September 2014

Research articles

    1. Neuroscience

    FGF14 modulates resurgent sodium current in mouse cerebellar Purkinje neurons

    Haidun Yan et al
    The N-terminus of the FGF14b isoform promotes the inactivation of voltage-gated Na+ channels to regulate the resurgent Na+ channel current needed for high frequency action potentials.
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    1. Neuroscience

    Phasic activation of ventral tegmental neurons increases response and pattern similarity in prefrontal cortex neurons

    Motoko Iwashita
    Transient increases in calcium release in prefrontal cortex neurons, observable only in awake animals, may form the basis of associative learning.
    Short Report
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Analysis of the crystal structure of an active MCM hexamer

    Justin M Miller et al
    Building on previous work (Froelich et al., 2014), we present the X-ray crystal structure of an active MCM hexamer, which suggests a mechanism for MCM regulation and demonstrates a key interaction between the major domains.
    Research Advance
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    1. Biochemistry
    2. Immunology

    Differential TAM receptor–ligand–phospholipid interactions delimit differential TAM bioactivities

    Erin D Lew et al
    Signaling by TAM receptor tyrosine kinases requires the coincident engagement of a TAM ligand with both its receptor and the phospholipid phosphatidylserine.
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    1. Genes and Chromosomes

    Synthetic CpG islands reveal DNA sequence determinants of chromatin structure

    Elisabeth Wachter et al
    Genomic landmarks, known generically as ‘CpG islands’, program chromatin structure via their richness in the dinucleotide CG and their skewed composition of DNA bases.
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    1. Genes and Chromosomes
    2. Genomics and Evolutionary Biology

    High-throughput engineering of a mammalian genome reveals building principles of methylation states at CG rich regions

    Arnaud R Krebs et al
    Large numbers of DNA sequence variants comprehensively define how transcription factor binding sites and CG density preserve mammalian promoters from repression by DNA methylation.
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    1. Developmental Biology and Stem Cells

    Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states

    Lauren LeBon et al
    Fringe proteins modulate cis inhibitory, same-cell interactions between the Notch receptor and its ligands to control whether, and in which direction, cells can signal to one another.
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    1. Biochemistry

    A distinct tethering step is vital for vacuole membrane fusion

    Michael Zick, William T Wickner
    Rigorous assays of membrane fusion show that a distinct tethering step is required for lumenal compartment mixing in a manner that extends beyond simply increasing the amount of total trans-SNARE complex.
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    1. Genomics and Evolutionary Biology

    Sequence co-evolution gives 3D contacts and structures of protein complexes

    Thomas A Hopf et al
    Interactions in protein complexes can be predicted from evolutionary information from genomic sequences.
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    1. Developmental Biology and Stem Cells

    The neural crest is a source of mesenchymal stem cells with specialized hematopoietic stem cell niche function

    Joan Isern et al
    Developing long bones contain distinct mesenchymal stem-cell populations derived from mesoderm and neural crest, which have specialized functions in skeleton formation and the establishment of the hematopoietic stem-cell niche, respectively.
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    1. Immunology

    Gamma delta T cells recognize haptens and mount a hapten-specific response

    Xun Zeng et al
    The T-cell receptors of gamma delta (γδ) T cells can recognize and trigger responses to small molecules and are thereby versatile drivers of immunity.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    How IGF-1 activates its receptor

    Jennifer M Kavran et al
    Ligand binding to the ectodomain of the insulin-like growth factor receptor destabilises an autoinhibitory inter-subunit interaction, which allows the transmembrane domains to associate and the intracellular regions to autophosphorylate.
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    1. Developmental Biology and Stem Cells
    2. Genes and Chromosomes

    Polycomb- and REST-associated histone deacetylases are independent pathways toward a mature neuronal phenotype

    James C McGann et al
    Poised neuronal genes are repressed by REST and Polycomb in embryonic stem cells independently and via different chromatin modifications.
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    1. Developmental Biology and Stem Cells
    2. Genes and Chromosomes

    The scaffold protein Nde1 safeguards the brain genome during S phase of early neural progenitor differentiation

    Shauna L Houlihan, Yuanyi Feng
    Differentiation-specific maintenance of genome integrity during S-phase is essential for establishing both the structure and function of the cerebral cortex.
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    1. Cell Biology
    2. Human Biology and Medicine

    Peroxisomal lactate dehydrogenase is generated by translational readthrough in mammals

    Fabian Schueren et al
    Whole-genome in silico screening for stop codon contexts that produce elevated translational readthrough and peroxisome targeting reveals that in mammals, the amount of lactate dehydrogenase in the peroxisome is controlled by translational readthrough.
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    1. Cell Biology
    2. Plant Biology

    Myosin VIII associates with microtubule ends and together with actin plays a role in guiding plant cell division

    Shu-Zon Wu, Magdalena Bezanilla
    Class VIII myosins mediate crosstalk between actin and microtubules to position cell division in plants.
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    1. Genes and Chromosomes
    2. Genomics and Evolutionary Biology

    Recurrent loss of CenH3 is associated with independent transitions to holocentricity in insects

    Ines A Drinnenberg et al
    CenH3, the defining component of centromeres in almost all eukaryotes, was independently lost in four insect lineages that transitioned from monocentricity to holocentricity.
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    1. Developmental Biology and Stem Cells

    Neuropilin-1 functions as a VEGFR2 co-receptor to guide developmental angiogenesis independent of ligand binding

    Maria V Gelfand et al
    Interactions between Neuropilin-1 and VEGFR2, rather than VEGF-Neuropilin-1 binding, underlie Neuropilin-1's critical function in VEGF-mediated vascular development.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB

    Thomas Eicher et al
    A transport mechanism is uncovered in the major drug-efflux system in E. coli involving two remote alternating-access conformational cycles, which could provide the basis for the development of allosteric inhibitors against multidrug resistance.
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    1. Genes and Chromosomes
    2. Immunology

    Active RNAP pre-initiation sites are highly mutated by cytidine deaminases in yeast, with AID targeting small RNA genes

    Benjamin JM Taylor et al
    Transcribed promoters are highly susceptible to mutation by cytidine deaminases, implicating stable exposure of single stranded DNA structures, rather than cofactors, in localising mutation during tumourigenesis and antibody maturation.
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    1. Biochemistry
    2. Microbiology and Infectious Disease

    Discovery of a small molecule that inhibits bacterial ribosome biogenesis

    Jonathan M Stokes et al
    The anticonvulsant drug lamotrigine inhibits bacterial ribosome biogenesis and reveals an unexplored role for initiation factor 2 (IF2) in ribosome assembly.
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    1. Neuroscience

    Texture coarseness responsive neurons and their mapping in layer 2–3 of the rat barrel cortex in vivo

    Liora Garion et al
    Neurons within rat somatosensory cortex are selective to texture and are spatially organized according to their texture preference.
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    1. Cell Biology

    Clathrin-independent pathways do not contribute significantly to endocytic flux

    Vassilis Bitsikas et al
    Chemical labelling of all primary endocytic vesicles allows the contribution of different endocytic mechanisms to the total endocytic uptake in cultured mammalian cells to be quantified.
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    1. Biochemistry
    2. Cell Biology

    The translation elongation factor eEF1A1 couples transcription to translation during heat shock response

    Maria Vera et al
    Eukaryotic translation elongation factor 1A1 controls the process of heat shock response, from transcriptional activation of the HSP70 gene, to HSP70 mRNA stabilization, nuclear export, and translation.
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    1. Genomics and Evolutionary Biology

    Long non-coding RNAs as a source of new peptides

    Jorge Ruiz-Orera et al
    Ribosome profiling data from several eukaryotic species provides strong evidence that many long non-coding RNA molecules encode novel short proteins.
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    1. Cell Biology
    2. Plant Biology

    A receptor-like kinase mutant with absent endodermal diffusion barrier displays selective nutrient homeostasis defects

    Alexandre Pfister et al
    The SCHENGEN3 protein is needed for the progression of isolated microdomains into a continuous band, which is necessary for the establishment of the major extracellular diffusion barrier in plant roots: the Casparian strip.
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    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway

    Barak Blum et al
    Loss of mature β cell identity in diabetes can be prevented and rescued by small molecule inhibitors of the TGFβ pathway.
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    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Cannabinoid-induced actomyosin contractility shapes neuronal morphology and growth

    Alexandre B Roland et al
    Cannabinoids inhibit neuronal expansion and growth through the rapid contraction of actomyosin.
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    1. Neuroscience

    Dopamine receptor 1 neurons in the dorsal striatum regulate food anticipatory circadian activity rhythms in mice

    Christian M Gallardo et al
    For mice, knowing when it is time to feed is dependent on the neurotransmitter dopamine and the D1R receptor of neurons in the dorsal striatum.
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    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Epidemiological dynamics of Ebola outbreaks

    Thomas House
    The pattern of past Ebola outbreaks is indicative of an effective reproductive ratio of less than 1, which can lead to the generation of a range of outbreak sizes consistent with the scale of the ongoing epidemic.
    Short Report
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    1. Human Biology and Medicine
    2. Microbiology and Infectious Disease

    HIV-1 DNA predicts disease progression and post-treatment virological control

    James P Williams et al
    Measuring HIV-1 DNA levels at the time of stopping antiretroviral therapy (when initiated during primary infection) predicts clinical progression and the time taken for plasma viraemia to become detectable.
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    1. Biophysics and Structural Biology

    Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

    Joseph Atherton et al
    Cryo-electron microscopy reconstructions of two microtubule-bound transport kinesins at 7 Å resolution reveal how microtubule track binding stimulates ADP release, primes the active site for ATP binding and enables force generation.
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    1. Biochemistry
    2. Genes and Chromosomes

    TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation

    Daniil Alpern et al
    Physical and functional interactions between HNF4A and TAF4 coordinate HNF4A genomic occupancy with pre-initiation complex formation to activate post-natal hepatocyte gene expression.
    Research Article
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    1. Developmental Biology and Stem Cells
    2. Genomics and Evolutionary Biology

    Divergent mechanisms regulate conserved cardiopharyngeal development and gene expression in distantly related ascidians

    Alberto Stolfi et al
    Embryos of distantly related sea squirt species are nearly identical but develop according to different gene regulatory mechanisms.
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    1. Cell Biology
    2. Genes and Chromosomes

    Histone supply regulates S phase timing and cell cycle progression

    Ufuk Günesdogan et al
    Controlling cell cycle progression in a developing embryo directly depends on de novo histone supply and a specialized surveillance mechanism for nucleosome assembly.
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    1. Neuroscience

    Coding of stimulus strength via analog calcium signals in Purkinje cell dendrites of awake mice

    Farzaneh Najafi et al
    Sensory-driven calcium spikes in Purkinje cells are not binary; instead, they are graded and can provide information about the strength of a periocular airpuff stimulus known to drive learning.
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    1. Cell Biology
    2. Human Biology and Medicine

    A critical role for mTORC1 in erythropoiesis and anemia

    Zachary A Knight et al
    Transcription profiling of activated cells using Phospho-Trap, a new method for identifying activated cells, reveals a critical role for mTOR signaling in red blood cell development and the pathogenesis of anemia
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    1. Developmental Biology and Stem Cells

    Pvr expression regulators in equilibrium signal control and maintenance of Drosophila blood progenitors

    Bama Charan Mondal et al
    The THAP-domain protein Bip1, along with other proteins Nup98 and RpS8, controls the expression of the protein Pvr, a critical non-cell-autonomous regulator of Drosophila blood progenitor maintenance.
    Research Article
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    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Mapping the zoonotic niche of Ebola virus disease in Africa

    David M Pigott et al
    Understanding where future Ebola virus outbreaks may start and the changing nature of the populations living in these places is of critical importance in helping to prepare for future outbreaks.
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    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Regulation of retinal axon growth by secreted Vax1 homeodomain protein

    Namsuk Kim et al
    Secreted Vax1 homeodomain protein supports the development of optic chiasm by directly acting at the retinal ganglion cell axon.
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    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Mother-daughter asymmetry of pH underlies aging and rejuvenation in yeast

    Kiersten A Henderson et al
    Protons are pumped out of mother cells by a protein that accumulates over time and this leads to cellular aging, but this protein is largely absent from daughter cells, which mediates rejuvenation.
    Short Report
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    1. Immunology

    Broad and direct interaction between TLR and Siglec families of pattern recognition receptors and its regulation by Neu1

    Guo-Yun Chen et al
    Sialoside-based pattern recognition by Siglecs directly regulates toll-like receptor signaling and a sialidase inhibitor protects against endotoxemia.
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    1. Immunology

    T cell-specific inhibition of multiple apoptotic pathways blocks negative selection and causes autoimmunity

    Megan L Burger et al
    Using mice expressing a Bcl-2 mutant protein to suppress multiple central tolerance pathways, it is shown that central tolerance is crucial for preventing autoimmunity.
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    1. Genomics and Evolutionary Biology
    2. Human Biology and Medicine

    Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks

    Luca Albergante et al
    The theory of Buffered Qualitative Stability uses the importance of biological robustness to explain many features of gene regulatory networks in a wide range of organisms, and has implications for diverse biological phenomena including the ability of bacteria and cancer cells to ‘loosen’ their robustness and hence evade treatment.
    Research Article
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    1. Human Biology and Medicine
    2. Neuroscience

    Nuclear envelope protein MAN1 regulates clock through BMAL1

    Shu-Ting Lin et al
    A protein within the nuclear membrane, MAN1, controls the expression of the circadian clock gene, BMAL1, in an example of cross-talk between two major gene regulatory pathways.
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    1. Biochemistry
    2. Microbiology and Infectious Disease

    Reconstitution of bacterial autotransporter assembly using purified components

    Giselle Roman-Hernandez et al
    A complex that catalyzes the membrane integration of β barrel proteins and a molecular chaperone promote the complete assembly of a bacterial virulence factor in vitro.
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    1. Biophysics and Structural Biology
    2. Microbiology and Infectious Disease

    Mechanistic insight into the conserved allosteric regulation of periplasmic proteolysis by the signaling molecule cyclic-di-GMP

    Debashree Chatterjee et al
    Structure-function analyses reveal the mechanistic underpinnings of inside-out transmembrane signaling that controls periplasmic proteolysis, and thereby biofilm formation, in bacteria and may be relevant in the context of other signaling proteins with similar control elements.
    Research Article
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    1. Microbiology and Infectious Disease

    Active invasion of bacteria into living fungal cells

    Nadine Moebius et al
    Bacteria invade living fungal cells using secreted chitinolytic enzymes that allow for a traceless entry, as shown by microscopic snapshots.
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