November 2017

Cover articles

    1. Biochemistry and Chemical Biology

    How ribosomes limit protein mobility

    Paul E Schavemaker, Wojciech M Śmigiel, Bert Poolman
    1. Neuroscience

    Cortical folding in mammalian brains

    Naoyuki Matsumoto, Yohei Shinmyo ... Hiroshi Kawasaki
    1. Cancer Biology
    2. Cell Biology

    Exploring hyaluronan biosynthesis in cancer

    Hiba Ahmad Zahreddine, Biljana Culjkovic-Kraljacic ... Katherine LB Borden

Highlights controls:

Research articles

    1. Cell Biology

    Time-gated detection of protein-protein interactions with transcriptional readout

    Min Woo Kim, Wenjing Wang ... Alice Y Ting
    A light-dependent two-hybrid tool with transcriptional readout detects multiple protein-protein interactions in living mammalian cells with high signal-to-background ratios and enables genetic selections.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Yeast eIF4A enhances recruitment of mRNAs regardless of their structural complexity

    Paul Yourik, Colin Echeverría Aitken ... Jon R Lorsch
    Eukaryotic translation initiation factor 4A is stimulated by the ribosomal pre-initiation complex and promotes the recruitment of mRNAs regardless of their degree of structure.
    1. Biochemistry and Chemical Biology

    Conserved RNA-binding specificity of polycomb repressive complex 2 is achieved by dispersed amino acid patches in EZH2

    Yicheng Long, Ben Bolanos ... Xin Liu
    Biochemical and mutagenesis analysis reveal the long-anticipated RNA-binding elements of Polycomb Repressive Complex 2 (PRC2), an important chromatin modifier, allowing construction of separation-of-function mutants of PRC2 defective in RNA binding but retaining histone-modifying activity.
    1. Cell Biology

    NuMA recruits dynein activity to microtubule minus-ends at mitosis

    Christina L Hueschen, Samuel J Kenny ... Sophie Dumont
    At mitosis, NuMA recruits dynein-dynactin to microtubule minus-ends, enabling robust microtubule clustering and the emergence of spindle poles.
    1. Cell Biology
    2. Developmental Biology

    Activation of Discs large by aPKC aligns the mitotic spindle to the polarity axis during asymmetric cell division

    Ognjen Golub, Brett Wee ... Kenneth E Prehoda
    The Par complex controls spindle orientation during asymmetric cell division by phosphorylating the tumor suppressor Discs large, overcoming its autoinhibited state, and allowing it to bind the microtubule-binding protein GukHolder.
    1. Cell Biology
    2. Genetics and Genomics

    Rapid re-identification of human samples using portable DNA sequencing

    Sophie Zaaijer, Assaf Gordon ... Yaniv Erlich
    DNA fingerprinting by portable nanopore sequencing is a novel re-identification method with applications in (clinical) laboratories and biobanks.
    1. Developmental Biology

    A predictive model of asymmetric morphogenesis from 3D reconstructions of mouse heart looping dynamics

    Jean-François Le Garrec, Jorge N Domínguez ... Sigolène M Meilhac
    A precise sequence of left-right asymmetries, combined with mechanical constraints, is sufficient to drive the looped morphogenesis of the embryonic heart tube, with potential impact for congenital heart defects.
    1. Neuroscience

    The effect of perinatal brain injury on dopaminergic function and hippocampal volume in adult life

    Sean Froudist-Walsh, Michael AP Bloomfield ... Oliver Howes
    Perinatal brain injury is associated with altered dopaminergic function and reduced hippocampal volume in adulthood in humans.
    1. Biochemistry and Chemical Biology

    Immunoproteasome functions explained by divergence in cleavage specificity and regulation

    Michael B Winter, Florencia La Greca ... Charles S Craik
    Divergence in immunoproteasome substrate specificity and regulation from the constitutive proteasome impacts peptide cleavage quantity and the cellular capacity of the ubiquitin-proteasome system.
    1. Developmental Biology
    2. Medicine

    CHARGE syndrome modeling using patient-iPSCs reveals defective migration of neural crest cells harboring CHD7 mutations

    Hironobu Okuno, Francois Renault Mihara ... Hideyuki Okano
    Neural crest cells differentiated from patient-derived cells with mutations in the chromatin remodeler CHD7 show defective delamination, migration and motility in vitro, and defective migration in chick embryos.
    1. Genetics and Genomics

    A new genus of horse from Pleistocene North America

    Peter D Heintzman, Grant D Zazula ... Beth Shapiro
    The extinct stilt-legged equids of North America are not related to Asiatic asses or horses, but instead represent a distinct lineage outside of living equid diversity that became extinct in the terminal Pleistocene.
    1. Cell Biology
    2. Neuroscience

    AKT isoforms have distinct hippocampal expression and roles in synaptic plasticity

    Josien Levenga, Helen Wong ... Charles A Hoeffer
    Three distinct AKT isoforms are found in the brain and show dissimilar patterns of expression, differential roles in the expression of synaptic plasticity, and different roles in neuronal signaling.
    1. Neuroscience

    Predicting non-linear dynamics by stable local learning in a recurrent spiking neural network

    Aditya Gilra, Wulfram Gerstner
    Recurrent neuronal networks learn to predict movement in a self-supervised way using biologically plausible learning rules.
    1. Genetics and Genomics

    The genome of an intranuclear parasite, Paramicrosporidium saccamoebae, reveals alternative adaptations to obligate intracellular parasitism

    C Alisha Quandt, Denis Beaudet ... Timothy Y James
    Parasitic lineages of Rozellomycota are shaped by repeated and independent gene losses.
    1. Ecology

    Sequestration and activation of plant toxins protect the western corn rootworm from enemies at multiple trophic levels

    Christelle AM Robert, Xi Zhang ... Jonathan Gershenzon
    The western corn rootworm escapes biological control by entomopathogenic nematodes by partitioning and phenocopying the plant defense system for self-protection.
    1. Immunology and Inflammation

    CRIg, a tissue-resident macrophage specific immune checkpoint molecule, promotes immunological tolerance in NOD mice, via a dual role in effector and regulatory T cells

    Xiaomei Yuan, Bi-Huei Yang ... Wenxian Fu
    Tissue-resident macrophages sense environmental cues and regulate adaptive immunity via an immune checkpoint molecule CRIg.
    1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    The mechanism of variability in transcription start site selection

    Libing Yu, Jared T Winkelman ... Richard H Ebright
    Variability in bacterial transcription start site selection involves DNA “scrunching” and “anti-scrunching,” which may represent a general mechanism for start site selection in all organisms.
    1. Cancer Biology
    2. Developmental Biology

    Jak2-mediated phosphorylation of Atoh1 is critical for medulloblastoma growth

    Tiemo J Klisch, Anna Vainshtein ... Huda Y Zoghbi
    Aberrant phosphorylation of tyrosine 78 on Atoh1 via Jak2 is responsible for sonic hedgehog type medulloblastoma growths in vivo.
    1. Developmental Biology

    Zfp281 is essential for mouse epiblast maturation through transcriptional and epigenetic control of Nodal signaling

    Xin Huang, Sophie Balmer ... Jianlong Wang
    Post-implantation epiblast maturation and patterning of anterior-posterior axis in mouse embryonic development are mediated by pluripotency transcription factor Zfp281 through transcriptional and epigenetic control of Nodal signaling.
    1. Neuroscience

    Neuromodulatory connectivity defines the structure of a behavioral neural network

    Feici Diao, Amicia D Elliott ... Benjamin H White
    Using targeted functional manipulations of neural activity to map neuromodulatory connections can deliver considerable insight into the functional architecture of a behaviorally important network even in the absence of information about its synaptic connectivity.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The gating cycle of a K+ channel at atomic resolution

    Luis G Cuello, D Marien Cortes, Eduardo Perozo
    X-ray crystallographic studies have completed the first atomic resolution description of the kinetic cycle of a potassium channel's pore domain.
    1. Structural Biology and Molecular Biophysics
    2. Neuroscience

    Fundamental constraints in synchronous muscle limit superfast motor control in vertebrates

    Andrew F Mead, Nerea Osinalde ... Coen PH Elemans
    Vertebrate superfast muscles employ similar excitation–contraction strategies but distinct myosin heavy chain genes to allow superfast performance, revealing a maximum speed that cannot be overcome without sacrificing neural control.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The AAA ATPase Vps4 binds ESCRT-III substrates through a repeating array of dipeptide-binding pockets

    Han Han, Nicole Monroe ... Christopher P Hill
    A 3.2 Å resolution structure of Vps4 provides a detailed model for protein substrate binding and translocation by AAA ATPases.
    1. Neuroscience

    Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation

    Bingshuo Li, Juha P Virtanen ... Alia Benali
    A cellular-level in vivo investigative method that provides unprecedented insights into the dynamics of neuronal activities evoked by transcranial magnetic stimulation.
    1. Neuroscience

    Computational modeling of spinal circuits controlling limb coordination and gaits in quadrupeds

    Simon M Danner, Natalia A Shevtsova ... Ilya A Rybak
    Organization of commissural and long propriospinal neuronal pathways defines gait expression in quadrupeds.
    1. Computational and Systems Biology
    2. Neuroscience

    T2N as a new tool for robust electrophysiological modeling demonstrated for mature and adult-born dentate granule cells

    Marcel Beining, Lucas Alberto Mongiat ... Peter Jedlicka
    T2N, a novel interface between Matlab, TREES toolbox and NEURON, was used to generate compartmental models that reproduce the electrophysiology of dentate granule cells over a multitude of species, experimental conditions and developmental stages.
    1. Biochemistry and Chemical Biology

    Regulatory coiled-coil domains promote head-to-head assemblies of AAA+ chaperones essential for tunable activity control

    Marta Carroni, Kamila B Franke ... Axel Mogk
    Head-to-head interactions of regulatory coiled-coil domains control activity of the central bacterial AAA+ protein ClpC by promoting formation of a reversible resting state.
    1. Cell Biology
    2. Neuroscience

    Clarinet (CLA-1), a novel active zone protein required for synaptic vesicle clustering and release

    Zhao Xuan, Laura Manning ... Peri T Kurshan
    Clarinet, a novel C. elegans active zone protein with homology to vertebrate Piccolo and Rim, uses its different isoforms for diverse functions, including synaptic vesicle clustering, vesicle release and synaptogenesis.
    1. Ecology

    Countercurrent heat exchange and thermoregulation during blood-feeding in kissing bugs

    Chloé Lahondère, Teresita C Insausti ... Claudio R Lazzari
    A novel thermoregulatory mechanism in blood-sucking insects, vectors of human disease, is described using a functional-morphological approach.
    1. Microbiology and Infectious Disease

    An orphan cbb3-type cytochrome oxidase subunit supports Pseudomonas aeruginosa biofilm growth and virulence

    Jeanyoung Jo, Krista L Cortez ... Lars EP Dietrich
    During growth in biofilms and host infection, the opportunistic pathogen Pseudomonas aeruginosa employs respiratory heterocomplexes that support extracellular electron shuttling and pathogenicity.
    1. Ecology

    Migration confers winter survival benefits in a partially migratory songbird

    Daniel Zúñiga, Yann Gager ... Jesko Partecke
    Testing of fitness-related benefits in migratory population of European blackbirds offers confirming predictions of theoretical models on the evolution and maintenance of migration.
    1. Neuroscience

    Diverse modes of synaptic signaling, regulation, and plasticity distinguish two classes of C. elegans glutamatergic neurons

    Donovan Ventimiglia, Cornelia I Bargmann
    Single-neuron synaptic imaging in vivo demonstrates that highly conserved molecules such as UNC-13, UNC-18, and protein kinase C, which are found at essentially every synapse make different functional contributions in Caenorhabditis elegans glutamatergic neurons.
    1. Cell Biology
    2. Neuroscience

    RNG105/caprin1, an RNA granule protein for dendritic mRNA localization, is essential for long-term memory formation

    Kei Nakayama, Rie Ohashi ... Nobuyuki Shiina
    The formation of long-term memory in mice requires an element of RNA granules that localizes messenger RNAs to dendrites.
    1. Biochemistry and Chemical Biology

    Ribosome surface properties may impose limits on the nature of the cytoplasmic proteome

    Paul E Schavemaker, Wojciech M Śmigiel, Bert Poolman
    The diffusion coefficients of proteins in the cytoplasm depend on their net charge and the distribution of charge over the protein surface, with positive proteins moving up to 100-fold slower because they bind to ribosomes.
    1. Developmental Biology
    2. Evolutionary Biology

    Functional divergence of paralogous transcription factors supported the evolution of biomineralization in echinoderms

    Jian Ming Khor, Charles A Ettensohn
    A gene duplication event has permitted the functional specialization of a homeodomain transcription factor through changes in exon-intron organization and these changes have supported the evolution of a major, phylum-level morphological novelty.
    1. Cell Biology

    Cyclin A/Cdk1 modulates Plk1 activity in prometaphase to regulate kinetochore-microtubule attachment stability

    Ana Maria G Dumitru, Scott F Rusin ... Duane A Compton
    Quantitative phosphoproteomics defines the substrates for Cyclin A/Cdk1 kinase during early mitosis and follow up studies validate that one identified substrate, MYPT1, influences the stability of k-MT attachments by regulating Plk1.
    1. Neuroscience

    Cocaine-induced adaptation of dopamine D2S, but not D2L autoreceptors

    Brooks G Robinson, Alec F Condon ... Kim A Neve
    Desensitization of the D2 autoreceptor is reduced following in vivo cocaine exposure due to plasticity in the D2S and not the D2L splice variant.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Cryo-EM structure of a late pre-40S ribosomal subunit from Saccharomyces cerevisiae

    André Heuer, Emma Thomson ... Roland Beckmann
    Near atomic resolution of late 40S ribosomal subunit assembly by cryo-EM reveals immature rRNA active sites stabilized by biogenesis factors.
    1. Developmental Biology

    Autophagic cell death is dependent on lysosomal membrane permeability through Bax and Bak

    Jason Karch, Tobias G Schips ... Jeffery D Molkentin
    Molecular pathways controlling autophagic cell death are regulated at the level of the lysosome through the activity of the pro-death Bcl-2 family member Bax/Bak.
    1. Neuroscience

    Small molecule Photoregulin3 prevents retinal degeneration in the RhoP23H mouse model of retinitis pigmentosa

    Paul A Nakamura, Andy A Shimchuk ... Thomas A Reh
    Regulating rod gene expression with a small molecule ligand for the orphan nuclear receptor Nr2e3 rescues photoreceptors from degeneration in a mouse model of retinitis pigmentosa.
    1. Chromosomes and Gene Expression

    Rapid DNA replication origin licensing protects stem cell pluripotency

    Jacob Peter Matson, Raluca Dumitru ... Jeanette Gowen Cook
    The unique cell cycle variations of pluripotent stem cells ensures that the first step in DNA replication is particularly fast and this rapid rate, in turn, restrains early differentiation.
    1. Immunology and Inflammation

    The somatically generated portion of T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor

    Philippa Marrack, Sai Harsha Krovi ... John Kappler
    The alleles of the major histocompatibility complex present in an individual affect the sequences, including, surprisingly, the nongerm line encoded amino acids, of the receptors on T cells that allow recognition of antigens.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Stabilization and structural analysis of a membrane-associated hIAPP aggregation intermediate

    Diana C Rodriguez Camargo, Kyle J Korshavn ... Ayyalusamy Ramamoorthy
    The ability of lipid nanodiscs to trap different types of amyloid intermediates, as successfully demonstrated in this study for human-IAPP, could become one of the most powerful approaches to dissect the complicated misfolding pathways of protein aggregation.
    1. Chromosomes and Gene Expression
    2. Genetics and Genomics

    Convergence of topological domain boundaries, insulators, and polytene interbands revealed by high-resolution mapping of chromatin contacts in the early Drosophila melanogaster embryo

    Michael R Stadler, Jenna E Haines, Michael B Eisen
    Fruit fly chromosomes are divided into discrete structural domains by regions of decompacted chromatin, suggesting a novel model for the formation of a known class of genetic elements.
    1. Neuroscience

    Revealing the distribution of transmembrane currents along the dendritic tree of a neuron from extracellular recordings

    Dorottya Cserpán, Domokos Meszéna ... Daniel K Wójcik
    A computational method reveals current sources along the dendritic tree of a single neuron of known morphology from extracellular potential.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    The structure of the COPI coat determined within the cell

    Yury S Bykov, Miroslava Schaffer ... John AG Briggs
    Cryo-electron tomography of COPI vesicles in the Golgi reveals coat structure, disassembly dynamics, cargo binding, and morphological variability.
    1. Cancer Biology

    Bladder-cancer-associated mutations in RXRA activate peroxisome proliferator-activated receptors to drive urothelial proliferation

    Angela M Halstead, Chiraag D Kapadia ... Vivek K Arora
    Bladder-cancer-associated RXRA mutations were found to stimulate urothelial proliferation through a mechanism susceptible to small molecule inhibitors of Peroxisome Proliferator-Activated Receptors, credentialing a new class of targetable drivers of bladder cancer.
    1. Cell Biology

    Atg9 antagonizes TOR signaling to regulate intestinal cell growth and epithelial homeostasis in Drosophila

    Jung-Kun Wen, Yi-Ting Wang ... Guang-Chao Chen
    Atg9 inhibits TOR signaling to regulate cell growth and tissue homeostasis in Drosophila adult midgut.
    1. Cell Biology

    LRP1 integrates murine macrophage cholesterol homeostasis and inflammatory responses in atherosclerosis

    Xunde Xian, Yinyuan Ding ... Joachim Herz
    Tyrosine phosphorylation of the intracellular domain of LRP1 serves as a molecular switch to regulate cellular cholesterol homeostasis through nuclear hormone receptor-mediated regulation of the cellular cholesterol exporter ABCA1.
    1. Developmental Biology
    2. Genetics and Genomics

    A high-resolution mRNA expression time course of embryonic development in zebrafish

    Richard J White, John E Collins ... Elisabeth M Busch-Nentwich
    Global gene expression analysis defines the transcriptional events during the development of zebrafish from fertilised egg to fully formed organism.
    1. Developmental Biology

    An Eya1-Notch axis specifies bipotential epibranchial differentiation in mammalian craniofacial morphogenesis

    Haoran Zhang, Li Wang ... Mai Har Sham
    Dephosphorylation of Notch1 intracellular domain by Eya1 leads to enhanced Notch signalling activity in the non-neuronal epibranchial placodal cells, revealing an essential regulation for the formation of proximal pharyngeal arches during mouse craniofacial development.
    1. Developmental Biology

    Vg1-Nodal heterodimers are the endogenous inducers of mesendoderm

    Tessa G Montague, Alexander F Schier
    Nodal is assumed to be the sole inducer of mesendoderm, but the related signal Vg1 is as essential as Nodal in this process.
    1. Neuroscience

    Subcellular analysis of pigeon hair cells implicates vesicular trafficking in cuticulosome formation and maintenance

    Simon Nimpf, Erich Pascal Malkemper ... David A Keays
    Cuticulosomes are organelles found in the hair cells of birds that are composed of ferritin nanoparticles, form rapidly after hatching by the fusion of vesicular structures, and may play an indirect role in magnetic sensation.
    1. Cell Biology

    Bacterial fumarase and L-malic acid are evolutionary ancient components of the DNA damage response

    Esti Singer, Yardena BH Silas ... Ophry Pines
    The dual function of an ancient prokaryotic enzyme, which is linked to specific metabolite signals, may have been the evolutionary driving force behind its dual localization in eukaryotes.
    1. Chromosomes and Gene Expression
    2. Plant Biology

    DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes

    David B Lyons, Daniel Zilberman
    Nucleosomes and linker histones block eukaryotic cytosine methylation.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    A recombinant BBSome core complex and how it interacts with ciliary cargo

    Björn Udo Klink, Eldar Zent ... Alfred Wittinghofer
    Six BBS proteins form a core BBSome transport vehicle, which is sufficient for recognizing membrane proteins for transport into the ciliary compartment.
    1. Neuroscience

    A versatile genetic tool for post-translational control of gene expression in Drosophila melanogaster

    Sachin Sethi, Jing W Wang
    A chemogenetic tool has been developed to map and manipulate neuronal circuits with spatial and temporal precision.
    1. Developmental Biology

    Maternal Gdf3 is an obligatory cofactor in Nodal signaling for embryonic axis formation in zebrafish

    Brent W Bisgrove, Yi-Chu Su, H Joseph Yost
    Maternal Gdf3 and Nodal are interdependent obligatory cofactors in the fundamental patterning of the vertebrate embryonic axis of zebrafish.
    1. Developmental Biology

    Gdf3 is required for robust Nodal signaling during germ layer formation and left-right patterning

    Jose L Pelliccia, Granton A Jindal, Rebecca D Burdine
    Genetic analyses demonstrate that Gdf3/Vg1 is a maternal effect gene required for robust Nodal signaling during different phases of embryogenesis including germ-layer formation, Kupffer's vesicle morphogenesis, and left-right patterning.
    1. Neuroscience

    Glutamate is required for depression but not potentiation of long-term presynaptic function

    Zahid Padamsey, Rudi Tong, Nigel Emptage
    Electrophysiological and optical analysis of neurotransmitter release at central synapses reveals that glutamate signalling is not required for the long-term potentiation (LTP) of presynaptic function, and instead only promotes presynaptic long-term depression (LTD).
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Transcriptomic and proteomic landscape of mitochondrial dysfunction reveals secondary coenzyme Q deficiency in mammals

    Inge Kühl, Maria Miranda ... Nils-Göran Larsson
    Comparative -omic analyses of five knockout mouse strains with disrupted mitochondrial DNA expression at different levels provide a high quality resource of altered gene expression patterns that reveal several common secondary patophysiological changes of mitochondrial dysfunction.
    1. Neuroscience

    Defective synaptic transmission causes disease signs in a mouse model of juvenile neuronal ceroid lipofuscinosis

    Benedikt Grünewald, Maren D Lange ... Christian Geis
    Impaired GABAergic and glutamatergic synaptic function and loss of interneurons in the amygdala, hippocampus, and cerebellum cause characteristic disease symptoms in a mouse model juvenile neuronal ceroid lipofuscinosis.
    1. Neuroscience

    Distinct spatial coordinate of visual and vestibular heading signals in macaque FEFsem and MSTd

    Lihua Yang, Yong Gu
    In both frontal and temporal–parietal visual cortices of macaque, distinct spatial coordinates of visual and vestibular signals are predominantly eye centered and head centered, respectively.
    1. Cell Biology

    An adaptation of astronomical image processing enables characterization and functional 3D mapping of individual sites of excitation-contraction coupling in rat cardiac muscle

    Qinghai Tian, Lars Kaestner ... Peter Lipp
    The fusion of astronomy and cellular cardiology reveals the 3D arrangement and the firing reliability of active excitation-contraction coupling sites in beating cardiac myocytes.
    1. Neuroscience

    Gyrification of the cerebral cortex requires FGF signaling in the mammalian brain

    Naoyuki Matsumoto, Yohei Shinmyo ... Hiroshi Kawasaki
    FGF signaling is crucial for gyrus formation, proliferation of outer radial glial cells and expansion of upper layers of the cerebral cortex in gyrencephalic mammals.
    1. Cancer Biology
    2. Computational and Systems Biology

    Simultaneous enumeration of cancer and immune cell types from bulk tumor gene expression data

    Julien Racle, Kaat de Jonge ... David Gfeller
    A novel method predicts cancer and immune cell types from bulk tumor gene expression data with the ability to consider uncharacterized and possibly highly variable cell types, which is validated in human genome.
    1. Cell Biology

    Ubiquitin turnover and endocytic trafficking in yeast are regulated by Ser57 phosphorylation of ubiquitin

    Sora Lee, Jessica M Tumolo ... Jason A MacGurn
    Ser57 phosphorylation regulates ubiquitin homeostasis by inhibiting deubiquitylase-mediated recycling and promoting vacuolar degradation.
    1. Genetics and Genomics

    Regulatory network structure determines patterns of intermolecular epistasis

    Mato Lagator, Srdjan Sarikas ... Călin C Guet
    Greater phenotypic variation is exposed by mutations in a gene regulatory system compared to mutations in its constitutive components, namely the transcription factor and the promoter, alone.
    1. Cancer Biology
    2. Neuroscience

    Pharmacological augmentation of nicotinamide phosphoribosyltransferase (NAMPT) protects against paclitaxel-induced peripheral neuropathy

    Peter M LoCoco, April L Risinger ... William P Clarke
    Stimulation of the rate-limiting enzyme in the NAD salvage pathway protected against neurotoxicity and subsequent peripheral neuropathy associated with the widely utilized anticancer drug, paclitaxel.
    1. Biochemistry and Chemical Biology

    Systematic proteomic analysis of LRRK2-mediated Rab GTPase phosphorylation establishes a connection to ciliogenesis

    Martin Steger, Federico Diez ... Matthias Mann
    Parkinson's kinase LRRK2 phosphorylates a distinct subset of Rabs, and LRRK2-dependent phosphorylation links LRKK2 to ciliogenesis.
    1. Microbiology and Infectious Disease

    Structural basis of host recognition and biofilm formation by Salmonella Saf pili

    Longhui Zeng, Li Zhang ... Guoyu Meng
    SafDAA-SafDAA structure and functional characterizations reveal a pili-mediated inter-cellular oligomerization mechanism for bacterial aggregation and biofilm formation in Salmonella enterica.
    1. Cell Biology

    Capillary pericytes mediate coronary no-reflow after myocardial ischaemia

    Fergus M O'Farrell, Svetlana Mastitskaya ... David Attwell
    Lack of reperfusion of cardiac capillaries, when an upstream artery is unblocked following heart attack, reflects contractile pericytes constricting capillaries and preventing blood flow, implying that cardiac pericytes are a therapeutic target for treating cardiac ischaemia.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Structural insight into TPX2-stimulated microtubule assembly

    Rui Zhang, Johanna Roostalu ... Eva Nogales
    A combination of cryo-electron microscopy of TPX2 bound to microtubules and in vitro reconstitution experiments reveals a novel microtubule interaction mode that explains how TPX2 promotes microtubule nucleation and stabilization.
    1. Structural Biology and Molecular Biophysics
    2. Cell Biology

    Mechanical force induces mitochondrial fission

    Sebastian Carsten Johannes Helle, Qian Feng ... Benoît Kornmann
    Mechanically stimulating mitochondria causes them to divide via the recruitment of the mitochondrial fission machinery to the mechanically strained site, showing that intracellular organelles can be mechanoresponsive.
    1. Structural Biology and Molecular Biophysics

    The liquid structure of elastin

    Sarah Rauscher, Régis Pomès
    Molecular simulations show how hydrophobicity and conformational disorder underlie the phase separation of elastin-like peptides and the elasticity of human tissues.
    1. Developmental Biology

    Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling

    Megan L Norris, Andrea Pauli ... Alexander F Schier
    Elucidation of direct and indirect roles of GPCR signaling during gastrulation.
    1. Neuroscience

    Neuropathological and transcriptomic characteristics of the aged brain

    Jeremy A Miller, Angela Guillozet-Bongaarts ... Ed Lein
    High variability in neuropathology burden and interactions between dementia diagnosis and RNA quality present underappreciated complications when studying dementia in an aged population.
    1. Neuroscience

    Maintained avalanche dynamics during task-induced changes of neuronal activity in nonhuman primates

    Shan Yu, Tiago L Ribeiro ... Dietmar Plenz
    Ongoing and stimulus-evoked brain activity in cortex are shown in nonhuman primates to follow the organization of neuronal avalanches, a core commonality that might guide optimal information processing in the brain.
    1. Developmental Biology
    2. Neuroscience

    Two receptor tyrosine phosphatases dictate the depth of axonal stabilizing layer in the visual system

    Satoko Hakeda-Suzuki, Hiroki Takechi ... Takashi Suzuki
    Two receptor tyrosine phosphatases having overlapping function for the determination of the final axon stabilizing layer is encoded for their cumulative cytoplasmic activity and ligand specificity in the visual system.
    1. Cell Biology
    2. Developmental Biology

    Nanos promotes epigenetic reprograming of the germline by down-regulation of the THAP transcription factor LIN-15B

    Chih-Yung Sean Lee, Tu Lu, Geraldine Seydoux
    Nanos is required for germline specification by erasure of maternal program in primordial germ cells.
    1. Cancer Biology
    2. Cell Biology

    The eukaryotic translation initiation factor eIF4E harnesses hyaluronan production to drive its malignant activity

    Hiba Ahmad Zahreddine, Biljana Culjkovic-Kraljacic ... Katherine LB Borden
    The eukaryotic translation initiation factor eIF4E induces hyaluronic acid (HA) synthesis to drive cancer metastasis which can be reversed following eIF4E inhibition and HA degradation.
    1. Neuroscience

    CD40 is a major regulator of dendrite growth from developing excitatory and inhibitory neurons

    Paulina Carriba, Alun M Davies
    CD40-activated CD40L-mediated reverse signalling has strikingly opposite effects on the growth of excitatory and inhibitory neuron dendrites in the developing brain of mice.
    1. Developmental Biology
    2. Microbiology and Infectious Disease

    Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium

    David R Hill, Sha Huang ... Jason R Spence
    Contact with bacteria and subsequent hypoxia promotes functional maturation of the immature gastrointestinal tract.
    1. Structural Biology and Molecular Biophysics
    2. Computational and Systems Biology

    Kinesin motility is driven by subdomain dynamics

    Wonmuk Hwang, Matthew J Lang, Martin Karplus
    The motor protein kinesin utilizes its fuel molecule by active and concerted motions of its subdomains, while it rapidly interacts with the microtubule track by forming a wet and dynamic interface.
    1. Neuroscience

    Otoferlin acts as a Ca2+ sensor for vesicle fusion and vesicle pool replenishment at auditory hair cell ribbon synapses

    Nicolas Michalski, Juan D Goutman ... Christine Petit
    Targeted mutations in a Ca2+-binding site of otoferlin, a transmembrane protein of synaptic vesicles defective in a recessive form of deafness, reveal its Ca2+ sensor role both for vesicle fusion and vesicle pool replenishment.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Architecture of TAF11/TAF13/TBP complex suggests novel regulation properties of general transcription factor TFIID

    Kapil Gupta, Aleksandra A Watson ... Imre Berger
    Integrative structural biology reveals a novel complex comprising the TATA-box-binding protein, TBP, and two subunits, TAF11 and TAF13, of General Transcription Factor TFIID, suggesting a new regulatory state in TFIID function in RNA polymerase II transcription initiation.
    1. Cell Biology

    Cytokinesis in vertebrate cells initiates by contraction of an equatorial actomyosin network composed of randomly oriented filaments

    Felix Spira, Sara Cuylen-Haering ... Daniel W Gerlich
    Asymmetric tension increase along the cell equator promotes self-organization of actomyosin into a partially aligned network during cytokinetic cleavage furrow ingression of vertebrate cells.
    1. Computational and Systems Biology
    2. Neuroscience

    The formation of the light-sensing compartment of cone photoreceptors coincides with a transcriptional switch

    Janine M Daum, Özkan Keles ... Botond Roska
    Correlating changes in structure and gene expression in cone photoreceptors of mice daily, between birth and eye opening, created a resource that supports research in photoreceptor function, development, transplantation and repair.
    1. Cancer Biology
    2. Chromosomes and Gene Expression

    53BP1 and BRCA1 control pathway choice for stalled replication restart

    Yixi Xu, Shaokai Ning ... Dongyi Xu
    53BP1 and BRCA1 antagonistically control a temporal choice of two distinct pathways to restart stalled replication forks in a DNA double stand repair-independent manner.
    1. Neuroscience

    The rate of transient beta frequency events predicts behavior across tasks and species

    Hyeyoung Shin, Robert Law ... Stephanie R Jones
    Across species, tasks and recording modalities, the rate of transient neocortical beta frequency (15-29Hz) events strongly predicts perceptual ability, providing fundamental mechanistic insight, with implications for tracking and manipulating brain dynamics.
    1. Cell Biology

    3D visualization of mitochondrial solid-phase calcium stores in whole cells

    Sharon Grayer Wolf, Yael Mutsafi ... Deborah Fass
    Mammalian mitochondria in living cells store calcium phosphate in solid form.
    1. Neuroscience

    Genetic and neuronal regulation of sleep by neuropeptide VF

    Daniel A Lee, Andrey Andreev ... David A Prober
    Genetic experiments in zebrafish identify neuropeptide VF (NPVF) signaling and NPVF-expressing neurons as a novel vertebrate hypothalamic sleep-promoting system that is functionally conserved with invertebrates.
    1. Microbiology and Infectious Disease

    Modifications at K31 on the lateral surface of histone H4 contribute to genome structure and expression in apicomplexan parasites

    Fabien Sindikubwabo, Shuai Ding ... Mohamed-ali Hakimi
    A versatile acetylation-methylation switch at lysine 31 on the lateral surface of histone H4 contributes to chromatin structure in apicomplexan parasites.
    1. Structural Biology and Molecular Biophysics
    2. Chromosomes and Gene Expression

    Nuclear microenvironments modulate transcription from low-affinity enhancers

    Albert Tsai, Anand K Muthusamy ... Justin Crocker
    Efficient transcription from low-affinity enhancers is driven by nuclear microenvironments of transcription factors.
    1. Cell Biology
    2. Computational and Systems Biology

    Intrinsically disordered linkers determine the interplay between phase separation and gelation in multivalent proteins

    Tyler S Harmon, Alex S Holehouse ... Rohit V Pappu
    Computational modeling and theoretical analysis reveal how disordered linkers determine whether linear multivalent proteins undergo gelation with or without phase separation.
    1. Stem Cells and Regenerative Medicine

    Reactive oxygen species-dependent Toll/NF-κB activation in the Drosophila hematopoietic niche confers resistance to wasp parasitism

    Isabelle Louradour, Anurag Sharma ... Nathalie Vanzo
    In the Drosophila hematopoietic microenvironment, a regulatory network involving Toll/NF-B, EGFR signaling and reactive oxygen species controls blood cell production in response to immune stress.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Inter-species population dynamics enhance microbial horizontal gene transfer and spread of antibiotic resistance

    Robert M Cooper, Lev Tsimring, Jeff Hasty
    Killing their neighbors allows bacteria to steal genes, including antibiotic resistance genes, which we observed under a microscope, quantified, modeled, and predicted potentially guiding strategies to combat it.
    1. Microbiology and Infectious Disease

    Cyclic di-GMP differentially tunes a bacterial flagellar motor through a novel class of CheY-like regulators

    Jutta Nesper, Isabelle Hug ... Urs Jenal
    Precise control of the bacterial flagellar motor determines bacterial cell dispersal and bacteria-surface interactions.
    1. Cell Biology

    Dnmt3a is an epigenetic mediator of adipose insulin resistance

    Dongjoo You, Emma Nilsson ... Sona Kang
    Mouse and tissue culture studies reveal that adipose DNA methyltransferase 3a mediates insulin resistance, partially through repressing the expression of FGF21.
    1. Genetics and Genomics

    Genomic regions controlling shape variation in the first upper molar of the house mouse

    Luisa F Pallares, Ronan Ledevin ... Sabrina Renaud
    An association mapping in wild mice revealed the first candidate loci for within-population molar shape variation and the phenotypic impact of such candidate loci was quantified and validated.
    1. Cell Biology

    CHIP as a membrane-shuttling proteostasis sensor

    Yannick Kopp, Wei-Han Lang ... R Martin Vabulas
    The mechanism is revealed that connects the protein degradation machinery to cellular membrane-bound compartments during proteostasis stress in mammalian cells.