The absolute affinities of thousands of variant antibodies are measured in parallel using a combination of cell sorting and high-throughput DNA sequencing.
Alex H Williams, Cian O'Donnell ... Timothy O'Leary
A simple model of active transport in neurons allows intracellular cargo to find sites of demand using only local signals, but predicts long delays in distributing cargo throughout a dendritic tree.
When the neuropeptide orexin is peripherally administered in mice with septic shock, it penetrates the blood-brain barrier and acts in the brain to improve survival through multiple autonomic and neuroendocrine pathways.
James Kolasinski, Tamar R Makin ... Heidi Johansen-Berg
A combination of 7 tesla fMRI and psychophysics revealed the reorganisation of the human somatosensory cortex and changes in tactile perceptual abilities after just 24 hours of altered hand use.
Robert F Levendosky, Anton Sabantsev ... Gregory D Bowman
Oriented hexasomes can be generated using the Widom 601 positioning sequence, which enables straightforward production of nucleosomes with asymmetrically modified H2A/H2B dimers.
The immediate response of the brain to a sudden, harmful drop in oxygen supply is the addition of SUMO proteins to sodium ion channels in neurons, increasing their activity.
Richard J Lindsay, Michael J Kershaw ... Ivana Gudelj
Cooperation theory and a novel synthetic infection system provides a mechanistic understanding of why a seemingly successful disease management strategy can have devastating consequences for infected hosts.
Astrocytes decode temporal interneuron activity and transform inhibitory into excitatory signals that impact excitatory synaptic strength and neuronal circuit function.
Biochemical and cell-based analyses reveal how a non-enveloped virus exploits the chaperone activity of an ER transmembrane protein to penetrate the ER membrane required for successful virus infection.
Pim J Huis in 't Veld, Sadasivam Jeganathan ... Andrea Musacchio
The centromeric protein CENP-T assembles the microtubule-binding interface of kinetochores through direct recruitment of two Ndc80 complexes and indirect recruitment of a third one through the Mis12 complex.
DNA-bound crystal structures of an essential Xer site-specific recombinase from the bacterium Helicobacter pylori reveal how large conformational changes initiate the untangling of chromosomes upon cell division.
Gervasio Batista, Jennifer Leigh Johnson ... Jose L Pena
Behavioral pharmacology and molecular biology reveal a translational control mechanism underlying auditory imprinting and structural plasticity that can be pharmacologically manipulated to reopen the critical period.
Johann Mignolet, Seamus Holden ... Patrick H Viollier
Forward genetics and super-resolution microscopy identifies ZitP as a conserved multifunctional regulator that accumulates at both cell extremities in distinct macromolecular structures to perform different functions in the asymmetric model bacterium Caulobacter crescentus.
Hydrogen-Deuterium exchange experiments show that Ric-8A induces similar dynamic changes in the structure of Gα as G protein-coupled receptors, yet protects a larger surface of the nucleotide-binding Ras domain.
The hepatitis C virus IRES binds and remodels preassembled eukaryotic translation preinitiation complexes, using specific initiation factor protein within a "bacterial-like" mode of initiation that can function in both stressed and unstressed cells.
Specialized fungal pathogen populations infect rice varieties with contrasting immune systems co-cultivated in a traditional agro-system, indicating the relevance of crop diversity to restricting epidemics in the landscape.
Matthieu Bergé, Sébastien Campagne ... Patrick H Viollier
Common ancestries, activities and structural determinants of a modular (bi-)polarization control system encoded in free-living and obligate intracellular α-proteobacteria, including the rickettsial pathogens, are described.
Spontaneous theta oscillations and interneuron-specific phase preferences emerge spontaneously in a full-scale model of the isolated hippocampal CA1 subfield, corroborating and extending recent experimental findings.
Building on previous work (Wilkinson et al, 2016), it is shown that inhibition of RecBCD-induced DNA break repair can be used as a co-antibacterial strategy with quinolones.
Urszula Piskurewicz, Mayumi Iwasaki ... Luis Lopez-Molina
A genomic imprinting program in the endosperm of Arabidopsis mature seeds is dynamically adjusted according to seed dormancy levels and regulates germination.
Residual activity from previous trials in a biophysical decision network model causes biases in choice behavior such that a previous response is more likely to be repeated.
Analyses with genetically engineered mouse models in combination with biochemical approaches reveal a crucial role of the receptor tyrosine kinase Tie2 mediated signals in venogenesis via an Akt mediated regulation of COUP-TFII protein stabilization.
Richard B Cooley, John P O’Donnell, Holger Sondermann
Building on previous work (Chatterjee et al., 2014), the mechanism of coincidence detection in bacterial second messenger signaling across membranes is revealed at a molecular level, providing insight into the regulation of a conserved transmembrane receptor.
Rebecca S Mathew, Antonis Tatarakis ... Danesh Moazed
A fear conditioning-induced miRNA acts in a negative feedback loop that targets vesicle exocytosis and neurotransmitter receptor trafficking, and inhibits memory formation.
A molecular model that provides a framework for interpreting the wealth of functional information obtained on the E. coli F-ATP synthase has been generated using cryo-electron microscopy.
Mitophagy regulates mitochondrial quality and mediates extensive mitochondrial degradation in (patho-)physiological settings and is one of the key components of hypoxic preconditioning which protects the heart from ischemia/reperfusion injury.
A systematic genetic analysis comprising seven genome-wide screens in haploid human cells uncovered new regulatory mechanisms at most levels in the WNT signaling pathway.
Jeremy F Atherton, Eileen L McIver ... Mark D Bevan
In mouse models of Huntington's disease, the subthalamic nucleus, which suppresses movements, also exhibits impaired glutamate homeostasis, NMDA receptor-dependent mitochondrial oxidant stress, firing disruption, and 30% neuronal loss.
Repression of the G protein-coupled chemokine receptor CCR5 enhances MAPK/CREB signaling, long-term potentiation, somatosensory cortical plasticity, and learning and memory, while CCR5 over-activation by viral proteins may contribute to HIV-associated cognitive deficits.
Carbon recovery in Amazonian forests disturbed by selective logging is higher in the Guiana Shield and in the west, and is mainly shaped by the carbon gain of trees that survived the disturbance.
Building on previous work (Fu et al., 2016), we demonstrate the critical role of Sam68 in orchestrating genotoxic stress-initiated NF-κB signaling in the colon and the pathophysiological relevance of Sam68-dependent NF-κB activation in colonic cell survival/recovery from extrinsic DNA damage.
Shahram Jevin Poureetezadi, Christina N Cheng ... Rebecca A Wingert
Prostaglandin synthesis and PGE2 receptor activity are essential for mediating segmentation of renal progenitors during pronephros formation in the zebrafish.
Benjamin Bonneau, Hideaki Ando ... Katsuhiko Mikoshiba
IRBIT and the Bcl-2 homolog Bcl2l10 form a complex at the endoplasmic reticulum that controls Ca2+ signaling, however IRBIT turns into an apoptosis facilitator following stress and inhibits anti-apoptotic activity of Bcl2l10.
De novo transcriptome assembly and comprehensive characterization of gene expression in proliferating cells of regeneration-capable flatworm Macrostomum lignano advance this organism as a powerful model for stem cell research.
Daniel L Kober, Jennifer M Alexander-Brett ... Thomas J Brett
Structural, biophysical, and functional analyses reveal that mutations in TREM2 trigger either misfolding or reduced binding to cell-surface glycosaminoglycans, which segregate with neurodegenerative disease link and highlight a functional surface linked to the pathogenesis of Alzheimer's disease.
Junichi Hachisuka, Kyle M Baumbauer ... Sarah E Ross
A new spinal somatosensory preparation is described which enables fine control of sensory input and the ability to manipulate spinal interneurons while recording from spinal projection neurons.
Heather L Smith, Jennifer N Bourne ... Kristen M Harris
Three-dimensional electron microscopy (3DEM) demonstrates the dependence on presynaptic mitochondria for vesicle mobilization as dendritic spines are silently added at P15 or synapses are silently enlarged in adults after long-term potentiation.
Vladimir Chubanov, Silvia Ferioli ... Thomas Gudermann
Mice deficient in the TRPM6 channel suffer from impaired prenatal development, shortened lifespan, growth deficit and disturbed energy balance due to a defect in epithelial Mg2+ uptake, thus highlighting a pivotal role of TRPM6 in organismal Mg2+ homeostasis.
A catalytically dead paralog activates its cognate enzyme through an allosteric mechanism that combined structural and phylogenomic analysis indicates arose through acquisition of a dimerization domain, suggesting a general model for how complex allostery evolves.
Tuan V Bui, Nicolas Stifani ... Robert M Brownstone
A genetically-defined population of spinal interneurons is reciprocally connected with spinal locomotor circuits and mediates recovery of locomotor function following spinal cord transection.
The response of the peptidergic neurons that control a stereotyped behavior depends on the actions of a triggering neuropeptide, downstream neuropeptides and GABA inhibitory influences.
Aline Jelenkovic, Yoon-Mi Hur ... Karri Silventoinen
Genetic variance of adult human height shows a generally increasing trend across the birth-year cohorts but heritability estimates do not present any clear pattern of secular changes over a century.
Fidelis T Masao, Elgidius B Ichumbaki ... Giorgio Manzi
Bipedal footprints made 3.66 million years ago provide the clearest available evidence to date of the occurrence of marked body size variation in Australopithecus afarensis..
Envel Kerdaffrec, Danièle L Filiault ... Magnus Nordborg
Natural variation for an adaptively important life history trait is largely due to variation at a single, major-effect locus with multiple alleles, demonstrating that not all complex traits are massively polygenic.
Martin L Basch, Rogers M Brown II ... Andrew K Groves
The cochlea deploys two Fringe proteins at exactly the same time and position to regulate a novel mode of Notch signaling that sets the boundary of the organ of Corti, the ear's hearing organ.
A C-type lectin domain protein is an anabolic growth factor that promotes mesenchymal progenitors in the bone marrow to differentiate into bone cells to maintain skeletal bone mass throughout adult life.
Thi-Minh Nguyen, Dietmar Schreiner ... Peter Scheiffele
Interneuron-specific alternative splice variants of the synaptic receptor neurexin are critical for hippocampal network activity and short-term memory.
Andon N Placzek, Gonzalo Viana Di Prisco ... Mauro Costa-Mattioli
Building on previous work (Huang et al., 2016), we show that translational control by p-eIF2α is a defense mechanism that prevents persistent cocaine-induced synaptic synaptic potentiation underlying compulsive drug seeking.
Felipe Trajtenberg, Juan A Imelio ... Alejandro Buschiazzo
The molecular mechanism of switching between phosphotransferase- and phosphatase-competent states in histidine-kinases has been uncovered, through direct crystallographic observation of bona fide complexes between a histidine-kinase and its response regulator from Bacillus subtilise.
Lilia Leisle, Rahul Chadda ... Christopher A Ahern
Cyanine fluorophores are encoded as non-canonical amino acids to produce functional proteins in cell-free translation systems and live cells for single-molecule imaging.
Akt mediated S14 phosphorylation of Id2 augments its protein stability and growth cone localization, promoting growth cone formation and axon growth in the developing neuron and contributing to axon regeneration in the damaged hippocampus slice.
Feedback mechanisms that contribute to the deactivation of the unfolded protein response lead to the dysregulation of mRNA expression during chronic stress in the liver, including that of the critical endoplasmic reticulum chaperone BiP.
Sanchari Bhattacharyya, Shimon Bershtein ... Eugene I Shakhnovich
Weak yet highly species-specific protein-protein interactions enhance the activity of metabolically related enzymes in bacteria at endogenous conditions, but also mean that overexpression of one partner leads to permanent non-physiological complexes and gene dosage toxicity.
Current findings help reconcile the contradictory reports regarding the role of infralimbic cortex in the environmental control of appetitive behavior.
Glutamate derived from thalamo-cortical axons regulates the radial dispersion of interneurons in the developing mouse neocortex by limiting the level of expression of the K/Cl co-transporter KCC2.
David GT Barrett, Sophie Denève, Christian K Machens
Spiking networks compensate the loss of neurons instantaneously, when restoration of excitatory/inhibitory balance becomes equivalent to restoration of functionality.
Zhiyong Yang, Marcus J Robinson ... Christopher D C Allen
The immunoglobulin E (IgE) B cell receptor promotes plasma cell differentiation in the absence of cognate antigen and limits the competitive fitness of IgE+ B cells in germinal centers.
Paul A Clarke, Maria-Jesus Ortiz-Ruiz ... Dirk Wienke
Detailed molecular profiling investigations alongside antitumor testing and tolerability studies in animals suggest caution when considering the clinical development of inhibitors of CDK8 and CDK19, since a clear therapeutic window could not be demonstrated with two structurally distinct, potent and selective prototype drugs.
Crystal structures of a mammalian P2X7 receptor and structure-based functional studies reveal a novel drug-binding site and subtype-specific conformational rearrangements required for channel opening.
Herpes simplex virus evades the immune response by inhibiting the TAP transporter with a peptide inhibitor ICP47 that has an extensive interface at the peptide translocation cavity and locks the transporter in an inactive state.
Activity-regulated genes in Drosophila neurons differ from the well-characterized situation in mammals, and these genes provided a strategy to construct reporters for monitoring neuronal activity in fly brains.
A toxin is used to introduce an otherwise cell-impermeant fluorophore-antibody (or some thing which is equally specific) to bind to an intracellular protein which allows for super resolution imaging and single particle tracking inside the living cell.
Angus Chadwick, Mark CW van Rossum, Matthew F Nolan
A new model for phase precession accounts for theta sequence generation, suggests critical roles for interneurons, and predicts circuit properties to optimise memory storage.
Diverse biophysical properties of β1 and β3 integrin transmembrane and cytoplasmic domains result in distinct mechanisms of integrin activation and function.
Simon Mysling, Kristian Kølby Kristensen ... Michael Ploug
Building on previous work (Mysling et al., 2016), it is shown that angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase activity by catalyzing the unfolding of its hydrolase domain.
Synapse-specific genetic manipulations show that distinct GABAergic inputs are differentially recruited to encode motion direction in the retina in a stimulus-dependent manner.
Tumor-induced myeloid-derived suppressor cells exert systemic suppression of adaptive immunity by limiting L-selectin-directed trafficking of T cells at vascular checkpoints in lymph nodes.
Phase-locking of hippocampal theta and gamma waves has been proposed to support memory formation, but an analysis using robust statistical methods finds no convincing evidence for the phenomenon.
Biochemical dissections show that the Guided Entry of Tail Anchored proteins (GET) pathway selects ER-destined tail-anchored proteins using at least two distinct molecular mechanisms, each recognizing a distinct physicochemical feature in the substrate.
Carsen Stringer, Marius Pachitariu ... Nicholas A Lesica
A new cortical network model fit directly to multi-neuron recordings reveals that local inhibitory feedback can control neural dynamics, modulate brain state and enhance sensory processing.
Pauline Wales, Christian E Schuberth ... Roland Wedlich-Söldner
Calcium influx during acute cell stimulation triggers a global actin reset in mammalian cells, which is linked to plasma membrane repair and transcription and has implications for our understanding of cell migration, cancer, inflammation and cell stress response.
Hanneke Vlaming, Thom M Molenaar ... Fred van Leeuwen
The interrogation of histone modifications on DNA barcodes enables efficient and direct screening for epigenetic regulators in thousands of mutants in parallel.
Serial-section EM analysis uncovers the CNS connectome of a Ciona larva, the second of any entire nervous system, and exposes left-right asymmetries in its synaptic circuits.
The catalytic activity of a Drosophila neprilysin is critical to proper insulin expression and food intake by regulating homeostasis of distinct signaling peptides.
Kristopher McEown, Yohko Takata ... Michael Lazarus
Loss of REM sleep increases sucrose and fat consumption in mice; and inhibiting the prefrontal cortex reverses the increased consumption of sucrose, but not fat, following REM sleep loss.
A structural study reveals how the simian virus 40 Large-T hexamer helicase interacts with its origin DNA and partially melts the origin double-stranded DNA within the hexamer channel.
Felicity Alcock, Phillip J Stansfeld ... Ben C Berks
Evolutionary bioinformatics and experimentation are applied to the components of the Tat protein transport system to elucidate the structure of the membrane-bound receptor complex and to deduce a molecular description for its substrate-triggered activation.
Filamin, by recruiting a signaling complex to the postsynapse, orchestrates the correct formation and growth of postsynaptic membranes and localization of glutamate receptor subunits.
Adult neurogenesis, although happening at a slow rate in the adult brain, plays an important role in learning and memory and has the ability to powerfully modulate large scale neural networks.
Brian W Jones, Jennifer Deem ... G Stanley McKnight
The PKA anchoring protein, AKAP7, localizes PKA in dentate granule mossy fibers and this localization plays an important role in contextual discrimination and cAMP-induced synaptic plasticity.
Fine mapping of transposable element presence/absence variation amongst 216 Arabidopsis strains uncovers widespread novel genetic diversity that underlies differences in transcription and DNA methylation patterns.
The structure, function and mechanism of the malaria vaccine candidate CelTOS reveal a unique pore-forming and membrane-disrupting protein with specificity for the inner leaflet of host and vector cells.
Human cell lines replicate and proliferate without ORC1 or ORC2, two subunits of the replication initiator protein complex ORC, which has till now been considered essential for DNA replication.
Genetic and biochemical approaches identify a new component of the cellular signaling machinery driving migration of limb muscle precursor cells during mouse embryogenesis and reveal the underlying molecular mechanism.
Molecular profiling of annelid myocytes reveals that the last common protostome-deuterostome ancestor already possessed a dual musculature, with visceral smooth muscles ensuring digestion and somatic striated muscles ensuring locomotion.