June 2014

Cover articles

    1. Structural Biology and Molecular Biophysics

    Cryo-EM as a tool for drug design

    Wilson Wong, Xiao-chen Bai ... Sjors HW Scheres
    1. Cell Biology
    2. Neuroscience

    Exploring a new pathway for synaptic vesicle recycling

    Yumei Wu, Eileen T O'Toole ... Pietro De Camilli
    1. Neuroscience

    MeCP2 and a tale of two domains

    Laura Dean Heckman, Maria H Chahrour, Huda Y Zoghbi

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Research articles

    1. Biochemistry and Chemical Biology

    Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks

    Suwen Zhao, Ayano Sakai ... Matthew P Jacobson
    Genome neighborhood networks provide an efficient large-scale approach to mine metabolic pathway context for entire families of proteins and enzymes.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A comprehensive search for calcium binding sites critical for TMEM16A calcium-activated chloride channel activity

    Jason Tien, Christian J Peters ... Huanghe Yang
    The identification of four acidic amino acids as potential calcium-binding residues in the TMEM16A calcium-activated chloride channel furthers the molecular understanding of this ion channel family.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Global distribution maps of the leishmaniases

    David M Pigott, Samir Bhatt ... Simon I Hay
    Maps defining environmental risk of the leishmaniases provide insights into the ecology of these diseases and identify regions to target public health measures and inform future burden estimates.
    1. Neuroscience

    Sensory experience during locomotion promotes recovery of function in adult visual cortex

    Megumi Kaneko, Michael P Stryker
    Mice that viewed a visual stimulus whilst running showed recovery of the neuronal responses that had been lost due to early visual deprivation, with potential relevance for amblyopia.
    1. Neuroscience

    Rett-causing mutations reveal two domains critical for MeCP2 function and for toxicity in MECP2 duplication syndrome mice

    Laura Dean Heckman, Maria H Chahrour, Huda Y Zoghbi
    Transgenic mice with Rett-causing mutations in MeCP2 reveal that a basic cluster in the C-terminus of the protein binds DNA and that both the methyl-CpG binding domain and the transcriptional repression domain are necessary to elicit toxicity in MECP2 duplication syndrome.
    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection

    Don B Gammon, Sophie Duraffour ... Craig C Mello
    Novel virus-host systems yield insights into how Lepidopterans (moths and butterflies) combat RNA virus infection and reveal that poxvirus A51R proteins can suppress the host's immune system and stabilize microtubules in host cells.
    1. Structural Biology and Molecular Biophysics
    2. Evolutionary Biology

    An atomic-resolution view of neofunctionalization in the evolution of apicomplexan lactate dehydrogenases

    Jeffrey I Boucher, Joseph R Jacobowitz ... Douglas L Theobald
    The convergent evolution of unusually strict substrate specificity in apicomplexan LDHs arose by classic neofunctionalization of a duplicated MDH gene via few mutations of large effect.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Genome rearrangements and pervasive meiotic drive cause hybrid infertility in fission yeast

    Sarah E Zanders, Michael T Eickbush ... Harmit Singh Malik
    Rapid acquisition of chromosome rearrangements, together with independently acting transmission distorter alleles on each chromosome, drive near complete sterility in fission yeast hybrids.
    1. Computational and Systems Biology
    2. Medicine

    Diagnostically relevant facial gestalt information from ordinary photos

    Quentin Ferry, Julia Steinberg ... Christoffer Nellåker
    An automatic computer vision analysis approach can assist in the diagnosis of rare genetic disorders by using ordinary photographs of patients.
    1. Neuroscience

    Enhancement of fear memory by retrieval through reconsolidation

    Hotaka Fukushima, Yue Zhang ... Satoshi Kida
    Retrieval enhances fear memory through reconsolidation by activating calcineurin-induced protein degradation and CREB-mediated gene expression in amygdala, hippocampus, and mPFC.
    1. Ecology
    2. Evolutionary Biology

    Extreme adaptations for aquatic ectoparasitism in a Jurassic fly larva

    Jun Chen, Bo Wang ... Jes Rust
    Well-preserved fossils reveal an extreme morphological specialization of fly larvae, and broaden our understanding of the diversity of ectoparasitism in Mesozoic insects.
    1. Cell Biology
    2. Neuroscience

    A dynamin 1-, dynamin 3- and clathrin-independent pathway of synaptic vesicle recycling mediated by bulk endocytosis

    Yumei Wu, Eileen T O'Toole ... Pietro De Camilli
    Analysis of neurons that lack the two neuronal dynamins, dynamin 1 and 3, demonstrates a pathway of synaptic vesicle reformation that does not require these two dynamins or clathrin-dependent budding.
    1. Immunology and Inflammation

    B cell activation involves nanoscale receptor reorganizations and inside-out signaling by Syk

    Kathrin Kläsener, Palash C Maity ... Michael Reth
    Studying the earliest events in B cell activation reveals that the B cell antigen receptor is opened and activated via the phosphorylation and binding by the spleen tyrosine kinase (Syk).
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Molecular mechanism for Rabex-5 GEF activation by Rabaptin-5

    Zhe Zhang, Tianlong Zhang ... Jianping Ding
    The GEF activity of Rabex-5 is weakly autoinhibited by its CC domain and activated by Rabaptin-5 and the two proteins work concertedly to activate Rab5.
    1. Plant Biology

    Host-induced bacterial cell wall decomposition mediates pattern-triggered immunity in Arabidopsis

    Xiaokun Liu, Heini M Grabherr ... Andrea A Gust
    Arabidopsis lysozyme LYS1 generates soluble peptidoglycan fragments to mediate pattern-triggered immunity.
    1. Cell Biology

    G-protein-coupled receptor signaling and polarized actin dynamics drive cell-in-cell invasion

    Vladimir Purvanov, Manuel Holst ... Robert Grosse
    siRNA knockdown experiments reveal in detail the signaling pathway that controls cytoskeletal function during cell-in-cell invasion.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A molecular model for the role of SYCP3 in meiotic chromosome organisation

    Johanna Liinamaria Syrjänen, Luca Pellegrini, Owen Richard Davies
    A structural and biochemical study of human SYCP3 provides the first molecular model for the three-dimensional organisation that is imposed upon chromosomal DNA during meiosis and is essential for genetic exchange and fertility.
    1. Plant Biology

    Auxin efflux by PIN-FORMED proteins is activated by two different protein kinases, D6 PROTEIN KINASE and PINOID

    Melina Zourelidou, Birgit Absmanner ... Claus Schwechheimer
    Two protein kinases are required to activate auxin efflux transporters from plants.
    1. Cell Biology
    2. Developmental Biology

    Thrombospondin-4 controls matrix assembly during development and repair of myotendinous junctions

    Arul Subramanian, Thomas F Schilling
    Functional attachments between muscles and tendons require pentameric Thrombospondin-4, revealing novel roles both as an integrin ligand and extracellular matrix scaffold.
    1. Cell Biology
    2. Developmental Biology

    tRNA synthetase counteracts c-Myc to develop functional vasculature

    Yi Shi, Xiaoling Xu ... Xiang-Lei Yang
    In addition to its cytoplasmic role for translation, the seryl-tRNA synthetase also antagonizes the c-Myc transcription factor in the nucleus to transcriptionally repress the growth factor VEGFA and ensure proper development of the vasculature in vertebrates.
    1. Neuroscience

    PDF neuron firing phase-shifts key circadian activity neurons in Drosophila

    Fang Guo, Isadora Cerullo ... Michael Rosbash
    A few circadian ‘evening’ neurons within the Drosophila brain play a key role in driving activity as well as keeping time, whereas the well-known PDF-containing morning cells are likely involved in integrating and transmitting light information.
    1. Cell Biology
    2. Evolutionary Biology

    Evolution of histone 2A for chromatin compaction in eukaryotes

    Benjamin R Macadangdang, Amit Oberai ... Siavash K Kurdistani
    The N-terminal domain in histone 2A serves as an evolutionary tool to enable greater chromatin compaction when genome size is disproportionately larger than the nuclear volume across eukaryotes.
    1. Evolutionary Biology
    2. Plant Biology

    The role of photorespiration during the evolution of C4 photosynthesis in the genus Flaveria

    Julia Mallmann, David Heckmann ... Udo Gowik
    Metabolic exaptation of an anaplerotic nitrogen cycle between bundle sheath and mesophyll cells may explain the remarkably frequent convergent evolution of C4 photosynthesis.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite

    Carina C Clingman, Laura M Deveau ... Sean P Ryder
    The RNA-binding protein MSI1, which is required for stem cell and cancer cell proliferation in the brain and epithelial tissues, also directly senses the concentration of long non-esterified omega-9 fatty acids.
    1. Neuroscience

    A role for descending auditory cortical projections in songbird vocal learning

    Yael Mandelblat-Cerf, Liora Las ... Michale S Fee
    Midbrain dopaminergic neurons and a cortex-like structure called the arcopallium form part of a circuit that enables young songbirds to compare their own song with a template stored in memory, and use any discrepancies to improve their performance.
    1. Developmental Biology

    The transcription factor Pou3f1 promotes neural fate commitment via activation of neural lineage genes and inhibition of external signaling pathways

    Qingqing Zhu, Lu Song ... Naihe Jing
    The transcription factor Pou3f1 triggers embryonic stem cells to become neuronal progenitor cells in two ways: by activating the expression of pro-neuronal genes and by blocking external inhibitory signaling cascades.
    1. Neuroscience

    Optimal multisensory decision-making in a reaction-time task

    Jan Drugowitsch, Gregory C DeAngelis ... Alexandre Pouget
    Through a combination of modeling and experiments it is shown that humans can near-optimally accumulate decision-related evidence across time and cues even when reaction time is under their control.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Single-molecule tracking in live cells reveals distinct target-search strategies of transcription factors in the nucleus

    Ignacio Izeddin, Vincent Récamier ... Xavier Darzacq
    While the transcription factor c-Myc explores the space in the nucleus in an unrestricted manner, the elongation factor P-TEFb's sampling of the nucleus is constrained to a complex domain with fractal characteristics.
    1. Developmental Biology

    Requirement of Smurf-mediated endocytosis of Patched1 in sonic hedgehog signal reception

    Shen Yue, Liu-Ya Tang ... Steven Y Cheng
    Smurf1 and Smurf2 have essential functions in the mammalian Shh signaling pathway, binding to and ubiquitylating Patched1, leading to its endocytosis and subsequent degradation in lysosomes.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Three pools of plasma membrane cholesterol and their relation to cholesterol homeostasis

    Akash Das, Michael S Brown ... Arun Radhakrishnan
    Precise control of cellular cholesterol levels is achieved by organization of cholesterol into three distinct pools in the plasma membrane.
    1. Neuroscience

    Hidden synaptic differences in a neural circuit underlie differential behavioral susceptibility to a neural injury

    Akira Sakurai, Arianna N Tamvacakis, Paul S Katz
    Animal-to-animal variability in neural circuit elements is often hidden under normal conditions, but becomes functionally relevant when the system is challenged by injury.
    1. Cell Biology

    Mechanisms of organelle biogenesis govern stochastic fluctuations in organelle abundance

    Shankar Mukherji, Erin K O'Shea
    A systematic comparison of experimentally measured and theoretically predicted magnitudes of organelle abundance fluctuations suggests that budding yeast produces the maximum level of variability in organelle abundance that can be generated by organelle biogenesis pathways.
    1. Neuroscience

    Caenorhabditis elegans male sensory-motor neurons and dopaminergic support cells couple ejaculation and post-ejaculatory behaviors

    Brigitte LeBoeuf, Paola Correa ... L René García
    In nematode worms, the length of the male refractory period–the time between matings–is regulated by multiple transmitters including dopamine, which both promotes ejaculation and reduces the activity of males post-copulation.
    1. Cell Biology

    Reconstitution of dynein transport to the microtubule plus end by kinesin

    Anthony J Roberts, Brian S Goodman, Samara L Reck-Peterson
    In vitro reconstitution reveals how a system of molecules works together to transport the motor protein dynein to the start of its track.
    1. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to the anti-protozoan drug emetine

    Wilson Wong, Xiao-chen Bai ... Sjors HW Scheres
    The molecular mechanism behind how emetine inhibits the ribosome of the human malaria parasite, along with structural details of the complex formed, is revealed at high resolution using cryo-electron microscopy.
    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever

    Elin Näsström, Nga Tran Vu Thieu ... Henrik Antti
    Metabolite analysis of plasma from enteric fever patients define signals of organism specific host–pathogen interactions and provides opportunities for new diagnostics.
    1. Cell Biology
    2. Neuroscience

    MUL1 acts in parallel to the PINK1/parkin pathway in regulating mitofusin and compensates for loss of PINK1/parkin

    Jina Yun, Rajat Puri ... Ming Guo
    By reducing mitochondrial fusion, MUL1 compensates for the mutations in PINK1 or parkin that underlie certain cases of Parkinson's disease.
    1. Stem Cells and Regenerative Medicine
    2. Chromosomes and Gene Expression

    Mof-associated complexes have overlapping and unique roles in regulating pluripotency in embryonic stem cells and during differentiation

    Sarina Ravens, Marjorie Fournier ... Làszlò Tora
    Two complexes that contain the histone acetyl transferase MOF have distinct regulatory roles in the growth and development of pluripotent embryonic stem cells
    1. Epidemiology and Global Health

    A user-friendly, open-source tool to project impact and cost of diagnostic tests for tuberculosis

    David W Dowdy, Jason R Andrews ... Robert H Gilman
    A freely available computer program that takes into account specific local conditions enables users to predict the impact of adopting different diagnostic strategies on the spread of tuberculosis in their region.
    1. Chromosomes and Gene Expression
    2. Cancer Biology

    Loss of the multifunctional RNA-binding protein RBM47 as a source of selectable metastatic traits in breast cancer

    Sakari Vanharanta, Christina B Marney ... Joan Massagué
    Inactivation of a multifunctional RNA-binding protein can lead to the acquisition of pro-metastatic phenotypes, possibly by stabilizing large-scale transcriptomic changes that provide a selective advantage during cancer progression.
    1. Genetics and Genomics

    High-resolution mapping reveals hundreds of genetic incompatibilities in hybridizing fish species

    Molly Schumer, Rongfeng Cui ... Peter Andolfatto
    Genetic incompatibilities are common and widely distributed throughout the genomes of swordtail fish, and prevent the regions of the genome around them from being exchanged between different species.
    1. Neuroscience

    Sex-specific processing of social cues in the medial amygdala

    Joseph F Bergan, Yoram Ben-Shaul, Catherine Dulac
    Male and female mice respond differently to the same pheromone signals, and the representation of these sensory stimuli by neurons in the medial amygdala correlates precisely with the differences in behavior.
    1. Cell Biology

    Symmetric exchange of multi-protein building blocks between stationary focal adhesions and the cytosol

    Jan-Erik Hoffmann, Yessica Fermin ... Eli Zamir
    In the cytosol, the proteins constituting cell-matrix adhesion sites form multi-protein building blocks which enter and leave these sites unaltered, thereby contributing to their rapid and correct self-assembly.
    1. Neuroscience

    Cell autonomous regulation of hippocampal circuitry via Aph1b-γ-secretase/neuregulin 1 signalling

    Pietro Fazzari, An Snellinx ... Bart De Strooper
    Genetic rescue experiments reveal that γ-secretase enzymes containing Aph1b subunits control signalling by type III neuregulin 1, with implications for schizophrenia.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Oxidation of cellular amino acid pools leads to cytotoxic mistranslation of the genetic code

    Tammy J Bullwinkle, Noah M Reynolds ... Michael Ibba
    Translation quality control protects the cell from environmental stresses that could potentially lead to the toxic accumulation of non-proteinogenic amino acids in the proteome.