January 2016

Research articles

    1. Immunology

    TGFβ-dependent expression of PD-1 and PD-L1 controls CD8+ T cell anergy in transplant tolerance

    Marije Baas et al
    The interplay between the cytokine TGFβ and the PD-1/PD-L1 pathway promotes CD8+ T cell anergy and tolerance towards transplanted tissues.
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    1. Computational and Systems Biology
    2. Genes and Chromosomes

    Single-cell analysis of transcription kinetics across the cell cycle

    Samuel O Skinner et al
    By properly accounting for gene copy number and cell-cycle effects, single cell snapshots of nascent and mature mRNA can be used to unveil the stochastic kinetics of gene activity.
    Short Report
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    1. Immunology
    2. Microbiology and Infectious Disease

    Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

    Curtis McMurtrey et al
    T. gondii infection alters how peptide ligands are presented to the immune system by inducing a previously unreported structural change in Human Leukocyte Antigens (HLAs).
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    1. Computational and Systems Biology
    2. Neuroscience

    A stochastic neuronal model predicts random search behaviors at multiple spatial scales in C. elegans

    William M Roberts et al
    A stochastic model of locomotory control in C. elegans based on an extensive new set of tracking data can explain and predict effects of ablations and mutations on behavior.
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    1. Biophysics and Structural Biology

    Mutational scanning reveals the determinants of protein insertion and association energetics in the plasma membrane

    Assaf Elazar et al
    Deep sequencing analysis quantifies the hydrophobicity of the plasma membrane and provides restraints for structure modeling of receptor homodimers to atomic precision.
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    1. Cell Biology
    2. Computational and Systems Biology

    An analysis toolbox to explore mesenchymal migration heterogeneity reveals adaptive switching between distinct modes

    Hamdah Shafqat-Abbasi et al
    “Discontinuous” and “Continuous” migration modes are divergent mesenchymal migration strategies that arise spontaneously in parallel in an equilibrium modulated by cell-matrix attachment and actomyosin contractility.
    Tools and Resources
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    1. Biochemistry
    2. Cell Biology

    Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases

    Martin Steger et al
    Discovery of a physiological LRRK2 substrate and a new mechanism of Rab regulation should aid Parkinson’s research and the understanding of Rab function.
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    1. Cell Biology
    2. Developmental Biology and Stem Cells

    The beetle amnion and serosa functionally interact as apposed epithelia

    Maarten Hilbrant et al
    Late morphogenesis of the insect extraembryonic epithelia involves transient formation of a basal-basal bilayer to coordinate the functional contributions of two discrete tissues.
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    1. Biochemistry
    2. Cell Biology

    Kindlin-2 cooperates with talin to activate integrins and induces cell spreading by directly binding paxillin

    Marina Theodosiou et al
    Kindlin-2 co-operates with talin to activate fibronectin-binding integrins on fibroblasts and subsequently induces cell spreading by recruiting paxillin to small, peripheral nascent adhesions.
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    1. Biophysics and Structural Biology
    2. Microbiology and Infectious Disease

    Guanylate binding proteins directly attack Toxoplasma gondii via supramolecular complexes

    Elisabeth Kravets et al
    Cellular immunity against Toxoplasma parasites is orchestrated by GBP complexes attacking the parasite membrane.
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    1. Developmental Biology and Stem Cells

    Maternally provided LSD1/KDM1A enables the maternal-to-zygotic transition and prevents defects that manifest postnatally

    Jadiel A Wasson et al
    Epigenetic reprogramming by LSD1/KDM1A acts at fertilization in mice to enable embryogenesis and prevent behavioural abnormalities.
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    1. Developmental Biology and Stem Cells

    Epigenetic regulation of hematopoiesis by DNA methylation

    Aniket V Gore et al
    Methylation of a key transcription factor gene by a de novo DNA methyltransferase assures the maintenance of hematopoietic stem cell fate.
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    1. Developmental Biology and Stem Cells
    2. Neuroscience

    Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

    Kawssar Harb et al
    Lmo4 specifies two neuron subclasses in the mouse neocortex by promoting postnatal co-expression of the transcription factors Ctip2 and Satb2 via chromatin remodelling in a time and area-specific manner.
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    1. Developmental Biology and Stem Cells
    2. Genes and Chromosomes

    An epigenetic switch ensures transposon repression upon dynamic loss of DNA methylation in embryonic stem cells

    Marius Walter et al
    The various transposon families of the mammalian genome can adopt different types of repressive chromatin responses upon DNA methylation loss.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Human cytomegalovirus IE1 protein alters the higher-order chromatin structure by targeting the acidic patch of the nucleosome

    Qianglin Fang et al
    Distinct binding of viral proteins to the same region on the nucleosome surface can result in contrasting changes to higher-order chromatin structure in the host cell.
    Short Report
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    1. Genomics and Evolutionary Biology
    2. Microbiology and Infectious Disease

    Population genomics reveals the origin and asexual evolution of human infective trypanosomes

    William Weir et al
    The protozoan parasite Trypanosoma brucei gambiense has undergone recent clonal evolution that reveals the theoretically predicted Meselson effect at a genome-wide level.
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    1. Human Biology and Medicine
    2. Neuroscience

    Mutation in ATG5 reduces autophagy and leads to ataxia with developmental delay

    Myungjin Kim et al
    A genetic mutation that impairs autophagic flux leads to neurodegeneration and can cause ataxia and developmental delay in children.
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    1. Cell Biology
    2. Developmental Biology and Stem Cells

    The tumor suppressor PTEN and the PDK1 kinase regulate formation of the columnar neural epithelium

    Joaquim Grego-Bessa et al
    In addition to its role in regulating proliferation and cell death, the PTEN tumor suppressor regulates epithelial morphogenesis through the PDK1 kinase.
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    1. Developmental Biology and Stem Cells
    2. Immunology

    MHC-compatible bone marrow stromal/stem cells trigger fibrosis by activating host T cells in a scleroderma mouse model

    Yoko Ogawa et al
    PDGFRα+ Sca-1+ bone marrow stromal/stem cells in whole bone marrow grafts can trigger the onset of autoimmune-related fibrosis in a mouse model of scleroderma.
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    1. Biophysics and Structural Biology
    2. Neuroscience

    Photo-switchable tweezers illuminate pore-opening motions of an ATP-gated P2X ion channel

    Chloé Habermacher et al
    The gating mechanism of trimeric ATP-gated P2X receptors has been explored using photo-switchable cross-linkers, via a versatile strategy that could be applied to other membrane proteins.
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    1. Developmental Biology and Stem Cells

    The ‘de novo’ DNA methyltransferase Dnmt3b compensates the Dnmt1-deficient intestinal epithelium

    Ellen N Elliott et al
    The maintenance methyltransferase Dnmt1 and the de novo methyltransferase Dnmt3b cooperate to maintain DNA methylation and genomic stability in the adult intestinal epithelium.
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    1. Cell Biology
    2. Neuroscience

    Systematic substrate identification indicates a central role for the metalloprotease ADAM10 in axon targeting and synapse function

    Peer-Hendrik Kuhn et al
    The metalloprotease ADAM10 modulates axon and synapse function by cleaving numerous synaptic and axonal membrane proteins in the central nervous system.
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    1. Immunology
    2. Microbiology and Infectious Disease

    Trogocytosis-associated cell to cell spread of intracellular bacterial pathogens

    Shaun Steele et al
    Live intracellular bacterial pathogens can transfer from infected cells to uninfected macrophages upon cell-to-cell contact.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Unnatural amino acid photo-crosslinking of the IKs channel complex demonstrates a KCNE1:KCNQ1 stoichiometry of up to 4:4

    Christopher I Murray et al
    The IKs potassium channel complex displays functional flexibility that depends on the ratio of its constituent KCNQ1 and KCNE1 protein subunits.
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    1. Biophysics and Structural Biology

    Revealing an outward-facing open conformational state in a CLC Cl/H+ exchange transporter

    Chandra M Khantwal et al
    The characterization of a previously unidentified “outward-facing open” conformational state provides a new framework for understanding the CLC transport mechanism.
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    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Eighteenth century Yersinia pestis genomes reveal the long-term persistence of an historical plague focus

    Kirsten I Bos et al
    The analysis of 18th century Y. pestis genomes reveals a bacterial lineage that might be responsible for the 400-year period of European plague epidemics from the Renaissance through early modern times.
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    1. Cell Biology

    Transmembrane chemokines act as receptors in a novel mechanism termed inverse signaling

    Kirsten Hattermann et al
    In a new mechanism of cellular communication termed “inverse signaling", a transmembrane chemokine acts as a "receptor" for its previously shed form.
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    1. Neuroscience

    A platform for brain-wide imaging and reconstruction of individual neurons

    Michael N Economo et al
    High-resolution fluorescence imaging of the complete mouse brain enables many neurons to be efficiently visualized in their entirety, revealing all targets of neurons that project widely across the brain.
    Tools and Resources
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    1. Biophysics and Structural Biology
    2. Cell Biology

    Myosin III-mediated cross-linking and stimulation of actin bundling activity of Espin

    Haiyang Liu et al
    The tail domain of Myosin III binds to and cross-links actin bundling protein Espin1 and thus modulates higher order actin bundle structures in cellular processes such as stereocilia and microvilli.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Molecular mechanism of thermosensory function of human heat shock transcription factor Hsf1

    Nikolai Hentze et al
    Heat-induced local unfolding allows Hsf1 to form trimers and bind to DNA, which depends on Hsf1 concentration and is promoted, not inhibited, by Hsp90.
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    1. Neuroscience

    The cerebellum linearly encodes whisker position during voluntary movement

    Susu Chen et al
    Cerebellar Purkinje cells represent movements via bidirectional linear changes in spike rate, and activity from single cells is sufficient to reconstruct kinematic changes during bouts of free whisking.
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    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Heart of glass anchors Rasip1 at endothelial cell-cell junctions to support vascular integrity

    Bart-Jan de Kreuk et al
    The proteins Heart of Glass (HEG1) and Rasip1 are both essential for cardiovascular development; and directly bind to each other to guide Rasip1 to endothelial cell junctions to support vascular integrity.
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    1. Immunology

    ILC3 GM-CSF production and mobilisation orchestrate acute intestinal inflammation

    Claire Pearson et al
    Innate lymphoid cells, which are dynamic under steady-state conditions, respond to a colitogenic stimulus by mobilizing from cryptopatches and secreting GM-CSF to organize the pro-inflammatory response.
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    1. Developmental Biology and Stem Cells

    Position-dependent plasticity of distinct progenitor types in the primitive streak

    Filip J Wymeersch et al
    Neuromesodermal and lateral/ventral mesoderm progenitors represent distinct committed states, governed by separate regulatory logics.
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    1. Biochemistry
    2. Neuroscience

    A chemical proteomic atlas of brain serine hydrolases identifies cell type-specific pathways regulating neuroinflammation

    Andreu Viader et al
    Cell-specific pathways regulate lipid transmitters and neuroinflammation in the brain.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    The magnesium transporter A is activated by cardiolipin and is highly sensitive to free magnesium in vitro

    Saranya Subramani et al
    A magnesium transporter from Escherichia coli depends strongly on the lipid cardiolipin and acts both as a sensor and a transporter of magnesium.
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    1. Biophysics and Structural Biology

    α/β coiled coils

    Marcus D Hartmann et al
    Simple insertions switch α-helical coiled coils into a novel fibrous protein fold that is periodically interspersed with short β-strands.
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    1. Neuroscience

    Motion along the mental number line reveals shared representations for numerosity and space

    Caspar M Schwiedrzik et al
    Looking at visual motion affects perception of nonsymbolic numerosity in a direction-specific way, indicating that motion and number are computed by the same neurons.
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    1. Microbiology and Infectious Disease
    2. Plant Biology

    An effector of the Irish potato famine pathogen antagonizes a host autophagy cargo receptor

    Yasin F Dagdas et al
    A plant pathogen effector evolved a short linear motif to subvert autophagic defenses by antagonising a host cargo receptor.
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    1. Neuroscience

    IK1 channels do not contribute to the slow afterhyperpolarization in pyramidal neurons

    Kang Wang et al
    The slow afterhyperpolarization that follows a burst of action potentials is a powerful regulator of neuronal excitability and is not due to IK1 (KCNN4), a member of the SK channel family.
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    1. Cancer biology
    2. Cell Biology

    Rho-associated kinase (ROCK) function is essential for cell cycle progression, senescence and tumorigenesis

    Sandra Kümper et al
    The Rho kinases ROCK1 and 2 act redundantly in regulating cell proliferation and their depletion causes cellular senescence.
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    1. Biophysics and Structural Biology
    2. Cell Biology

    The Sec7 N-terminal regulatory domains facilitate membrane-proximal activation of the Arf1 GTPase

    Brian C Richardson et al
    A new structure reveals two Arf-GEF regulatory domains form a single structural unit that stimulates Arf-GEF activity.
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    1. Computational and Systems Biology
    2. Genomics and Evolutionary Biology

    NF-κB oscillations translate into functionally related patterns of gene expression

    Samuel Zambrano et al
    NF-κB oscillations synchronize to external perturbations as a damped oscillator, producing different transcription dynamics.
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    1. Developmental Biology and Stem Cells

    An oxygen-insensitive Hif-3α isoform inhibits Wnt signaling by destabilizing the nuclear β-catenin complex

    Peng Zhang et al
    Hif/Hif-3α has two distinct roles in cells: activating HRE-dependent gene expression and binding to β-catenin to destabilize the nuclear β-catenin complex.
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    1. Developmental Biology and Stem Cells
    2. Human Biology and Medicine

    Genetic dissection of Down syndrome-associated congenital heart defects using a new mouse mapping panel

    Eva Lana-Elola et al
    A panel of seven new mouse strains with chromosomal duplications is used to identify a minimal genetic region required in three copies to cause congenital heart defects typical of human Down syndrome.
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    1. Cell Biology
    2. Computational and Systems Biology

    Evaluation of predictions of the stochastic model of organelle production based on exact distributions

    C Jeremy Craven
    A reanalysis of the stochastic model of organelle production (Mukherji and O'Shea, 2014) suggests that this model requires significant further discussion.
    Short Report
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    1. Cell Biology
    2. Developmental Biology and Stem Cells

    NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

    Lindsey Seldin et al
    A newly identified microtubule binding activity of NuMA is required for orienting the mitotic spindle.
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    1. Cell Biology
    2. Computational and Systems Biology

    Bistability of a coupled Aurora B kinase-phosphatase system in cell division

    Anatoly V Zaytsev et al
    Self-activating Aurora B kinase, opposed by an inhibitory phosphatase, forms spatial phosphorylation patterns during cell division.
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    1. Biochemistry
    2. Computational and Systems Biology

    Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution

    Scott M Coyle, Wendell A Lim
    A systems level reconstitution of H-Ras GTPase signaling reveals a rich space of tunable dynamic outputs and clarifies the consequences of oncogenic perturbations to signaling.
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    1. Biophysics and Structural Biology
    2. Cell Biology

    Mapping translation 'hot-spots' in live cells by tracking single molecules of mRNA and ribosomes

    Zachary B Katz et al
    A method that involves simultaneous tracking of individual mRNAs and their associated ribosomes can be used to determine when and where individual molecules get translated in living cells.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Blue light-induced LOV domain dimerization enhances the affinity of Aureochrome 1a for its target DNA sequence

    Udo Heintz, Ilme Schlichting
    Light absorption by the algal transcription factor Aureochrome 1a causes dimerization at the light-oxygen-voltage (LOV) sensing domain, which has implications for the design of synthetic photoreceptors for optogenetics.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Molecular basis for allosteric specificity regulation in class Ia ribonucleotide reductase from Escherichia coli

    Christina M Zimanyi et al
    Substrate and effector bound structures of a bacterial ribonucleotide reductase reveal the molecular basis by which substrate preference is modulated by a distal site on the enzyme.
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    1. Neuroscience

    Rhythmic coordination of hippocampal neurons during associative memory processing

    Lara M Rangel et al
    Different rhythms uniquely contribute to task-related processing in the hippocampus, and changes in the rhythmic profile of the hippocampus reflect dynamic coordination of its cell activity.
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    1. Genes and Chromosomes

    Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis

    Cen Zhang et al
    The GLS2 enzyme suppresses cancer metastasis by interacting with the small GTPase Rac1 and inhibiting its activity.
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    1. Cell Biology
    2. Developmental Biology and Stem Cells

    Local mechanical forces promote polarized junctional assembly and axis elongation in Drosophila

    Jessica C Yu, Rodrigo Fernandez-Gonzalez
    Polarized assembly of cell-cell junctions drives Drosophila axis elongation.
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    1. Biophysics and Structural Biology

    Atomic structure of the 26S proteasome lid reveals the mechanism of deubiquitinase inhibition

    Corey M Dambacher et al
    Within the isolated lid sub-complex of the proteasome, a finely tuned network of interactions maintains the deubiquitinase in an inhibited conformation; dramatic rearrangements of the lid subunits upon incorporation into the holoenzyme lead to the deubiquitinase’s activation.
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    1. Biophysics and Structural Biology
    2. Computational and Systems Biology

    The yin–yang of kinase activation and unfolding explains the peculiarity of Val600 in the activation segment of BRAF

    Christina Kiel et al
    The V600E mutation in BRAF is a cancer hot spot because it opens the activation segment through destabilization of autoinhibitory interactions, but it does not significantly impair folding of the inactive or active kinase domain.
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    1. Biochemistry
    2. Microbiology and Infectious Disease

    Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway

    Zhiyun Ge et al
    The RNA-binding protein PTBP1 is recruited to sites near stop codons in retroviral and human mRNAs, shielding them from detection and degradation by the nonsense-mediated mRNA decay pathway.
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    1. Biochemistry
    2. Biophysics and Structural Biology

    Structural basis of nucleic-acid recognition and double-strand unwinding by the essential neuronal protein Pur-alpha

    Janine Weber et al
    The crystal structure of Pur-alpha in complex with DNA reveals its molecular mechanisms of nucleic-acid binding and unwinding, allowing for a better understanding of its essential role in neurons.
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    1. Developmental Biology and Stem Cells

    The REST remodeling complex protects genomic integrity during embryonic neurogenesis

    Tamilla Nechiporuk et al
    The untimely loss of the transcriptional repressor REST from dividing neural progenitors during embryogenesis leads to compromised genomic integrity.
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    1. Cell Biology
    2. Neuroscience

    Dendritic mitochondria reach stable positions during circuit development

    Michelle C Faits et al
    Mitochondria reach stable positions in dendrites during a critical developmental period of high motility.
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    1. Cell Biology
    2. Genes and Chromosomes

    Chromatin-prebound Crm1 recruits Nup98-HoxA9 fusion to induce aberrant expression of Hox cluster genes

    Masahiro Oka et al
    Nup98-HoxA9 is recruited to Hox gene cluster regions together with the chromosomally pre-bound nuclear export factor Crm1, which induces aberrant expression of several Hox genes and affecting the differentiation of embryonic stem cells.
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    1. Cell Biology
    2. Genomics and Evolutionary Biology

    Evolution of an ancient protein function involved in organized multicellularity in animals

    Douglas P Anderson et al
    Experimentally reconstructing the evolution of the molecular complex that animals use to orient the mitotic spindle establishes a simple genetic and physical mechanism for the emergence of a function essential for multicellularity.
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    1. Cell Biology

    Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity

    Bernadette Carroll et al
    Signaling pathway mTOR can sense its principal activator amino acid arginine via a different mechanism than that previously described for other amino acids.
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    1. Computational and Systems Biology
    2. Genes and Chromosomes

    Tunable protein synthesis by transcript isoforms in human cells

    Stephen N Floor, Jennifer A Doudna
    Measurements of transcript isoform specific translation across the human genome reveal that isoforms from the same gene can differ in protein production by two orders of magnitude.
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    1. Cell Biology
    2. Neuroscience

    The p38 MAP kinase pathway modulates the hypoxia response and glutamate receptor trafficking in aging neurons

    Eun Chan Park, Christopher Rongo
    The subcellular localization of the prolyl hydroxylase oxygen sensor in C. elegans neurons is regulated by p38 MAP kinase signaling.
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    1. Neuroscience

    Arf6 regulates the cycling and the readily releasable pool of synaptic vesicles at hippocampal synapse

    Erica Tagliatti et al
    The small GTPase Arf6 plays a role in setting the size of the readily releasable pool of synaptic vesicles and in the definition of the recycling route for endocytosed vesicles.
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    1. Genes and Chromosomes
    2. Human Biology and Medicine

    Bromodomain inhibition of the transcriptional coactivators CBP/EP300 as a therapeutic strategy to target the IRF4 network in multiple myeloma

    Andrew R Conery et al
    CBP/EP300 bromodomain inhibitors have a therapeutic application in oncology via targeting the IRF4 transcriptional program, a clinically validated network critical for multiple myeloma cell viability.
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    1. Biophysics and Structural Biology
    2. Human Biology and Medicine

    The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain

    Simon Mysling et al
    Intravascular triglyceride hydrolysis by lipoprotein lipase is crucial for delivering lipid nutrients to vital tissues, such as the heart, skeletal muscle, and adipose tissue.
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