Gareth W Fearnley, Katherine A Young ... Hayley J Sharpe
Systematic proteomic approaches identify several cell junction regulators as substrates for the homophilic receptor tyrosine phosphatase PTPRK and implicate its pseudophosphatase domain in substrate recognition.
Pia Schröder, Timo Torsten Schmidt, Felix Blankenburg
Neural correlates of somatosensory target detection are restricted to secondary somatosensory cortex, whereas activity in insular, cingulate, and motor regions reflects stimulus uncertainty and overt reports.
Optical recordings reveal previously unknown neuromodulator dynamics in the striatum during animal movements that suggest a new interpretation of the underpinnings of bradykinetic movements exhibited in Parkinson's Disease patients.
Linda V Sinclair, Andrew JM Howden ... Doreen A Cantrell
Antigen receptor control of methionine transport is critical to co-ordinate protein synthesis and the production of methyl donors for nucleotide and protein methylations which are required for T cell differentiation.
Cryo-EM structures of RNA polymerase I reveal considerable 'transformers-like' rearrangements where one subcomplex dissociates and is replaced by one domain of another subunit, possibly as an additional layer of transcriptional control.
Comprehensive scRNA-seq analysis of cardiac stromal cells in healthy and injured hearts reveals novel cell types and non-linear cell dynamics, providing new insights into cardiac inflammation, fibrosis and repair.
A cell-cell contact between microglial SIRPα and CD47 on neighboring cells is a critical module for phase conversion of microglia in the brain white matter and controls demyelination.
Unique heterochrony in the cranial segments in bichirs triggers the early formation of their external gills, and might be informative about developmental mechanisms facilitating increased breathing capacity.
Katarina Valoskova, Julia Biebl ... Daria E Siekhaus
T antigen glycosylation, which marks metastatic cancer cells, is modulated on a small set of proteins by a conserved multipass transmembrane protein to allow tissue invasion by Drosophila macrophages.
Mayumi Iwasaki, Lena Hyvärinen ... Luis Lopez-Molina
Seed-specific and cold-induced DNA methylation is deposited in the seed progeny to form a transient and transgenerational memory of past environmental conditions to optimize seed germination timing.
Meghna Sobti, Robert Ishmukhametov ... Alastair G Stewart
Cryo-EM studies reveal that incubation with ATP produces conformational intermediates of E. coli ATP synthase, in which the ε subunit is no longer in its autoinhibitory conformation.
Development and application of highly sensitive in situ transcriptomics method, Flura-seq, in identifying dynamic organ-specific transcriptomes in early stage breast cancer metastasis have been described.
Erika Tsingos, Burkhard Höckendorf ... Joachim Wittbrodt
3D niche topology imposes a spatially biased random stem cell loss, which is differentially fine-tuned in neural retina and retinal pigmented epithelium to regulate growth, shape, and cellular topology.
M Catarina Silva, Fleur M Ferguson ... Stephen J Haggarty
A new Cereblon-recruiting bifunctional tau ligand, QC-01-175, promotes aberrant tau degradation and rescue of stress vulnerability in human neuronal cell models of tauopathy.
Simone Lieb, Silvia Blaha-Ostermann ... Simon Wöhrle
Targeting Werner syndrome helicase might constitute a novel opportunity for the treatment of a clinically defined subset of patients harboring MSI-H/MMR-deficient tumors.
Julene Madariaga-Marcos, Cesar L Pastrana ... Fernando Moreno-Herrero
A single-molecule biophysical approach reveals that the C-terminal domain of ParB blocks ParB network formation by heterodimerization with the full-length protein, which remains bound to the DNA.
C Joseph Burnett, Samuel C Funderburk ... Michael J Krashes
A rich behavioral data set reveals the complex interactions and influence motivational systems have on one another, driving competition and optimal expression of behavior.
Computational modeling motivated by recent experiments clarifies biophysical mechanisms generating the rhythm and amplitude of breathing at the level of neurons and brain circuits in mammals.
Enhanced hippocampal-cortical network communication during memory retrieval flexibly tracks the quality and content of memories for complex past events.
Marijn de Boer, Giorgos Gouridis ... Thorben Cordes
Selective import via bacterial ABC importers is facilitated by a hitherto unrecognized complexity in the conformational dynamics of the substrate-binding proteins.
The zinc finger protein Nerfin-1 represses the transcriptional output of Hippo signaling in cell competition by binding to the TEA DNA-binding domain of Scalloped.
Austin D Hocker, Sarah A Beyeler ... Adrianne G Huxtable
A single neonatal inflammatory event induces long-term impairments in two forms of adult respiratory motor plasticity, an important aspect of the control of breathing for compensation after injury or disease.
Suparna Ray, Miriam I Rosenberg ... François Payre
mille-pattes micropeptides have conserved function in insect embryonic patterning together with transcription factor Shaven-baby and ubiquitin ligase Ubr3, except in flies wherein restoring broad embryonic Svb expression restores patterning potency.
Mashaal Sohail, Robert M Maier ... Shamil R Sunyaev
Polygenic selection signals in humans estimated from previously existing GWAS should be viewed with caution due to concerns about residual population stratification.
Wenli Dai, Brigitte Laforest ... Christopher R Weber
TBX5-loss associated cardiomyocyte ectopy and atrial fibrillation is prevented by augmentation of SERCA2 activity, establishing a mechanism underlying the genetic basis for a Ca2+-dependent pathway for AF risk.
OptoGranules reveal the function of G3BP1 as a stress granule scaffold and demonstrate that protracted stress granule assembly is sufficient to drive neurodegeneration and the evolution of ALS-FTD pathology.
Gestational age estimation models derived from newborn screening bloodspot samples are effective on data obtained from both heel prick and cord blood samples in low-resource settings.
For the first time in a mosquito species an initial Y chromosome signal has been shown to regulate dosage compensation by increasing X chromosome gene expression.
Benjamin T Donovan, Hengye Chen ... Michael G Poirier
The budding yeast transcription factors Reb1 and Cbf1 function as pioneer factors by slowly dissociating from nucleosomes, allowing them to target and unwrap nucleosomes efficiently to regulate transcription.
Natural step-to-step variations show how human running is stabilized, underscoring the importance of center of mass control and showing how humans run without falling despite muscle noise and uneven terrain.
The consolidation of newly acquired motor skills induces a functional reorganization of sequential information representations within secondary motor cortex, basal ganglia and hippocampus.
Subtypes of dendrite-targeting somatostatin cells segregate into separate networks by specifically connecting with neurons in different layers, forming circuits that could independently control different input pathways to the neocortex.
Jochem van Kempen, Gerard M Loughnane ... Mark A Bellgrove
A direct relationship between pupil diameter and electrophysiological correlates of attention, sensory stimulus processing and target detection was observed demonstrating that arousal has a substantial influence on perceptual decision-making.
The SNAP-25 linker acts as a functional component of SNARE complexes, initially facilitating SNARE interactions and later promoting fusion triggering and pore evolution by local membrane contacts.
Humans and other animals have different strategies for extracting the pitch of sounds, potentially driven by the species-specific frequency selectivity of the ear.
Karine Casier, Valérie Delmarre ... Antoine Boivin
Activation of a piRNA cluster is achieved by high temperature and without maternal inheritance of homologous piRNAs highlighting how variations of species natural habitat can become heritable and shape epigenome.
Patrick D Cherry, Sally E Peach, Jay R Hesselberth
RNA decay is used at multiple points in the budding yeast unfolded protein response to regulate its suppression and activation, and possibly its attenuation.
The extent of (proteotoxic) endoplasmic reticulum stress, and the ensuing unfolded protein response activation, are commensurate with the extent of the chaperone BiP being sequestered by its client proteins.
In Caenorhabditis elegans histone methylation (H3K9me3) controls the synthesis of heritable small RNAs in a gene-specific manner and thus enables 'flagging' of newly-acquired genes.
Angelika Manhart, Téa Aleksandra Icheva ... Alex Mogilner
Cells are able to control the actin network length and steering by adjusting geometric, structural, or biochemical parameters such as ADF/Cofilin and actin concentrations, and network width.
Shahrzad Kharabian Masouleh, Simon B Eickhoff ... Alzheimer's Disease Neuroimaging Initiative
Empirical evaluations demonstrate the low probability of finding and replicating significant associations between psychological tests and brain structure in healthy adults, highlighting the importance out-of-sample replication of exploratory findings.
Nils Rademacher, Benno Kuropka ... Sarah A Shoichet
Binding of ligands to PSD-95 PDZ domains induces a conformational change within the C-terminal domain module that enables differential binding to synaptic interactors.
Lipid efflux by the retinal pigment epithelium is crucial for proper retinal integrity and function, and its impairment may contribute to diseases like age-related macular degeneration.
Rolf M Schmidt, Julia P Schessner ... Sebastian Schuck
Endoplasmic reticulum stress in yeast activates not only the UPR but also Rpn4, promoting the clearance of misfolded proteins from the cytosol as part of a modular cross-compartment stress response.
In vivo recordings and computational modeling of the electrosensory lobe of mormyrid fish provide a circuit-level description of how learning generalizes to new situations.
Cryo-EM structures of human TPC2 channel in the ligand-bound and apo states reveal the structural mechanism of PI(3,5)P2 lipid regulated gating of TPC2.
Faithful models of RMC require SMARCB1 loss for survival, and genetic and small-molecule screens identify inhibition of the ubiquitin-proteasome system (UPS) as a potential therapeutic approach for SMARCB1 deficient cancers.
The structure of human transcription factor IIH, a critical DNA repair and transcription initiation factor, has been determined by cryo-electron microscopy.
A multipartite virus functionally spreads its distinct genome segments in distinct individual cells of the host plant, and complementation of the viral genes across cells allows a pluricellular infection cycle.
Qian Liu, Elizabeth J Osterlund ... David William Andrews
The pro-apoptotic BH3-protein Bim contains two distinct binding sites for anti-apoptotic proteins that together confer resistance of Bim/Bcl-2 and Bim/Bcl-XL complexes to BH3-mimetic drugs under development for use in humans.
Mirko Francesconi, Bruno Di Stefano ... Thomas Graf
Variation in efficiency, speed and path during transdifferentiation and reprogramming originates from two pre-B cell subpopulations with reciprocal propensity towards each fate conversion.
Adi Naamati, James C Williamson ... Nicholas J Matheson
Identification and characterisation of proteins and processes regulated by HIV in primary human CD4+ T cells using an HIV reporter virus for one-step, antibody-free magnetic selection.
A 3D model captures the growth and expansion dynamics of bacterial colonies, revealing distinct effects of surface tension, mechanical forces, and nutrients on the speed of radial and vertical expansion.
Lateral habenula neurons participate in motivated behavior via their activation by negative affective stimuli, a major source of which arises from the rostral entopeduncular nucleus.
Epidermal cells in vertebrates and invertebrates ensheath portions of somatosensory neurons via a conserved morphogenetic mechanism, and this ensheathment regulates morphogenesis and function of Drosophila nociceptive neurons.
Mechanical instabilities are shown to underlie the development of bacterial biofilm morphology, suggesting an ancient origin for mechano-morphogenesis, which is known to drive developmental processes in tissues in higher organisms.
Single-unit activity in the ventrolateral periaqueductal gray, a brain region implicated in organizing fear output, is found to reflect threat probability, a more versatile threat signal.
Dynamic calcium activity in the hippocampus changes markedly across behavioral and physiological states and depends on muscarinic acetylcholine receptor activation.
Blake W Tye, Nicoletta Commins ... L Stirling Churchman
Rapidly proliferating cells are at risk of compromised cell fitness due to proteostasis collapse from perturbations that interfere with ribosome biogenesis.
Cloning-free 3Cs technology is developed for the generation of sequence-bias-free covalently closed circular synthesized (3Cs) CRISPR/Cas gRNA libraries that can interrogate the coding and noncoding human genome.
The transition in basal ganglia output from the healthy to the diseased state is biphasic, stereotyped across models, and suggests key time points for delivering therapeutic interventions.
The zebrafish lateral line utilizes multiple, genetically distinct, independently regulated progenitors to generate new hair cells during homeostasis and regeneration, and to maintain progenitor pools.
Multiple biochemical assays show that the topology of CCR5 and possibly other GPCRs may be inverted by ceramide or other sphingolipids through the process of regulated alternative translocation.
Measles immunization campaigns in India accelerated declines in child measles mortality rates and averted 41,000-56,000 child measles deaths during 2010 to 2013.
Amanda Lea, Meena Subramaniam ... Julien F Ayroles
Infection and metabolic syndrome lead to a loss of molecular regulation, and changes in molecular correlations are under genetic control as revealed by the presence of correlation quantitative trait loci.
Giulia Vallardi, Lindsey A Allan ... Adrian T Saurin
Distinct PP2A-B56 complexes use isoform-selective interactions to localise to either the centromere or kinetochore and control different processes during mitosis.
Perception in autism is sensitive to absolute rather than to relative metrics of the environment, encoding changes in the environment without calibrating the changes relative to reference stimulation.
Endothelial cells express a soluble isoform of the L1CAM cell adhesion molecule that is generated by the splicing factor NOVA2 and induces angiogenesis, with relevant implications for ovarian cancer vascularization.
Maxim Igaev, Carsten Kutzner ... Helmut Grubmüller
Correlation-driven molecular dynamics provides a fully automated and human-bias-free framework for quantitative interpretation of modern cryo-electron microscopy data.
Live cell imaging demonstrates that the dynamics of ligand presentation influence signaling through two closely related morphogen signaling pathways in dramatically different ways.
Maria Paz Prada, Arsalan U Syed ... Manuel F Navedo
A multi-pronged approach shows that a Gs-coupled purinergic receptor is a sensor for glucose-mediated, PKA-dependent potentiation of vascular L-type calcium channels and vasoconstriction.
