May 2018

Research articles

    1. Cell Biology

    Dynein–Dynactin–NuMA clusters generate cortical spindle-pulling forces as a multi-arm ensemble

    Masako Okumura et al.
    Optogenetic reconstitution reveals core functional modules and architecture of the cortical force-generating machinery in human cells.
    1. Neuroscience

    Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex

    Maria M Diehl et al.
    Avoiding danger requires inhibitory signaling in the prelimbic prefrontal cortex, as evidenced by optogenetic manipulations based on neuronal firing patterns.
    1. Microbiology and Infectious Disease
    2. Structural Biology and Molecular Biophysics

    IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis

    Donna L Mallery et al.
    The inositol phosphate IP6 is selectively packaged into HIV virions, where it coordinates electropositive pores in the capsid to prevent spontaneous collapse and promote encapsidated DNA synthesis.
    1. Epidemiology and Global Health

    Predicting the likelihood and intensity of mosquito infection from sex specific Plasmodium falciparum gametocyte density

    John Bradley et al.
    Malaria transmission between human and mosquito depends on the number of male and female gametocytes in the blood.
    1. Neuroscience

    Striatal action-value neurons reconsidered

    Lotem Elber-Dorozko, Yonatan Loewenstein
    The numerous reports in support of action-value representation in the striatum are based on statistical analyses that are subject to two critical confounds and, thus, this long-held belief of striatal action-value representation should be retested using different experiments and analyses.
    1. Biochemistry and Chemical Biology

    Crystallographic observation of nonenzymatic RNA primer extension

    Wen Zhang et al.
    Time resolved crystal structures reveal the binding of activated monomers to the template, followed by generation of the imidazolium-bridged dinucleotide intermediate, and finally formation of a phosphodiester bond between the primer and the adjacent monomer.
    1. Cell Biology
    2. Human Biology and Medicine

    Mucosal absorption of therapeutic peptides by harnessing the endogenous sorting of glycosphingolipids

    Maria Daniela Garcia-Castillo et al.
    Non-native synthetic short-chain glycosphingolipids fused to GLP-1 enable intestinal absorption with high bioavailability in vivo.
    1. Evolutionary Biology

    Gene family innovation, conservation and loss on the animal stem lineage

    Daniel J Richter et al.
    The genomes of animal progenitors evolved as mosaics of old, new, rearranged, and repurposed protein domains, genes and pathways and paved the way for the origin and evolution of animals.
    1. Chromosomes and Gene Expression
    2. Immunology and Inflammation

    ZFP36 RNA-binding proteins restrain T cell activation and anti-viral immunity

    Michael J Moore et al.
    By attenuating the translation of key mRNA targets, ZFP36 RNA binding proteins restrain the expansion and effector activity of T cells.
    1. Evolutionary Biology

    Metabolic co-dependence drives the evolutionarily ancient Hydra–Chlorella symbiosis

    Mayuko Hamada et al.
    The symbiotic relationship between Hydra and Chlorella is driven by metabolic co-dependence and characterized by changes in the photobiont genome in terms of lack of genes essential in free-living algae.
    1. Neuroscience

    Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques

    Evan Wicker et al.
    Transient suppression of activity in the macaque mediodorsal thalamus impairs adjustment of secondary reinforcer values and disrupts appropriate action selection in a reinforcer devaluation task; this profile is distinct from that of amygdala or subregions of orbitofrontal cortex.
    1. Neuroscience

    Functional limb muscle innervation prior to cholinergic transmitter specification during early metamorphosis in Xenopus

    Francois M Lambert et al.
    Molecular labeling, electrophysiology and calcium imaging have revealed a novel switching of neurotransmitter at the frog neuromuscular junction where motoneurons transiently release glutamate before acetylcholine at synapses on developing hindlimb muscles at the onset of metamorphosis.
    1. Computational and Systems Biology
    2. Human Biology and Medicine

    The MR-Base platform supports systematic causal inference across the human phenome

    Gibran Hemani et al.
    Compiling public datasets into a single, centralised repository and linking directly to analytical software completely transforms the scale and scope of causal inference across the phenome.
    1. Cell Biology
    2. Developmental Biology

    A transcriptomics resource reveals a transcriptional transition during ordered sarcomere morphogenesis in flight muscle

    Maria L Spletter et al.
    A developmental transcriptomics resource from Drosophila flight muscles quantifies the transcriptional dynamics during muscle morphogenesis and identifies three ordered phases of sarcomere morphogenesis.
    1. Biochemistry and Chemical Biology

    The HIV-1 Tat protein recruits a ubiquitin ligase to reorganize the 7SK snRNP for transcriptional activation

    Tyler B Faust et al.
    The HIV-1 Tat protein hijacks host non-degradative ubiquitination to trigger the nuclear import of the transcription elongation factor, P-TEFb.
    1. Cell Biology

    The ER membrane protein complex interacts cotranslationally to enable biogenesis of multipass membrane proteins

    Matthew J Shurtleff et al.
    The ER membrane protein complex promotes the biogenesis of a subset multipass membrane proteins enriched for transporters and other proteins with destabilizing features in transmembrane domains.
    1. Cell Biology
    2. Computational and Systems Biology

    Transcriptional profiling reveals extraordinary diversity among skeletal muscle tissues

    Erin E Terry et al.
    There is no such thing as a representative skeletal muscle tissue, as each member of this family of tissues expresses a specialized mRNA program.
    1. Chromosomes and Gene Expression
    2. Human Biology and Medicine

    Covalent linkage of the DNA repair template to the CRISPR-Cas9 nuclease enhances homology-directed repair

    Natasa Savic et al.
    Linking the DNA repair template to the Cas9 ribonucleoprotein complex enhances homology-directed repair of the induced DNA double strand break.
    1. Cell Biology
    2. Chromosomes and Gene Expression

    Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila

    Zaijun Ma et al.
    Epigenetic drift of H3K27me3 is one of the molecular mechanisms that contribute to aging, and stimulation of glycolysis promotes metabolic health and longevity.
    1. Structural Biology and Molecular Biophysics

    Structure of the CLC-1 chloride channel from Homo sapiens

    Eunyong Park, Roderick MacKinnon
    A cryo-electron microscopy study of the human CLC-1 chloride ion channel reveals the structural basis of why some CLC proteins function as passive chloride channels whereas others function as an active proton-chloride antiporters.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Functional and structural characterization of an ECF-type ABC transporter for vitamin B12

    Joana A Santos et al.
    ECF-CbrT is a bacterial vitamin B12 transporter that is structurally different from the well-characterized transporter BtuCDF, yet has similar functional properties.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    FBXL19 recruits CDK-Mediator to CpG islands of developmental genes priming them for activation during lineage commitment

    Emilia Dimitrova et al.
    The ZF-CxxC protein FBXL19 recruits kinase-associated Mediator to CpG islands of silent developmental genes in embryonic stem cells, which primes these genes for activation during differentiation and is required for embryonic development.
    1. Neuroscience

    Rem2 stabilizes intrinsic excitability and spontaneous firing in visual circuits

    Anna R Moore et al.
    In vivo and ex vivo analysis of the activity-regulated gene Rem2 in the mouse visual system sheds new light on the contribution of intrinsic excitability in circuit plasticity.
    1. Cell Biology

    Exportin Crm1 is repurposed as a docking protein to generate microtubule organizing centers at the nuclear pore

    Xun X Bao et al.
    Microtubule nucleation from the nuclear envelope in fission yeast involves repurposing of nuclear export proteins for a non-export-related function, docking cytoplasmic proteins at nuclear pore complexes.
    1. Structural Biology and Molecular Biophysics

    Routine single particle CryoEM sample and grid characterization by tomography

    Alex J Noble et al.
    Fiducial-less tomography on single particle cryoEM samples reveals that most particles are adsorbed to the air-water interface and allows for researchers to diagnose and solve sample, grid, ice thickness, collection, and processing issues.
    1. Neuroscience

    Ciliary and rhabdomeric photoreceptor-cell circuits form a spectral depth gauge in marine zooplankton

    Csaba Verasztó et al.
    In a zooplankton larva, ciliary and rhabdomeric photoreceptor cells work antagonistically to form a spectral depth gauge.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    A twist defect mechanism for ATP-dependent translocation of nucleosomal DNA

    Jessica Winger et al.
    Based on its nucleotide-bound state, the Chd1 chromatin remodeler can locally alter DNA twist on the nucleosome, which either pulls in or expels ~1 bp of DNA at the internal SHL2 binding site.
    1. Neuroscience

    Cognitive regulation alters social and dietary choice by changing attribute representations in domain-general and domain-specific brain circuits

    Anita Tusche, Cendri A Hutcherson
    Regulatory success operates by goal-consistent increases and decreases of distinct attribute representations in generic neural hubs and in domain-specific brain regions, explaining when and why regulatory success generalizes across domains and contexts.
    1. Neuroscience

    Prediction error induced motor contagions in human behaviors

    Tsuyoshi Ikegami et al.
    A new type of implicit effects on one's actions induced by prediction errors during action observation is discovered.
    1. Neuroscience

    Microglial transglutaminase-2 drives myelination and myelin repair via GPR56/ADGRG1 in oligodendrocyte precursor cells

    Stefanie Giera et al.
    A combined approach of unbiased proteomics, biochemistry, genetics, and transgenic animal models reveals that GPR56/ADGRG1 regulates myelin formation and repair by interacting with its microglial-derived ligand transglutaminase 2.
    1. Immunology and Inflammation

    mTORC1 and mTORC2 differentially promote natural killer cell development

    Chao Yang et al.
    mTORC1 and mTORC2 play a central role in the development of natural killer (NK) cells.
    1. Evolutionary Biology

    Neurocranial anatomy of an enigmatic Early Devonian fish sheds light on early osteichthyan evolution

    Alice M Clement et al.
    Stunning new scan data of an enigmatic fish from the Early Devonian of Australia, Ligulalepis, is identified as a stem osteichthyan, specifically, as the sister taxon to the 'psarolepids' plus crown osteichthyans.
    1. Cell Biology
    2. Human Biology and Medicine

    Deficiency of parkin and PINK1 impairs age-dependent mitophagy in Drosophila

    Tom Cornelissen et al.
    Mitophagy occurs in Drosophila flight muscle and dopaminergic neurons in vivo and increases with aging in a PINK1/parkin-dependent fashion.
    1. Neuroscience

    Differential temporal dynamics during visual imagery and perception

    Nadine Dijkstra et al.
    In contrast to perception, during visual imagery, there are no clear time-locked processing stages and imagery specifically overlaps with perceptual processing around 160 ms after stimulus onset and from 300 ms onwards.
    1. Evolutionary Biology
    2. Neuroscience

    A cerebellar substrate for cognition evolved multiple times independently in mammals

    Jeroen B Smaers et al.
    Multiple independent directional selection events on a neural substrate that underpins domain-general associative abilities partly explains independent occurrences of complex behavior in different lineages of mammals.
    1. Biochemistry and Chemical Biology

    Semisynthetic biosensors for mapping cellular concentrations of nicotinamide adenine dinucleotides

    Olivier Sallin et al.
    A family of fluorescent biosensors for nicotinamide adenine dinucleotides allows quantification of these cofactors in live cells with spatio-temporal resolution.
    1. Biochemistry and Chemical Biology

    A surface proton antenna in carbonic anhydrase II supports lactate transport in cancer cells

    Sina Ibne Noor et al.
    Carbonic anhydrase II features a surface proton antenna that exclusively mediates proton exchange with monocarboxylate transporters to facilitate proton-coupled lactate transport in cancer cells.
    1. Developmental Biology

    Hippo signaling determines the number of venous pole cells that originate from the anterior lateral plate mesoderm in zebrafish

    Hajime Fukui et al.
    The Hippo signaling restricts the number of SHF cardiomyocytes in the venous pole by negatively regulating Bmp-Smad signaling in the cells of lateral plate mesoderm.
    1. Computational and Systems Biology
    2. Microbiology and Infectious Disease

    Metabolic interactions between dynamic bacterial subpopulations

    Adam Z Rosenthal et al.
    Metabolic division of labor in B. subtilis controls the extracellular environment.
    1. Neuroscience

    Targeted cortical reorganization using optogenetics in non-human primates

    Azadeh Yazdan-Shahmorad et al.
    Focal optogenetic stimulation strengthens functional connectivity between primary somatosensory and motor cortices in macaques, in a manner consistent with a Hebbian model of stimulus-driven plasticity.
    1. Neuroscience
    2. Microbiology and Infectious Disease

    Social interaction-induced activation of RNA splicing in the amygdala of microbiome-deficient mice

    Roman M Stilling et al.
    Social-interaction impairment in germ-free mice is associated with a markedly altered transcriptional response to social novelty in the amygdala, as characterised by replacement of upregulation of common stimulus-induced pathways with upregulation of the splicing machinery.
    1. Neuroscience

    Energy exchanges at contact events guide sensorimotor integration

    Ali Farshchian et al.
    The brain obtains and preserves a consistent temporal alignment of multisensory and motor information flowing along staggered streams by maintaining an invariant estimate across modalities of the energy exchanged with the environment at discrete events.
    1. Biochemistry and Chemical Biology

    Cdc48-like protein of actinobacteria (Cpa) is a novel proteasome interactor in mycobacteria and related organisms

    Michal Ziemski et al.
    Cdc48-like protein of actinobacteria (Cpa) is a AAA+ proteasomal interactor involved in adaptation of mycobacteria to carbon limitation and potentially influencing ribosomal composition of the cell.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Modulation of formin processivity by profilin and mechanical tension

    Luyan Cao et al.
    Profilin helps to maintain formin at the growing barbed end of an actin filament, while piconewton mechanical tension drastically enhances formin dissociation from the barbed end.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Synthetic single domain antibodies for the conformational trapping of membrane proteins

    Iwan Zimmermann et al.
    Synthetic single domain antibody libraries and a binder selection cascade encompassing ribosome and phage display enable the selection of conformation-specific binders against previously intractable membrane proteins within three weeks.
    1. Structural Biology and Molecular Biophysics

    Structure-based analysis of CysZ-mediated cellular uptake of sulfate

    Zahra Assur Sanghai et al.
    Structures of CysZ show a antiparallel membrane protein with an unanticipated fold and together with functional characterization provide insight into a bacterial sulfate translocating system.
    1. Chromosomes and Gene Expression

    BRG1 governs glucocorticoid receptor interactions with chromatin and pioneer factors across the genome

    Jackson A Hoffman et al.
    Within distinct chromatin landscapes, the BRG1 chromatin remodeling enzyme patterns hormone-dependent chromatin interactions, pioneer factor recruitment, and transcriptional activity.
    1. Ecology

    Increasing plant diversity with border crops reduces insecticide use and increases crop yield in urban agriculture

    Nian-Feng Wan et al.
    Plant diversification can make an important contribution to ecological intensification and the sustainable use of associated ecosystem services in an urban ecosystem.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    An NMDAR positive and negative allosteric modulator series share a binding site and are interconverted by methyl groups

    Riley Perszyk et al.
    A series of novel compounds selective for N-methyl-D-aspartate-type glutamate receptor includes positive and negative allosteric modulators that act at the same site, show use-dependence, increase agonist potency, and have differential activity based on the agonist concentration.
    1. Computational and Systems Biology
    2. Neuroscience

    Post-decision biases reveal a self-consistency principle in perceptual inference

    Long Luu, Alan A Stocker
    Humans are biased in their assessment of sensory information by their own preceding categorical judgment in an attempt to remain self-consistent.
    1. Microbiology and Infectious Disease
    2. Genetics and Genomics

    Dissection of the in vitro developmental program of Hammondia hammondi reveals a link between stress sensitivity and life cycle flexibility in Toxoplasma gondii

    Sarah L Sokol et al.
    A derived stress response trait may have contributed to the emergence of a globally dominant and promiscuous parasite.
    1. Ecology

    First bone-cracking dog coprolites provide new insight into bone consumption in Borophagus and their unique ecological niche

    Xiaoming Wang et al.
    Fossilized feces (coprolites) of extinct bone-crushing dogs, Borophagus parvus, from late Miocene (6 million years ago) of California demonstrates consumption and preservation of bones in digestive tracts and potential social hunting behavior by these predators.
    1. Biochemistry and Chemical Biology
    2. Microbiology and Infectious Disease

    Novel transgenic pigs with enhanced growth and reduced environmental impact

    Xianwei Zhang et al.
    Transgenic expression of glucanase, xylanase and phytase in pigs enhances growth performance and reduces nitrogen/phosphorus emission, and offers a very valuable biological strategy for sustainable resource utilization and environmental protection in the pork industry.
    1. Computational and Systems Biology
    2. Evolutionary Biology

    Shearing in flow environment promotes evolution of social behavior in microbial populations

    Gurdip Uppal, Dervis Can Vural
    Shearing in fluid flow induces or enhances budding dispersal in microbial populations, resulting in stronger cooperative behavior.
    1. Neuroscience

    Perception of social interaction compresses subjective duration in an oxytocin-dependent manner

    Rui Liu et al.
    The subjective time of social interactions reflects one's autistic-like tendency and is critically mediated by oxytocin, indicating that time perception is ingrained with personality traits, which likely have neuroendocrine origins as per previous research.
    1. Human Biology and Medicine
    2. Neuroscience

    A homozygous loss-of-function CAMK2A mutation causes growth delay, frequent seizures and severe intellectual disability

    Poh Hui Chia et al.
    A biallelic missense mutation in the highly conserved, neuron-specific kinase CAMK2A abrogates holoenzyme assembly and causes a new inherited neurodevelopmental disease.
    1. Biochemistry and Chemical Biology

    Ribozyme-catalysed RNA synthesis using triplet building blocks

    James Attwater et al.
    Adopting RNA trinucleotides as substrates, ribozymes can catalyse the copying of structured RNA sequences, allowing self-synthesis by part of a newly evolved symbiotic ribozyme pair.
    1. Microbiology and Infectious Disease

    Discovery and characterization of a prevalent human gut bacterial enzyme sufficient for the inactivation of a family of plant toxins

    Nitzan Koppel et al.
    A unique, widely distributed gut bacterial enzyme selectively metabolizes plant-derived cardiac glycoside drugs.
    1. Developmental Biology

    Ripply2 recruits proteasome complex for Tbx6 degradation to define segment border during murine somitogenesis

    Wei Zhao et al.
    Inducing presomitic mesoderm (PSM)-fated ES cells clarified that Ripply2 directly interacts with Tbx6 and degrades Tbx6 in proteasome-ubiquitin pathway by recruiting the 26S proteasome, which is a PSM-specific event to define the segment border during mouse somitogenesis.
    1. Cell Biology
    2. Neuroscience

    Identification of a critical sulfation in chondroitin that inhibits axonal regeneration

    Craig S Pearson et al.
    4-sulfation at the non-reducing end of chondroitin sulfate glycosaminoglycan chains is essential for inhibition of axonal growth.
    1. Neuroscience

    Preoptic leptin signaling modulates energy balance independent of body temperature regulation

    Sangho Yu et al.
    The preoptic area (POA) regulates distinct metabolic adaptations, via leptin-dependent (fasting-induced hypometabolism and high-fat-diet-induced hypermetabolism), or leptin-independent mechanisms (temperature induced metabolic changes) and thus significantly contributes to body weight homeostasis.
    1. Developmental Biology

    Distinct myocardial lineages break atrial symmetry during cardiogenesis in zebrafish

    Almary Guerra et al.
    A discovery of two previously unknown, molecularly distinct fields of cardiac progenitors in zebrafish provides evidence for cardiac laterality prior to the emergence of cardiac septation and allows novel insights into cardiac development and disease.
    1. Chromosomes and Gene Expression
    2. Computational and Systems Biology

    Computational prediction of CTCF/cohesin-based intra-TAD loops that insulate chromatin contacts and gene expression in mouse liver

    Bryan J Matthews, David J Waxman
    Certain types of 3D chromatin loops are easy to predict from existing or easily obtainable 2D information, which benefits gene expression studies in tissues/cells/organisms without extensive pre-existing 3D information.
    1. Microbiology and Infectious Disease

    Septal secretion of protein A in Staphylococcus aureus requires SecA and lipoteichoic acid synthesis

    Wenqi Yu et al.
    Surface protein precursors traffic to lipoteichoic acid-rich septal membranes of Staphylococcus aureus for cleavage of their YSIRK-GXXS motif signal peptides and SecA-mediated translocation across the plasma membrane.
    1. Microbiology and Infectious Disease
    2. Plant Biology

    The plant-specific transcription factors CBP60g and SARD1 are targeted by a Verticillium secretory protein VdSCP41 to modulate immunity

    Jun Qin et al.
    Genetic and biochemical analyses reveal a virulence mechanism employed by V. dahliae that involves inhibition of the transcription factor activity of CBP60g and SARD1.
    1. Neuroscience

    Autistic traits, but not schizotypy, predict increased weighting of sensory information in Bayesian visual integration

    Povilas Karvelis et al.
    Autistic traits are associated with weaker influence of prior expectations in visual perception, which is due to more precise sensory representations.
    1. Cancer Biology
    2. Immunology and Inflammation

    Tumor-derived CSF-1 induces the NKG2D ligand RAE-1δ on tumor-infiltrating macrophages

    Thornton W Thompson et al.
    Macrophages respond to elevated levels of CSF-1 in tumor micro-environments by expressing a ligand for the NKG2D immunoreceptor.
    1. Neuroscience

    Whole brain comparative anatomy using connectivity blueprints

    Rogier B Mars et al.
    White matter connectivity assessed using diffusion MRI allows one to compare whole-brain organization between different animal species in a quantitative fashion, identifying homologous areas and regions of unique specialization.
    1. Structural Biology and Molecular Biophysics

    Specific Eph receptor-cytoplasmic effector signaling mediated by SAM–SAM domain interactions

    Yue Wang et al.
    Comparative structural studies reveal how the cytoplasmic tails of Eph receptors can differentiate different downstream target proteins via highly specific SAM–SAM domain interactions.
    1. Neuroscience
    2. Structural Biology and Molecular Biophysics

    High-quality ultrastructural preservation using cryofixation for 3D electron microscopy of genetically labeled tissues

    Tin Ki Tsang et al.
    A broadly applicable method that faithfully preserves genetically labeled cellular structures for 3D electron microscopy (EM) and correlated light and electron microscopy (CLEM).
    1. Computational and Systems Biology
    2. Developmental Biology

    The transcriptomic and epigenetic map of vascular quiescence in the continuous lung endothelium

    Katharina Schlereth et al.
    The acquisition of vascular quiescence during transition to adulthood is driven by distinct transcriptional and epigenetic programs of pro- and anti-angiogenic genes, with the most prominent effect on the suppression of TGFß family signaling.
    1. Cell Biology
    2. Plant Biology

    Integration of two RAB5 groups during endosomal transport in plants

    Emi Ito et al.
    Plant-unique RAB5 effector 2 (PUF2) is an effector of plant-unique ARA6, which plays a key role in plant endosomal transport, integrating functions of the two plant RAB5 groups by an unprecedented mechanism.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    G9a regulates temporal preimplantation developmental program and lineage segregation in blastocyst

    Jan J Zylicz et al.
    Loss of a maternally inherited epigenetic modifier leads to establishment of an aberrant regulatory network in preimplantation embryos, developmental delay and destabilisation of cell-fate choices.
    1. Neuroscience

    Downregulation of ribosome biogenesis during early forebrain development

    Kevin F Chau et al.
    Unbiased transcriptome analyses reveal that neural progenitor cells downregulate protein biosynthetic machinery during early forebrain development, and this fundamental process matches proteomic changes in the adjacent cerebrospinal fluid and is regulated in part by MYC.
    1. Biochemistry and Chemical Biology
    2. Cell Biology

    Identification of a transporter complex responsible for the cytosolic entry of nitrogen-containing bisphosphonates

    Zhou Yu et al.
    Identification of a transporter complex comprised of SLC37A3 and ATRAID is required for nitrogen-containing bisphosphonates to enter the cytosol from lysosomes and exert their therapeutic effects on bone.
    1. Structural Biology and Molecular Biophysics

    Structure of a TRPM2 channel in complex with Ca2+ explains unique gating regulation

    Zhe Zhang et al.
    The 3Å structure and correlated functional analysis of the TRPM2 cation channel from Nematostella vectensis shed light on the molecular mechanisms of TRPM2 regulation by intra- and extracellular Ca2+, and of inactivation of human TRPM2.
    1. Genetics and Genomics
    2. Microbiology and Infectious Disease

    Neolithic and medieval virus genomes reveal complex evolution of hepatitis B

    Ben Krause-Kyora et al.
    Ancient hepatitis B virus (HBV) genomes were reconstructed from up to 7000-year-old Stone Age human skeletons, suggesting a long-time complex co-evolution with human populations.
    1. Cell Biology
    2. Developmental Biology

    Somatic clones heterozygous for recessive disease alleles of BMPR1A exhibit unexpected phenotypes in Drosophila

    Takuya Akiyama et al.
    Clonal heterozygosity for recessive disease alleles can elicit unexpected phenotypes in vivo, suggesting a new genetic concept relevant to understanding pathogenesis (deleterious heteromosaicism).
    1. Immunology and Inflammation

    Empty conformers of HLA-B preferentially bind CD8 and regulate CD8+ T cell function

    Jie Geng et al.
    HLA-B*35:01 molecules that are peptide-deficient are thermostable, bind CD8 with higher affinity than their peptide-filled versions, accumulate at immunological synapses and enhance antigen-specific CD8+ T cell immune responses.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    The universally-conserved transcription factor RfaH is recruited to a hairpin structure of the non-template DNA strand

    Philipp K Zuber et al.
    Transcription factors can read out both the sequence and the structure of the non-template DNA strand in the transcription bubble, expanding the repertoire of mechanisms to control transcription.
    1. Chromosomes and Gene Expression
    2. Stem Cells and Regenerative Medicine

    SRSF3 promotes pluripotency through Nanog mRNA export and coordination of the pluripotency gene expression program

    Madara Ratnadiwakara et al.
    RNA-binding protein SRSF3 mediates critical changes in RNA processing of pluripotency genes, which reveals functional consequences of regulated RNA processing during stem cell self-renewal and early development.
    1. Cell Biology

    A novel Cep120-dependent mechanism inhibits centriole maturation in quiescent cells

    Ewelina Betleja et al.
    Cells have evolved a mechanism that actively regulates centriole maturation during quiescence.
    1. Cell Biology
    2. Structural Biology and Molecular Biophysics

    Systematic studies of all PIH proteins in zebrafish reveal their distinct roles in axonemal dynein assembly

    Hiroshi Yamaguchi et al.
    Zebrafish genetics and cryo-electron tomography reveal distinct roles of all vertebrate PIH family proteins in axonemal dynein assembly and cilia/flagella motions, assigning specific dynein subtypes to each PIH protein.
    1. Chromosomes and Gene Expression

    Distinct roles of ATM and ATR in the regulation of ARP8 phosphorylation to prevent chromosome translocations

    Jiying Sun et al.
    ATM plays an important role in maintaining the fidelity of DNA repair through the regulation of ARP8 phosphorylation to prevent the chromosome abnormality.
    1. Neuroscience

    Value generalization in human avoidance learning

    Agnes Norbury et al.
    Individual differences in generalization of aversive value (but not safety information) during human active avoidance learning specifically predict experience of anxiety and intrusive thoughts.
    1. Neuroscience

    The causal role of the somatosensory cortex in prosocial behaviour

    Selene Gallo et al.
    A combination of human imaging and brain stimulation techniques show that the somatosensory cortex is essential to prosocial decision making, by transforming observed pain in accurate perception of others' distress.
    1. Genetics and Genomics

    Determining the genetic basis of anthracycline-cardiotoxicity by molecular response QTL mapping in induced cardiomyocytes

    David A Knowles et al.
    Genetic variants that modulate transcriptomic response to doxorubicin in human iPSC-derived cardiomyocytes are predictive of cardiac damage and in vivo sensitivity to anthracycline cardiotoxicity.
    1. Structural Biology and Molecular Biophysics

    Structure of the human lipid-gated cation channel TRPC3

    Chen Fan et al.
    Cryo-EM structure reveals architecture, lipid-binding sites, and ion-conducting pore of the human TRPC3 cation channel.
    1. Biochemistry and Chemical Biology
    2. Structural Biology and Molecular Biophysics

    Cryo-EM structure of the adenosine A2A receptor coupled to an engineered heterotrimeric G protein

    Javier García-Nafría et al.
    The adenosine A2a receptor couples to the heterotrimeric G protein Gs using both conserved contacts seen in other complexes and, in addition, novel contacts to the beta subunit of the G protein.
    1. Chromosomes and Gene Expression

    Distinct ‘safe zones’ at the nuclear envelope ensure robust replication of heterochromatic chromosome regions

    Hani Ebrahimi et al.
    The nuclear periphery houses compositionally and functionally distinct domains, one of which provides a 'safe zone' for replication and reassembly of heterochromatic genome regions.
    1. Computational and Systems Biology
    2. Structural Biology and Molecular Biophysics

    Linking time-series of single-molecule experiments with molecular dynamics simulations by machine learning

    Yasuhiro Matsunaga, Yuji Sugita
    A general machine learning scheme for integrating time-series data from single-molecule experiments and molecular dynamics simulations is proposed and successfully demonstrated for the folding dynamics of the WW domain.
    1. Neuroscience

    Network oscillation rules imposed by species-specific electrical coupling

    Stefanos Stagkourakis et al.
    An unexpected species difference in electrical coupling of analogous neuroendocrine dopamine neurons in rats and mice reveals a role for gap junction connectivity as a band-pass filter for oscillation frequency in neural networks.
    1. Structural Biology and Molecular Biophysics

    Electron cryo-microscopy structure of the canonical TRPC4 ion channel

    Deivanayagabarathy Vinayagam et al.
    Structural insights into the architecture and functional properties of zebrafish TRPC4 are revealed by high-resolution cryo-EM.
    1. Neuroscience

    5-HT2a receptor in mPFC influences context-guided reconsolidation of object memory in perirhinal cortex

    Juan Facundo Morici et al.
    Serotonin, a neurotransmitter mostly studied in relation with emotions, also plays an important role in the control of episodic memories.
    1. Biochemistry and Chemical Biology
    2. Chromosomes and Gene Expression

    Boosting ATM activity alleviates aging and extends lifespan in a mouse model of progeria

    Minxian Qian et al.
    The ATM-SIRT6 axis integrates the DNA repair machinery to longevity-promoting pathways.
    1. Ecology

    A SLC4 family bicarbonate transporter is critical for intracellular pH regulation and biomineralization in sea urchin embryos

    Marian Y Hu et al.
    Cellular carbon accumulation systems are a fundamental prerequisite for biomineralization to stabilize pH and to supply inorganic carbon for CaCO3 precipitation under changing environmental conditions.
    1. Structural Biology and Molecular Biophysics

    Multivalency regulates activity in an intrinsically disordered transcription factor

    Sarah Clark et al.
    Binding of multiple LC8 copies to the intrinsically disordered region of the transcription factor ASCIZ exemplifies a new and potentially widespread molecular mechanism for negative feedback regulation.
    1. Immunology and Inflammation

    Variant proteins stimulate more IgM+ GC B-cells revealing a mechanism of cross-reactive recognition by antibody memory

    Bronwen R Burton et al.
    Investigation of antibody responses to variant Dengue virus proteins demonstrate new mechanisms that could increase the potential for vaccines to protect against mutable pathogens such as Flu, Dengue and HIV.
    1. Chromosomes and Gene Expression
    2. Developmental Biology

    SET-9 and SET-26 are H3K4me3 readers and play critical roles in germline development and longevity

    Wenke Wang et al.
    Two SET-domain containing proteins regulate H3K4me3 by their binding to H3K4me3 through their PHD domain and directly regulate expression of a subset of genes.
    1. Structural Biology and Molecular Biophysics

    Oligomerization of a molecular chaperone modulates its activity

    Tomohide Saio et al.
    A combined NMR and kinetic study demonstrates how the dynamic transition of a molecular chaperone between different oligomerization states can modulate its activity by altering the binding kinetics and energetics of non-native proteins.
    1. Neuroscience

    Differential inputs to striatal cholinergic and parvalbumin interneurons imply functional distinctions

    Jason R Klug et al.
    A brain-wide mapping of the direct inputs to striatal cholinergic and parvalbumin interneurons reveals connectivity differences and implies their distinct roles in regulating striatal function.
    1. Plant Biology

    Synthetic hormone-responsive transcription factors can monitor and re-program plant development

    Arjun Khakhar et al.
    The hormonal circuitry controlling development in plants can be studied and re-programmed with hormone activated Cas9-based repressors.
    1. Neuroscience

    Combinatorial programming of human neuronal progenitors using magnetically-guided stoichiometric mRNA delivery

    Sayyed M Azimi et al.
    A technology allows rapid screening of vast numbers of transcriptional factor combinatorials on stem cell programming.
    1. Cancer Biology
    2. Cell Biology

    Inhibitor-induced HER2-HER3 heterodimerisation promotes proliferation through a novel dimer interface

    Jeroen Claus et al.
    The clinically approved HER2 inhibitor lapatinib causes HER2 and HER3 kinase domains to dimerise in a non-canonical, symmetric orientation, providing a platform for oligomerisation and predisposing to receptor-driven cell proliferation.
    1. Cell Biology
    2. Developmental Biology

    Temporospatial induction of homeodomain gene cut dictates natural lineage reprogramming

    Ke Xu et al.
    Spatial and temporal cues intersect, likely via enhancer-promoter looping, to turn on a master identity switch that in turn dictates natural lineage reprogramming with high efficiency and temporospatial precision.
    1. Microbiology and Infectious Disease

    Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells

    Emilie Battivelli et al.
    Analysis of HIV integration sites from induced and non-induced latently infected populations reveals the role of genomic localization and chromatin context in the fate of HIV-1 infection and the reversal of viral latency.
    1. Cancer Biology
    2. Cell Biology

    Lymphatic endothelium stimulates melanoma metastasis and invasion via MMP14-dependent Notch3 and β1-integrin activation

    Pirita Pekkonen et al.
    The melanoma cell interaction with lymphatic endothelial cells promotes melanoma metastasis by inducing a reversible switch to invasively sprouting melanoma cells.