Martina Riva, Ioana Genescu ... Alessandra Pierani
The complete elimination of a transient superficial population of neurons, and associated immature circuits, is required for the emergence of functional properties in the mature cerebral cortex.
Cdc7 and CK1g1 independently and additively phosphorylate the Chk1-binding domain of claspin to activate replication checkpoint with differential contribution of each kinase in different cell types.
Edwige Michel, Jean Gaudart ... Stanislas Rebaudet
Case-area targeted interventions conducted by rapid response teams appeared significantly effective to mitigate and shorten local cholera outbreaks in the Centre department of Haiti in 2015-2017.
Nicole Poweleit, Nadine Czudnochowski ... Oren S Rosenberg
The structure of the endogenous ESX-3 secretion system reveals a highly coordinated inner membrane complex and suggests a mechanism for the regulated secretion of ESX substrates.
The structure of the yeast RSC complex, a member of the SWI/SNF chromatin remodeling family, determined by cryo-electron microscopy, reveals a conserved structural core and the mode of nucleosome engagement.
The structure of the mechanosensitive channel MscS embedded in a lipid bilayer redefines the nature, location and importance of lipid–protein interactions in the gating of mechanosensitive channels.
Valerio Francioni, Zahid Padamsey, Nathalie L Rochefort
Layer 5 neuron apical tuft in mouse visual cortex display widespread, highly correlated calcium signals, with a strong and asymmetric coupling to somatic signals, independent of visual stimulation and locomotion.
Benjamin A Clarke, Saurav Majumder ... Richard L Proia
The ORMDL proteins function to restrain the de novo sphingolipid biosynthetic pathway during myelination, when there is a high demand for sphingolipids to prevent excessive accumulation of metabolic intermediates.
Luis V Nobre, Katie Nightingale ... Michael P Weekes
The human cytomegalovirus (HCMV) interactome systematically characterises high-confidence viral-viral and viral-host protein interactions in HCMV-infected cells, facilitating multiple novel insights into HCMV and herpesviral function.
When pioneer metastatic cells enter a sentinel lymph node through afferent lymphatics subcapsular sinus, macrophages provide them soil to proliferate and colonize lymph node.
Andrew G Marshall, Manohar L Sharma ... Francis P McGlone
Pleasant touch perception in humans is unaffected by spinothalamic disruption indicating integrated spinal processing of hedonic and discriminative tactile inputs rather than privileged C-tactile-lamina I-spinothalamic projections.
Client protein-driven reversal of endoplasmic reticulum chaperone (BiP) mediated-repression is revealed as a principal component of the regulation of the unfolded protein response transducer IRE1 in cells.
Pascal Branchereau, Elodie Martin ... Daniel Cattaert
Electrophysiological and simulation approaches show that a chloride-related longer relaxation of the inhibitory synaptic events partially compensates the early defect in the chloride homeostasis detected in fetal SOD spinal motoneurons.
Generation of a premotor/motor neuron comprehensive TEM reconstruction, functional optogenetics, and recurrent network modeling reveals different phase relationships among a subset of Drosophila motor neurons in forward versus backward locomotion.
Alec K Gramann, Arvind M Venkatesan ... Craig J Ceol
The oncogenic role ligand-dependent BMP signaling plays in suppressing differentiation in melanoma is a reiteration of its physiological roles during melanocyte development.
Hessel Honkoop, Dennis EM de Bakker ... Jeroen Bakkers
Single-cell RNA sequencing reveals Nrg1/ErbB2-induced metabolic reprogramming as a pivotal event for cardiomyocyte proliferation during heart regeneration.
Eva Harde, LaShae Nicholson ... Amparo Acker-Palmer
The internalization of the angiogenic receptor VEGFR2 expressed in neurons is controlled by ephrinB2 and is required for neuronal dendritic arborization, spine morphogenesis and circuitry development in the hippocampus.
Homology of vertebrate skull structures should be based on evolutionary continuity and an appreciation of germ layer origins and inductive signaling in the embryonic head.
Self-reactive thymocyte death is most efficient when peptide-presenting cells are phagocytic, and blocking phagocytosis inhibits self-reactive thymocyte death, suggesting that phagocytes play central roles during thymocyte negative selection.
Sachiko Murase, Dan Winkowski ... Elizabeth M Quinlan
Dark exposure lowers the MMP9 activation threshold, and subsequent light stimulation to an amblyopic eye is sufficient to induce proteolysis at thalamo-cortical synapses in deprived mouse visual cortex.
Human cullin-RING ligases are buffered to a much greater extent than had been previously appreciated, and the roles of ubiquitin chain extension enzymes are far more nuanced at physiological concentrations.
Aleksandra Shcherbakova, Matthias Preller ... Hans Bakker
C-mannosylation supports native folding of thrombospondin type 1 repeats in the endoplasmic reticulum and stabilizes the folded proteins by modulating the dynamics of the tryptophan-arginine ladder.
Fabian Pallasdies, Sven Goedeke ... Raoul-Martin Memmesheimer
A multiscale computational nerve net model describes how the activity of individual neurons controls the swimming motion of a jellyfish in its hydrodynamic environment.
Jakub Tomek, Alfonso Bueno-Orovio ... Blanca Rodriguez
A computer model of human cardiomyocyte was produced and validated on independent datasets, overcoming shortcomings of its predecessors, also yielding broadly relevant insights and results on major ionic currents.
Acute knock down of Sgce that is mutated in Myoclonus Dystonia (DYT11), in the cerebellum of mice, leads to dystonia and myoclonus-like motor signs that like patients improve with alcohol.
Celso M Teixeira-Duarte, Fátima Fonseca, João H Morais-Cabral
Cations are essential cofactors in the ATP activation mechanism of the KtrAB cation channel and appear to be cofactors of many other nucleotide-dependent RCK domains.
Georgia Panagiotakos, Christos Haveles ... Ricardo E Dolmetsch
The Timothy syndrome mutation in Cav1.2 gives rise to defects in neuronal differentiation by preventing a developmental switch in channel splicing and elevating calcium signaling in differentiating cells.
Single molecular imaging of MeCP2 at high spatial/temporal resolution identifies distinct structural domains contributing to its dynamic behaviors and chromatin interactions in live neurons.
The pseudoenzyme CPT1C is able to sense changes in intracellular malonyl-CoA levels caused by nutrients or energy stress and regulate late endosomes/lysosomes anterograde transport, necessary for proper axon growth.
Identifying FMRP-bound mRNAs in hippocampal CA1 pyramidal neurons reveals cell-type specific regulation of autism-candidate and circadian mRNAs and FMRP-mediated control of memory across the circadian cycle.
B Semihcan Sermet, Pavel Truschow ... Carl CH Petersen
Two distinct thalamocortical pathways were found to provide differential excitatory synaptic input to distinct cell-types across layers of mouse primary somatosensory barrel cortex.
The first successful de novo design of a homo-trimeric protein that binds a C3 symmetric small molecule larger than a metal ion is an advance for computational protein design.
Io Nam Wong, Jacqueline PS Neo ... Matthew C Whitby
Genomic deletions formed from inter-fork strand annealing associated with a collapsed replication fork are suppressed by the FANCM-related DNA helicase Fml1 in conjunction with its partner proteins Mhf1 and Mhf2.
The main proteins of clathrin-mediated endocytosis bind and unbind rapidly, continuously turning over about five times during the formation of an endocytic vesicle in yeast.
Sander AL Palit, Daniel Vis ... Michiel S van der Heijden
A mechanistic link between TLE3 loss and glucocorticoid receptor-mediated androgen receptor inhibitor resistance supports the rationale to target GR during anti-hormonal treatment in castrate-resistant prostate cancer.
Giardia, a multi-ciliated parasitic protist, maintains four different flagellar lengths by balancing flagellar length-independent IFT-mediated assembly with length-dependent kinesin-13 mediated disassembly.
Oscar Woolnough, Kiefer James Forseth ... Nitin Tandon
Direct insular recordings in humans reveal that contrary to several prominent models of speech production, it is not engaged in pre-articulatory planning, but in auditory and somatosensory components of speech.
Contrary to previous findings, class A GPCRs share a common activation pathway that directly links ligand binding to G-protein activation, as revealed by novel quantitative analysis.
Wenchang Zhou, Giacomo Fiorin ... José D Faraldo-Gómez
The conformational mechanism of a transporter protein is found to have profound and energetically costly effects on the morphology of the surrounding membrane.
Jennifer L Cook, Jennifer C Swart ... Roshan Cools
A human psychopharmacology study reveals that a drug that affects the dopamine and noradrenaline systems enhances people's ability to adapt their learning rate to suit the volatility of the environment.
Just 2-4 follicle stem cells maintain each follicle epithelium in the Drosophila ovary, and they reside within a single ring at the anterior edge of the tissue.
Michael Morse, M Nabuan Naufer ... Mark C Williams
APOBEC3G, an anti-viral protein with the capability to inhibit HiV-1 infectivity, binds single stranded DNA in multiple physical conformations, enabling complex interactions that allow APOBEC3G to perform multiple diverse functions.
The conductance-based encoding model creates a new bridge between statistical models and biophysical models of neurons, and infers visually-evoked excitatory and inhibitory synaptic conductances from spike trains in macaque retina.
Martina R Laidemitt, Larissa C Anderson ... Eric S Loker
Interactions among parasites in snails create cascading effects on their transmission and highlight that biodiversity has complex, context-dependent and important effects on human schistosomiasis transmission dynamics.
Anwesha Chaudhury, Geoff D Miller ... John M Higgins
Unsteady state modeling of blood cell populations reveals that blood loss triggers a cellular clearance delay and a cellular production increase, and modeling provides earlier detection and individualized patient characterization.
Céline Portal, Panteleimos Rompolas ... Carlo Iomini
Primary cilia of neural crest-derived cells mediate Indian hedgehog-induced signal transduction in the periocular mesenchyme and are required for normal anterior segment development.
Nathan R Johnson, Claude W dePamphilis, Michael J Axtell
Superfamilies of trans-species small RNAs from the parasitic plant Cuscuta have sequence variation that correspond to synonymous site variation in host plant target mRNAs.
Joseph Crispell, Clare H Benton ... Rowland Raymond Kao
Analyses combining genomic and epidemiological data of Mycobacterium bovis, which causes bovine tuberculosis, revealed evidence of transmission within and between cattle and badger populations.
Functional hypoconnectivity between ‘social brain’ default mode circuitry and visual association cortex underpins a subtype of autistic toddlers with a strong preference to attend to the non-social visual world.
Cell-based high-throughput screening identifies IBT21 as a chemical chaperone, that inhibits ER protein aggregation and prevents the cell death caused by a proteotoxin, the aggregation-prone prion protein.
Salvatore Assenza, Alberto Stefano Sassi ... Alessandro Barducci
A multiscale modeling approach reveals how the energy from ATP hydrolysis is used by Hsp70 chaperones to remodel the conformation of their substrates through a novel force-generating mechanism.
Satyam P Srivastav, Reazur Rahman ... Nelson C Lau
A female fertility syndrome in Drosophila called gonadal dysgenesis is caused by the P-transposase actively mobilizing a very short P-element variant that has been named the Har-P.
Norihiro Yamaguchi, Ethan M Weinberg ... Sohail F Tavazoie
The gluconeogenic enzyme PCK1 and pyrimidine nucleotide biosynthetic enzyme DHODH drive hypoxic pyrimidine nucleotide biosynthesis and liver metastatic colonization in colorectal cancer, which is therapeutically exploitable by DHODH pharmacologic inhibition.
Ribosome production is unexpectedly integrated into innate cell-intrinsic responses that regulate double strand DNA-sensing and inflammatory cytokine induction in infected and uninfected cells.
Tina B Lonsdorf, Maren Klingelhöfer-Jens ... Christian J Merz
Exclusion of participants in tasks with a learning element can introduce substantial bias and needs to be carefully considered and transparently reported and justified.
Cryo-electron microscopy structures, combined with biochemical experiments, show how the E. coli F element-encoded TraR protein regulates transcription initiation by altering RNA polymerase conformation and conformational heterogeneity.
Inspiratory rhythmogenesis is mediated by an emergent mechanism independent of bursts associated with motor output and is modulated by opioids, pointing to strategies for ameliorating opioid-induced respiratory depression.
In small cell lung cancer, the transition from a neuroendocrine state to a more neuronal state endows these cancer cells with increased migration and metastatic potential.
Kendall J Lough, Kevin M Byrd ... Scott E Williams
Telophase reorientation corrects errors in spindle orientation that persist after imprecise initial spindle positioning during early mitosis, and contributes to balancing self-renewal with differentiation during epidermal development.
Emilie Auxerre-Plantié, Masayuki Nakamori ... Krzysztof Jagla
Drosophila DM1 models suggest that elevated cardiac expression of straightjacket/α2δ3, a regulatory subunit of voltage-gated calcium channel, contributes to cardiac conduction defects in DM1.
Quantitative comparison of clathrin-mediated endocytosis in budding and fission yeast identified conserved mechanisms and species-specific adaptations with broad implications that extend from yeast to humans.
Roger Pique-Regi, Roberto Romero ... Nardhy Gomez-Lopez
Parturition gene regulation across multiple cell-types and placental compartments is deciphered at single cell resolution, highlighting the common role of the NFKB pathway in both term and preterm birth.
Low-field single-sided magnetic resonance diffusion methods detect and measure permeability of sub-micron compartments which likely include cell processes, organelles, and cellular vesicles within ex vivo mouse spinal cords.
InSyn1 is a new inhibitory post-synaptic protein that is essential for the dystroglycan complex, neuronal activity in vitro and in vivo, and cognitive behavior.
Kaushikaram Subramanian, Martin Weigert ... Moritz Kreysing
Establishing retinal contrast transmission as a novel determinant of mammalian fitness, this research adds functional significance to a prominent exception of nuclear organization, previously described in nocturnal rod photoreceptor cells.
Flavio H Beraldo, Daniel Palmer ... Marco AM Prado
Comprehensive dataset of high-level cognitive assessment in mouse models of neurodegeneration, accompanied by an open-access database/repository to change the paradigm of how cognitive studies in animal models can be shared/re-used.
Restoring locomotion after complete spinal cord injury does not require locomotor training, only the return of sufficient excitability within neurons of the spinal cord.
Jacob M Garrigues, Brian V Tsu ... Amy E Pasquinelli
Helitron transposable elements, by providing high density transcription factor binding sites upstream of host genes, have diversified the heat shock response within and among Caenorhabditis species.
In the orbitofrontal cortex, mTORC1, a multiprotein complex centered around the kinase mTOR, contributes to the development and/or maintenance of habitual alcohol seeking.
By performing 15N pulse-labeling of mice, the turnover of hundreds of proteins in eye tissues was measured by mass spectrometry that revealed long-lived metabolic enzymes in the lens.
Christian Damsgaard, Henrik Lauridsen ... Mark Bayley
Multiple respiratory and vascular mechanisms have recurrently evolved across the vertebrates to alleviate the oxygen diffusion limitations inherent to the morphology of the retina.
Jean-André Lapart, Marco Gottardo ... Bénédicte Durand
Genetic analyses in Drosophila establish the functional hierarchy of the ciliary transition zone module, Dzip1/Fam92/Cby, and reveal tissue specific variations in basal body anchoring pathways in fly ciliated tissues.
The momentary levels of local cortical desynchronization and pupil-linked arousal pose dissociable influences not only on the processing of sensory information but also on human perceptual performance.
Isa Kristina Kirk, Christian Simon ... Søren Brunak
Text mining of complete EHRs for 14,017 diabetes patients and subsequent clustering led to phenotypically deep clusters, showing distinct glycemic profiles, comorbidities, and SNP association patterns.
Identification of viral and host determinants of broadly neutralizing antibodies targeting a new epitope on dengue virus that can be used to guide vaccine design.
Sergey D Stavisky, Francis R Willett ... Jaimie M Henderson
Neurons in human dorsal motor cortex, an area involved in controlling arm and hand movements, are also active – and show similar ensemble dynamics – during speaking.
The structures of Slo1 in complex with b4 imply that the auxiliary beta subunits modulate the channel's gating properties through stabilizing ‘pre-existing’ conformations rather than creating new ones.
Sequential phosphorylation of NDEL1 Ser336/Ser332 by DYRK2 and GSK3β is a novel regulatory step for actin dynamics that contributes to the neurite outgrowth and neuronal arborization in the developing brain.
Ricardo Guerrero-Ferreira, Nicholas MI Taylor ... Henning Stahlberg
Two new polymorphic structures of recombinant human alpha-synuclein fibrils show striking differences to previous structures, while familial PD mutation sites remain crucial for protofilament interaction and fibril stability.
Ryoji Amamoto, Mauricio D Garcia ... Constance L Cepko
Probe-Seq is a cell type specific bulk RNA sequencing method that can be applied to a wide-ranging tissue types from both vertebrates and invertebrates without genetic labeling.
Andrew B Morgenthaler, Wallis R Kinney ... Shelley D Copley
Mutations elsewhere in the genome play critical roles in improving fitness during amplification and divergence of a gene encoding a weak-link enzyme whose inefficiency limits growth rate.
In mouse cardiomyocytes, (lymph)angiogenic growth factors are induced during early hypoxia by a translational mechanism involving a new IRES trans-acting factor, vasohibin-1.
Joana B Pereira, Rik Ossenkoppele ... Oskar Hansson
The amyloid patterns overlap with the default-mode network, whereas the tau patterns overlap with distinct functional networks and are associated with a loss of anatomical connectivity and multiple cognitive functions.
Despite BCAAs being de novo-synthesized in chloroplasts, TOR activation by BCAAs is conserved in plants and triggers a re-organization of actin and actin-associated endomembranes.
Three-dimensional imaging was used to identify structural and quantitative features of developing lymphatics in the kidneys of mice, humans and in a genetic mouse model of polycystic kidney disease.
A computational model, based on single-cell features like contractility and polarizability, quantitatively describes cellular dynamics from the single cell level up to small cohorts and confluent tissues.
Human chromosome-microtubule attachments are stabilised by Astrin-mediated dynamic delivery of PP1 phosphatase to the attachment site, which ensures the normal segregation of chromosomes.
Pim J Huis in 't Veld, Vladimir A Volkov ... Marileen Dogterom
Binding of two macromolecular complexes allows kinetochores to capture force produced by the depolymerising ends of microtubules, allowing chromosomes to be transmitted from a mother cell to its two daughters.
Raffaele Tucciarelli, Moritz Wurm ... Angelika Lingnau
Representational similarity analysis of human functional magnetic resonance imaging data demonstrates that the lateral occipitotemporal cortex represents action knowledge along dimensions that are in accordance with behavioural judgements.
The structural and mechanistic characterization of competitive inhibition of human DMT1 offers a promising route for the development of compounds for the treatment of iron overload disorders.
Constraint-based modelling predicts C4 photosynthesis evolves under resource limitation from an ancestral ground state of C3 photosynthesis and attributes divergent metabolic routes in extant C4 subtypes to light.
George Khelashvili, Neha Chauhan ... Anant K Menon
The capture and export of a hydrophobic sterol molecule from the binding pocket of a Lam/GramD1 sterol-binding protein is unexpectedly mediated by water.
Enteroendocrine cells sense nutrients in the gut and regulate digestive physiology but are rendered insensitive following fat ingestion due to alteration of gut microbiota.
Intravital imaging with HIV-1 viral-like particle in mouse model reveals a mechanism for HIV-1 uptake by subcapsular sinus macrophages that facilitates HIV-1 spreading tofollicular dendritic and B cells.
Tim A Crombie, Stefan Zdraljevic ... Erik C Andersen
Hawaiian Caenorhabditis elegans harbor high levels of genetic diversity that might represent the complex patterns of ancestral diversity in the species prior to human influence.
Helena Brezovjakova, Chris Tomlinson ... Vania MM Braga
Junction Mapper is a powerful new semi-automated software that provides a fingerprint of cell–cell contact morphometry and receptor density alterations.
King Faisal Yambire, Christine Rostosky ... Nuno Raimundo
Impaired lysosomal acidification results in retention of iron inside lysosomes, triggering functional iron deficiency, dysfunctional mitochondria (especially mtDNA loss), and inflammation in vivo in a mouse model of lysosomal disease.
Sara Garbarino, Marco Lorenzi ... Daniel C Alexander
Computational-driven, imaging-based topological profiles of neurodegeneration differ substantially in different neurodegenerative conditions, suggesting distinct modes of dependence of the pathological spread on the underlying connectivity.
Sepsis-induced long-term muscle weakness was reproduced using a refined murine model, which was accompanied by mitochondrial dysfunction in the absence of sustained atrophy, suggesting the promise of mitochondria-targeted post-sepsis therapies.
Colonisation with resistant Klebsiella pneumoniae in a Cambodian neonatal unit is driven by person-to-person transmission, transmissibility varies by sequence type, and antibiotic consumption generally increases the risk of acquisition.
Cynthia B Silveira, Antoni Luque ... Forest Rohwer
Coral reef heterotrophic bacteria and fleshy macroalgae cause oxygen loss from reef systems through microbial biomass accumulation and ebullition from algae surfaces.
Raphael M Bendriem, Shawn Singh ... M Elizabeth Ross
That early cortical neural progenitor divisions strictly require OCLN isoform expression is a paradigm shift in the functional consideration of this protein best known for promoting between-cell barrier functions.
Andrew R McKinstry-Wu, Andrzej Z Wasilczuk ... Alexander Proekt
Responses to anesthetics differ among individuals and fluctuate stochastically despite constant drug concentration, however, the amount of noise driving transitions between the responsive and the unresponsive state is conserved.
OCT4 and SOX2 display partially independent activity to regulate chromatin accessibility, and highly dynamic activity of OCT4 is required throughout the cell cycle to maintain pluripotency enhancer accessibility.
Rita A Batista, Jordi Moreno-Romero ... Claudia Köhler
Jumping of transposable elements provides DNA-binding sites for the MADS-box transcription factor PHERES1, allowing the regulation of imprinted genes and other key endosperm development genes.
The ES6S region of the small subunit ribosome makes a place for the threading and secondary structure unwinding of mRNA, which regulates genome-wide translation.
Hyung Suk Oh, Werner M Neuhausser ... David M Knipe
CRISPR genome editing technology can efficiently introduce mutations into lytic and latent HSV genomes to block lytic replication and reactivation of latent herpes simplex virus genome though differential mechanisms.
Judith Hagenbuchner, Veronika Obsilova ... Michael J Ausserlechner
The mode of binding and cellular effect of the first FOXO3-DNA-binding-domain targeting small compound discovered by a combined pharmacophore-based/biochemical screening approach is reported.
Stanislao Igor Travisano, Vera Lucia Oliveira ... José Luis de la Pompa
Notch ligands Jag1 and Dll4 and their effector Ephb2 are required in sinus venosus endocardium for primitive coronary vasculature formation and later for arterial differentiation and maturation of coronary endothelium.
