News Article | December 1, 2016
When we are in a deep slumber our brain's activity ebbs and flows in big, obvious waves, like watching a tide of human bodies rise up and sit down around a sports stadium. It's hard to miss. Now, Stanford researchers have found, those same cycles exist in wake as in sleep, but with only small sections sitting and standing in unison rather than the entire stadium. It's as if tiny portions of the brain are independently falling asleep and waking back up all the time. What's more, it appears that when the neurons have cycled into the more active, or "on," state they are better at responding to the world. The neurons also spend more time in the on state when paying attention to a task. This finding suggests processes that regulate brain activity in sleep might also play a role in attention. "Selective attention is similar to making small parts of your brain a little bit more awake," said Tatiana Engel, a postdoctoral fellow and co-lead author on the research, which is scheduled to publish Dec. 1 in Science. Former graduate student Nicholas Steinmetz was the other co-lead author, who carried out the neurophysiology experiments in the lab of Tirin Moore, a professor of neurobiology and one of the senior authors. Understanding these newly discovered cycles requires knowing a bit about how the brain is organized. If you were to poke a pin directly into the brain, all the brain cells you'd hit would respond to the same types of things. In one column they might all be responding to objects in a particular part of the visual field - the upper right, for example. The team used what amounts to sets of very sensitive pins that can record activity from a column of neurons in the brain. In the past, people had known that individual neurons go through phases of being more or less active, but with this probe they saw for the first time that all the neurons in a given column cycled together between firing very rapidly then firing at a much slower rate, similar to coordinated cycles in sleep. "During an on state the neurons all start firing rapidly," said Kwabena Boahen, a professor of bioengineering and electrical engineering at Stanford and a senior author on the paper. "Then all of a sudden they just switch to a low firing rate. This on and off switching is happening all the time, as if the neurons are flipping a coin to decide if they are going to be on or off." Those cycles, which occur on the order of seconds or fractions of seconds, weren't as visible when awake because the wave doesn't propagate much beyond that column, unlike in sleep when the wave spreads across almost the entire brain and is easy to detect. The team found that the higher and lower activity states relate to the ability to respond to the world. The group had their probe in a region of the brain in monkeys that specifically detects one part of the visual world. The monkeys had been trained to pay attention to a cue indicating that something in a particular part of the visual field - the upper right, say, or the lower left - was about to change slightly. The monkeys then got a treat if they correctly identified that they'd seen that change. When the team gave a cue to where a change might occur, the neurons within the column that senses that part of the world all began spending more time in the active state. In essence, they all continued flipping between states in unison, but they spent more time in the active state if they were paying attention. If the stimulus change came when the cells were in a more active state, the monkey was also more likely to correctly identify the change. "The monkey is very good at detecting stimulus changes when neurons in that column are in the on state but not in the off state," Engel said. Even when the monkey knew to pay attention to a particular area, if the neurons cycled to a lower activity state the monkey frequently missed stimulus change. Engel said this finding is something that might be familiar to many people. Sometimes you think you are paying attention, she pointed out, but you will still miss things. The scientists said the findings also relate to previous work, which found that more alert animals and humans tend to have pupils that are more dilated. In the current work, when the brain cells were spending more time in an active state the monkey's pupils were also more dilated. The findings demonstrate an interaction between synchronous oscillations in the brain, attention to a task and external signs of alertness. "It seems that the mechanisms underlying attention and arousal are quite interdependent," Moore said. A question that comes out of this work is why the neurons cycle into a lower activity state when we're awake. Why not just stay in the more active state all the time in case that's when the saber tooth tiger attacks? One answer could relate to energy. "There is a metabolic cost associated with neurons firing all the time," Boahen said. The brain uses a lot of energy and maybe giving the cells a chance to do the energetic equivalent of sitting down allows the brain to save energy. Also, when neurons are very active they generate cellular byproducts that can damage the cells. Engel pointed out that the low-activity states could allow time to clear out this neuronal waste. "This paper suggests places to look for these answers," Engel said. Additional co-authors include colleagues from Newcastle University. Kwabena Boahen is also a member of Stanford Bio-X and the Stanford Neurosciences Institute. Tirin Moore is also an HHMI investigator as well as a member of Stanford Bio-X, the Stanford Neurosciences Institute and the Child Health Research Institute. The work was funded by the NIH, Stanford NeuroVentures, the HHMI, the MRC and the Wellcome Trust.
News Article | February 22, 2017
HOBOKEN, N.J.--(BUSINESS WIRE)--The Wiley Foundation, part of John Wiley & Sons, Inc. (NYSE: JWa and JWb) today announced the 16th annual Wiley Prize in Biomedical Sciences will be awarded to Joachim Frank, Richard Henderson, and Marin van Heel for pioneering developments in electron microscopy that are transforming structural studies of biological molecules and their complexes. Dr. Joachim Frank is an HHMI investigator, a Professor of Biochemistry and Molecular Biophysics and of Biological Sciences at Columbia University, and Distinguished Professor of the State University of New York at Albany. Dr. Richard Henderson is a scientist at the MRC Laboratory of Molecular Biology in Cambridge, UK. He was Director from 1996 to 2006, and is a fellow of the Royal Society and a Foreign Associate of the US National Academy of Sciences. Dr. Marin van Heel is a visiting Professor at the National Nanotechnology Laboratory – LNNano/CNPEM, Campinas, Brazil. He is an Emeritus Professor at the Institute of Biology Leiden (NeCEN) and the Department of Life Sciences, Imperial College London. “The 2017 Wiley Prize honors scientists who have developed cryo-electron microscopy to be the most important new tool for establishing atomic structures of large molecular complexes," said Dr. Günter Blobel, Chairman of the awards jury for the Wiley Prize. First awarded in 2002, The Wiley Prize in Biomedical Sciences is presented annually to recognize contributions that have opened new fields of research or have advanced concepts in a particular biomedical discipline. Among the many distinguished recipients of the Wiley Prize in Biomedical Sciences, six have gone on to be awarded the Nobel Prize in Physiology or Medicine. “The Wiley Foundation honors leadership and innovation in the development of techniques that greatly advance scientific discovery. The work of the 2017 Wiley Prize recipients Joachim Frank, Richard Henderson, and Marin van Heel truly upholds this mission,” said Deborah E. Wiley, Chair of the Wiley Foundation. “We are pleased to highlight the impact that cryo-electron microscopy has had in advancing knowledge of molecular structure and resulting cellular functions.” This year’s award of $50,000 will be presented to the winners on April 7, 2017 at the Wiley Prize luncheon at The Rockefeller University. The winners will then deliver an honorary lecture as part of The Rockefeller University Lecture Series. This event will be live streamed via the Current Protocols’ Webinar Series and registration is free. Wiley, a global company, helps people and organizations develop the skills and knowledge they need to succeed. Our online scientific, technical, medical, and scholarly journals, combined with our digital learning, assessment and certification solutions help universities, learned societies, businesses, governments and individuals increase the academic and professional impact of their work. For more than 200 years, we have delivered consistent performance to our stakeholders. Dr. Joachim Frank is an HHMI investigator, a Professor of Biochemistry and Molecular Biophysics and of Biological Sciences at Columbia University, and Distinguished Professor of the State University of New York at Albany. He is a Member of the National Academy of Sciences, and Fellow of the American Academy of Arts and Sciences, the American Association for the Advancement of Science, and the Biophysical Society. In 2014 he received the Franklin Medal in Life Science, bestowed by the Franklin Institute in Philadelphia. Dr. Richard Henderson is a scientist at the MRC Laboratory of Molecular Biology in Cambridge, UK. He was Director from 1996 to 2006, and is a fellow of the Royal Society and a Foreign Associate of the US National Academy of Sciences. Dr. Marin van Heel is a visiting Professor at the National Nanotechnology Laboratory – LNNano/CNPEM, Campinas, Brazil. He is an Emeritus Professor at the Institute of Biology Leiden (NeCEN) and the Department of Life Sciences, Imperial College London. After studying theoretical optics at the University of Groningen, his PhD thesis marked the beginning of a career in methodology development in structural biology by cryo-EM. He received the Ernst Ruska Prize 1987.
News Article | March 31, 2016
Abstract: Bacteria are the most abundant form of life on Earth, and they are capable of living in diverse habitats ranging from the surface of rocks to the insides of our intestines. Over millennia, these adaptable little organisms have evolved a variety of specialized mechanisms to move themselves through their particular environments. In two recent Caltech studies, researchers used a state-of-the-art imaging technique to capture, for the first time, three-dimensional views of this tiny complicated machinery in bacteria. Credit: Science/AAAS "Bacteria are widely considered to be 'simple' cells; however, this assumption is a reflection of our limitations, not theirs," says Grant Jensen, a professor of biophysics and biology at Caltech and an investigator with the Howard Hughes Medical Institute (HHMI). "In the past, we simply didn't have technology that could reveal the full glory of the nanomachines--huge complexes comprising many copies of a dozen or more unique proteins--that carry out sophisticated functions." Jensen and his colleagues used a technique called electron cryotomography to study the complexity of these cell motility nanomachines. The technique allows them to capture 3-D images of intact cells at macromolecular resolution--specifically, with a resolution that ranges from 2 to 5 nanometers (for comparison, a whole cell can be several thousand nanometers in diameter). First, the cells are instantaneously frozen so that water molecules do not have time to rearrange to form ice crystals; this locks the cells in place without damaging their structure. Then, using a transmission electron microscope, the researchers image the cells from different angles, producing a series of 2-D images that--like a computed tomography, or CT, scan--can be digitally reconstructed into a 3-D picture of the cell's structures. Jensen's laboratory is one of only a few in the entire world that can do this type of imaging. In a paper published in the March 11 issue of the journal Science, the Caltech team used this technique to analyze the cell motility machinery that involves a structure called the type IVa pilus machine (T4PM). This mechanism allows a bacterium to move through its environment in much the same way that Spider-Man travels between skyscrapers; the T4PM assembles a long fiber (the pilus) that attaches to a surface like a grappling hook and subsequently retracts, thus pulling the cell forward. Although this method of movement is used by many types of bacteria, including several human pathogens, Jensen and his team used electron cryotomography to visualize this cell motility mechanism in intact Myxococcus xanthus--a type of soil bacterium. The researchers found that the structure is made up of several parts, including a pore on the outer membrane of the cell, four interconnected ring structures, and a stemlike structure. By systematically imaging mutants, each of which lacked one of the 10 T4PM core components, and comparing these mutants with normal M. xanthus cells, they mapped the locations of all 10 T4PM core components, providing insights into pilus assembly, structure, and function. "In this study, we revealed the beautiful complexity of this machine that may be the strongest motor known in nature. The machine lets M. xanthus, a predatory bacterium, move across a field to form a 'wolf pack' with other M. xanthus cells, and hunt together for other bacteria on which to prey," Jensen says. Another way that bacteria move about their environment is by employing a flagellum--a long whiplike structure that extends outward from the cell. The flagellum is spun by cellular machinery, creating a sort of propeller that motors the bacterium through a substrate. However, cells that must push through the thick mucus of the intestine, for example, need more powerful versions of these motors, compared to cells that only need enough propeller power to travel through a pool of water. In a second paper, published in the online early edition of the Proceedings of the National Academy of Sciences (PNAS) on March 14, Jensen and his colleagues again used electron cryotomography to study the differences between these heavy-duty and light-duty versions of the bacterial propeller. The 3-D images they captured showed that the varying levels of propeller power among several different species of bacteria can be explained by structural differences in these tiny motors. In order for the flagellum to act as a propeller, structures in the cell's motor must apply torque--the force needed to cause an object to rotate--to the flagellum. The researchers found that the high-power motors have additional torque-generating protein complexes that are found at a relatively wide radius from the flagellum. This extra distance provides greater leverage to rotate the flagellum, thus generating greater torque. The strength of the cell's motor was directly correlated with the number of these torque-generating complexes in the cell. "These two studies establish a technique for solving the complete structures of large macromolecular complexes in situ, or inside intact cells," Jensen says. "Other structure determination methods, such as X-ray crystallography, require complexes to be purified out of cells, resulting in loss of components and possible contamination. On the other hand, traditional 2-D imaging alone doesn't let you see where individual protein pieces fit in the complete structure. Our electron cryotomography technique is a good solution because it can be used to look at the whole cell, providing a complete picture of the architecture and location of these structures." ### The work involving the type IVa pilus machinery was published in a Science paper titled "Architecture of the type IVa pilus machine." First author Yi-Wei Chang is a research scientist at Caltech; additional coauthors include collaborators from the Max Planck Institute for Terrestrial Microbiology, in Marburg, Germany, and from the University of Utah. The study was funded by the National Institutes of Health (NIH), HHMI, the Max Planck Society, and the Deutsche Forschungsgemeinschaft. Work involving the flagellum machinery was published in a PNAS paper titled "Diverse high-torque bacterial flagellar motors assemble wider stator rings using a conserved protein scaffold." Additional coauthors include collaborators from Imperial College London; the University of Texas Southwestern Medical Center; and the University of Wisconsin-Madison. The study was supported by funding from the UK's Biotechnology and Biological Sciences Research Council and from HHMI and NIH. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.
News Article | December 6, 2016
SAN FRANCISCO--(BUSINESS WIRE)--Nurix, Inc., a private drug discovery company, today announced the appointment of Dr. Robert Tjian to the company’s board of directors. Dr. Tjian is a member of the National Academy of Sciences and has received numerous awards including the Alfred P. Sloan Prize and the Louisa Gross Horwitz Prize. He was a co-founder of Tularik with Dave Goeddel and Steve McKnight and most recently served as president of the Howard Hughes Medical Institute (HHMI) from 2009 to 2016. After leaving HHMI, Dr. Tjian joined The Column Group as a discovery partner in September 2016. “It is indeed a privilege to welcome Dr. Tjian to the Nurix board of directors,” said Arthur T. Sands, M.D., Ph.D., chief executive officer of Nurix. “Dr. Tjian’s unique combination of scientific expertise and biotechnology business insight will be of great value to Nurix as we translate our breakthrough science into breakthrough drugs for patients.” Dr. Tjian discovered the first transcription factors, human proteins that bind to specific sections of DNA and play a critical role in regulating how genetic information is expressed into the thousands of biomolecules that keep cells, tissues and organisms alive. Dr. Tjian's laboratory has focused on disruptions in the process of transcription that cause diseases such as cancer, metabolic syndromes and neuro-degenerative diseases. In recent years, much of Dr. Tjian’s research has focused on key transcription events in embryonic stem cells. He joined the University of California, Berkeley faculty in 1979, where he assumed several leadership roles including director of the Berkeley Stem Cell Center, faculty director of the Li Ka Shing Center for Biomedical and Health Sciences, and head of the Siebel Stem Initiative. He currently serves as scientific advisor to the Chan Zuckerberg Initiative and the BioHub, and continues to serve on the faculty of the University of California, Berkeley. With his appointment, Dr. Tjian will assume the board seat previously occupied by David Goeddel, Ph.D. of The Column Group. “Dave has made significant contributions to Nurix since its inception and has been a guiding influence for the advancement of Nurix’s scientific and business initiatives, said Dr. Sands. “He has successfully established the company as a leader in the protein homeostasis field and we thank him for his leadership.” Nurix, Inc. is a leader in the discovery of small molecules that modulate the ubiquitin proteasome system (UPS) to address significant, unmet medical needs. The UPS is a regulatory pathway that controls protein levels, a function vital to the healthy life of a cell, and presents therapeutic opportunities in multiple disease areas. Nurix was founded by internationally-recognized experts in the ubiquitin proteasome field and is funded by leading life science investors, Third Rock Ventures and The Column Group. In September 2015, Nurix and Celgene entered into a broad collaboration targeting protein homeostasis for next-generation therapies in oncology, inflammation and immunology. The company is headquartered in San Francisco, California. For more information, please visit www.nurix-inc.com.
News Article | December 14, 2016
(New York, NY - December 12, 2016) -- Even before tumors develop, breast cancer cells with a few defined molecular alterations can spread to organs, remain quiet for long periods of time, and then awaken to form aggressive, deadly breast cancer metastasis, says a team of investigators led by researchers at Icahn School of Medicine at Mount Sinai and the University of Regensburg in Germany. They say their finding, published in two papers in the journal Nature, and conducted in animal models and tested in human samples, now solves the mystery of how breast cancer metastasis forms without a primary tumor in this new model of early dissemination and metastasis. Furthermore, a clinical primary tumor may never develop, investigators say. The University of Regensburg team had discovered that cancer cells could spread not only from a highly mutated, overtly evolved and pathologically-defined invasive tumors, but also from early stage cancers commonly considered incapable of spreading cells. However, how these early cancer lesions could spawn cells with traits of malignant tumors was unknown. In two papers published in the journal Nature, and conducted in animal models and tested in human samples, the two teams now have identified the first mechanisms that allow cells to spread early in cancer progression and contribute to metastasis. In the study from Mount Sinai, two changes in mammary cancer cells -- a switched-on oncogene and a turned-off tumor suppressor-- motivated cells to travel from breast tissue to the lungs and other parts of the body. There, the cells stayed quiet until a growth switch was activated and metastases developed in lungs. "This research provides insight into the mechanisms of early cancer spread and may shed light into unexplained phenomena -- among them, why as many as 5 percent of cancer patients worldwide have cancer metastases but no original tumor, and most importantly, why it is so difficult to treat cancer that has spread," says the study's senior investigators, Julio A. Aguirre-Ghiso, PhD, Professor of Medicine, Hematology and Medical Oncology, Maria Soledad Sosa, PhD, Assistant Professor of Pharmacological Sciences, and graduate student Kathryn Harper of The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai. "Biologically, this new model of early metastasis challenges everything we thought we knew about how cancer spreads and forms metastasis. It feels like we are going to have to adjust our ideas about the subject of metastasis," he says. "Our hope is that these findings will reshape the way we think about how metastasis should be treated." An important finding from the Mount Sinai team is that most early spread cells remain dormant and most chemotherapy and targeted therapies are aimed at those cells that are proliferative. So early spread cancer cells would escape these conventional therapies even if it kills a primary tumor, Dr. Aguirre-Ghiso says. The work also poses new questions on how early spread cancer cells support metastasis development. Do they do it on their own, do they set the soil for later arriving cells from tumors not caught early, or do they cooperate with later arriving cells? This study reveals a new biological mechanism of early dissemination that must be explored to fully understand how to target the seeds of metastasis. The companion paper headed by Dr. Christoph Klein at the University of Regensburg in Germany, published in the same issue of Nature and co-authored by Dr. Aguirre-Ghiso and members of his team provides additional key mechanistic clues on how early spread is controlled and proof in human cancer cells and tumors of the preclinical findings in this study. Researchers from both teams arrived at their findings independently and then collaborated on the project. Researchers from both teams studied very early stages of breast cancer including DCIS (ductal carcinoma in situ), a noninvasive breast lesion, since 2-3 percent of women who have been treated for DCIS die of metastasis without ever developing a primary tumor. "The best explanation for this phenomenon is that early metastasis occurs before or as DCIS develops. A key finding from this second paper is that in the mouse models, 80% of metastasis originated from the early spread cells and not from the large tumors. In fact, the Klein group identified a mechanism by which spread is more efficient in early lesions than in large tumors. In both studies, investigators found that early cancer cell spread is an extension of the normal process of creating a branching tree of breast milk ducts in females. Two major pathways are activated in this ancient process -- p38, a tumor suppressor, and HER2, an oncogene. Switching off p38 and turning on HER2 activates a module of the EMT (epithelial to mesenchymal transition) signaling pathway. EMT promotes movement of cells during embryogenesis and tissue development. The Klein paper also shows that progesterone receptor signaling, which controls branching of the mammary tree, is important for this early spread by regulating cues involved in EMT and growth programs, a mechanism that was hinted in his earlier studies. As a mammary tree develops, p38, HER2, and EMT are alternatively turned on and off. This, in cooperation with progesterone signaling, allows mammary cells to move through the mammary gland, hollow out a tubular, branching network of milk ducts that flow to the nipple. "Tweaking these pathways are a normal way of forming hollow branching tubes," Dr. Aguirre-Ghiso says. But in their experiments, they found that if HER2 is over-activated (not switched off) or mutated, and p38 is permanently turned off, EMT was continually activated, allowing cells to move out of the mammary gland and into the animal's body through the blood. "We were able to use organoids in three-dimensional cultures, and high resolution imaging directly in the live animal models to actually see these cells enter the blood stream from the mammary tree and travel to the lung, the bone marrow, and other places," he says. "We hadn't thought about oncogenes and tumor suppressors in this way before. This is a new function for these pathways." John S. Condeelis, PhD, co-Director of the Gruss Lipper Biophotonics Center and its Integrated Imaging Program at Einstein, where the high resolution intravital imaging was performed, noted that "We were surprised to learn that cancer cells from DCIS-like lesions could show such robust dissemination using similar machinery found in tumor cells from invasive carcinoma. This is a new insight with implications beyond our expectations." Also David Entenberg MSc, Director of Technological Development and Intravital Imaging who led the imaging efforts within the same Center said, "A few years ago, it would not have been possible to image these disseminating cells inside a living animal with this level of detail. We're pleased that Einstein's imaging technology could, through this collaboration, contribute to the definitive proof of early dissemination." And while both studies focus on the mechanisms of early dissemination in breast cancer, similar processes could control early dissemination and metastasis in other human cancers, including melanoma and pancreatic cancer. In fact, pancreatic cancer early dissemination has also been linked to an EMT process, Dr. Aguirre-Ghiso says. Among the critical avenues they are investigating, Mount Sinai researchers are looking for the growth switch that pushes early spread of dormant cancer cells to form metastases. "While our findings add a whole new level of complexity to the understanding of cancer, they also add energy to our efforts to finally solve the big issue in cancer -- stop the metastasis that kills patients," Dr. Aguirre-Ghiso says. Study contributors include lead co-authors Kathryn L. Harper, PhD, Maria Soledad Sosa, PhD, Julie F. Cheung, BSc, Rita Nobre MSc, Alvaro Avivar-Valderas, PhD, Chandandaneep Nagi, MD, and Eduardo F. Farias, PhD, from Icahn School of Medicine at Mount Sinai; Christoph Klein, MD and Hedayatollah Hosseini, PhD from the University of Regensburg, Germany; Nomeda Girnius, PhD and Roger J. Davis, PhD from Howard Hughes Medical Institute at the University of Massachusetts Medical School; and David Entenberg, MSc and John Condeelis, PhD from Albert Einstein College of Medicine in New York. The study was supported by grants SWCRF, CA109182, CA196521, CA163131, CA100324, F31CA183185, BC132674, BC112380, NIH 1S10RR024745 Microscopy CoRE at ISMMS, the Integrated Imaging Program at Einstein, HHMI, DFG KL 1233/10-1 and the ERC (322602). For a video on this release: https:/ The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care. The System includes approximately 7,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is on the "Honor Roll" of best hospitals in America, ranked No. 15 nationally in the 2016-2017 "Best Hospitals" issue of U.S. News & World Report. The Mount Sinai Hospital is also ranked as one of the nation's top 20 hospitals in Geriatrics, Gastroenterology/GI Surgery, Cardiology/Heart Surgery, Diabetes/Endocrinology, Nephrology, Neurology/Neurosurgery, and Ear, Nose & Throat, and is in the top 50 in four other specialties. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 10 nationally for Ophthalmology, while Mount Sinai Beth Israel, Mount Sinai St. Luke's, and Mount Sinai West are ranked regionally. Mount Sinai's Kravis Children's Hospital is ranked in seven out of ten pediatric specialties by U.S. News & World Report in "Best Children's Hospitals." For more information, visit http://www. or find Mount Sinai on Facebook, Twitter and YouTube.
News Article | February 15, 2017
Life scientists keen to share their findings online before peer review are spoilt for choice. Whereas physicists gravitate to one repository — the ‘preprint’ server arXiv — life sciences has a fast-growing roster of venues for preprints. There’s the biology-focused bioRxiv, and a biology section on arXiv too. But other sites have sprouted up in the past year, or soon will do, and these too provide opportunities for life sciences: ChemRxiv for chemistry, psyArXiv for psychology; even AgriXiv for agricultural sciences and paleorXiv for palaeontology. Now, a coalition of biomedical funders and scientists is throwing its weight behind a ‘one-stop shop’ for all life-sciences preprints — a move that its backers argue should clarify any confusion and make it easier to mine the preprint literature for insights. On 13 February, ASAPbio, a grassroots group of biologists that advocates for preprints, issued a funding call to build a central preprint site; the US National Institutes of Health (NIH), the Wellcome Trust and several other leading funders announced their support for the concept. “The landscape could become fragmented very quickly,” says Robert Kiley, head of digital services at the London-based Wellcome Trust. “We want to find a way of ensuring that, although this content is distributed far and wide, there’s a central place that brings it all together”. The details of the service are inchoate: its scope will depend on specific scientific fields and their funders, says Jessica Polka, the director of ASAPbio. But as well as aggregating content from other biology-focused preprint sites, ASAPbio wants the site to mesh with arXiv and with ChemRxiv, which the American Chemical Society in Washington DC plans to launch soon. Proponents hope that a central site will lure biologists to embrace the practice as wholeheartedly as physical scientists have. Physics manuscripts routinely appear at arXiv.org months before publication in peer-reviewed journals, as researchers race to release their findings online before their rivals. And preprints are now accepted currency in determining priority for a discovery, as well as in winning grants and jobs. ArXiv handles more than 100,000 manuscripts each year in physics, mathematics and computer science. (The largest life-sciences preprint server, bioRxiv, posted around 5,000 manuscripts in 2016.) “One of the lessons of arXiv is that users prefer ‘one-stop shopping’,” says Paul Ginsparg, a theoretical physicist at Cornell University in Ithaca, New York, who founded the site in 1991. He could see a preprint aggregation site for life sciences working just as well, so long as disparate sites can agree on uniform technical standards. A central preprint service could also help scientists to use automated software to mine the literature for insights, says Ron Vale, a cell biologist at the University of California, San Francisco, and a founder of ASAPbio. At the moment, researchers who want to mine peer-reviewed papers face myriad hurdles, from publisher copyrights to disparate websites that make bulk-downloading difficult. “We’re trying to think of preprints as data,” says Vale. It would be both technically and legally straightforward for computers to crawl the collection of preprints on the central site, where they would appear under an open-access licence. Polka would not say how much ASAPbio expects the site to cost, but arXiv funding totals about US$925,000 a year, paid for by a global collective of more than 200 research institutions and funders; a large donation has come from the Simons Foundation, a private organization based in New York City. Ginsparg says expenses for the life-sciences site should be around $5 a manuscript, once it is publishing tens of thousands of manuscripts each year. Funders who support the site have not yet committed to paying for it, but Kiley expects that funders will do so once details are hashed out. Other funders that have come out in support of the central service include the UK Medical Research Council, the Howard Hughes Medical Institute (HHMI), the Canadian Institutes of Health Research and the European Research Council. “That’s going to send a strong message to the science community that this kind of communication is encouraged,” says Vale. Last month, the HHMI announced that it would consider preprints in deciding whether or not to renew the prestigious five-year grants it gives to investigators. Jason Hoyt, chief executive of the journal PeerJ (which also operates a preprint service), says he supports a central preprint site and that his company might bid to help create it. But such a site will succeed only if it can induce a large proportion of life scientists to view preprints as the dominant currency for career progression, he says. “The challenge is to overturn the thinking in biology.” ASAPbio and the funders supporting a central preprint service emphasize that it’s no replacement for peer-reviewed journals. They note that the vast majority (over 80% in some fields) of arXiv posts wind up in journals. “We really see this as a complement to the journal system, rather than anything that could be threatening,” says Polka, who adds that a central service will not attempt to organize peer review. That would be a missed opportunity, says Rebecca Lawrence, managing director of London-based F1000Research, which posts papers before they are peer reviewed at the journal (but does not consider these preprints). She would like to see peer review occur through a central preprint service, thereby reducing the influence that traditional journals have on scientists’ careers. “It’s a great shift in the right direction,” Lawrence says, “but I think we need to go a lot further.” Ginsparg ultimately envisions a "federated repository" that spans scientific disciplines and aggregates preprints from arXiv and other fields, including the life sciences. “Twenty-five years ago, I thought we’d be much closer to that point by now, but I still think it’s inevitable,” he says.
News Article | December 7, 2016
In contradicting a theory that's been the standard for over eighty years, researchers at the University of Illinois at Urbana-Champaign have made a discovery holding major promise for the petroleum industry. The research has revealed that in the foreseeable future products such as crude oil and gasoline could be transported across country 30 times faster, and the several minutes it takes to fill a tank of gas could be reduced to mere seconds. Over the past year, using high flux neutron sources at the National Institute of Standards and Technology (NIST) and Oak Ridge National Laboratory (ORNL), an Illinois group led by Yang Zhang, assistant professor of nuclear, plasma, and radiological engineering (NPRE) and Beckman Institute at Illinois, has been able to videotape the molecular movement of alkanes, the major component of petroleum and natural gas. The group has learned that the thickness of liquid alkanes can be significantly reduced, allowing for a marked increase in the substance's rate of flow. "Alkane is basically a chain of carbon atoms," Zhang said. "By changing one carbon atom in the backbone of an alkane molecule, we can make it flow 30 times faster." The group's discovery disproves a well-known theory that Princeton University professors Walter Kauzmann and Henry Eyring formed in the late 1940s. They had predicted that all alkanes have a universal viscosity near their melting points. Zhang said the theory had been cited over 3,000 times. However, a rather distinct odd-even effect of the liquid alkane dynamics was discovered. The odd-even effect in solid alkanes is taught in almost every introductory organic chemistry textbook, i.e., the difference in the periodic packing of odd- and even-numbered alkane solids results in odd-even variation of their densities and melting points. However, the same effect was not expected in liquid alkanes because of the lack of periodic structures in liquids. "The classical Kauzmann-Eyring theory of molecular viscous flow is over simplified," Zhang said. "It seems some chemistry textbooks may need revisions." The Illinois scientists had the technological advantage of super high-speed (at the pico-second, 1 trillionth of a second) and super high-resolution (at the nano-meter, 1 billionth of a meter) "video cameras" making use of neutrons to take movies of the molecules. "A neutron 'microscope' is the major breakthrough in materials research and we use it to look at everything. There are things we've never seen before," Zhang said. The research, "Dynamic Odd-Even Effect in Liquid n-Alkanes near Their Melting Points," has been published in the German publication Angewandte Chemie International Edition. The reported research discovery is fundamental to understand and improve a wide spectrum of chemical processes, such as lubrication, diffusion through porous media, and heat transfer. Zhang conducted the research after being selected in fall 2015 for an American Chemical Society Petroleum Research Fund Doctoral New Investigator Award. The first author of the paper, Ke Yang, graduated in summer 2016 and now works at the Dow Chemical Company. Other collaborators include NPRE graduate students Zhikun Cai, and Abhishek Jaiswal, Dr. Madhusudan Tyagi at NIST, and Jeffrey S. Moore, interim director of the Beckman Institute and HHMI Professor of Chemistry at Illinois.
News Article | November 28, 2016
Elaine Fuchs, Ph.D., whose innovative use of reverse genetics has helped redefine the study of skin diseases and cancer stem cells, is the recipient of the 2016 Vanderbilt Prize in Biomedical Science, officials at Vanderbilt University Medical Center (VUMC) announced today. Fuchs is the Rebecca C. Lancefield Professor and head of the Robin Chemers Neustein Laboratory of Mammalian Cell Biology and Development at Rockefeller University in New York, and, since 1988, a Howard Hughes Medical Institute (HHMI) investigator. She is the 11th recipient of the Vanderbilt Prize in Biomedical Science. Established by Vanderbilt University School of Medicine in 2006, the competitive prize honors women scientists with a "stellar record" of research accomplishments who have made significant contributions to mentoring other women in science. Prize winners receive an honorarium, meet with Vanderbilt faculty and deliver a Flexner Discovery Lecture. They also mentor Vanderbilt Prize Scholars, women who are pursuing graduate studies in the biomedical sciences in the School of Medicine. Fuchs will receive the prize on March, 30, 2017, when she is scheduled to give a Flexner Discovery Lecture. "Dr. Fuchs is a world leader in stem cell research and pioneered the approach of reverse genetics to decipher human diseases. In addition to her many contributions to our understanding of genetic diseases of the skin, she is an inspiring researcher who is a passionate mentor and advocate for careers in science for women," said Jeff Balser, M.D., Ph.D., President and CEO of Vanderbilt University Medical Center, and Dean of the Vanderbilt University School of Medicine. "I want to congratulate her as the recipient of this year's prize." Fuchs grew up in a suburb of Chicago, majored in Chemistry at the University of Illinois, and earned her Ph.D. in Biochemistry from Princeton University. As a postdoctoral fellow in the lab of the late Howard Green, M.D., at MIT, she studied the growth and differentiation of epidermal keratinocytes. Her work there demonstrated that keratins - the fibrous structural proteins that protect epithelial cells from mechanical stress - were likely distinct proteins coming from different genes that were differentially expressed. In 1980, Fuchs was recruited by the University of Chicago as the first woman faculty member in Biochemistry. There she was mentored by the late Janet Rowley, M.D., and Susan Lindquist, Ph.D., winner of the 2014 Vanderbilt Prize in Biomedical Science, who died last month. Fuchs' lab immediately set about to clone and sequence various keratin genes. It employed a reverse genetics approach, transgenic mice that expressed mutant genes, to elucidate the function of the normal keratin proteins. One mutation resulted in a disease that resembled epidermolysis bullosa simplex (EBS), a human skin disease characterized by severe blistering. Skin biopsies from EBS patients confirmed that the disease resulted from keratin mutations. While at the University of Chicago, Fuchs began studies that led to her current focus - how multipotent stem cells of mammalian skin give rise to the epidermis and hair follicles. After moving to Rockefeller University in 2002, her team developed a way to fluorescently tag these slow-proliferating cells. The approach yielded insights into normal tissue formation and wound repair, and malignant transformation as well. In 2011, her lab defined how stem cells can acquire mutations that go on to initiate squamous cell carcinoma, a type of skin cancer. Fuchs has received numerous honors for her scientific achievements, including the National Medal of Science from the National Science Foundation and the E.B. Wilson Medal from the American Society for Cell Biology. She is a member of the National Academy of Sciences and the American Academy of Arts and Sciences. In 2010 she received the L'Oréal-UNESCO Award in the Life Sciences. The award recognizes outstanding women scientists who also have been a source of support, motivation and inspiration for other women in science. For a complete list of Vanderbilt Prize winners, go to https:/ and click on "Vanderbilt Prize."
News Article | February 15, 2017
FILE - This Tuesday, April 26, 2016 file photo shows The Associated Press logo in New York. The Associated Press is teaming with the Howard Hughes Medical Institute’s Department of Science Education to expand its coverage of science, medicine and health journalism. (AP Photo/Hiro Komae) NEW YORK (AP) -- The Associated Press is teaming up with the Howard Hughes Medical Institute's Department of Science Education to expand its coverage of science, medicine and health journalism. The initial collaboration includes two pilot projects. With the first project, AP will create and distribute a series of stories, profiles, videos and graphics focusing on genetic medicine. The second project will look at a variety of science topics in the news that will help readers stay current on the latest science research and make informed decisions on topics ranging from the environment, to public health. "This collaboration brings wider attention and new storytelling tools to evidence-based, factual science," AP Executive Editor Sally Buzbee said. HHMI, based in Chevy Chase, Maryland, supports the advancement of biomedical research and science education. The organization's origin dates back to the late 1940s when a small group of physicians and scientists advised Hughes. The medical institute was created in 1953. The primary purpose of the organization is to promote human knowledge in the field of the basic sciences and its effective application for the benefit of mankind, according to its charter. In fiscal 2016, it provided $663 million in U.S. biomedical research and $86 million in grants and other support for science education. HHMI's Department of Science Education, the largest private, nonprofit supporter of science education in the country, will provide funding for the AP projects. The funding will allow AP to increase the amount of science-related stories it provides to news organizations and add more journalists to support its current science reporting team. HHMI will also offer expert background information and educational material. While the AP will receive funding and utilize HHMI's expertise when crafting its content, it maintains full editorial control of published material. "We're proud to stand shoulder to shoulder with the world's most respected news organization to ensure that the best evidence around important scientific topics is presented clearly and distributed widely," said Sean B. Carroll, vice president of HHMI's Department of Science Education.
News Article | February 16, 2017
(AP) — The Associated Press is teaming up with the Howard Hughes Medical Institute's Department of Science Education to expand its coverage of science, medicine and health journalism. The initial collaboration includes two pilot projects. With the first project, AP will create and distribute a series of stories, profiles, videos and graphics focusing on genetic medicine. The second project will look at a variety of science topics in the news that will help readers stay current on the latest science research and make informed decisions on topics ranging from the environment, to public health. "This collaboration brings wider attention and new storytelling tools to evidence-based, factual science," AP Executive Editor Sally Buzbee said. HHMI, based in Chevy Chase, Maryland, supports the advancement of biomedical research and science education. The organization's origin dates back to the late 1940s when a small group of physicians and scientists advised Hughes. The medical institute was created in 1953. The primary purpose of the organization is to promote human knowledge in the field of the basic sciences and its effective application for the benefit of mankind, according to its charter. In fiscal 2016, it provided $663 million in U.S. biomedical research and $86 million in grants and other support for science education. HHMI's Department of Science Education, the largest private, nonprofit supporter of science education in the country, will provide funding for the AP projects. The funding will allow AP to increase the amount of science-related stories it provides to news organizations and add more journalists to support its current science reporting team. HHMI will also offer expert background information and educational material. While the AP will receive funding and utilize HHMI's expertise when crafting its content, it maintains full editorial control of published material. "We're proud to stand shoulder to shoulder with the world's most respected news organization to ensure that the best evidence around important scientific topics is presented clearly and distributed widely," said Sean B. Carroll, vice president of HHMI's Department of Science Education.