbitt and his co-authors report online today in Nature, belongs at the very base of the avian lineage that later gave rise to dinosaurs. It has a characteristic muscle scar on the upper leg bone that is found only in the avian lineage of birds and dinosaurs and is missing in crocodiles and their relatives. But Teleocrater also had a crocodilelike ankle, with a ball-and-socket joint. That suggests that the crocodile ankle came first, and the bird ankle evolved later.

    That’s key, because the ankle joint has been used for decades as an indicator of avian versus crocodilian lineage, so Teleocrater must be close to the split between them. And in several respects, Nesbitt says, “Teleocrater looks more like the relatives of the crocodiles than the relatives of dinosaurs.” The carnivorous animal, which was roughly the size of a small lion, walked on all fours, its forelimbs and hindlimbs are similar in proportion, and the limbs themselves are pretty short relative to the length of the body.

    Seemingly small details like these can produce ripples throughout paleontology collections, because they can help researchers properly classify fossils that had seemed to be walking contradictions. “These fossils exist in museums around the world, but until you find a keystone—something that helps you understand the full anatomy [of a species]—you won’t understand where these animals go on the tree of life,” Nesbitt says.

    After identifying Teleocrater as an ancestor along the avian lineage, the authors could group it with several other difficult-to-place animals, including Dongusuchus and Spondylosoma, naming a new group of long-necked, carnivorous quadrupeds dubbed Aphanosauria (hidden or obscure lizards, in Greek). Aphanosaurs, they suggest, are the earliest group in the avian stem lineage to diverge from the crocodile lineage. And that suggests that these bird and dinosaur ancestors were far more diverse and widely distributed across the globe during the middle Triassic than once thought.

    The find may also alter what paleontologists hunt for in the field, as well as how they understand existing collections, says Max Langer, a paleontologist at the University of São Paulo in Rio Claro, Brazil. “Now that we know the diagnostic features of this group of archosaurs, everybody working on middle Triassic rocks will be looking for something similar.”

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  • richardmitnick 7:18 pm on February 24, 2017 Permalink | Reply
    Tags: , , Science   

    From Science: “Spinning black holes could fling off clouds of dark matter particles” 

    ScienceMag
    Science Magazine

    Feb. 22, 2017
    Adrian Cho

    1

    A spinning black hole (white) should produce huge clouds of particles called axions (blue), which would then produce detectable gravitational waves, a new calculation predicts. Masha Baryakhtar

    Few things are more mind bending than black holes, gravitational waves, and the nearly massless hypothetical particles called axions, which could be the mysterious dark matter whose gravity holds galaxies together. Now, a team of theoretical physicists has tied all three together in a surprising way. If the axion exists and has the right mass, they argue, then a spinning black hole should produce a vast cloud of the particles, which should, in turn, produce gravitational waves akin to those discovered a year ago by the Laser Interferometer Gravitational-Wave Observatory (LIGO). If the idea is correct, LIGO might be able to detect axions, albeit indirectly.

    “It’s an awesome idea,” says Tracy Slatyer, a particle astrophysicist at the Massachusetts Institute of Technology (MIT) in Cambridge, who was not involved in the work. “The [LIGO] data is going to be there, and it would be amazing if we saw something.” Benjamin Safdi, a theoretical particle physicist at MIT, is also enthusiastic. “This is really the best idea we have to look for particles in this mass range,” he says.

    A black hole is the intense gravitational field left behind when a massive star burns out and collapses to a point. Within a certain distance of that point—which defines the black hole’s “event horizon”—gravity grows so strong that not even light can escape. In September 2015, LIGO detected a burst of ripples in space called gravitational waves that emanated from the merging of two black holes.

    The axion—if it exists—is an uncharged particle perhaps a billionth as massive as the electron or lighter. Dreamed up in the 1970s, it helps explain a curious mathematical symmetry in the theory of particles called quarks and gluons that make up protons and neutrons. Axions floating around might also be the dark matter that’s thought to make up 85% of all matter in the universe. Particle physicists are searching for axions in experiments that try to convert them into photons using magnetic fields.

    But it may be possible to detect axions by studying black holes with LIGO and its twin detectors in Louisiana and Washington states, argue Asimina Arvanitaki and Masha Baryakhtar, theorists at the Perimeter Institute for Theoretical Physics in Waterloo, Canada, and their colleagues.

    If its mass is in the right range, then an axion stuck in orbit around a black hole should be subject to a process called superradiance that occurs in many situations and causes photons to multiply in a certain type of laser. If an axion strays near, but doesn’t cross, a black hole’s event horizon, then the black hole’s spin will give the axion a boost in energy. And because the axion is a quantum particle with some properties like those of the photon, that boost will create more axions, which will, in turn, interact with the black hole in the same way. The runaway process should thus generate vast numbers of the particles.

    But for this to take place, a key condition has to be met. A quantum particle like the axion can also act like a wave, with lighter particles having longer wavelengths. For superradiance to kick in, the axion’s wavelength must be as long as the black hole is wide. So the axion’s mass must be extremely light: between 1/10,000,000 and 1/10,000 the range probed in current laboratory experiments. The axions wouldn’t just emerge willy-nilly, either, but would crowd into huge quantum waves like the orbitals of the electrons in an atom. As fantastical as that sounds, the basic physics of superradiance is well established, Safdi says.

    The axion cloud might reveal itself in multiple ways, Baryakhtar says. Most promising, axions colliding in the cloud should annihilate one another to produce gravitons, the particles thought to make up gravitational waves just as photons make up light. Emerging from orderly quantum clouds, the gravitons would form continuous waves with a frequency set by the axion’s mass. LIGO would be able to spot thousands of such sources per year [Physical Review D], Baryakhtar and colleagues estimate in a paper published 8 February in Physical Review D—although tracking those continuous signals may be harder than detecting bursts from colliding black holes. Spotting multiple same-frequency sources would be a “smoking gun” for axions, Slatyer says.

    The axion clouds could produce indirect signals, too. In principle, a black hole can spin at near light speed. However, generating axions would sap a black hole’s angular momentum and slow it. As a result, LIGO should observe that the spins of colliding black holes never reach that ultimate speed, but top out well below it, Baryakhtar says. Detecting that limit on spin would be challenging, as LIGO can measure a colliding black hole’s spin with only 25% precision.

    Safdi cautions that the analysis assumes that LIGO will see lots of black-hole mergers and will perform as expected. And if LIGO doesn’t see the signals, it won’t rule out the axion, he says. Still, he says, “This is probably the most promising paper I’ve seen so far on the new physics we might probe with gravitational waves.”

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  • richardmitnick 11:29 am on January 22, 2017 Permalink | Reply
    Tags: , , How white blood cells rip holes in your blood vessels—and how your blood vessels recover, Science   

    From Science: “How white blood cells rip holes in your blood vessels—and how your blood vessels recover” 

    ScienceMag
    Science Magazine

    1
    A. Barzilai et. al. Cell Reports 18, 3 (17 January 2017) © 2017 Elsevier Inc.

    Jan. 17, 2017
    Emma Hiolski

    White blood cells are constantly tearing holes in your blood vessel walls. But these guardians of the immune system are doing it to protect you: Once they ride through the bloodstream to infected tissues—where they make antibodies and eat foreign invaders—they need a way to get inside. Now, scientists have discovered just how they do it without permanently damaging blood vessels, which they slip into and out of up to 10 times each day. First, researchers added fluorescent tags to their nuclei and to the structural fibers of blood vessel walls, which keep out foreign particles and seal in blood, plasma, and immune cells. The researchers then tracked the process with video-microscopy. They found that blood vessel cells were not the ones making the openings, as previously thought. Instead, immune cells make their own way across. By softening their bulky nuclei and pushing them to the front edge of their cells, white blood cells probe apart scaffolding in the blood vessel walls and squeeze through, researchers report online today in Cell Reports. This process (seen above) snaps smaller, threadlike fibers that form the flexible scaffolding of blood vessel walls; the cells easily repair that breakage later as part of routine cellular maintenance. The researchers hope to use their discovery to better understand how metastatic cancer cells migrate into the bloodstream and spread cancer throughout the body.

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  • richardmitnick 2:41 pm on January 9, 2017 Permalink | Reply
    Tags: , Science, The fetal brain   

    From Science: “Pioneering study images activity in fetal brains” 

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    Science

    1
    The human brain undergoes a remarkable transition in utero, but until recently scientists have had few tools to study how this process unfolds.
    iStock Photo

    Jan. 9, 2017
    Greg Miller

    Babies born prematurely are prone to problems later in life—they’re more likely to develop autism or attention deficit hyperactivity disorder, and more likely to struggle in school. A new study that’s among the first to investigate brain activity in human fetuses suggests that the underlying neurological issues may begin in the womb. The findings provide the first direct evidence of altered brain function in fetuses that go on to be born prematurely, and they might ultimately point to ways to remediate or even prevent such early injuries.

    In the new study, published 9 January in Scientific Reports, developmental neuroscientist Moriah Thomason of Wayne State University School of Medicine in Detroit, Michigan, and colleagues report a difference in how certain brain regions communicate with each other in fetuses that were later born prematurely compared with fetuses that were carried to term. Although the findings are preliminary because the study was small, Thomason and other researchers say the work illustrates the potential (and the challenges) of the emerging field of fetal neuroimaging. “Harnessing the power of these advanced tools is offering us for the very first time the opportunity to explore the onset of neurologic insults that are happening in utero,” says Catherine Limperopoulos, a pediatric neuroscientist at Children’s National Medical Center in Washington, D.C.

    Thomason and colleagues used functional magnetic resonance imaging (fMRI) to investigate brain activity in 32 fetuses. The pregnant mothers were participants in a larger, long-term study of brain development led by Thomason. “The majority have just normal pregnancies, but they’re drawn from a low-resource population that’s at greater risk of early delivery and developmental problems,” she says. In the end, 14 of the fetuses were born prematurely.

    The team’s approach relied on methods developed in the past decade or so to study “functional connectivity” in the adult human brain—essentially using fMRI to determine which brain regions have synchronized activity when the subject is not engaged in any particular task. Synchronized activity between brain regions, the thinking goes, shows that those regions are well connected and sharing information.

    2
    Colored regions in these MRI images of a human fetus (shown from two perspectives) indicate brain regions where connectivity grows stronger between the 20th and 40th weeks of gestation. Data courtesy of Moriah E. Thomason, Wayne State University School of Medicine.

    One feature stood out in the brains of the fetuses that were ultimately born prematurely: A small patch on the left side of the brain, in an area that develops into a language processing center, had weaker connectivity with other brain regions than it did in fetuses carried to full term. “That they can detect this difference in connectivity so early is something interesting,” says Hao Huang, who studies neonatal brain development at the University of Pennsylvania. “Usually with earlier detection you have better chances for intervention.” Language problems are common in children born prematurely, and Thomason plans to track these children as they develop.

    Previous studies have reported altered connectivity in the brains of premature infants, but only after birth, leaving open the possibility that stress, oxygen deprivation, or other injury during delivery is to blame. But Thomason and her colleagues not only found that the impairment starts earlier; they also found a hint of a cause. The mothers who delivered prematurely had more inflammation in their placental tissue, which leads Thomason to suspect that maternal infection or inflammation might play a role.

    This type of study would have been impossible only a short time ago. One of the biggest problems in fetal neuroimaging is that a fetus is a moving target, bobbing around inside the amniotic sac. “A fetus has so many degrees of freedom,” says Veronika Schöpf, a mathematician at the University of Graz in Austria who is developing computational tools for fetal neuroimaging. That’s a problem because an MRI scan is like a stack of pancakes—thin slices piled neatly on top of one another. Any movement throws the slices out of register. But Schöpf says better algorithms are helping scientists stitch together slices taken from slightly different angles because the subject moved. At the same time, MRI machines have gotten faster, making it possible to collect more slices in a shorter time. That’s a big deal, Thomason says, because it means getting more data during periods when a fetus is staying still.

    The fetal brain is a moving target in another sense, too. Its anatomy is in constant flux as it matures, which means researchers need templates and atlases for different developmental time points to be able to make comparisons across subjects. Several research groups around the world are currently developing these resources.

    The ability to image the fetal brain at work opens up questions in basic science, too, Huang says. In the course of a pregnancy, the human brain transforms from a simple fluid-filled tube into a complex organ ready to perceive and interact with the outside world. How this process unfolds is largely a mystery, and Huang is eager to probe such questions as how and when the networks found in the mature brain develop and become active for the first time. At last, he says, “The techniques are catching up” to the questions.

    See the full article here .

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  • richardmitnick 2:28 pm on December 4, 2016 Permalink | Reply
    Tags: , , Cold brown dwarfs, , Science   

    From Science: “Alien life could thrive in the clouds of failed stars” 

    ScienceMag
    Science Magazine

    1
    The comfortably warm atmosphere of a brown dwarf is an underappreciated potential home for alien life, scientists say. Mark Garlick/Science Source

    Dec. 2, 2016
    Joshua Sokol

    There’s an abundant new swath of cosmic real estate that life could call home—and the views would be spectacular. Floating out by themselves in the Milky Way galaxy are perhaps a billion cold brown dwarfs, objects many times as massive as Jupiter but not big enough to ignite as a star. According to a new study, layers of their upper atmospheres sit at temperatures and pressures resembling those on Earth, and could host microbes that surf on thermal updrafts.

    The idea expands the concept of a habitable zone to include a vast population of worlds that had previously gone unconsidered. “You don’t necessarily need to have a terrestrial planet with a surface,” says Jack Yates, a planetary scientist at the University of Edinburgh in the United Kingdom, who led the study.

    Atmospheric life isn’t just for the birds. For decades, biologists have known about microbes that drift in the winds high above Earth’s surface. And in 1976, Carl Sagan envisioned the kind of ecosystem that could evolve in the upper layers of Jupiter, fueled by sunlight. You could have sky plankton: small organisms he called “sinkers.” Other organisms could be balloonlike “floaters,” which would rise and fall in the atmosphere by manipulating their body pressure. In the years since, astronomers have also considered the prospects of microbes in the carbon dioxide atmosphere above Venus’s inhospitable surface.

    Yates and his colleagues applied the same thinking to a kind of world Sagan didn’t know about. Discovered in 2011, some cold brown dwarfs have surfaces roughly at room temperature or below; lower layers would be downright comfortable. In March 2013, astronomers discovered WISE 0855-0714, a brown dwarf only 7 light-years away that seems to have water clouds in its atmosphere. Yates and his colleagues set out to update Sagan’s calculations and to identify the sizes, densities, and life strategies of microbes that could manage to stay aloft in the habitable region of an enormous atmosphere of predominantly hydrogen gas. Sink too low and you are cooked or crushed. Rise too high and you might freeze.

    On such a world, small sinkers like the microbes in Earth’s atmosphere or even smaller would have a better chance than Sagan’s floaters, the researchers will report in an upcoming issue of The Astrophysical Journal. But a lot depends on the weather: If upwelling winds are powerful on free-floating brown dwarfs, as seems to be true in the bands of gas giants like Jupiter and Saturn, heavier creatures can carve out a niche. In the absence of sunlight, they could feed on chemical nutrients. Observations of cold brown dwarf atmospheres reveal most of the ingredients Earth life depends on: carbon, hydrogen, nitrogen, and oxygen, though perhaps not phosphorous.

    The idea is speculative but worth considering, says Duncan Forgan, an astrobiologist at the University of St. Andrews in the United Kingdom, who did not participate in the study but says he is close to the team. “It really opens up the field in terms of the number of objects that we might then think, well, these are habitable regions.”

    So far, only a few dozen cold brown dwarfs have been discovered, though statistics suggest there should be about 10 within 30 light-years of Earth. These should be ripe targets for the James Webb Space Telescope (JWST), which is sensitive in the infrared where brown dwarfs shine brightest.

    NASA/ESA/CSA Webb Telescope annotated
    NASA/ESA/CSA Webb Telescope annotated

    After it launches in 2018, the JWST should reveal the weather and the composition of their atmospheres, says Jackie Faherty, an astronomer at the Carnegie Institution for Science in Washington, D.C. “We’re going to start getting gorgeous spectra of these objects,” she says. “This is making me think about it.”

    Testing for life would require anticipating a strong spectral signature of microbe byproducts like methane or oxygen, and then differentiating it from other processes, Faherty says. Another issue would be explaining how life could arise in an environment that lacks the water-rock interfaces, like hydrothermal vents, where life is thought to have begun on Earth. Perhaps life could develop through chemical reactions on the surfaces of dust grains in the brown dwarf’s atmosphere, or perhaps it gained a foothold after arriving as a hitchhiker on an asteroid. “Having little microbes that float in and out of a brown dwarf atmosphere is great,” Forgan says. “But you’ve got to get them there first.”

    See the full article here .

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  • richardmitnick 7:54 am on August 11, 2016 Permalink | Reply
    Tags: , , Science, Yellow Fever   

    From Science: “Yellow fever emergency forces officials to combat virus with tiny dose of vaccine” 

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    Aug. 10, 2016
    Kai Kupferschmidt

    1
    Mothers wait to have their children vaccinated during routine vaccination at a health center in the town of Nyunzu in the Democratic Republic of the Congo. Olivier Asselin/Alamy Stock Photo

    It’s an unprecedented emergency measure, but one that could become the norm: In a bid to stop an outbreak of yellow fever, more than 8 million people in Kinshasa, the capital of the Democratic Republic of the Congo (DRC), will be vaccinated using just one-fifth the normal dose. The campaign, scheduled to start next week, comes as yellow fever continues to spread in the DRC and vaccine demand outstrips supply.

    Scientists feel confident that the lower doses will offer protection, at least for the short term, but they are urging studies accompanying the campaign to assess whether routine use of the lower dose is an option.

    The current outbreak started in neighboring Angola in December of last year and later spread to the DRC. According to the World Health Organization (WHO), more than 16 million people in the two countries have already been vaccinated, and Angola has reported no new cases for more than 6 weeks. But new cases are still emerging in the DRC, which has reported more than 2000 suspected cases so far and 95 deaths.

    WHO’s emergency stockpile of yellow fever vaccine, which was depleted earlier this year, has been restocked and is now back to 5 million doses. But the Congolese government, worried that the virus could spread rapidly among Kinshasa’s 10 million residents, has decided to stretch the 1.7 million doses it has received by giving people 0.1 milliliters of the vaccine each instead of the standard 0.5 milliliters.

    The yellow fever virus is primarily transmitted by Aedes aegypti, the mosquito species that also spreads Zika and dengue. Most people who are infected have no symptoms, but about 15% develop serious disease, and about half these patients die. There is no cure, but the vaccine, although cumbersome to produce, is highly effective: A single dose confers lifelong protection.

    Fearing that the disease could spread to Asia, which has never seen a yellow fever outbreak, some experts had urged governments and WHO to adopt the vaccine-saving strategy. In June, WHO’s Strategic Advisory Group of Experts (SAGE) on Immunization concluded that the lower dose would still offer protection for at least 12 months. (The recommendation was made in an emergency session, but the group has planned a formal evaluation for October.) “We felt very comfortable with the data that was presented to go ahead and make the recommendation,” says SAGE chair Jon Abramson, a pediatrician at Wake Forest School of Medicine in Winston-Salem, North Carolina. “We feel the benefit of vaccinating as many people as we can far outweighs the small risk that somebody won’t respond who could have responded to a larger dose.”

    SAGE advised that children under 2 years of age should receive the full dose, however, and it pointed out some practical problems as well, such as the need for millions of smaller syringes. A WHO spokesperson says that problem has been solved by using syringes stored in China and Denmark for polio vaccination programs.

    Abramson and other experts argue that the effects of the campaign need to be studied. One important question is safety. The yellow fever vaccine is itself a living virus that can replicate inside the body and, in very rare cases, cause a disease in which the vaccine virus proliferates in multiple organs, often leading to death. Although a lower dose would be expected to lead to fewer side effects, that may not be the case. Some researchers have argued that lower doses may be slower to kick the immune system into gear, which could cause the vaccine virus to linger in the body for longer and actually increase the risk of some side effects. A few studies have found no such effect, but because severe side effects are very rare (about one in 2 million), small trials cannot provide definitive answers.

    The other question is efficacy. A recent study on 749 men in Brazil showed that a 46-fold diluted vaccine triggered the same antibody response as a full dose. A study in the Netherlands found that a fifth of a normal dose injected intradermally was just as effective as a normal dose injected subcutaneously (the usual route).

    But more data on the efficacy of the lower dose need to be collected, especially because an African population may react differently to those studied in the trials. Ideally, scientists would set up a randomized, controlled clinical trial to assess the immune response to the lower dose, says Tom Monath, a virologist who has studied yellow fever for decades and currently works at NewLink Genetics, a biotech company in Ames, Iowa. But Monath concedes that that is unlikely given the time pressure and the logistical problems. At the very least, researchers should collect blood samples and compare the antibody responses from people who received the full and the lower dose, he argues. “It wouldn’t be a formal study but it would give you some confidence that people have responded appropriately,” Monath says. “I think that really should be done.”

    Another important question is whether 0.1 milliliters of the vaccine also offers lifelong protection. If not, the population will have to be revaccinated in the future. It’s also not clear whether lower doses will be protective in young children.

    In a paper advocating the dose-sparing strategy that Monath and eight other scientists just submitted, they go one step further. “If the worst-case scenario were to come to pass and yellow fever spread in Asia, serious consideration should be given to using a one-tenth dose,” the authors write. “Although it would probably protect any age group for only a few months, a one-tenth dose should mitigate the severity of a yellow fever infection, preventing some deaths.“

    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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  • richardmitnick 9:37 am on August 3, 2016 Permalink | Reply
    Tags: Antiaging trial, , , Science   

    From Science: “Young blood antiaging trial raises questions” 

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    AAAS

    Aug. 1, 2016
    Jocelyn Kaiser

    1
    A controversial pay-to-participate clinical trial will test whether plasma from young donors can counteract aging. Martin Schutt/picture-alliance/dpa/AP Images

    It was one of the most mind-bending scientific reports in 2014: Injecting old mice with the plasma portion of blood from young mice seemed to improve the elderly rodents’ memory and ability to learn. Inspired by such findings, a startup company has now launched the first clinical trial in the United States to test the antiaging benefits of young blood in relatively healthy people. But there’s a big caveat: It’s a pay-to-participate trial, a type that has raised ethical concerns before, most recently in the stem cell field.

    The firm’s co-founder and trial principal investigator is a 31-year-old physician named Jesse Karmazin. His company, Ambrosia in Monterey, California, plans to charge participants $8000 for lab tests and a one-time treatment with young plasma. The volunteers don’t have to be sick or even particularly aged—the trial is open to anyone 35 and older. Karmazin notes that the study passed ethical review and argues that it’s not that unusual to charge people to participate in clinical trials.

    To some ethicists and researchers, however, the trial raises red flags, both for its cost to participants and for a design that they say is unlikely to deliver much science. “There’s just no clinical evidence [that the treatment will be beneficial], and you’re basically abusing people’s trust and the public excitement around this,” says neuroscientist Tony Wyss-Coray of Stanford University in Palo Alto, California, who led the 2014 young plasma study in mice.

    Decades ago, so-called parabiosis studies, in which the circulation of old and young animals was connected so that their blood mingles, suggested that young blood can rejuvenate aging mice. A recent revival of the unusual approach has shown beneficial effects on muscle, the heart, brain, and other organs, and some researchers are scrutinizing young blood for specific factors that explain these observations. The 2014 study, however, suggested that repeated injections of plasma from young animals were an easy alternative to parabiosis. Wyss-Coray has since started a company, Alkahest, that, with Stanford, has launched a study of young plasma in 18 people with Alzheimer’s disease, evaluating its safety and monitoring whether the treatment relieves any cognitive problems or other symptoms. The company covers the participants’ costs. Wyss-Coray expects results by the end of this year. (Another trial at a research hospital in South Korea is examining whether cord blood or plasma can prevent frailty in the elderly.)

    In Ambrosia’s trial, 600 people age 35 and older would receive plasma from a donor under age 25, according to the description registered on ClinicalTrials.gov, the federal website intended to track human trials and their results. Karmazin says each person will receive roughly 1.5 liters over 2 days. Before the infusions and 1 month after, their blood will be tested for more than 100 biomarkers that may vary with age, from hemoglobin level to inflammation markers. The $8000 fee—not mentioned on ClinicalTrials.gov—will cover costs such as plasma from a blood bank, lab tests, the ethics review, insurance, and an administrative fee, Karmazin says. “It adds up fairly quickly.”

    Kamarzin became interested in aging as an undergraduate. In medical school at Stanford, where he rotated through labs focused on stem cells and aging, he took note of the young plasma mouse study and other parabiosis research. Karmazin was also intrigued by the story of a Russian physician named Alexander Bogdanov, who in the 1920s gave himself infusions of young human blood that he claimed boosted his energy level and bestowed a more youthful appearance. There are “overwhelming data” suggesting that young plasma will be beneficial to people, Karmazin says.

    Last year, Karmazin co-founded a company called xVitality Sciences that aimed to offer plasma treatments at clinics overseas. The venture didn’t pan out—Karmazin left, and the company is now apparently defunct. Karmazin then started Ambrosia with Craig Wright, a former chief scientific officer at a vaccine company, who now runs a clinic in Monterey. The company’s study, which was reviewed by a commercial ethics board used by some for-profit stem cell clinics, doesn’t need approval by the U.S. Food and Drug Administration, the pair says, because plasma transfusions are a well-established, standard treatment. Karmazin says he and Wright have now heard from about 20 prospective participants, and have enrolled three, all elderly. Wright will likely transfuse plasma into the first person in late August.

    To bioethicist Leigh Turner at the University of Minnesota, Twin Cities, the study brings to mind a growing number of scientifically dubious trials registered in ClinicalTrials.gov by private, for-profit stem cell clinics. The presence of such trials in the database confers “undeserved legitimacy,” he says.

    The scientific design of the trial is drawing concerns as well. “I don’t see how it will be in any way informative or convincing,” says aging biologist Matt Kaeberlein of the University of Washington, Seattle. The participants won’t necessarily be elderly, making it hard to see any effects, and there are no well-accepted biomarkers of aging in blood, he says. “If you’re interested in science,” Wyss-Coray adds, why doesn’t such a large trial include a placebo arm? Karmazin says he can’t expect people to pay knowing they may get a placebo. With physiological measurements taken before and after treatment, each person will serve as their own control, he explains.

    Doubts aside, Ambrosia’s trial has already attracted attention from the investment company of billionaire Peter Thiel, who is apparently interested in trying young plasma treatments himself, Inc. reported today. Karmazin says he’s filling a void, suggesting that most companies wouldn’t be interested in developing human plasma as an antiaging treatment. “It’s this extremely abundant therapeutic that’s just sitting in blood banks,” he insists.

    *Correction, 2 August, 10:23 a.m.: This story has been corrected to clarify that it is the enrolled patients in the study who are elderly.

    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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