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  • Genome-wide identification of bacterial plant colonization genes
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-22
    Benjamin J. Cole, Meghan E. Feltcher, Robert J. Waters, Kelly M. Wetmore, Tatiana S. Mucyn, Elizabeth M. Ryan, Gaoyan Wang, Sabah Ul-Hasan, Meredith McDonald, Yasuo Yoshikuni, Rex R. Malmstrom, Adam M. Deutschbauer, Jeffery L. Dangl, Axel Visel
    更新日期:2017-09-23
  • A new discrete dynamic model of ABA-induced stomatal closure predicts key feedback loops
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-22
    Réka Albert, Biswa R. Acharya, Byeong Wook Jeon, Jorge G. T. Zañudo, Mengmeng Zhu, Karim Osman, Sarah M. Assmann
    更新日期:2017-09-23
  • Development of rat female genital cortex and control of female puberty by sexual touch
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-21
    Constanze Lenschow, Johanna Sigl-Glöckner, Michael Brecht
    更新日期:2017-09-21
  • What do we talk about when we talk about rhythm?
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-19
    Jonas Obleser, Molly J. Henry, Peter Lakatos
    更新日期:2017-09-20
  • Dance to the rhythm, cautiously: Isolating unique indicators of oscillatory entrainment
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-19
    Assaf Breska, Leon Y. Deouell
    更新日期:2017-09-20
  • 60 years ago, Francis Crick changed the logic of biology
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-18
    Matthew Cobb
    更新日期:2017-09-19
  • Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-13
    Hrvoje Augustin, Kieran McGourty, Marcus J. Allen, Sirisha Kudumala Madem, Jennifer Adcott, Fiona Kerr, Chi Tung Wong, Alec Vincent, Tanja Godenschwege, Emmanuel Boucrot, Linda Partridge
    更新日期:2017-09-14
  • Place field assembly distribution encodes preferred locations
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-12
    Omar Mamad, Lars Stumpp, Harold M. McNamara, Charu Ramakrishnan, Karl Deisseroth, Richard B. Reilly, Marian Tsanov
    更新日期:2017-09-12
  • ‘Spin’ in published biomedical literature: A methodological systematic review
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-11
    Kellia Chiu, Quinn Grundy, Lisa Bero
    更新日期:2017-09-11
  • A map of protein dynamics during cell-cycle progression and cell-cycle exit
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-11
    Sara Gookin, Mingwei Min, Harsha Phadke, Mingyu Chung, Justin Moser, Iain Miller, Dylan Carter, Sabrina L. Spencer
    更新日期:2017-09-11
  • Extreme genome diversity in the hyper-prevalent parasitic eukaryote Blastocystis
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-11
    Eleni Gentekaki, Bruce A. Curtis, Courtney W. Stairs, Vladimír Klimeš, Marek Eliáš, Dayana E. Salas-Leiva, Emily K. Herman, Laura Eme, Maria C. Arias, Bernard Henrissat, Frédérique Hilliou, Mary J. Klute, Hiroshi Suga, Shehre-Banoo Malik, Arthur W. Pightling, Martin Kolisko, Richard A. Rachubinski, Alexander Schlacht, Darren M. Soanes, Anastasios D. Tsaousis, John M. Archibald, Steven G. Ball, Joel B. Dacks, C. Graham Clark, Mark van der Giezen, Andrew J. Roger
    更新日期:2017-09-11
  • Simple rules can guide whether land- or ocean-based conservation will best benefit marine ecosystems
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-06
    Megan I. Saunders, Michael Bode, Scott Atkinson, Carissa J. Klein, Anna Metaxas, Jutta Beher, Maria Beger, Morena Mills, Sylvaine Giakoumi, Vivitskaia Tulloch, Hugh P. Possingham
    更新日期:2017-09-07
  • Identifying genetic variants that affect viability in large cohorts
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-05
    Hakhamanesh Mostafavi, Tomaz Berisa, Felix R. Day, John R. B. Perry, Molly Przeworski, Joseph K. Pickrell
    更新日期:2017-09-06
  • Systematic analysis of transcription start sites in avian development
    PLOS Bio. (IF 9.797) Pub Date : 2017-09-05
    Marina Lizio, Ruslan Deviatiiarov, Hiroki Nagai, Laura Galan, Erik Arner, Masayoshi Itoh, Timo Lassmann, Takeya Kasukawa, Akira Hasegawa, Marian A. Ros, Yoshihide Hayashizaki, Piero Carninci, Alistair R. R. Forrest, Hideya Kawaji, Oleg Gusev, Guojun Sheng
    更新日期:2017-09-06
  • Genomic dissection of conserved transcriptional regulation in intestinal epithelial cells
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-29
    Colin R. Lickwar, J. Gray Camp, Matthew Weiser, Jordan L. Cocchiaro, David M. Kingsley, Terrence S. Furey, Shehzad Z. Sheikh, John F. Rawls
    更新日期:2017-08-30
  • Lef1-dependent hypothalamic neurogenesis inhibits anxiety
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-24
    Yuanyuan Xie, Dan Kaufmann, Matthew J. Moulton, Samin Panahi, John A. Gaynes, Harrison N. Watters, Dingxi Zhou, Hai-Hui Xue, Camille M. Fung, Edward M. Levine, Anthea Letsou, K. C. Brennan, Richard I. Dorsky
    更新日期:2017-08-25
  • Spontaneous mutation rate is a plastic trait associated with population density across domains of life
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-24
    Rok Krašovec, Huw Richards, Danna R. Gifford, Charlie Hatcher, Katy J. Faulkner, Roman V. Belavkin, Alastair Channon, Elizabeth Aston, Andrew J. McBain, Christopher G. Knight
    更新日期:2017-08-25
  • Understanding and overcoming antibiotic resistance
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-23
    Lauren A. Richardson
    更新日期:2017-08-24
  • Different patterns of neuronal activity trigger distinct responses of oligodendrocyte precursor cells in the corpus callosum
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-22
    Balint Nagy, Anahit Hovhannisyan, Ruxandra Barzan, Ting-Jiun Chen, Maria Kukley
    更新日期:2017-08-23
  • Object segmentation controls image reconstruction from natural scenes
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-21
    Peter Neri
    更新日期:2017-08-22
  • Rictor positively regulates B cell receptor signaling by modulating actin reorganization via ezrin
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-18
    Lu Huang, Yongjie Zhang, Chenguang Xu, Xiaomei Gu, Linlin Niu, Jinzhi Wang, Xiaoyu Sun, Xiaoming Bai, Xingtian Xuan, Qubei Li, Chunwei Shi, Bing Yu, Heather Miller, Gangyi Yang, Lisa S. Westerberg, Wanli Liu, Wenxia Song, Xiaodong Zhao, Chaohong Liu
    更新日期:2017-08-19
  • Let’s rise up to unite taxonomy and technology
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-18
    Holly M. Bik
    更新日期:2017-08-19
  • Perceived effort for motor control and decision-making
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-18
    Ignasi Cos
    更新日期:2017-08-19
  • The ESCRT-III pathway facilitates cardiomyocyte release of cBIN1-containing microparticles
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-14
    Bing Xu, Ying Fu, Yan Liu, Sosse Agvanian, Robert C. Wirka, Rachel Baum, Kang Zhou, Robin M. Shaw, TingTing Hong
    更新日期:2017-08-15
  • History of antibiotic adaptation influences microbial evolutionary dynamics during subsequent treatment
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-08
    Phillip Yen, Jason A. Papin
    更新日期:2017-08-09
  • Regulation of Gli ciliary localization and Hedgehog signaling by the PY-NLS/karyopherin-β2 nuclear import system
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-04
    Yuhong Han, Yue Xiong, Xuanming Shi, Jiang Wu, Yun Zhao, Jin Jiang
    更新日期:2017-08-05
  • EBV epigenetically suppresses the B cell-to-plasma cell differentiation pathway while establishing long-term latency
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-03
    Christine T. Styles, Quentin Bazot, Gillian A. Parker, Robert E. White, Kostas Paschos, Martin J. Allday
    更新日期:2017-08-04
  • A flagellum-specific chaperone facilitates assembly of the core type III export apparatus of the bacterial flagellum
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-03
    Florian D. Fabiani, Thibaud T. Renault, Britta Peters, Tobias Dietsche, Eric J. C. Gálvez, Alina Guse, Karen Freier, Emmanuelle Charpentier, Till Strowig, Mirita Franz-Wachtel, Boris Macek, Samuel Wagner, Michael Hensel, Marc Erhardt
    更新日期:2017-08-04
  • Assembly and stoichiometry of the core structure of the bacterial flagellar type III export gate complex
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-03
    Takuma Fukumura, Fumiaki Makino, Tobias Dietsche, Miki Kinoshita, Takayuki Kato, Samuel Wagner, Keiichi Namba, Katsumi Imada, Tohru Minamino
    更新日期:2017-08-04
  • The Genomic Observatories Metadatabase (GeOMe): A new repository for field and sampling event metadata associated with genetic samples
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-03
    John Deck, Michelle R. Gaither, Rodney Ewing, Christopher E. Bird, Neil Davies, Christopher Meyer, Cynthia Riginos, Robert J. Toonen, Eric D. Crandall
    更新日期:2017-08-04
  • Sequential sampling of visual objects during sustained attention
    PLOS Bio. (IF 9.797) Pub Date : 2017-06-28
    Jianrong Jia, Ling Liu, Fang Fang, Huan Luo
    更新日期:2017-08-03
  • Integration of individual and social information for decision-making in groups of different sizes
    PLOS Bio. (IF 9.797) Pub Date : 2017-06-28
    Seongmin A. Park, Sidney Goïame, David A. O'Connor, Jean-Claude Dreher
    更新日期:2017-08-03
  • Identifiers for the 21st century: How to design, provision, and reuse persistent identifiers to maximize utility and impact of life science data
    PLOS Bio. (IF 9.797) Pub Date : 2017-06-29
    Julie A. McMurry, Nick Juty, Niklas Blomberg, Tony Burdett, Tom Conlin, Nathalie Conte, Mélanie Courtot, John Deck, Michel Dumontier, Donal K. Fellows, Alejandra Gonzalez-Beltran, Philipp Gormanns, Jeffrey Grethe, Janna Hastings, Jean-Karim Hériché, Henning Hermjakob, Jon C. Ison, Rafael C. Jimenez, Simon Jupp, John Kunze, Camille Laibe, Nicolas Le Novère, James Malone, Maria Jesus Martin, Johanna R. McEntyre, Chris Morris, Juha Muilu, Wolfgang Müller, Philippe Rocca-Serra, Susanna-Assunta Sansone, Murat Sariyar, Jacky L. Snoep, Stian Soiland-Reyes, Natalie J. Stanford, Neil Swainston, Nicole Washington, Alan R. Williams, Sarala M. Wimalaratne, Lilly M. Winfree, Katherine Wolstencroft, Carole Goble, Christopher J. Mungall, Melissa A. Haendel, Helen Parkinson
    更新日期:2017-08-03
  • Chemosensory and hyperoxia circuits in C. elegans males influence sperm navigational capacity
    PLOS Bio. (IF 9.797) Pub Date : 2017-06-29
    Hieu D. Hoang, Michael A. Miller
    更新日期:2017-08-03
  • Can cancer researchers accurately judge whether preclinical reports will reproduce?
    PLOS Bio. (IF 9.797) Pub Date : 2017-06-29
    Daniel Benjamin, David R. Mandel, Jonathan Kimmelman
    更新日期:2017-08-03
  • A multiscale cerebral neurochemical connectome of the rat brain
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-03
    Hamid R. Noori, Judith Schöttler, Maria Ercsey-Ravasz, Alejandro Cosa-Linan, Melinda Varga, Zoltan Toroczkai, Rainer Spanagel

    Understanding the rat neurochemical connectome is fundamental for exploring neuronal information processing. By using advanced data mining, supervised machine learning, and network analysis, this study integrates over 5 decades of neuroanatomical investigations into a multiscale, multilayer neurochemical connectome of the rat brain. This neurochemical connectivity database (ChemNetDB) is supported by comprehensive systematically-determined receptor distribution maps. The rat connectome has an onion-type structural organization and shares a number of structural features with mesoscale connectomes of mouse and macaque. Furthermore, we demonstrate that extremal values of graph theoretical measures (e.g., degree and betweenness) are associated with evolutionary-conserved deep brain structures such as amygdala, bed nucleus of the stria terminalis, dorsal raphe, and lateral hypothalamus, which regulate primitive, yet fundamental functions, such as circadian rhythms, reward, aggression, anxiety, and fear. The ChemNetDB is a freely available resource for systems analysis of motor, sensory, emotional, and cognitive information processing.

    更新日期:2017-08-03
  • Early postnatal exposure to isoflurane causes cognitive deficits and disrupts development of newborn hippocampal neurons via activation of the mTOR pathway
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-06
    Eunchai Kang, Danye Jiang, Yun Kyoung Ryu, Sanghee Lim, Minhye Kwak, Christy D. Gray, Michael Xu, Jun H. Choi, Sue Junn, Jieun Kim, Jing Xu, Michele Schaefer, Roger A. Johns, Hongjun Song, Guo-Li Ming, C. David Mintz

    Clinical and preclinical studies indicate that early postnatal exposure to anesthetics can lead to lasting deficits in learning and other cognitive processes. The mechanism underlying this phenomenon has not been clarified and there is no treatment currently available. Recent evidence suggests that anesthetics might cause persistent deficits in cognitive function by disrupting key events in brain development. The hippocampus, a brain region that is critical for learning and memory, contains a large number of neurons that develop in the early postnatal period, which are thus vulnerable to perturbation by anesthetic exposure. Using an in vivo mouse model we demonstrate abnormal development of dendrite arbors and dendritic spines in newly generated dentate gyrus granule cell neurons of the hippocampus after a clinically relevant isoflurane anesthesia exposure conducted at an early postnatal age. Furthermore, we find that isoflurane causes a sustained increase in activity in the mechanistic target of rapamycin pathway, and that inhibition of this pathway with rapamycin not only reverses the observed changes in neuronal development, but also substantially improves performance on behavioral tasks of spatial learning and memory that are impaired by isoflurane exposure. We conclude that isoflurane disrupts the development of hippocampal neurons generated in the early postnatal period by activating a well-defined neurodevelopmental disease pathway and that this phenotype can be reversed by pharmacologic inhibition.

    更新日期:2017-08-03
  • RNA stores tau reversibly in complex coacervates
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-06
    Xuemei Zhang, Yanxian Lin, Neil A. Eschmann, Hongjun Zhou, Jennifer N. Rauch, Israel Hernandez, Elmer Guzman, Kenneth S. Kosik, Songi Han

    Nonmembrane-bound organelles that behave like liquid droplets are widespread among eukaryotic cells. Their dysregulation appears to be a critical step in several neurodegenerative conditions. Here, we report that tau protein, the primary constituent of Alzheimer neurofibrillary tangles, can form liquid droplets and therefore has the necessary biophysical properties to undergo liquid-liquid phase separation (LLPS) in cells. Consonant with the factors that induce LLPS, tau is an intrinsically disordered protein that complexes with RNA to form droplets. Uniquely, the pool of RNAs to which tau binds in living cells are tRNAs. This phase state of tau is held in an approximately 1:1 charge balance across the protein and the nucleic acid constituents, and can thus be maximal at different RNA:tau mass ratios, depending on the biopolymer constituents involved. This feature is characteristic of complex coacervation. We furthermore show that the LLPS process is directly and sensitively tuned by salt concentration and temperature, implying it is modulated by both electrostatic interactions between the involved protein and nucleic acid constituents, as well as net changes in entropy. Despite the high protein concentration within the complex coacervate phase, tau is locally freely tumbling and capable of diffusing through the droplet interior. In fact, tau in the condensed phase state does not reveal any immediate changes in local protein packing, local conformations and local protein dynamics from that of tau in the dilute solution state. In contrast, the population of aggregation-prone tau as induced by the complexation with heparin is accompanied by large changes in local tau conformations and irreversible aggregation. However, prolonged residency within the droplet state eventually results in the emergence of detectable β-sheet structures according to thioflavin-T assay. These findings suggest that the droplet state can incubate tau and predispose the protein toward the formation of insoluble fibrils.

    更新日期:2017-08-03
  • Correction: 1.2 million kids and counting—Mobile science laboratories drive student interest in STEM
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-11
    Amanda L. Jones, Mary K. Stapleton
    更新日期:2017-08-03
  • Hierarchical patterning modes orchestrate hair follicle morphogenesis
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-11
    James D. Glover, Kirsty L. Wells, Franziska Matthäus, Kevin J. Painter, William Ho, Jon Riddell, Jeanette A. Johansson, Matthew J. Ford, Colin A. B. Jahoda, Vaclav Klika, Richard L. Mort, Denis J. Headon

    Two theories address the origin of repeating patterns, such as hair follicles, limb digits, and intestinal villi, during development. The Turing reaction–diffusion system posits that interacting diffusible signals produced by static cells first define a prepattern that then induces cell rearrangements to produce an anatomical structure. The second theory, that of mesenchymal self-organisation, proposes that mobile cells can form periodic patterns of cell aggregates directly, without reference to any prepattern. Early hair follicle development is characterised by the rapid appearance of periodic arrangements of altered gene expression in the epidermis and prominent clustering of the adjacent dermal mesenchymal cells. We assess the contributions and interplay between reaction–diffusion and mesenchymal self-organisation processes in hair follicle patterning, identifying a network of fibroblast growth factor (FGF), wingless-related integration site (WNT), and bone morphogenetic protein (BMP) signalling interactions capable of spontaneously producing a periodic pattern. Using time-lapse imaging, we find that mesenchymal cell condensation at hair follicles is locally directed by an epidermal prepattern. However, imposing this prepattern’s condition of high FGF and low BMP activity across the entire skin reveals a latent dermal capacity to undergo spatially patterned self-organisation in the absence of epithelial direction. This mesenchymal self-organisation relies on restricted transforming growth factor (TGF) β signalling, which serves to drive chemotactic mesenchymal patterning when reaction–diffusion patterning is suppressed, but, in normal conditions, facilitates cell movement to locally prepatterned sources of FGF. This work illustrates a hierarchy of periodic patterning modes operating in organogenesis.

    更新日期:2017-08-03
  • Four simple rules that are sufficient to generate the mammalian blastocyst
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-12
    Silas Boye Nissen, Marta Perera, Javier Martin Gonzalez, Sophie M. Morgani, Mogens H. Jensen, Kim Sneppen, Joshua M. Brickman, Ala Trusina

    Early mammalian development is both highly regulative and self-organizing. It involves the interplay of cell position, predetermined gene regulatory networks, and environmental interactions to generate the physical arrangement of the blastocyst with precise timing. However, this process occurs in the absence of maternal information and in the presence of transcriptional stochasticity. How does the preimplantation embryo ensure robust, reproducible development in this context? It utilizes a versatile toolbox that includes complex intracellular networks coupled to cell—cell communication, segregation by differential adhesion, and apoptosis. Here, we ask whether a minimal set of developmental rules based on this toolbox is sufficient for successful blastocyst development, and to what extent these rules can explain mutant and experimental phenotypes. We implemented experimentally reported mechanisms for polarity, cell—cell signaling, adhesion, and apoptosis as a set of developmental rules in an agent-based in silico model of physically interacting cells. We find that this model quantitatively reproduces specific mutant phenotypes and provides an explanation for the emergence of heterogeneity without requiring any initial transcriptional variation. It also suggests that a fixed time point for the cells’ competence of fibroblast growth factor (FGF)/extracellular signal—regulated kinase (ERK) sets an embryonic clock that enables certain scaling phenomena, a concept that we evaluate quantitatively by manipulating embryos in vitro. Based on these observations, we conclude that the minimal set of rules enables the embryo to experiment with stochastic gene expression and could provide the robustness necessary for the evolutionary diversification of the preimplantation gene regulatory network.

    更新日期:2017-08-03
  • The selfish germ
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-12
    Andrew F. Read

    Curiosity about the sex life of a wasp led to a new way of thinking and a powerful demonstration that evolutionary science could be predictive. That same approach could help find ways to slow or prevent treatment failures in cancer and infectious diseases.

    更新日期:2017-08-03
  • Dramatic and concerted conformational changes enable rhodocetin to block α2β1 integrin selectively
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-13
    Johannes A. Eble, Matthew McDougall, George L. Orriss, Stephan Niland, Benjamin Johanningmeier, Gottfried Pohlentz, Markus Meier, Simone Karrasch, Maria Inacia Estevão-Costa, Augusto Martins Lima, Jörg Stetefeld

    The collagen binding integrin α2β1 plays a crucial role in hemostasis, fibrosis, and cancer progression amongst others. It is specifically inhibited by rhodocetin (RC), a C-type lectin-related protein (CLRP) found in Malayan pit viper (Calloselasma rhodostoma) venom. The structure of RC alone reveals a heterotetramer arranged as an αβ and γδ subunit in a cruciform shape. RC specifically binds to the collagen binding A-domain of the integrin α2 subunit, thereby blocking collagen-induced platelet aggregation. However, until now, the molecular basis for this interaction has remained unclear. Here, we present the molecular structure of the RCγδ-α2A complex solved to 3.0 Å resolution. Our findings show that RC undergoes a dramatic structural reorganization upon binding to α2β1 integrin. Besides the release of the nonbinding RCαβ tandem, the RCγ subunit interacts with loop 2 of the α2A domain as result of a dramatic conformational change. The RCδ subunit contacts the integrin α2A domain in the “closed” conformation through its helix C. Combined with epitope-mapped antibodies, conformationally locked α2A domain mutants, point mutations within the α2A loop 2, and chemical modifications of the purified toxin protein, this molecular structure of RCγδ-α2A complex explains the inhibitory mechanism and specificity of RC for α2β1 integrin.

    更新日期:2017-08-03
  • Building the biomedical data science workforce
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-17
    Michelle C. Dunn, Philip E. Bourne

    This article describes efforts at the National Institutes of Health (NIH) from 2013 to 2016 to train a national workforce in biomedical data science. We provide an analysis of the Big Data to Knowledge (BD2K) training program strengths and weaknesses with an eye toward future directions aimed at any funder and potential funding recipient worldwide. The focus is on extramurally funded programs that have a national or international impact rather than the training of NIH staff, which was addressed by the NIH’s internal Data Science Workforce Development Center. From its inception, the major goal of BD2K was to narrow the gap between needed and existing biomedical data science skills. As biomedical research increasingly relies on computational, mathematical, and statistical thinking, supporting the training and education of the workforce of tomorrow requires new emphases on analytical skills. From 2013 to 2016, BD2K jump-started training in this area for all levels, from graduate students to senior researchers.

    更新日期:2017-08-03
  • Extracellular phosphorylation of a receptor tyrosine kinase controls synaptic localization of NMDA receptors and regulates pathological pain
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-18
    Kenji Hanamura, Halley R. Washburn, Sean I. Sheffler-Collins, Nan L. Xia, Nathan Henderson, Dipti V. Tillu, Shayne Hassler, Daniel S. Spellman, Guoan Zhang, Thomas A. Neubert, Theodore J. Price, Matthew B. Dalva

    Extracellular phosphorylation of proteins was suggested in the late 1800s when it was demonstrated that casein contains phosphate. More recently, extracellular kinases that phosphorylate extracellular serine, threonine, and tyrosine residues of numerous proteins have been identified. However, the functional significance of extracellular phosphorylation of specific residues in the nervous system is poorly understood. Here we show that synaptic accumulation of GluN2B-containing N-methyl-D-aspartate receptors (NMDARs) and pathological pain are controlled by ephrin-B-induced extracellular phosphorylation of a single tyrosine (p*Y504) in a highly conserved region of the fibronectin type III (FN3) domain of the receptor tyrosine kinase EphB2. Ligand-dependent Y504 phosphorylation modulates the EphB-NMDAR interaction in cortical and spinal cord neurons. Furthermore, Y504 phosphorylation enhances NMDAR localization and injury-induced pain behavior. By mediating inducible extracellular interactions that are capable of modulating animal behavior, extracellular tyrosine phosphorylation of EphBs may represent a previously unknown class of mechanism mediating protein interaction and function.

    更新日期:2017-08-03
  • The €100 lab: A 3D-printable open-source platform for fluorescence microscopy, optogenetics, and accurate temperature control during behaviour of zebrafish, Drosophila, and Caenorhabditis elegans
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-18
    Andre Maia Chagas, Lucia L. Prieto-Godino, Aristides B. Arrenberg, Tom Baden

    Small, genetically tractable species such as larval zebrafish, Drosophila, or Caenorhabditis elegans have become key model organisms in modern neuroscience. In addition to their low maintenance costs and easy sharing of strains across labs, one key appeal is the possibility to monitor single or groups of animals in a behavioural arena while controlling the activity of select neurons using optogenetic or thermogenetic tools. However, the purchase of a commercial solution for these types of experiments, including an appropriate camera system as well as a controlled behavioural arena, can be costly. Here, we present a low-cost and modular open-source alternative called ‘FlyPi’. Our design is based on a 3D-printed mainframe, a Raspberry Pi computer, and high-definition camera system as well as Arduino-based optical and thermal control circuits. Depending on the configuration, FlyPi can be assembled for well under €100 and features optional modules for light-emitting diode (LED)-based fluorescence microscopy and optogenetic stimulation as well as a Peltier-based temperature stimulator for thermogenetics. The complete version with all modules costs approximately €200 or substantially less if the user is prepared to ‘shop around’. All functions of FlyPi can be controlled through a custom-written graphical user interface. To demonstrate FlyPi’s capabilities, we present its use in a series of state-of-the-art neurogenetics experiments. In addition, we demonstrate FlyPi’s utility as a medical diagnostic tool as well as a teaching aid at Neurogenetics courses held at several African universities. Taken together, the low cost and modular nature as well as fully open design of FlyPi make it a highly versatile tool in a range of applications, including the classroom, diagnostic centres, and research labs.

    更新日期:2017-08-03
  • Seed size and its rate of evolution correlate with species diversification across angiosperms
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-19
    Javier Igea, Eleanor F. Miller, Alexander S. T. Papadopulos, Andrew J. Tanentzap

    Species diversity varies greatly across the different taxonomic groups that comprise the Tree of Life (ToL). This imbalance is particularly conspicuous within angiosperms, but is largely unexplained. Seed mass is one trait that may help clarify why some lineages diversify more than others because it confers adaptation to different environments, which can subsequently influence speciation and extinction. The rate at which seed mass changes across the angiosperm phylogeny may also be linked to diversification by increasing reproductive isolation and allowing access to novel ecological niches. However, the magnitude and direction of the association between seed mass and diversification has not been assessed across the angiosperm phylogeny. Here, we show that absolute seed size and the rate of change in seed size are both associated with variation in diversification rates. Based on the largest available angiosperm phylogenetic tree, we found that smaller-seeded plants had higher rates of diversification, possibly due to improved colonisation potential. The rate of phenotypic change in seed size was also strongly positively correlated with speciation rates, providing rare, large-scale evidence that rapid morphological change is associated with species divergence. Our study now reveals that variation in morphological traits and, importantly, the rate at which they evolve can contribute to explaining the extremely uneven distribution of diversity across the ToL.

    更新日期:2017-08-03
  • Global economic trade-offs between wild nature and tropical agriculture
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-21
    Luis R. Carrasco, Edward L. Webb, William S. Symes, Lian P. Koh, Navjot S. Sodhi

    Global demands for agricultural and forestry products provide economic incentives for deforestation across the tropics. Much of this deforestation occurs with a lack of information on the spatial distribution of benefits and costs of deforestation. To inform global sustainable land-use policies, we combine geographic information systems (GIS) with a meta-analysis of ecosystem services (ES) studies to perform a spatially explicit analysis of the trade-offs between agricultural benefits, carbon emissions, and losses of multiple ecosystem services because of tropical deforestation from 2000 to 2012. Even though the value of ecosystem services presents large inherent uncertainties, we find a pattern supporting the argument that the externalities of destroying tropical forests are greater than the current direct economic benefits derived from agriculture in all cases bar one: when yield and rent potentials of high-value crops could be realized in the future. Our analysis identifies the Atlantic Forest, areas around the Gulf of Guinea, and Thailand as areas where agricultural conversion appears economically efficient, indicating a major impediment to the long-term financial sustainability of Reducing Emissions from Deforestation and forest Degradation (REDD+) schemes in those countries. By contrast, Latin America, insular Southeast Asia, and Madagascar present areas with low agricultural rents (ARs) and high values in carbon stocks and ES, suggesting that they are economically viable conservation targets. Our study helps identify optimal areas for conservation and agriculture together with their associated uncertainties, which could enhance the efficiency and sustainability of pantropical land-use policies and help direct future research efforts.

    更新日期:2017-08-03
  • Neuronal synchrony and the relation between the blood-oxygen-level dependent response and the local field potential
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-24
    Dora Hermes, Mai Nguyen, Jonathan Winawer

    The most widespread measures of human brain activity are the blood-oxygen-level dependent (BOLD) signal and surface field potential. Prior studies report a variety of relationships between these signals. To develop an understanding of how to interpret these signals and the relationship between them, we developed a model of (a) neuronal population responses and (b) transformations from neuronal responses into the functional magnetic resonance imaging (fMRI) BOLD signal and electrocorticographic (ECoG) field potential. Rather than seeking a transformation between the two measures directly, this approach interprets each measure with respect to the underlying neuronal population responses. This model accounts for the relationship between BOLD and ECoG data from human visual cortex in V1, V2, and V3, with the model predictions and data matching in three ways: across stimuli, the BOLD amplitude and ECoG broadband power were positively correlated, the BOLD amplitude and alpha power (8–13 Hz) were negatively correlated, and the BOLD amplitude and narrowband gamma power (30–80 Hz) were uncorrelated. The two measures provide complementary information about human brain activity, and we infer that features of the field potential that are uncorrelated with BOLD arise largely from changes in synchrony, rather than level, of neuronal activity.

    更新日期:2017-08-03
  • Bacterial deception of MAIT cells in a cloud of superantigen and cytokines
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-24
    Johan K. Sandberg, Anna Norrby-Teglund, Edwin Leeansyah

    The bacterium Staphylococcus aureus is an important cause of the life-threatening condition toxic shock syndrome in humans. Bacterial toxins known as superantigens (SAgs) generate this illness by acting as broad activators of a substantial fraction of all T lymphocytes, bypassing the normally highly stringent T-cell receptor antigen specificity to cause a systemic inflammatory cytokine storm in the host. In a new study, Shaler et al. found that immune cells called mucosa-associated invariant T (MAIT) cells make an unexpectedly large contribution to the SAg response in a largely T-cell receptor–independent, cytokine-driven manner. Subsequent to such activation, the MAIT cells remain unresponsive to stimulation with bacterial antigen. Thus, S. aureus hijacks MAIT cells in the cytokine storm and leaves them functionally impaired. This work provides new insight into the role of MAIT cells in antibacterial immunity and opens new avenues of investigation to understand and possibly treat bacterial toxic shock and sepsis.

    更新日期:2017-08-03
  • Multiple visual objects are sampled sequentially
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-24
    Ole Jensen, Marlies E. Vissers

    When acting in a complex visual environment, it is essential to be able to flexibly allocate attention to parts of the visual scene that may contain goal-relevant information. The paper by Jia et al. provides novel evidence that our brains sequentially sample different objects in a visual scene. The results were obtained using “temporal response functions,” in which unique electroencephalographic (EEG) signals corresponding to the processing of 2 continuously presented objects were isolated in an object-specific way. These response functions were dominated by 10-Hz alpha-band activity. Crucially, the different objects were sequentially sampled at a rate of about 2 Hz. These findings provide important neurophysiological insights into how our visual system operates in complex environments.

    更新日期:2017-08-03
  • Genes, cells, and biobanks: Yes, there’s still a consent problem
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-25
    Timothy Caulfield, Blake Murdoch

    From a research perspective, the interest in biobanking continues to intensify. Governments and industry have invested heavily in biobanks, as exemplified by initiatives like the United Kingdom Biobank and United States' Precision Medicine Initiative. But despite this enthusiasm, many profound legal and ethical challenges remain unresolved. Indeed, there continues to be disagreements about how best to obtain consent and the degree and nature of control that research participants retain over donated samples and health information. Emerging social trends—including concerns about commercialization and perceived rights of continuing control (“biorights”)—seem likely to intensify these issues.

    更新日期:2017-08-03
  • Integrated time-lapse and single-cell transcription studies highlight the variable and dynamic nature of human hematopoietic cell fate commitment
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-27
    Alice Moussy, Jérémie Cosette, Romuald Parmentier, Cindy da Silva, Guillaume Corre, Angélique Richard, Olivier Gandrillon, Daniel Stockholm, András Páldi

    Individual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterising transcriptional changes in cord blood-derived CD34+ cells at the single-cell level and integrating data with cell division history and morphological changes determined by time-lapse microscopy. We show that major transcriptional changes leading to a multilineage-primed gene expression state occur very rapidly during the first cell cycle. One of the 2 stable lineage-primed patterns emerges gradually in each cell with variable timing. Some cells reach a stable morphology and molecular phenotype by the end of the first cell cycle and transmit it clonally. Others fluctuate between the 2 phenotypes over several cell cycles. Our analysis highlights the dynamic nature and variable timing of cell fate commitment in hematopoietic cells, links the gene expression pattern to cell morphology, and identifies a new category of cells with fluctuating phenotypic characteristics, demonstrating the complexity of the fate decision process (which is different from a simple binary switch between 2 options, as it is usually envisioned).

    更新日期:2017-08-03
  • Comparative genomics of the tardigrades Hypsibius dujardini and Ramazzottius varieornatus
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-27
    Yuki Yoshida, Georgios Koutsovoulos, Dominik R. Laetsch, Lewis Stevens, Sujai Kumar, Daiki D. Horikawa, Kyoko Ishino, Shiori Komine, Takekazu Kunieda, Masaru Tomita, Mark Blaxter, Kazuharu Arakawa

    Tardigrada, a phylum of meiofaunal organisms, have been at the center of discussions of the evolution of Metazoa, the biology of survival in extreme environments, and the role of horizontal gene transfer in animal evolution. Tardigrada are placed as sisters to Arthropoda and Onychophora (velvet worms) in the superphylum Panarthropoda by morphological analyses, but many molecular phylogenies fail to recover this relationship. This tension between molecular and morphological understanding may be very revealing of the mode and patterns of evolution of major groups. Limnoterrestrial tardigrades display extreme cryptobiotic abilities, including anhydrobiosis and cryobiosis, as do bdelloid rotifers, nematodes, and other animals of the water film. These extremophile behaviors challenge understanding of normal, aqueous physiology: how does a multicellular organism avoid lethal cellular collapse in the absence of liquid water? Meiofaunal species have been reported to have elevated levels of horizontal gene transfer (HGT) events, but how important this is in evolution, and particularly in the evolution of extremophile physiology, is unclear. To address these questions, we resequenced and reassembled the genome of H. dujardini, a limnoterrestrial tardigrade that can undergo anhydrobiosis only after extensive pre-exposure to drying conditions, and compared it to the genome of R. varieornatus, a related species with tolerance to rapid desiccation. The 2 species had contrasting gene expression responses to anhydrobiosis, with major transcriptional change in H. dujardini but limited regulation in R. varieornatus. We identified few horizontally transferred genes, but some of these were shown to be involved in entry into anhydrobiosis. Whole-genome molecular phylogenies supported a Tardigrada+Nematoda relationship over Tardigrada+Arthropoda, but rare genomic changes tended to support Tardigrada+Arthropoda.

    更新日期:2017-08-03
  • The costs of saving nature: Does it make “cents”?
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-31
    Andrew J. Tanentzap
    更新日期:2017-08-03
  • 更新日期:2017-08-03
  • Dynamic transcriptome changes during adipose tissue energy expenditure reveal critical roles for long noncoding RNA regulators
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-01
    Zhiqiang Bai, Xiao-ran Chai, Myeong Jin Yoon, Hye-Jin Kim, Kinyui Alice LO, Zhi-chun Zhang, Dan Xu, Diana Teh Chee Siang, Arcinas Camille Esther Walet, Shao-hai Xu, Sook-Yoong Chia, Peng Chen, Hongyuan Yang, Sujoy Ghosh, Lei Sun
    更新日期:2017-08-03
  • Developing international open science collaborations: Funder reflections on the Open Science Prize
    PLOS Bio. (IF 9.797) Pub Date : 2017-08-01
    Elizabeth Kittrie, Audie A. Atienza, Robert Kiley, David Carr, Aki MacFarlane, Vinay Pai, Jennifer Couch, Jared Bajkowski, Joseph F. Bonner, Daniel Mietchen, Philip E. Bourne
    更新日期:2017-08-03
  • The selfish germ
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-12
    Andrew F. Read
    更新日期:2017-08-03
  • A multiscale cerebral neurochemical connectome of the rat brain
    PLOS Bio. (IF 9.797) Pub Date : 2017-07-03
    Hamid R. Noori, Judith Schöttler, Maria Ercsey-Ravasz, Alejandro Cosa-Linan, Melinda Varga, Zoltan Toroczkai, Rainer Spanagel
    更新日期:2017-08-03
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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