April 2015

Research articles

    1. Neuroscience

    Automatic discovery of cell types and microcircuitry from neural connectomics

    Eric Jonas, Konrad Kording
    An algorithm for analysing brain connectivity data identifies cell types and connections in simple (C. elegans) and complex (mouse) nervous systems, and can even resolve structure and connectivity in a man-made microprocessor.
    1. Cell Biology
    2. Genes and Chromosomes

    The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin

    Sumanprava Giri et al.
    Origin recognition complex-associated (ORCA) is crucial for the stability of the Histone H3 lysine 9 methyltransferase megacomplex, which is essential for heterochromatin organization.
    1. Computational and Systems Biology
    2. Genes and Chromosomes

    A simple biophysical model emulates budding yeast chromosome condensation

    Tammy MK Cheng et al.
    A computational model of a yeast chromosome, based on first principles, recapitulates in vivo chromosome behavior, and thus provides unprecedented insight into what the inside of a chromosome is likely to look like.
    1. Genomics and Evolutionary Biology
    2. Microbiology and Infectious Disease

    Whole genome comparison of a large collection of mycobacteriophages reveals a continuum of phage genetic diversity

    Welkin H Pope et al.
    A continuum of genome relationships is discovered through comparative genomics of 627 sequenced mycobacteriophages isolated and characterized in an integrated research/education initiative.
    1. Genes and Chromosomes

    The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer

    Eric Wang et al.
    TRIM33 performs an essential function in B cell acute lymphoblastic leukemia through an association with a single cis element.
    1. Cell Biology
    2. Neuroscience

    Synaptojanin cooperates in vivo with endophilin through an unexpected mechanism

    Yongming Dong et al.
    The Sac1 phosphatase domain, rather than the proline-rich domain, plays an essential role in synaptojanin activity during endocytosis.
    1. Cell Biology

    MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture

    Jonathan R Friedman et al.
    A conserved mitochondrial inner membrane complex called MICOS works together with the mitochondrial lipid cardiolipin and respiratory complexes to direct the position, copy number and stabilization of cristae structures for efficient respiration.
    1. Biochemistry
    2. Biophysics and Structural Biology

    TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

    Qiaozhen Ye et al.
    TRIP13 inactivates the spindle assembly checkpoint by converting MAD2 from its active ‘closed’ state to its inactive ‘open’ state.
    1. Biochemistry
    2. Biophysics and Structural Biology

    The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch

    Sandeep K Talapatra et al.
    Structural analysis of the kinesin-13 MCAK bound to its C-terminal tail reveals the molecular basis for the conformation of kinesin-13 in solution and the mechanism that triggers long-range conformational changes upon microtubule binding.
    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Tight Junction Protein 1a regulates pigment cell organisation during zebrafish colour patterning

    Andrey Fadeev et al.
    The changes in shape of iridophores that underlie adult colour pattern formation in zebrafish depend on the levels of Tight Junction Protein 1a in these cells.
    1. Neuroscience

    Visual processing of informative multipoint correlations arises primarily in V2

    Yunguo Yu et al.
    Building on recent findings that central sensory processing allocates resources according to the informativeness of statistical features (Hermundstad et al., 2014), we identify visual area V2 as the site of the relevant computations for local image statistics, thus providing a common underpinning for diverse aspects of its neuronal selectivity.
    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Cochlear progenitor number is controlled through mesenchymal FGF receptor signaling

    Sung-Ho Huh et al.
    Otic epithelial Fibroblast Growth Factors control the number of cochlear sensory progenitor cells through an FGF responsive periotic mesenchyme.
    1. Computational and Systems Biology
    2. Neuroscience

    Neural tuning matches frequency-dependent time differences between the ears

    Victor Benichoux et al.
    Complex properties of space-sensitive auditory neurons in cats mirror the complexity of acoustical environments.
    1. Genes and Chromosomes
    2. Human Biology and Medicine

    Recurrent gain of function mutation in calcium channel CACNA1H causes early-onset hypertension with primary aldosteronism

    Ute I Scholl et al.
    A novel Mendelian disease featuring early-onset hypertension is caused by a recurrent gain of function mutation in CACNA1H, which encodes the voltage-gated calcium channel Cav3.2.
    1. Computational and Systems Biology
    2. Neuroscience

    Probable nature of higher-dimensional symmetries underlying mammalian grid-cell activity patterns

    Alexander Mathis et al.
    Mathematical analysis confirms that hexagonal patterns of neuronal activity are the most efficient means for the brain to represent 2D space, and predicts that activity patterns resembling densely packed lattices are optimal for representing 3D space.
    1. Biophysics and Structural Biology
    2. Neuroscience

    C-terminal threonines and serines play distinct roles in the desensitization of rhodopsin, a G protein-coupled receptor

    Anthony W Azevedo et al.
    Serine and threonine phosphorylation sites work in concert to provide rapid and reproducible desensitization of the G-protein coupled receptor rhodopsin.
    1. Biochemistry
    2. Cell Biology

    The E3 ubiquitin ligase TRIM23 regulates adipocyte differentiation via stabilization of the adipogenic activator PPARγ

    Masashi Watanabe et al.
    TRIM23 plays a critical role in the switching from early to late adipogenic enhanceosomes by stabilizing the PPARγ protein.
    1. Computational and Systems Biology
    2. Immunology

    Stimulus-selective crosstalk via the NF-κB signaling system reinforces innate immune response to alleviate gut infection

    Balaji Banoth et al.
    The integration of signals via the pleiotropic NF-kappaB (NF-κB) system enables microenvironmental cues to tune cellular responses to pathogenic substances.
    1. Genes and Chromosomes
    2. Genomics and Evolutionary Biology

    Quality control of transcription start site selection by nonsense-mediated-mRNA decay

    Christophe Malabat et al.
    RNA polymerase II generates numerous transcript isoforms, including transcripts initiating downstream of the START codon, that are efficiently degraded by the nonsense-mediated mRNA decay pathway.
    1. Computational and Systems Biology
    2. Genomics and Evolutionary Biology

    Mapping and analysis of Caenorhabditis elegans transcription factor sequence specificities

    Kamesh Narasimhan et al.
    Protein binding microarrays highlight the diversification of DNA-binding motifs for the nuclear hormone receptor and C2H2 zinc finger transcription factor families, and reveal unexpected diversity in motifs for the T-box and DM families.
    1. Biochemistry
    2. Cell Biology

    The coordinated action of the MVB pathway and autophagy ensures cell survival during starvation

    Martin Müller et al.
    A catabolic cascade is essential to enter a stable G1/G0 quiescent state and survive extended periods of starvation.
    1. Neuroscience

    Interneurons and oligodendrocyte progenitors form a structured synaptic network in the developing neocortex

    David Orduz et al.
    During the second postnatal week, a temporary circuit made up of specific types of neurons plus the precursors of oligodendrocytes is established in the brain, and may promote the maturation of oligodendrocytes in preparation for myelination.
    1. Biochemistry

    Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site

    Fanny Sunden et al.
    Conventional studies have focused on enzymatic residues directly involved in catalysis; dissecting a potential interaction network within which these ‘catalytic residues’ are embedded provides insights fundamental to enzyme function, evolution, and engineering.
    1. Biophysics and Structural Biology

    Examining kinesin processivity within a general gating framework

    Johan OL Andreasson et al.
    A general framework for gating reveals that inter-head tension is not essential for coordinating kinesin stepping, and that neck-linker length is tuned to enhance processivity and velocity.
    1. Neuroscience

    An opioid-like system regulating feeding behavior in C. elegans

    Mi Cheong Cheong et al.
    The discovery that opioid neuropeptide neuronal signaling controls feeding behavior in a genetically tractable invertebrate model may help unravel the mechanisms of appetite control in humans.
    1. Biochemistry
    2. Cell Biology

    A non-canonical mechanism for Crm1-export cargo complex assembly

    Ute Fischer et al.
    Slx9 is a newly discovered type of RanGTP-binding protein required for Crm1-mediated nuclear export.
    1. Cell Biology

    A novel isoform of MAP4 organises the paraxial microtubule array required for muscle cell differentiation

    Binyam Mogessie et al.
    oMAP4 is a microtubule crosslinker that restricts motor driven microtubule motility and cooperates with microtubule motors in the establishment of paraxial microtubule arrangements in differentiating muscle cells.
    1. Biochemistry

    Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport

    Tomomi Hashidate-Yoshida et al.
    LPCAT3 incorporates arachidonic acid into membrane phospholipids, which promotes lipoprotein assembly by enabling triacylgylcerols to cluster in the membrane.
    1. Neuroscience

    fMRI reveals neural activity overlap between adult and infant pain

    Sezgi Goksan et al.
    The newborn infant experience of pain closely resembles that observed in adults, suggesting that infants have the sensory and emotional capacity to experience pain.
    1. Cell Biology
    2. Immunology

    The mucosal adjuvant cyclic di-GMP enhances antigen uptake and selectively activates pinocytosis-efficient cells in vivo

    Steven M Blaauboer et al.
    In mice, cyclic di-GMP is an effective mucosal pneumococcal vaccine adjuvant that stimulates the immune response via two distinct mechanisms.
    1. Developmental Biology and Stem Cells

    Distinct mechanisms underlie oral vs aboral regeneration in the cnidarian Hydractinia echinata

    Brian Bradshaw et al.
    Stem cell migration underlies head regeneration in the cnidarian (jellies and their kin) Hydractinia, but the regeneration of other body parts is based on the gradual transformation of one tissue type into another.
    1. Neuroscience

    Palmitoylation of LIM Kinase-1 ensures spine-specific actin polymerization and morphological plasticity

    Joju George et al.
    The protein-lipid modification palmitoylation targets the kinase LIMK1 to dendritic spines to ensure precise control of the size of individual spines in response to synaptic activation.
    1. Neuroscience

    Homeostatic synaptic depression is achieved through a regulated decrease in presynaptic calcium channel abundance

    Michael A Gaviño et al.
    Experiments at synapses between nerve and muscle cells in genetically modified fruit flies reveal how neurons compensate for perturbations that would otherwise cause excessive synaptic transmission.
    1. Neuroscience

    Sensitivity and kinetics of signal transmission at the first visual synapse differentially impact visually-guided behavior

    Ignacio Sarria et al.
    Adjusting key parameters of the synaptic transmission at a single defined synapse of the visual circuit can affect properties of this circuit and animal behavior.
    1. Biochemistry
    2. Cell Biology

    Pharmacological dimerization and activation of the exchange factor eIF2B antagonizes the integrated stress response

    Carmela Sidrauski et al.
    A drug-like molecule called ISRIB, which activates the translation initiation factor eIF2B, antagonizes stress responses as diverse as protein misfolding and nutrient deprivation, and restores protein synthesis, enhancing memory.
    1. Ecology
    2. Plant Biology

    Plant defense phenotypes determine the consequences of volatile emission for individuals and neighbors

    Meredith C Schuman et al.
    Both the frequency of sesquiterpene-emitting individuals and the defense capacity of individual plants determine the consequences of sesquiterpene volatile emission for individuals and their neighbors in populations of the wild tobacco Nicotiana attenuata.
    1. Developmental Biology and Stem Cells

    Dynamic filopodia are required for chemokine-dependent intracellular polarization during guided cell migration in vivo

    Dana Meyen et al.
    Functional analysis of filopodia by specific interference with their formation and distribution reveals a critical role in conferring intracellular polarity and in controlling the dynamic properties of chemokine-guided cell migration in vivo.
    1. Biochemistry
    2. Biophysics and Structural Biology

    Reconstitution of a eukaryotic replisome reveals suppression mechanisms that define leading/lagging strand operation

    Roxana E Georgescu et al.
    The different polymerases at eukaryotic replication forks achieve their asymmetric placement on the leading and lagging strands through exclusion processes that prevent their function on the 'wrong' strand.
    1. Genomics and Evolutionary Biology

    Inhibitory activities of short linear motifs underlie Hox interactome specificity in vivo

    Manon Baëza et al.
    Short peptide motifs can confer specificity to developmental networks by inhibiting protein–protein interactions.
    1. Biophysics and Structural Biology
    2. Neuroscience

    Additive effects on the energy barrier for synaptic vesicle fusion cause supralinear effects on the vesicle fusion rate

    Sebastiaan Schotten et al.
    Independent osmotic, genetic and biochemical perturbations modulate neurotransmitter release in a multiplicative manner.
    1. Neuroscience

    Distinct effects of prefrontal and parietal cortex inactivations on an accumulation of evidence task in the rat

    Jeffrey C Erlich et al.
    Quantitative modeling of inactivations shows the prefrontal cortex (but not parietal cortex) of the rat is obligatory for decisions guided by evidence accumulating longer than 240 ms.
    1. Developmental Biology and Stem Cells

    Response to Nodal morphogen gradient is determined by the kinetics of target gene induction

    Julien Dubrulle et al.
    A kinetic model of morphogen interpretation is more suitable than classic threshold or ratchet models to understand how a signal gradient generates different target gene expression patterns.
    1. Developmental Biology and Stem Cells
    2. Genomics and Evolutionary Biology

    Constraint and divergence of global gene expression in the mammalian embryo

    Noah Spies et al.
    Embryonic gene expression is strongly influenced by maternal genetic variation and by embryonic variation that acts in cis but not in trans.
    1. Developmental Biology and Stem Cells

    Reciprocal and dynamic polarization of planar cell polarity core components and myosin

    Erin Newman-Smith et al.
    Planar cell polarity (PCP) components and myosin show a parallel temporal polarization in the Ciona notochord and the mutual interaction between these proteins is required for proper tissue-wide polarity.
    1. Neuroscience

    The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2

    Pierre-Louis Ruffault et al.
    The location of neurons responsible for increasing the breathing rate upon detecting elevated levels of CO2 in the blood has been pinpointed to the retrotrapezoid nucleus in the brainstem.
    1. Ecology
    2. Genomics and Evolutionary Biology

    Natural genetic variation in Arabidopsis thaliana defense metabolism genes modulates field fitness

    Rachel Kerwin et al.
    Environmental heterogeneity may contribute to the high levels of genetic variation in glucosinolate genes found in Arabidopsis thaliana.
    1. Genes and Chromosomes

    Assessing long-distance RNA sequence connectivity via RNA-templated DNA–DNA ligation

    Christian K Roy et al.
    SeqZip is a new DNA ligation-based method to condense and maintain exon connectivity information within individual RNA molecules, which can provide new insights into alternative splicing.
    1. Neuroscience

    Recruitment of the default mode network during a demanding act of executive control

    Ben M Crittenden et al.
    The default mode network in the brain is activated during the performance of executive-type tasks when a substantial change in cognitive contents is required.
    1. Immunology

    Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding

    Paul E Chappell et al.
    The number of different peptides presented by major histocompatibility complex class I molecules to the immune system's T lymphocytes is inversely correlated with cell surface expression and is strongly associated with the response to infectious disease.
    1. Cell Biology

    Cytosolic Hsp70 and co-chaperones constitute a novel system for tRNA import into the nucleus

    Akira Takano et al.
    A major cytoplasmic chaperone, Ssa2p, acts as a nuclear import carrier for tRNAs upon nutrient starvation in Saccharomyces cerevisiae.
    1. Developmental Biology and Stem Cells
    2. Genomics and Evolutionary Biology

    In vivo targeting of de novo DNA methylation by histone modifications in yeast and mouse

    Marco Morselli et al.
    DNA methylation deposition is dependent on the presence of H3K4me3 and H3K36me3 histone marks.
    1. Cell Biology
    2. Genes and Chromosomes

    The asymmetry of female meiosis reduces the frequency of inheritance of unpaired chromosomes

    Daniel B Cortes et al.
    Female meiotic spindles correct trisomy by expelling extra chromosomes into the first polar body.
    1. Microbiology and Infectious Disease

    Release of human cytomegalovirus from latency by a KAP1/TRIM28 phosphorylation switch

    Benjamin Rauwel et al.
    Inactivation of KAP1 by mTOR-mediated phosphorylation releases human cytomegalovirus from latency, and has the potential to be used as a therapy to purge the virus from transplant organs.
    1. Genomics and Evolutionary Biology
    2. Immunology

    Siglec receptors impact mammalian lifespan by modulating oxidative stress

    Flavio Schwarz et al.
    By contributing to the maintenance of ROS homeostasis, CD33-related Siglecs control oxidative damage and influence rate of aging and lifespan.
    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Cis and trans RET signaling control the survival and central projection growth of rapidly adapting mechanoreceptors

    Michael S Fleming et al.
    Cis and trans activation of the receptor tyrosine kinase RET lead to similar biological outcomes in rapidly adapting mechanoreceptors in vivo.
    1. Biochemistry
    2. Biophysics and Structural Biology

    Re-visiting the trans insertion model for complexin clamping

    Shyam S Krishnakumar et al.
    Biochemical experiments provide support for the trans insertion model for clamping in the regulation of neurotransmitter release by complexin.
    1. Developmental Biology and Stem Cells
    2. Genomics and Evolutionary Biology

    Systematic imaging reveals features and changing localization of mRNAs in Drosophila development

    Helena Jambor et al.
    Genome wide analysis reveals that many transcripts are localized in cells of the ovary and that the localization status of mRNAs changes over time and in different cell types.