August 2015

Cover articles

Research articles

    1. Cell Biology

    The vacuole/lysosome is required for cell-cycle progression

    Yui Jin, Lois S Weisman
    The endo-lysosomal system plays a positive essential role in the initiation of the cell cycle in yeast.
    1. Neuroscience

    Dopamine neurons projecting to the posterior striatum form an anatomically distinct subclass

    William Menegas et al.
    Dopamine neurons projecting to different targets receive a similar set of inputs, rather than forming reciprocal connections, whereas those projecting to the posterior striatum receive a distinct set of inputs.
    1. Neuroscience

    Normative evidence accumulation in unpredictable environments

    Christopher M Glaze et al.
    Theoretically optimal dynamics for making decisions in unpredictable environments provide a broadly applicable framework for understanding choice behavior and underlying neural signals.
    1. Cell Biology
    2. Genomics and Evolutionary Biology

    KPNB1 mediates PER/CRY nuclear translocation and circadian clock function

    Yool Lee et al.
    KPNB1 regulates rhythmic spatio-temporal nuclear import of the PER/CRY complex and is required for negative feedback repression in mammalian and fly clock function.
    1. Neuroscience

    Dissociable roles of the inferior longitudinal fasciculus and fornix in face and place perception

    Carl J Hodgetts et al.
    Structure-function associations in medial temporal lobe reflect specialised, behaviourally-relevant neurocognitive circuits for the perception of faces and places.
    1. Biochemistry
    2. Cell Biology

    Distinct transcriptional responses elicited by unfolded nuclear or cytoplasmic protein in mammalian cells

    Yusuke Miyazaki et al.
    A new unfolded protein response has been discovered that is distinct from the heat shock response and protects mammalian cells from proteotoxic stress.
    1. Biochemistry
    2. Genes and Chromosomes

    Chemical perturbation of an intrinsically disordered region of TFIID distinguishes two modes of transcription initiation

    Zhengjian Zhang et al.
    An inorganic tin oxochloride cluster specifically binds to an intrinsically disordered, histidine-rich, low complexity protein region and arrests de novo transcription initiation without affecting reinitiation.
    1. Neuroscience

    NUDT21-spanning CNVs lead to neuropsychiatric disease and altered MeCP2 abundance via alternative polyadenylation

    Vincenzo A Gennarino et al.
    Individuals with deletions or duplications of the NUDT21 gene have altered levels of MeCP2 protein and intellectual disabilities.
    1. Biophysics and Structural Biology
    2. Developmental Biology and Stem Cells

    An ancient Pygo-dependent Wnt enhanceosome integrated by Chip/LDB-SSDP

    Marc Fiedler et al.
    The Chip/LDB-SSDP complex integrates multiple signals to render TCF/LEF enhancers Wnt responsive.
    1. Neuroscience

    Noise-induced plasticity of KCNQ2/3 and HCN channels underlies vulnerability and resilience to tinnitus

    Shuang Li et al.
    Mice that successfully avoid developing tinnitus despite exposure to excessive noise show spontaneous recovery of KCNQ2/3 potassium channel activity associated with a reduction in HCN channel activity in auditory brainstem neurons.
    1. Genes and Chromosomes

    Progerin reduces LAP2α-telomere association in Hutchinson-Gilford progeria

    Alexandre Chojnowski et al.
    Expression of the lamina-associated polypeptide α (LAP2α) prevents premature cellular ageing caused by expression of progerin in Hutchinson-Gilford progeria syndrome.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Inducible depletion of adult skeletal muscle stem cells impairs the regeneration of neuromuscular junctions

    Wenxuan Liu et al.
    Skeletal muscle stem cells play important roles in the regeneration of neuromuscular junctions, and so present new targets for therapies to treat neuromuscular decline observed in the context of aging and various neuromuscular diseases.
    1. Neuroscience

    Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

    Stephanie C Gantz et al.
    The loss of calcium-dependent D2 autoreceptor desensitization caused by prior in vivo cocaine exposure may be conferred by an unexpected role of the D2L splice variant as an autoreceptor.
    1. Neuroscience

    Rapid learning in visual cortical networks

    Ye Wang, Valentin Dragoi
    The rapid learning of sensory information in cortical circuits is accompanied by a tight coordination of spike timing with the local theta-band population activity in visual cortex.
    1. Neuroscience

    Phase-amplitude coupling supports phase coding in human ECoG

    Andrew J Watrous et al.
    Electrocorticography (ECoG) reveals that phase-amplitude coupling relates to phase-dependent coding in the human brain.
    1. Neuroscience
    2. Computational and Systems Biology

    Unified pre- and postsynaptic long-term plasticity enables reliable and flexible learning

    Rui Ponte Costa et al.
    Combined pre- and postsynaptically expressed long-term plasticity of neuronal connections improves sensory discrimination, and enables rapid relearning of previously encountered information.
    1. Neuroscience

    Nemo-like kinase is a novel regulator of spinal and bulbar muscular atrophy

    Tiffany W Todd et al.
    Nemo-like kinase is a key protein promoting the pathogenesis of spinal and bulbar muscular atrophy.
    1. Cell Biology
    2. Computational and Systems Biology

    Regulation of mRNA translation during mitosis

    Marvin E Tanenbaum et al.
    Ribosomal profiling reveals that translational repression is an important mechanism for cell cycle control and can complement protein degradation.
    1. Genes and Chromosomes

    Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication

    FuJung Chang et al.
    Biochemical and genetic characterization of the Cdc6 replication initiator reveals similarities in the helicase loading reaction between bacteria and eukaryotes.
    1. Biophysics and Structural Biology

    Structural dynamics of E. coli single-stranded DNA binding protein reveal DNA wrapping and unwrapping pathways

    Sukrit Suksombat et al.
    Single-molecule force and fluorescence spectroscopy reveal the structural states and dynamics of E. coli single-stranded DNA binding proteins and the energy landscape of the nucleo–protein complex.
    1. Biophysics and Structural Biology
    2. Plant Biology

    Structural basis of pathogen recognition by an integrated HMA domain in a plant NLR immune receptor

    A Maqbool et al.
    Structure/function studies of a plant pathogen effector in complex with a host disease resistance protein domain reveal the molecular basis for recognition and underpin future engineering of immunity in crops.
    1. Cell Biology

    A mitochondria-anchored isoform of the actin-nucleating spire protein regulates mitochondrial division

    Uri Manor et al.
    An actin nucleating protein, Spire1C, localizes to the mitochondrial outer membrane and interacts with the endoplasmic reticulum-anchored formin protein INF2 to drive mitochondrial fission.
    1. Developmental Biology and Stem Cells
    2. Genomics and Evolutionary Biology

    Genome-wide errant targeting by Hairy

    Kurtulus Kok et al.
    Pervasive ‘futile cycling’ by chromatin-modifying factors suggests a mechanism for creating new links in gene regulatory networks.
    1. Cell Biology
    2. Immunology

    Small molecule inhibition of Csk alters affinity recognition by T cells

    Boryana N Manz et al.
    The T cell response, especially to weak agonists, is enhanced by acute Csk inhibition.
    1. Computational and Systems Biology

    Phenotypic states become increasingly sensitive to perturbations near a bifurcation in a synthetic gene network

    Kevin Axelrod et al.
    Perturbations in the extracellular environment drive transitions from a highly stable memory state to an alternative phenotype in microorganisms.
    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Neuropilin-2/Semaphorin-3F-mediated repulsion promotes inner hair cell innervation by spiral ganglion neurons

    Thomas M Coate et al.
    The development of the mammalian cochlea undergoes a period of embryonic refinement in which the outer hair cell region repels incoming type I spiral ganglion neurons, thus ensuring these neurons instead form connections with inner hair cells.
    1. Cell Biology
    2. Neuroscience

    The 133-kDa N-terminal domain enables myosin 15 to maintain mechanotransducing stereocilia and is essential for hearing

    Qing Fang et al.
    Two myosin 15 isoforms are required separately for the development and long-term maintenance of hearing.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication

    Andrew Kodani et al.
    To control centriole duplication, centriolar satellite proteins assemble a microcephaly-associated protein complex at the centrosome and activate cyclin-dependent kinase 2.
    1. Biophysics and Structural Biology
    2. Cell Biology

    Conformational change of Dishevelled plays a key regulatory role in the Wnt signaling pathways

    Ho-Jin Lee et al.
    The ligand-binding pocket of the Dishevelled PDZ domain can be occupied by Dishevelled's own highly conserved C-terminus, inducing a closed conformation that is ‘opened’ when Wnt signaling stimulates interaction between Frizzled and Dishevelled.
    1. Genomics and Evolutionary Biology

    Wild worm embryogenesis harbors ubiquitous polygenic modifier variation

    Annalise B Paaby et al.
    Cryptic alleles affecting embryonic development are widespread in wild C. elegans populations.
    1. Biochemistry
    2. Cell Biology

    Lamellipodin promotes actin assembly by clustering Ena/VASP proteins and tethering them to actin filaments

    Scott D Hansen, R Dyche Mullins
    Lamellipodin, an important regulator of cytoskeletal and assembly cell migration, enhances the activity of Ena/VASP family actin polymerases by clustering them on leading-edge membranes and tethering them to actin filaments.
    1. Cell Biology

    DNA damage induces nuclear actin filament assembly by Formin-2 and Spire-1/2 that promotes efficient DNA repair

    Brittany J Belin et al.
    An efficient response to DNA damage requires the assembly of actin filaments in the nucleus.
    1. Cell Biology
    2. Plant Biology

    Orchestration of microtubules and the actin cytoskeleton in trichome cell shape determination by a plant-unique kinesin

    Juan Tian et al.
    Kinesin-like calmodulin-binding protein integrates microtubules and F-actin to assemble the cytoskeletal configuration needed for trichome formation.
    1. Plant Biology

    GLO-Roots: an imaging platform enabling multidimensional characterization of soil-grown root systems

    Rubén Rellán-Álvarez et al.
    A luminescence-based imaging system is presented that allows soil-based environmental stimuli to be studied in root systems under physiologically relevant conditions.
    1. Cell Biology

    Centrosome age regulates kinetochore–microtubule stability and biases chromosome mis-segregation

    Ivana Gasic et al.
    The presence of cenexin at the old centrosome imposes a functional asymmetry on the mitotic spindle that impacts chromosome alignment and segregation.
    1. Neuroscience

    A central role for the retrosplenial cortex in de novo environmental learning

    Stephen D Auger et al.
    Functional brain imaging of subjects while travelling through an alien virtual world reveals how brain regions encode novel environments from scratch thus enabling navigation.
    1. Biochemistry

    Intrinsic sequence specificity of the Cas1 integrase directs new spacer acquisition

    Clare Rollie et al.
    The acquisition of new foreign DNA by the prokaryotic adaptive immune system CRISPR-Cas is shown to depend on the fundamental sequence specificity of the Cas1 integrase.
    1. Biochemistry
    2. Biophysics and Structural Biology

    A molecular tweezer antagonizes seminal amyloids and HIV infection

    Edina Lump et al.
    CLR01 is a small molecule that could be an effective topical microbicide to eliminate HIV (and other enveloped viruses), and to antagonize host-encoded amyloid fibrils that promote HIV infection.
    1. Developmental Biology and Stem Cells
    2. Genomics and Evolutionary Biology

    A shift in anterior–posterior positional information underlies the fin-to-limb evolution

    Koh Onimaru et al.
    A shift in antero-posterior positional information may contribute to the fin-to-limb transformation.
    1. Cell Biology
    2. Computational and Systems Biology

    Perturbation biology nominates upstream–downstream drug combinations in RAF inhibitor resistant melanoma cells

    Anil Korkut et al.
    Data-driven systems biology models of signaling predict cellular response to untested perturbations and can nominate drug combinations to overcome drug resistance in cancer cells.
    1. Biochemistry
    2. Genomics and Evolutionary Biology

    Reverse evolution leads to genotypic incompatibility despite functional and active site convergence

    Miriam Kaltenbach et al.
    Enzyme evolution is reversible on a structural and functional (phenotypic) level, but through a different mutational pathway that leads to genotypic incompatibility with the ancestor.
    1. Biophysics and Structural Biology
    2. Cell Biology

    Specific cancer-associated mutations in the switch III region of Ras increase tumorigenicity by nanocluster augmentation

    Maja Šolman et al.
    Rare mutations in the switch III region of Ras can increase its nanoscale clustering, which enhances effector recruitment and downstream signaling.
    1. Neuroscience

    Neuron-glia signaling in developing retina mediated by neurotransmitter spillover

    Juliana M Rosa et al.
    Retinal waves are correlated with calcium transients in Müller cells, demonstrating that spontaneous activity encompasses both neuronal and glial networks during a crucial period of retinal development.
    1. Biochemistry
    2. Cell Biology

    Down-regulation of TORC2-Ypk1 signaling promotes MAPK-independent survival under hyperosmotic stress

    Alexander Muir et al.
    Building on previous work (Muir et al., 2014), we validate the utility of a screen for new protein kinase substrates and define the underlying molecular basis of a new mechanism for responding to hypertonic conditions.
    1. Biochemistry
    2. Cell Biology

    FAK/PYK2 promotes the Wnt/β-catenin pathway and intestinal tumorigenesis by phosphorylating GSK3β

    Chenxi Gao et al.
    Dual FAK/PYK2 kinase inhibition disrupts GSK3β phosphorylation and may present a new treatment for colorectal cancer in patients carrying APC mutations.
    1. Neuroscience

    A high affinity RIM-binding protein/Aplip1 interaction prevents the formation of ectopic axonal active zones

    Matthias Siebert et al.
    High affinity interactions with transport adaptors are important to shield the interaction surfaces of cytomatrix components to block fatal premature oligomerization of active zone proteins during axonal transport.
    1. Microbiology and Infectious Disease

    Longitudinal analysis of Plasmodium sporozoite motility in the dermis reveals component of blood vessel recognition

    Christine S Hopp et al.
    Malaria parasites enter the host via the skin, where they are inoculated by an infected mosquito as it probes for blood: the inoculation site is a bottleneck for the parasite and the only time when the parasite is extracellular for more than a few minutes, thus possibly presenting the best opportunity for antibody-mediated inhibition of infection.
    1. Cell Biology
    2. Human Biology and Medicine

    BAG2 promotes tumorigenesis through enhancing mutant p53 protein levels and function

    Xuetian Yue et al.
    Overexpression of BAG2—a novel mutant p53 binding protein—in tumors inhibits MDM2-mediated mutant p53 degradation, which leads to the accumulation of mutant p53 protein and promotes tumorigenesis.
    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Ngn1 inhibits astrogliogenesis through induction of miR-9 during neuronal fate specification

    Jing Zhao et al.
    During neurogenesis, Neurogenin 1 activates the microRNA miR-9, which directly targets the Jak-Stat pathway to inhibit astrogliogenesis.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Reduced matrix rigidity promotes neonatal cardiomyocyte dedifferentiation, proliferation and clonal expansion

    Yfat Yahalom-Ronen et al.
    Compliant matrix provides a permissive micoenvironment for cardiomyocyte dedifferentiation, cell division and expansion, and thus may open a new avenue towards cardiac regeneration.
    1. Computational and Systems Biology
    2. Genomics and Evolutionary Biology

    Predicting effective microRNA target sites in mammalian mRNAs

    Vikram Agarwal et al.
    Many experimentally identified microRNA-binding sites are ineffective at mediating repression, and an improved quantitative model for predicting the effective sites is as informative as high-throughput experimental approaches.
    1. Biochemistry
    2. Cell Biology

    Aven recognition of RNA G-quadruplexes regulates translation of the mixed lineage leukemia protooncogenes

    Palaniraja Thandapani et al.
    Arginine methylation regulates mRNA translation of key protooncogenes via an RGG/RG motif-containing protein called Aven.
    1. Biophysics and Structural Biology
    2. Developmental Biology and Stem Cells

    Enhancer additivity and non-additivity are determined by enhancer strength in the Drosophila embryo

    Jacques P Bothma et al.
    Quantitative live imaging assays reveal that multiple enhancers often fail to work in an additive fashion in the patterning of the Drosophila embryo, and sometimes even interfere with one another.
    1. Cell Biology
    2. Microbiology and Infectious Disease

    ISG15 counteracts Listeria monocytogenes infection

    Lilliana Radoshevich et al.
    The induction of ISG15 during bacterial infection can be independent of Type I Interferons and leads to an increase in the secretion of cytokines known to be critical for bacterial clearance.
    1. Cell Biology
    2. Plant Biology

    SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy response in plants

    Andrea Mair et al.
    The transcription factor bZIP63 is a key regulator of the starvation response in the model plant Arabidopsis thaliana and is directly targeted by the kinase SnRK1.
    1. Immunology
    2. Microbiology and Infectious Disease

    The viral context instructs the redundancy of costimulatory pathways in driving CD8+ T cell expansion

    Suzanne PM Welten et al.
    Redundancy in the costimulatory signals that drive CD8+ T cell expansion is dictated by pathogen-specific cues.
    1. Neuroscience

    Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation

    Natalya Korogod et al.
    Snap-freezing of brain tissue reveals its true structure-showing that cells are less squashed together, and the connections between neurons are less enclosed than previously thought.
    1. Biophysics and Structural Biology

    Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1

    Agata Butryn et al.
    A structural analysis of the transcription regulator Mot1 in complex with promoter DNA and the proteins TBP and NC2 provides a first structural framework for how a Swi2/Snf2 type remodeler interacts with a histone fold protein:DNA complex.
    1. Immunology

    Antigen presentation kinetics control T cell/dendritic cell interactions and follicular helper T cell generation in vivo

    Robert A Benson et al.
    Temporal availability of antigen presentation by dendritic cells influences the differentiation of follicular helper T (Tfh) cells, which enhances germinal centre responses and induces protective immunity.
    1. Immunology

    The activation of IgM- or isotype-switched IgG- and IgE-BCR exhibits distinct mechanical force sensitivity and threshold

    Zhengpeng Wan et al.
    The B cell receptors of naïve B cells need higher levels of mechanical force to be fully activated than those of memory B cells.
    1. Immunology

    The HIV-1 envelope protein gp120 is captured and displayed for B cell recognition by SIGN-R1+ lymph node macrophages

    Chung Park et al.
    Lymph node gp120 specific B cells extract locally injected HIV-1 gp120 from SIGN-R1 positive macrophages that line the subcapsular sinus overlying the lymph node interfollicular channels.
    1. Genes and Chromosomes

    Transcription dynamically patterns the meiotic chromosome-axis interface

    Xiaoji Sun et al.
    Distributed cohesin rings flexibly tether the axial element structure of meiotic chromosomes to the underlying chromatin to readily accommodate ongoing transcription.
    1. Ecology

    Mass enhances speed but diminishes turn capacity in terrestrial pursuit predators

    Rory P Wilson et al.
    Increased mass enhances speed but compromises turning capacity in pursuit predators; this has widespread ramifications for the best strategies for predators and prey during chases according to their relative masses.
    1. Cell Biology

    The RhoGAP activity of CYK-4/MgcRacGAP functions non-canonically by promoting RhoA activation during cytokinesis

    Donglei Zhang, Michael Glotzer
    Activation of the key regulator of cytokinesis, RhoA, involves an unexpected contribution by a RhoGAP domain.
    1. Immunology
    2. Microbiology and Infectious Disease

    Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity

    Meghan O Altman et al.
    Antibody responses are remarkably similar in widely disparate hosts.
    1. Neuroscience

    Dendritic sodium spikes are required for long-term potentiation at distal synapses on hippocampal pyramidal neurons

    Yujin Kim et al.
    At distal synapses onto hippocampal CA1 pyramidal neurons, synaptic plasticity is dependent on dendritically initiated sodium spikes, thus establishing a new role for voltage-gated sodium channels in the dendrites that may have important implications for how learning rules are implemented.
    1. Neuroscience

    Low-noise encoding of active touch by layer 4 in the somatosensory cortex

    Samuel Andrew Hires et al.
    Touch information is represented with minimal noise in the somatosensory cortex during tactile exploration.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Developmental alterations in centrosome integrity contribute to the post-mitotic state of mammalian cardiomyocytes

    David C Zebrowski et al.
    Mammal hearts are unable to replace lost cardiomyocytes, which may be due to the loss of centrosome integrity in these cells after birth.
    1. Immunology
    2. Microbiology and Infectious Disease

    An extrafollicular pathway for the generation of effector CD8+ T cells driven by the proinflammatory cytokine, IL-12

    Suhagi Shah et al.
    Proliferation and differentiation of CD8+ T cells into terminal effectors occurs in the marginal zone and red pulp, and is promoted by IL-12 through direct and indirect mechanisms.
    1. Biochemistry
    2. Biophysics and Structural Biology

    A putative ATPase mediates RNA transcription and capping in a dsRNA virus

    Xuekui Yu et al.
    Atomic structures suggest a novel mechanism for the regulation of mRNA transcription and capping in dsRNA viruses.
    1. Neuroscience

    Peripheral sensory coding through oscillatory synchrony in weakly electric fish

    Christa A Baker et al.
    Sensory receptors encode stimuli by transiently synchronizing ongoing electrical oscillations, conferring enhanced sensitivity to communication signals produced by large groups of conspecifics.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Species-wide whole genome sequencing reveals historical global spread and recent local persistence in Shigella flexneri

    Thomas R Connor et al.
    Shigella flexneri, globally the most frequent cause of bacterial dysentery, is far more diverse, and has caused disease around the world for far longer than other Shigella species by persisting in local environments over extended timescales.
    1. Biochemistry
    2. Cell Biology

    Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules

    Sonja Kroschwald et al.
    A comparison in yeast and human cells reveals a remarkable variability in the properties of RNP granules and highlights a key role for protein disaggregation machines in regulating RNP granule assembly.
    1. Cell Biology
    2. Genomics and Evolutionary Biology

    Selections that isolate recombinant mitochondrial genomes in animals

    Hansong Ma, Patrick H O'Farrell
    Recombinant mitochondrial genomes can be selected, traits can be genetically mapped and new genetic combinations can be made.