May 2014

Cover articles

    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    The repression of X-inactivation

    Tomasz Chelmicki, Friederike Dündar ... Asifa Akhtar
    1. Neuroscience

    Secrets of the cerebellum

    Haibo Zhou, Zhanmin Lin ... Martijn Schonewille
    1. Ecology

    Social insects and climate change

    Syuan-Jyun Sun, Dustin R Rubenstein ... Sheng-Feng Shen

Highlights controls:

Research articles

    1. Cell Biology

    Structure of cellular ESCRT-III spirals and their relationship to HIV budding

    Anil G Cashikar, Soomin Shim ... Phyllis I Hanson
    Electron microscopy on native membranes reveals the shape and potential function of protein machinery responsible for budding vesicles and viruses away from the cytoplasm.
    1. Cell Biology
    2. Developmental Biology

    Coordinated control of senescence by lncRNA and a novel T-box3 co-repressor complex

    Pavan Kumar P, Uchenna Emechebe ... Anne M Moon
    A novel master regulatory mechanism of cell proliferation and senscence employs the lncRNA UCA1 and a CAPERα/TBX3 corepressor.
    1. Developmental Biology

    TAF7L modulates brown adipose tissue formation

    Haiying Zhou, Bo Wan ... Robert Tjian
    TAF7L acts as a molecular switch that regulates the development of mesenchymal stem cells.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Cyclin D activates the Rb tumor suppressor by mono-phosphorylation

    Anil M Narasimha, Manuel Kaulich ... Steven F Dowdy
    The retinoblastoma tumor suppressor regulates cell cycle progression when it's in 14 mono-phosphorylated isoforms.
    1. Plant Biology

    Cell elongation is regulated through a central circuit of interacting transcription factors in the Arabidopsis hypocotyl

    Eunkyoo Oh, Jia-Ying Zhu ... Zhi-Yong Wang
    Signals from major hormones and the environment are integrated in the Arabidopsis hypocotyl to control gene expression and plant stem elongation.
    1. Chromosomes and Gene Expression
    2. Cancer Biology

    Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms

    Mary Ann Allen, Zdenek Andrysik ... Joaquin M Espinosa
    The first global analysis of the effects of the transcription factor p53 on RNA synthesis illuminates several novels aspects of the molecular mechanism of action of this potent tumor suppressor.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    MicroRNAs shape circadian hepatic gene expression on a transcriptome-wide scale

    Ngoc-Hien Du, Alaaddin Bulak Arpat ... David Gatfield
    In the liver, microRNAs exert widespread functions in the modulation of phases and amplitudes of clock-controlled gene expression, but their influence on the core clock is remarkably mild.
    1. Cell Biology

    Ki-67 is a PP1-interacting protein that organises the mitotic chromosome periphery

    Daniel G Booth, Masatoshi Takagi ... Paola Vagnarelli
    The mitotic chromosome periphery is organised by the PP1 binding protein Ki-67 and contributes to nucleolar re-activation upon mitotic exit.
    1. Biochemistry and Chemical Biology
    2. Physics of Living Systems

    Hsp70 chaperones are non-equilibrium machines that achieve ultra-affinity by energy consumption

    Paolo De Los Rios, Alessandro Barducci
    ATP consumption enables chaperones to exploit the different kinetic properties of their conformational states to exhibit a non-equilibrium affinity for their substrates that is orders of magnitude higher than its equilibrium value.
    1. Stem Cells and Regenerative Medicine
    2. Neuroscience

    Distinct and separable roles for EZH2 in neurogenic astroglia

    William W Hwang, Ryan D Salinas ... Daniel A Lim
    A number of genes associated with the development of brain tumors are epigenetically repressed in specialized astrocytes to enable the production of neurons in the postnatal brain.
    1. Neuroscience

    Neuronal connectome of a sensory-motor circuit for visual navigation

    Nadine Randel, Albina Asadulina ... Gáspár Jékely
    Three-dimensional mapping of the neural circuitry that controls movement of a marine worm in response to light provides insights into the evolution of complex visual systems.
    1. Neuroscience

    A neural mechanism of speed-accuracy tradeoff in macaque area LIP

    Timothy Hanks, Roozbeh Kiani, Michael N Shadlen
    To establish a trade-off between the speed and accuracy of a decision, neurons in lateral intraparietal cortex combine evidence bearing on the decision with a signal that incorporates the cost of time into the decision-making process.
    1. Cell Biology

    Transport of soluble proteins through the Golgi occurs by diffusion via continuities across cisternae

    Galina V Beznoussenko, Seetharaman Parashuraman ... Alberto Luini
    The soluble cargo protein albumin traverses the Golgi stack at much faster rates than procollagen aggregates, by diffusion via intercisternal continuities.
    1. Cell Biology
    2. Evolutionary Biology

    Characterization of TSET, an ancient and widespread membrane trafficking complex

    Jennifer Hirst, Alexander Schlacht ... Margaret S Robinson
    A missing link between the AP complexes and COPI sheds light on the evolution of vesicle coat proteins and trafficking pathways in the earliest eukaryotes.
    1. Cell Biology
    2. Plant Biology

    Natural variation reveals that intracellular distribution of ELF3 protein is associated with function in the circadian clock

    Muhammad Usman Anwer, Eleni Boikoglou ... Seth Jon Davis
    In Arabidopsis, a natural variant of the ELF3 protein, which originated in Central Asia, is less likely to accumulate in the nucleus, and causes the circadian clock to run faster and be less responsive to environmental cues.
    1. Physics of Living Systems

    Rheotaxis facilitates upstream navigation of mammalian sperm cells

    Vasily Kantsler, Jörn Dunkel ... Raymond E Goldstein
    Mammalian sperm subject to shear flow swim in upstream spirals along the walls bounding such flows, thereby demonstrating a robust mechanism for upstream navigation to the ovum.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2

    Adelajda Zorba, Vanessa Buosi ... Dorothee Kern
    Aurora A kinase, an anti-cancer drug target, can be activated by two independent mechanisms.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    Evidence for a DNA-relay mechanism in ParABS-mediated chromosome segregation

    Hoong Chuin Lim, Ivan Vladimirovich Surovtsev ... Christine Jacobs-Wagner
    In vitro, in vivo and in silico evidence suggests that bacteria exploit intrinsic chromosomal fluctuations to achieve intracellular transport.
    1. Cell Biology
    2. Developmental Biology

    miR-142 orchestrates a network of actin cytoskeleton regulators during megakaryopoiesis

    Elik Chapnik, Natalia Rivkin ... Eran Hornstein
    miR-142 is instrumental for actin homeostasis, and its loss disrupts the cytoskeleton organization and thrombopoiesis of megakaryocytes.
    1. Plant Biology

    Phosphoprotein SAK1 is a regulator of acclimation to singlet oxygen in Chlamydomonas reinhardtii

    Setsuko Wakao, Brian L Chin ... Krishna K Niyogi
    SAK1, a novel cytoplasmic phosphoprotein, is a key intermediate component of the retrograde signaling pathway controlling nuclear gene expression during acclimation of Chlamydomonas cells to singlet oxygen stress.
    1. Neuroscience

    The inhibitory microcircuit of the substantia nigra provides feedback gain control of the basal ganglia output

    Jennifer Brown, Wei-Xing Pan, Joshua Tate Dudman
    Negative feedback signals within the substantia nigra regulate the output of the basal ganglia, with implications for disorders such as Parkinson's disease.
    1. Developmental Biology

    Local cell interactions and self-amplifying individual cell ingression drive amniote gastrulation

    Octavian Voiculescu, Lawrence Bodenstein ... Claudio D Stern
    A combination of two local cell interactions, intercalation and ingression amplified by a community-effect, is sufficient to explain the global movements of amniote gastrulation.
    1. Cell Biology

    Pharmacological inhibition of cystine–glutamate exchange induces endoplasmic reticulum stress and ferroptosis

    Scott J Dixon, Darpan N Patel ... Brent R Stockwell
    Erastin and sorafenib inhibit system xc- and induce ER stress, suggesting these may be useful tools for probing the functions of system xc- and its role in inducing ER stress and ferroptosis.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Expression site attenuation mechanistically links antigenic variation and development in Trypanosoma brucei

    Christopher Batram, Nicola G Jones ... Markus Engstler
    The VSG gene controls its monoallelic expression, and expression site activity determines developmental progression.
    1. Neuroscience

    Inferring eye position from populations of lateral intraparietal neurons

    Arnulf BA Graf, Richard A Andersen
    An area of visual-motor cortex called the lateral intraparietal area encodes eye position signals that support visually-guided behaviors and image stabilization.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Imaging the fate of histone Cse4 reveals de novo replacement in S phase and subsequent stable residence at centromeres

    Jan Wisniewski, Bassam Hajj ... Carl Wu
    Internally tagged, functional Cse4/CENP-A/CenH3 histone variant is exclusively centromeric and stable through the budding yeast cell cycle after replacement in S phase.
    1. Cell Biology
    2. Cancer Biology

    MELK is an oncogenic kinase essential for mitotic progression in basal-like breast cancer cells

    Yubao Wang, Young-Mi Lee ... Jean J Zhao
    Maternal embryonic leucine zipper kinase (MELK) is a new anti-cancer target that is highly selective for basal-like breast cancer.
    1. Cell Biology

    SLY1 and Syntaxin 18 specify a distinct pathway for procollagen VII export from the endoplasmic reticulum

    Cristina Nogueira, Patrik Erlmann ... Vivek Malhotra
    A cross-linking screen finds proteins that interact with TANGO1 to export Procollagen VII, and suggests a new model for the secretion of these bulky cargoes that are involved in skin and bone formation.
    1. Immunology and Inflammation

    T cell-intrinsic role of IL-6 signaling in primary and memory responses

    Simone A Nish, Dominik Schenten ... Ruslan Medzhitov
    IL-6 signaling in T cells controls how sensitive they are to suppression by T regulatory cells, and the way mature to become memory T cells.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Coupled ion binding and structural transitions along the transport cycle of glutamate transporters

    Grégory Verdon, SeCheol Oh ... Olga Boudker
    Crystal structures of an archaeal homologue of mammalian glutamate transporters in apo and ion-only bound outward- and inward-facing states reveal ion-coupled conformational changes supporting mechanisms of coupling, gating, and transport.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    MOF-associated complexes ensure stem cell identity and Xist repression

    Tomasz Chelmicki, Friederike Dündar ... Asifa Akhtar
    Two complexes that contain the histone acetyl transferase MOF engage in a two-pronged approach to ensure the repression of X inactivation in mouse embryonic stem cells.
    1. Structural Biology and Molecular Biophysics
    2. Microbiology and Infectious Disease

    Drastic changes in conformational dynamics of the antiterminator M2-1 regulate transcription efficiency in Pneumovirinae

    Cedric Leyrat, Max Renner ... Jonathan M Grimes
    A combination of X-ray crystallography, molecular dynamics and small angle X-ray scattering shows that the transcription antiterminator M2-1 is a structurally dynamic homotetramer that undergoes large concerted conformational changes upon binding its target RNA.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    SM proteins Sly1 and Vps33 co-assemble with Sec17 and SNARE complexes to oppose SNARE disassembly by Sec18

    Braden T Lobingier, Daniel P Nickerson ... Alexey J Merz
    Sec1/Munc18 (SM) proteins shield SNARE complexes from NSF/Sec18-mediated disassembly through cooperative binding interactions with SNARE complexes and the universal co-chaperone α-SNAP/Sec17.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Conformational dynamics of the nucleotide binding domains and the power stroke of a heterodimeric ABC transporter

    Smriti Mishra, Brandy Verhalen ... Hassane S Mchaourab
    The conformational cycle of an ABC heterodimeric transporter reveals a divergence in the structural mechanism of ABC exporters.
    1. Neuroscience

    Atoh1-dependent rhombic lip neurons are required for temporal delay between independent respiratory oscillators in embryonic mice

    Srinivasan Tupal, Wei-Hsiang Huang ... Paul A Gray
    The rhythmic patterns of activity that underlie breathing are generated and coordinated by distinct populations of neurons within the brainstem.
    1. Ecology

    Climate-mediated cooperation promotes niche expansion in burying beetles

    Syuan-Jyun Sun, Dustin R Rubenstein ... Sheng-Feng Shen
    Cooperation enables burying beetles to outcompete flies and adapt to a wider range of temperatures as thermal generalists.
    1. Immunology and Inflammation

    Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation

    Hyewon Phee, Byron B Au-Yeung ... Arthur Weiss
    The p21-activated kinase 2 (Pak2) is an essential regulator that governs the actin cytoskeleton-dependent signaling to ensure normal thymocyte development, maturation and egress.
    1. Cancer Biology

    Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis

    William W Wheaton, Samuel E Weinberg ... Navdeep S Chandel
    The anti-diabetic drug metformin, currently in clinical trials as a potential anti-cancer agent, reduces tumor growth by inhibiting mitochondrial complex I of human cancer cells.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Distinct stages of the translation elongation cycle revealed by sequencing ribosome-protected mRNA fragments

    Liana F Lareau, Dustin H Hite ... Patrick O Brown
    The size of the mRNA fragment protected by a ribosome depends on the ribosome's conformation, which enables studies of the distinct steps of decoding and translocation at single-codon resolution.
    1. Chromosomes and Gene Expression

    Tyrosine phosphorylation of RNA polymerase II CTD is associated with antisense promoter transcription and active enhancers in mammalian cells

    Nicolas Descostes, Martin Heidemann ... Jean-Christophe Andrau
    Genome-wide analysis reveals novel functions for a post-translational modification to the carboxy-terminal domain (CTD) of RNA Polymerase II in mammals.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Re-examining how complexin inhibits neurotransmitter release

    Thorsten Trimbuch, Junjie Xu ... Christian Rosenmund
    Challenging a widespread model, biophysical and electrophysiological experiments suggest a new mechanism whereby complexins inhibit neurotransmitter release through electrostatic repulsion between their accessory helix and the membranes.
    1. Neuroscience

    Cell-intrinsic mechanisms of temperature compensation in a grasshopper sensory receptor neuron

    Frederic A Roemschied, Monika JB Eberhard ... Susanne Schreiber
    The firing rates of neurons in the grasshopper auditory system are surprisingly robust to changes in temperature, and cell-intrinsic mechanisms are sufficient to explain this temperature insensitivity.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    RNAP II CTD tyrosine 1 performs diverse functions in vertebrate cells

    Jing-Ping Hsin, Wencheng Li ... James L Manley
    Phosphorylation of tyrosine 1 in the carboxy-terminal domain (CTD) of the largest subunit of RNA Polymerase (RNAP) II functions to stabilize this domain, and facilitates turnover of upstream antisense RNAs.
    1. Ecology
    2. Epidemiology and Global Health

    Hidden shift of the ionome of plants exposed to elevated CO2 depletes minerals at the base of human nutrition

    Irakli Loladze
    Increasing levels of atmospheric carbon dioxide reduce the mineral content but increase the levels of starch and sugars found in crop plants; which could exacerbate both obesity and malnutrition in some human populations.
    1. Neuroscience

    Cerebellar modules operate at different frequencies

    Haibo Zhou, Zhanmin Lin ... Martijn Schonewille
    Zebrin-positive cerebellar Purkinje cells fire at lower frequencies than zebrin-negative cells, indicating that cerebellar circuits are not physiologically homogeneous.
    1. Cell Biology
    2. Neuroscience

    Complete morphologies of basal forebrain cholinergic neurons in the mouse

    Hao Wu, John Williams, Jeremy Nathans
    The first complete 3D structures of mouse cholinergic neurons reveal the length and complexity of their axons, while calculations suggest that equivalent axons in the human brain are approximately than 100 meters long.
    1. Stem Cells and Regenerative Medicine

    Prospective identification of functionally distinct stem cells and neurosphere-initiating cells in adult mouse forebrain

    John K Mich, Robert AJ Signer ... Sean J Morrison
    Flow cytometric isolation and fate mapping shows that neurosphere-initiating cells are highly mitotically active and persist only transiently in vivo, and are distinct from quiescent, long-lived neural stem cells.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    The translational landscape of the splicing factor SRSF1 and its role in mitosis

    Magdalena M Maslon, Sara R Heras ... Javier F Cáceres
    Identifying the translational targets of the shuttling protein, SRSF1, reveals that it is needed for normal cell division, and suggests that it couples pre-mRNA splicing and translation.
    1. Chromosomes and Gene Expression

    SETD2 is required for DNA double-strand break repair and activation of the p53-mediated checkpoint

    Sílvia Carvalho, Alexandra C Vítor ... Sérgio F de Almeida
    The involvement of SETD2 in an important DNA repair pathway could explain the high frequency of SETD2 mutations in several cancers and may provide an alternative mechanism to evade the p53-mediated checkpoint.
    1. Cell Biology

    A sphingolipid-dependent diffusion barrier confines ER stress to the yeast mother cell

    Lori Clay, Fabrice Caudron ... Yves Barral
    Sphingolipids govern the compartmentalization of yeast cells through the assembly of lateral diffusion barriers in ER membranes.
    1. Cell Biology
    2. Immunology and Inflammation

    Epidermal barrier defects link atopic dermatitis with altered skin cancer susceptibility

    Sara Cipolat, Esther Hoste ... Fiona M Watt
    A mouse model of atopic dermatitis provides mechanistic evidence for an association between allergic disease and skin cancer.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Bacterial actin MreB forms antiparallel double filaments

    Fusinita van den Ent, Thierry Izoré ... Jan Löwe
    The prokaryotic actin homologue MreB forms antiparallel double filaments in vitro and in vivo, an architecture that is unprecedented among the actin family of proteins.
    1. Evolutionary Biology

    Robust and accurate prediction of residue–residue interactions across protein interfaces using evolutionary information

    Sergey Ovchinnikov, Hetunandan Kamisetty, David Baker
    Co-evolving residue pairs in the different components of a protein complex almost always make contact across the protein–protein interface, thus providing powerful restraints for the modeling of protein complexes.