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https://www.readbyqxmd.com/read/27914200/assembling-the-tat-protein-translocase
#1
Felicity Alcock, Phillip J Stansfeld, Hajra Basit, Johann Habersetzer, Matthew Ab Baker, Tracy Palmer, Mark I Wallace, Ben C Berks
The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, molecular simulations, and experimentation to define the interactions between the Tat proteins of Escherichia coli at molecular-level resolution. In the TatBC receptor complex the transmembrane helix of each TatB molecule is sandwiched between two TatC molecules, with one of the inter-subunit interfaces incorporating a functionally important cluster of interacting polar residues...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27914199/filamin-a-synaptic-organizer-in-drosophila-determines-glutamate-receptor-composition-and-membrane-growth
#2
GaYoung Lee, Thomas L Schwarz
Filamin is a scaffolding protein that functions in many cells as an actin-crosslinker. FLN90, an isoform of the Drosophila ortholog Filamin/cheerio that lacks the actin-binding domain, is here shown to govern the growth of postsynaptic membrane folds and the composition of glutamate receptor clusters at the larval neuromuscular junction. Genetic and biochemical analyses revealed that FLN90 is present surrounding synaptic boutons. FLN90 is required in the muscle for localization of the kinase dPak and, downstream of dPak, for localization of the GTPase Ral and the exocyst complex to this region...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27914198/spatial-patterning-of-p-granules-by-rna-induced-phase-separation-of-the-intrinsically-disordered-protein-meg-3
#3
Jarrett Smith, Deepika Calidas, Helen Schmidt, Tu Lu, Dominique Rasoloson, Geraldine Seydoux
RNA granules are non-membrane bound cellular compartments that contain RNA and RNA binding proteins. The molecular mechanisms that regulate the spatial distribution of RNA granules in cells are poorly understood. During polarization of the C. elegans zygote, germline RNA granules, called P granules, assemble preferentially in the posterior cytoplasm. We present evidence that P granule asymmetry depends on RNA-induced phase separation of the granule scaffold MEG-3. MEG-3 is an intrinsically disordered protein that binds and phase separates with RNA in vitro...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27914197/young-adult-born-neurons-enhance-hippocampal-dependent-performance-via-influences-on-bilateral-networks
#4
Jia-Min Zhuo, Hua-An Tseng, Mitul Desai, Mark E Bucklin, Ali I Mohammed, Nick Tm Robinson, Edward S Boyden, Lara M Rangel, Alan P Jasanoff, Howard J Gritton, Xue Han
Adult neurogenesis supports performance in many hippocampal dependent tasks. Considering the small number of adult-born neurons generated at any given time, it is surprising that this sparse population of cells can substantially influence behavior. Recent studies have demonstrated that heightened excitability and plasticity may be critical for the contribution of young adult-born cells for certain tasks. What is not well understood is how these unique biophysical and synaptic properties may translate to networks that support behavioral function...
December 3, 2016: ELife
https://www.readbyqxmd.com/read/27911260/population-scale-mapping-of-transposable-element-diversity-reveals-links-to-gene-regulation-and-epigenomic-variation
#5
Tim Stuart, Steven Eichten, Jonathan Cahn, Yuliya Karpievitch, Justin Borevitz, Ryan Lister
Variation in the presence or absence of transposable elements (TEs) is a major source of genetic variation between individuals. Here, we identified 23,095 TE presence/absence variants between 216 Arabidopsis accessions. Most TE variants were rare, and we find these rare variants associated with local extremes of gene expression and DNA methylation levels within the population. Of the common alleles identified, two thirds were not in linkage disequilibrium with nearby SNPs, implicating these variants as a source of novel genetic diversity...
December 2, 2016: ELife
https://www.readbyqxmd.com/read/27906130/braf-activates-pax3-to-control-muscle-precursor-cell-migration-during-forelimb-muscle-development
#6
Jaeyoung Shin, Shuichi Watanabe, Soraya Hoelper, Marcus Krüger, Sawa Kostin, Jochen Pöling, Thomas Kubin, Thomas Braun
Migration of skeletal muscle precursor cells is a key step during limb muscle development and depends on the activity of PAX3 and MET. Here, we demonstrate that BRAF serves a crucial function in formation of limb skeletal muscles during mouse embryogenesis downstream of MET and acts as a potent inducer of myoblast cell migration. We found that a fraction of BRAF accumulates in the nucleus after activation and endosomal transport to a perinuclear position. Mass spectrometry based screening for potential interaction partners revealed that BRAF interacts and phosphorylates PAX3...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27906129/the-evolutionary-origin-of-bilaterian-smooth-and-striated-myocytes
#7
Thibaut Brunet, Antje Hl Fischer, Patrick Rh Steinmetz, Antonella Lauri, Paola Bertucci, Detlev Arendt
The dichotomy between smooth and striated myocytes is fundamental for bilaterian musculature, but its evolutionary origin is unsolved. In particular, interrelationships of visceral smooth muscles remain unclear. Absent in fly and nematode, they have not yet been characterized molecularly outside vertebrates. Here, we characterize expression profile, ultrastructure, contractility and innervation of the musculature in the marine annelid Platynereis dumerilii and identify smooth muscles around the midgut, hindgut and heart that resemble their vertebrate counterparts in molecular fingerprint, contraction speed, and nervous control...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27906128/two-subunits-of-human-orc-are-dispensable-for-dna-replication-and-proliferation
#8
Etsuko Shibata, Manjari Kiran, Yoshiyuki Shibata, Samarendra Singh, Shashi Kiran, Anindya Dutta
The six-subunit Origin Recognition Complex (ORC) is believed to be an essential eukaryotic ATPase that binds to origins of replication as a ring-shaped heterohexamer to load MCM2-7 and initiate DNA replication. We have discovered that human cell lines in culture proliferate with intact chromosomal origins of replication after disruption of both alleles of ORC2 or of the ATPase subunit, ORC1. The ORC1 or ORC2-depleted cells replicate with decreased chromatin loading of MCM2-7 and become critically dependent on another ATPase, CDC6, for survival and DNA replication...
December 1, 2016: ELife
https://www.readbyqxmd.com/read/27901466/differentiation-alters-stem-cell-nuclear-architecture-mechanics-and-mechano-sensitivity
#9
Su-Jin Heo, Tristan P Driscoll, Stephen D Thorpe, Nandan L Nerurkar, Brendon M Baker, Michael T Yang, Christopher S Chen, David A Lee, Robert L Mauck
Mesenchymal stem cell (MSC) differentiation is mediated by soluble and physical cues. In this study, we investigated differentiation induced transformations in MSC cellular and nuclear biophysical properties and queried their role in mechanosensation. Our data show that nuclei in differentiated bovine and human MSCs stiffen and become resistant to deformation. This attenuated nuclear deformation was governed by restructuring of Lamin A/C and increased heterochromatin content. This change in nuclear stiffness sensitized MSCs to mechanical loading induced calcium signaling and differentiated marker expression...
November 30, 2016: ELife
https://www.readbyqxmd.com/read/27897973/structure-in-the-variability-of-the-basic-reproductive-number-r0-for-zika-epidemics-in-the-pacific-islands
#10
Clara Champagne, David Georges Salthouse, Richard Paul, Van-Mai Cao-Lormeau, Benjamin Roche, Bernard Cazelles
Before the outbreak that reached the Americas in 2015, Zika virus (ZIKV) circulated in Asia and the Pacific: these past epidemics can be highly informative on the key parameters driving virus transmission, such as the basic reproduction number (R0). We compare two compartmental models with different mosquito representations, using surveillance and seroprevalence data for several ZIKV outbreaks in Pacific islands (Yap, Micronesia 2007, Tahiti and Moorea, French Polynesia 2013-2014, New Caledonia 2014). Models are estimated in a stochastic framework with recent Bayesian techniques...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27897972/mechanism-of-allosteric-regulation-of-%C3%AE-2-adrenergic-receptor-by-cholesterol
#11
Moutusi Manna, Miia Niemelä, Joona Tynkkynen, Matti Javanainen, Waldemar Kulig, Daniel J Müller, Tomasz Rog, Ilpo Vattulainen
There is evidence that lipids can be allosteric regulators of membrane protein structure and activation. However, there are no data showing how exactly the regulation emerges from specific lipid-protein interactions. Here we show in atomistic detail how the human β2-adrenergic receptor (β2AR) - a prototypical G protein-coupled receptor - is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates β2AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located near the transmembrane helices 5-7 of the receptor...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27897971/transformation-of-temporal-sequences-in-the-zebra-finch-auditory-system
#12
Yoonseob Lim, Ryan Lagoy, Barbara G Shinn-Cunningham, Timothy J Gardner
This study examines how temporally patterned stimuli are transformed as they propagate from primary to secondary zones in the thalamo-recipient auditory pallium in zebra finches. Using a new class of synthetic click stimuli, we find a robust mapping from temporal sequences in the primary zone to distinct population vectors in secondary auditory areas. We tested whether songbirds could discriminate synthetic click sequences in an operant setup and found that a robust behavioral discrimination is present for click sequences composed of intervals ranging from 11-40ms, but breaks down for stimuli composed of longer inter-click intervals...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27897970/an-essential-cell-autonomous-role-for-hepcidin-in-cardiac-iron-homeostasis
#13
Samira Lakhal-Littleton, Magda Wolna, Yu Jin Chung, Helen C Christian, Lisa C Heather, Marcella Brescia, Vicky Ball, Rebeca Diaz, Ana Santos, Daniel Biggs, Kieran Clarke, Benjamin Davies, Peter A Robbins
Hepcidin is the master regulator of systemic iron homeostasis. Derived primarily from the liver, it inhibits the iron exporter ferroportin in the gut and spleen, the sites of iron absorption and recycling respectively. Recently, we demonstrated that ferroportin is also found in cardiomyocytes, and that its cardiac-specific deletion leads to fatal cardiac iron overload. Hepcidin is also expressed in cardiomyocytes, where its function remains unknown. To define the function of cardiomyocyte hepcidin, we generated mice with cardiomyocyte-specific deletion of hepcidin, or knock-in of hepcidin-resistant ferroportin...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27897969/satb2-determines-mirna-expression-and-long-term-memory-in-the-adult-central-nervous-system
#14
Clemens Jaitner, Chethan Reddy, Andreas Abentung, Nigel Whittle, Dietmar Rieder, Andrea Delekate, Martin Korte, Gaurav Jain, Andre Fischer, Farahnaz Sananbenesi, Isabella Cera, Nicolas Singewald, Georg Dechant, Galina Apostolova
SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27894417/oral-transfer-of-chemical-cues-growth-proteins-and-hormones-in-social-insects
#15
Adria C LeBoeuf, Patrice Waridel, Colin S Brent, Andre N Gonc Alves, Laure Menin, Daniel Ortiz, Oksana Riba-Grognuz, Akiko Koto, Zamira G Soares, Eyal Privman, Eric A Miska, Richard Benton, Laurent Keller
Social insects frequently engage in oral fluid exchange - trophallaxis - between adults, and between adults and larvae. Although trophallaxis is widely considered a food-sharing mechanism, we hypothesized that endogenous components of this fluid might underlie a novel means of chemical communication between colony members. Through protein and small- molecule mass spectrometry and RNA sequencing, we found that trophallactic fluid in the ant Camponotus floridanus contains a set of specific digestion- and non-digestion related proteins, as well as hydrocarbons, microRNAs, and a key developmental regulator, juvenile hormone...
November 29, 2016: ELife
https://www.readbyqxmd.com/read/27892854/a-comprehensive-excitatory-input-map-of-the-striatum-reveals-novel-functional-organization
#16
Barbara J Hunnicutt, Bart C Jongbloets, William T Birdsong, Katrina J Gertz, Haining Zhong, Tianyi Mao
The striatum integrates excitatory inputs from the cortex and the thalamus to control diverse functions. Although the striatum is thought to consist of sensorimotor, associative and limbic domains, their precise demarcations and whether additional functional subdivisions exist remain unclear. How striatal inputs are differentially segregated into each domain is also poorly understood. This study presents a comprehensive map of the excitatory inputs to the mouse striatum. The input patterns reveal boundaries between the known striatal domains...
November 28, 2016: ELife
https://www.readbyqxmd.com/read/27892853/structure-of-the-germline-genome-of-tetrahymenathermophila-and-relationship-to-the-massively-rearranged-somatic-genome
#17
Eileen P Hamilton, Aurélie Kapusta, Piroska E Huvos, Shelby L Bidwell, Nikhat Zafar, Haibao Tang, Michalis Hadjithomas, Vivek Krishnakumar, Jonathan H Badger, Elisabet V Caler, Carsten Russ, Qiandong Zeng, Lin Fan, Joshua Z Levin, Terrance Shea, Sarah K Young, Ryan Hegarty, Riza Daza, Sharvari Gujja, Jennifer R Wortman, Bruce W Birren, Chad Nusbaum, Jainy Thomas, Clayton M Carey, Ellen J Pritham, Cédric Feschotte, Tomoko Noto, Kazufumi Mochizuki, Romeo Papazyan, Sean D Taverna, Paul H Dear, Donna M Cassidy-Hanley, Jie Xiong, Wei Miao, Eduardo Orias, Robert S Coyne
The germline genome of the binucleated ciliate Tetrahymenathermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally...
November 28, 2016: ELife
https://www.readbyqxmd.com/read/27892852/physical-basis-of-large-microtubule-aster-growth
#18
Keisuke Ishihara, Kirill S Korolev, Timothy J Mitchison
Microtubule asters - radial arrays of microtubules organized by centrosomes - play a fundamental role in the spatial coordination of animal cells. The standard model of aster growth assumes a fixed number of microtubules originating from the centrosomes. However, aster morphology in this model does not scale with cell size, and we recently found evidence for non-centrosomal microtubule nucleation. Here, we combine autocatalytic nucleation and polymerization dynamics to develop a biophysical model of aster growth...
November 28, 2016: ELife
https://www.readbyqxmd.com/read/27885988/global-mapping-of-highly-pathogenic-avian-influenza-h5n1-and-h5nx-clade-2-3-4-4-viruses-with-spatial-cross-validation
#19
Madhur S Dhingra, Jean Artois, Timothy P Robinson, Catherine Linard, Celia Chaiban, Ioannis Xenarios, Robin Engler, Robin Liechti, Dimitry Kuznetsov, Xiangming Xiao, Sophie Von Dobschuetz, Filip Claes, Scott H Newman, Gwenaëlle Dauphin, Marius Gilbert
Global disease suitability models are essential tools to inform surveillance systems and enable early detection. We present the first global suitability model of highly pathogenic avian influenza (HPAI) H5N1 and demonstrate that reliable predictions can be obtained at global scale. Best predictions are obtained using spatial predictor variables describing host distributions, rather than land use or eco-climatic spatial predictor variables, with a strong association with domestic duck and extensively raised chicken densities...
November 25, 2016: ELife
https://www.readbyqxmd.com/read/27885987/accelerated-cell-divisions-drive-the-outgrowth-of-the-regenerating-spinal-cord-in-axolotls
#20
Fabian Rost, Aida Rodrigo Albors, Vladimir Mazurov, Lutz Brusch, Andreas Deutsch, Elly M Tanaka, Osvaldo Chara
Axolotls are unique in their ability to regenerate the spinal cord. However, the mechanisms that underlie this phenomenon remain poorly understood. Previously, we showed that regenerating stem cells in the axolotl spinal cord revert to a molecular state resembling embryonic neuroepithelial cells and functionally acquire rapid proliferative divisions (Rodrigo Albors et al., 2015). Here, we refine the analysis of cell proliferation in space and time and identify a high-proliferation zone in the regenerating spinal cord that shifts posteriorly over time...
November 25, 2016: ELife
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