β3-AR signalling via cGMP in cardiomyocytes is regulated via phosphodiesterase 2 and 5 degradation, it is potentially cardioprotective, but dysregulated in heart failure through signal redistribution and higher phosphodiesterase activity.
Structures of the non-canonical potassium channel TMEM175 in open and closed states reveal unique mechanisms for channel gating and the selective permeation of K+ ions.
Distortion and elimination of limb visual feedback affects low-level stretch reflex control, indicating the involvement of a high-level and multimodal representation of the limb state in orchestrating hierarchical sensorimotor control.
By combining structure-based computational predictions and a thorough structural analysis, a highly thermostable enzyme, alcohol dehydrogenase, has been engineered.
Time-resolved crystallography provides insight into the photochemical reactions in photoreceptor proteins, explaining the earliest steps of how plants, fungi and bacteria sense red light.
The safety and strong antitumor effects of GPC1-specific CAR-T cells against GPC1-expressing solid tumors were demonstrated by using both syngeneic and xenogeneic mouse models.
The probability of occupancy of individual synaptic release sites at rest sets an upper limit to synaptic output when increasing action potential related calcium entry.
An optogenetic approach has been developed to model Alzheimer's disease allowing light-induced Amyloid-β aggregation and tested in three model organisms, Drosophila, C. elegans and D. rerio.
A fibronectin matrix constantly remodels to the area of highest mechanical stress, and the resulting fibronectin-mediated inter-tissue adhesion impedes neural tube convergence.
A novel mechanoelectrical transduction pathway can regulate the interactions of melanoma cells and their surrounding microenvironment, impacting both migration and cell dissociation from organotypic spheroids.
A multi-species chemical screening platform reveals a conserved role for p38 inhibition in modulating ryanodine receptor-related phenotypes and is adaptable to a range of neuromuscular disorders.
Distinct regulation endows two isoforms of the transcription factor LIN-29 with distinct functions to achieve coordinated execution of separate juvenile-to-adult transition events in Caenorhabditis elegans..
Keeping flexible adaptable representations of speech categories at different time scales allows the brain to maintain stable perception in the face of varying speech sound characteristics.
Type-I interferon enriched microenvironment generated by Mycobacterium tuberculosis induces the Siglec-1 receptor expression in human macrophages, including on tunneling nanotubes, and contributes to the exacerbation of cell-to-cell transfer of HIV-1.
Targeting mir128-3p could prevent cardiac insulin resistance in the non-infarcted myocardium and limit cardiac injury after myocardial infarction, delaying the development of heart failure.
Mycobacterium tuberculosis (Mtb), effectors secreted through SecA2 pathway cause double strand breaks (DSBs) in the host DNA, which in turn activates ATM kinase to gain survival advantages, through Akt.
DNA methylation status can be exploited to finely and reversibly tune the expression of highly inducible genes with CpG-poor promoters in response to environmental cues.
TRIM32-mediated glycolytic flux generates precursors that are utilized for biomass production in non-dividing muscle, brain and tumor cells, demonstrating a universal metabolic function for TRIM32 in cell growth.
Protein IGFBP-4 acts as a genotoxic stress mediator that, entering into circulation after its secretion by senescent cells, could promote further senescence phenomena in non-injured cells thus impairing tissues’ homeostasis.
Measurement of the distribution of fitness effects of new mutations arising in human oesophagus and skin, via new mathematical theory linking dn/ds values and fitness coefficients.
Emerging evidence suggests a broad role for cerebellar circuits in generating and testing predictions about movement, reward, and diverse cognitive processes.
Perceived imminence of threat and resulting intensity of defensive responses during serial compound stimulus conditioning are determined by auditory stimulus salience, not cue sequence as recently reported.
Generation of stable transgenic opsin lines together with in vivo calibration of their efficacy using behavioural and electrophysiological assays constitutes a novel optogenetic toolkit in zebrafish.
Structural network topology develops during adolescence to facilitate activation of the fronto-parietal executive system with lower theoretical energetic cost.
A trypanosome DYRK kinase that exhibits fundamental differences to conventional DYRK family regulation links parasite quorum sensing, signal transduction and developmental gene expression.
Cell-specific alternative splicing of the synaptic calcium channel gene Cacna1b is controlled by exon hypomethylation and CTCF binding and is disrupted following nerve injury.
A fungal bioluminescence pathway can be reconstituted in planta to create luminescence in many plant species without external substrate addition, and be used to design customizable reporters of gene-expression.
Zebrafish studies are able to predict loci and biological pathways affecting human behaviour, paving the way to better understanding of the biological underpinnings of psychiatric disease.
Genomic data for the parasites that cause visceral leishmaniasis provides the first global picture of the diversity and evolution of the pathogen and the epidemiology of this fatal tropical disease.
Computational analyses quantitatively account for optical refraction at air-water interfaces to enable visual neuroscientists to present distortion-free stimuli to underwater animals.
Lifelong HAO1 knockout was safe and without clinical phenotype in an identified healthy woman, de-risking a rare disease therapeutic approach through the power of naturally occurring human genetic variation.
Global brain transduction of the instability-prone Mecp2 transgene by systemic AAV-PHP.eB administration is safe and effective in protecting male and female Mecp2 mutant mice from the Rett syndrome disease phenotype.
Polyunsaturated fatty acid analogues show selectivity for different cardiac ion channels, suggesting their potential use for the treatment of different subtypes of Long QT Syndrome.
Direct estimation of the Hurst exponent shows that endosomes and lysosomes reside in regimes of persistent and anti-persistent motion with heavy-tailed residence time distributions and motion correlated with endocytic function.
Collapse of bacterial communities containing antibiotic-resistant and susceptible cells can be driven by increased population size or delayed drug exposure.
Cumulatively, from 1950 to 2015, smoking-related disease has been the biggest cause of premature death in high-income countries, with elevated risks of smoking continuing well into the 21st century.
Older individuals have impaired conventional dendritic cell and T follicular helper cell formation upon vaccination, which can be rescued by treatment with a TLR7 agonist.
The intrinsically disordered N-terminus of Sfr1 contains two Rad51 binding sites that facilitate Rad51 filament stabilization and ATPase stimulation by the Swi5-Sfr1 complex, leading to efficient Rad51-driven strand exchange.
The mouse cerebellum regulates innate defensive neural circuitry by tonically controlling dopamine release in the periaqueductal gray, thereby modulating synaptic responses of the Chx10-positive neurons that generate freezing behavior.
The development of genomic tools and publicly available resources in polyploid wheat provides a framework to understand biologically important traits in crops with large genomes.
A cytorhabdovirus phosphoprotein hijacks host CCR4 to trigger turnover of viral nucleoprotein (N)-bound cellular RNAs, thereby releasing nascent RNA-free N protein molecules to bind viral genomic RNAs for optimal replication.
Postsynaptic MT1-MMP serves as a molecular switch to synaptogenesis by clearing the surrounding ECM environment that allows effective deposition of nerve-derived synaptogenic factors to induce postsynaptic differentiation at developing NMJs.
Integrative structural biology reveals a conformational equilibrium in the Box C/D methylation enzyme that regulates the extent of site-specific 2'-O-rRNA methylation in dependence of the RNA sequence.
Glutamatergic projections from basolateral to central amygdala, implicated in neuropsychiatric disorders, develop rapidly during early postnatal period and their development is modulated via endogenously active kainate receptors.
Cross-species alignment based on cortical myelin content can dissociate cortical expansion and relocation from changes in connectivity profiles in the temporal lobe of higher primates.
Bioinformatic analysis of mesenchymal stem cell chondrogenesis identified a novel long noncoding RNA, GRASLND, which suppresses interferon signaling and enhances chondrogenesis.
Enhancing levels of the torsinA paralog torsinB prevents essentially all torsinA loss-of-function neuropathological and behavioral phenotypes, identifying torsinB as a novel therapeutic target for DYT1 dystonia.
Site-specific modification of NEMO facilitates RANKL signal specificity in myeloid progenitors and serves as a potential target to modulate inflammatory osteolysis through ISG15-dependent autophagy.
Knockout of both latrophilin-2 and latrophilin-3 from Purkinje cells in mice selectively impairs parallel-fiber synapses, revealing a redundant but critical function for latrophilins at specific synapses.
Everyday soundscapes dynamically engage attention towards target sounds or salient ambient events, with both attentional forms engaging the same fronto-parietal network but in a push-pull competition for limited neural resources.
Song learning accuracy can be predicted and traced in the structural properties of the brains of juvenile male zebra finches already at 20 days post-hatching.
A novel dynamic charge-charge interaction between B56 and a subset of PP2A-B56 substrates is essential for substrate specificity, dephosphorylation and, for KIF4A, binding condensin I.
The axonal cytoskeletal contains an actomyosin-II network that controls circumferential axonal contraction and expansion with the potential of regulating fluctuations in diameter during action potential firing, trafficking, and degeneration.
The first overview of fitness interactions within a species provides information how genetic interactions and ecology combine together to determine trait evolution.
Transcription factor Sox9 has an important role in neocortex expansion, where its expression in basal progenitors increases proliferation, induces premature gliogenesis and promotes the expression of extracellular matrix components.
Directly exerting force on the mammalian spindle reveals local and short-lived reinforcement in the spindle center, well-suited to preserve connections to chromosomes over seconds and yet allow remodeling over minutes.
Mechanosensitive channels Piezo1/2 are required for osteoblast differentiation from progenitors by sensing fluid sheer stress and matrix rigidity and regulating NFATc1, YAP1 and ß-catenin activities through Ca2+ stimulated phosphatase calcineurin.
Virtual lesions of the left posterior inferior frontal gyrus in patients with lesions in the left temporo-parietal cortex disrupt phonologial decisions and lead to compensatory upregulation of the lesion homologue.
Hedgehog-pathway activation in adjacent epithelial and stromal cells, but not in epithelial or stromal cells alone, enables the generation of functional de novo hair follicles in unwounded adult mouse skin.
Scale-up of piped water coverage in the local community strongly protects against S. haematobium re-infection intensity among primary school-going children following treatment with praziquantel.
Novel transgenic zebrafish lines allow selective ablation of neuronal mitochondria by far red light, providing a powerful tool for investigating mitochondrial homeostasis in neurons and mitochondrial mechanisms in neurological disease.
The common post-translational modification trans-4-hydroxy-L-proline is reversed by gut microbes with the help of hydroxyproline dehydratase (HypD), an enzyme that performs a radical chemical mechanism.
Neurons differ in their impact on collective cortical activity, with sensitive neurons forming a stable topological core, implicated in cortical-state transitions, while peripheral insensitive neurons are more responsive to stimuli.
Afferent-derived factors control the elaboration of appropriate and robust sizes of dendritic arbors by dynamically modulating dendritic growth parameters.
Changes in the interactome of the Rel family of transcription factors control adaptation to the environmental stress of hyperosmolarity and determine cell fate.
Drosophila renal stem cells are exceptional in abundance, require induction to produce a single cell type, principal cells, and mitigate damage during adulthood associated with external stresses.
Multi-fiber photometry recording and circuit-based manipulation in vivo identify a long-range SuM-DG circuit linking two highly correlated subcortical regions to regulate spatial memory retrieval through SuM glutamate transmission.
A dedicated structural element facilitates chaperone and antigenic peptide selector function of TAP-associated glycoprotein, a major quality assurance auditor in adaptive immunity.
A broadly useful phenotypic profiling dataset was generated and used to identify a cofactor required for a polar cell wall synthase in Corynebacterium glutamicum that is conserved throughout the Actinobacteria.
Neonatal mouse heart regeneration relies on the presence of mononuclear diploid cardiomyocytes, which unites this process with embryonic heart growth and adult heart regeneration.
The hippocampus and neocortex engage in waves of mutual excitation wherein a sharp wave-ripple may occur at any time before, during or after the peak of the hippocampal-neocortical activation.
Biochemical reconstitution experiments uncover the ubiquitin-mediated function of a DNA repair protein, key to the understanding of Fanconi Anemia, a cancer-associated bone marrow failure syndrome.
Proline/glycine kink in the helical peptides affects the peptide ability to form membrane pores by stabilising toroidal pore structures but disrupting barrel-stave pore structures.
ATR protects stem cell genomes by activating a transcriptional response mediated by totipotency genes, conferring trophoblast differentiation potential, the derepression of which in somatic cells might favour cancer features emergence.
HIPK4 is a male germ cell-enriched kinase that regulates cytoskeletal rearrangements in spermatids during spermiogenesis and is required for male fertility in mice.
Electrophysiological recordings and a large-scale biophysical model show that a unique inhibitory neuron plays a central role in structuring olfactory codes in the insect brain.
Sharing synthetic datasets that mimic original datasets that could not otherwise be made publicly available can help ensure reproducibility and facilitate data exploration while maintaining participant privacy.
Novel insights into LIS1-dependent regulation of cell membrane contractility and cleavage axis specification identify a key molecular network regulating mitoses of neural progenitors and somatic cells during development.
When coupling between STN spikes and cortical gamma oscillations was strong, subsequent movement was initiated earlier, independent of changes in mean firing rates, demonstrating the importance of relative spike timing.
A multi-cohort analysis of 2,500 gut microbiomes and five major diseases discovers that disease-microbiome associations display specific age-centric trends, with diseases characterized by age-centric trends of species gain/loss.
The corkscrew-like motility of Spirochete bacteria is enabled by a unique, asymmetrically constructed flagellum that wraps around the cell body within the periplasm.
Dnmt3a regulates gene expression in inhibitory neurons by writing all mCH and some mCG, and MeCP2 reads some of these mCH sites driving a portion of these gene expression changes.
Mouse genetic approaches show that multiple Wnt endothelial sources orchestrate the spatiotemporal distribution of hepatocyte functions during liver maturation and respecify metabolic zonation during liver repair.
The tubulin GTPase cycle structurally modulates the microtubule cap, causing lattice expansion, which is an intermediate state involved in phosphate release and regulatory signaling.
Depletion of PHF19 in prostate cancer cells leads to an increase in MTF2 and PRC2 chromatin occupancy causing deregulation of key genes critical for proliferation and metastasis.
Identifying the patient-specific mutation that shifted the antibody light chain to the deadly fibrillar species provides new insight in the molecular pathogenesis of AL amyloidosis.
Cue cells in the medial entorhinal cortex encode visual cues during virtual navigation, supporting the hypothesis that the brain represents visual cue information to error-correct grid cell firing during path-integration.
Nonlinear receptive field subunits in retinal ganglion cells are isolated and characterized by clustering spike-triggered stimuli, and validated on population responses to naturalistic and novel closed loop stimuli.
Adult-born neurons in the olfactory bulb that develop in the absence of microglia have a higher density of small spines but weaker excitatory inputs and reduced responses to sensory stimuli.
Model-based analyses of human behaviour and neural activity show that representations of concurrent task-sets emerge by merging together representations of individual stimulus-response associations that occur in temporal proximity.
Quantitative, experimentally testable predictions allow discrimination between contraction mechanisms in disordered actomyosin and microtubule/motor bundles.
A key enzyme of central energy metabolism, citrate synthase, regulates bacterial cell cycle progression at a very specific stage (S-phase) and independently of its enzymatic activity.
Differences in the flexible linkers connecting the kinase domain to an oligomeric hub modulate CaMKII activity by changing the balance between activating and inhibitory autophosphorylation.
The slope of the chemoattractant concentration gradient is a driving force for sperm chemotaxis, by coordinating the entrainment of information flow between sensing, signaling and motility.
Chromosome segregation in male spermatocytes exhibits anaphase A without shortening of autosome-associated microtubules and partitioning of an unpaired X chromosome that is initiated by an imbalance of attached kinetochore microtubules.
The application of long-read sequencing to the pea aphid wing dimorphism system reveals genomic structural divergence as a genetic mechanism of adaptation.
Presynaptic adhesion molecule PTPσ in the hippocampus regulates postsynaptic NMDA receptor function and behavioral novelty recognition through mechanisms independent of their trans-synaptic binding partners.
Experimental manipulation of a core DNA damage response factor and cell-cycle checkpoint regulators reveals a key role for these processes in the progenitor cells that fuel limb regeneration.
Electrophysiological recording and optogenetic manipulation approaches reveal that a multisensory bottom-up SC-LP-A1 pathway plays a role in contextual and cross-modality modulation of auditory cortical processing.
A user-friendly genetically-encoded fluorescent sensor of improved dynamic range is introduced to facilitate the study of mitochondrial metabolism and diversity.
Fusion proteins composed of the Sleeping Beauty transposase and catalytically inactive Cas9 target transposon integration into genomic regions specified by single guide RNAs.
Imaging of structure and function in the brain from thousands of participants was used along with genetics and biophysical measures to study many different aspects of how the brain ages.
The ability to smoothly perceive the environment across saccades without disturbing retinal motion sensations is generated by eye movement contingent habituation.
Mycobacterium tuberculosis penetrates the airway mucosa through M cells via the mycobacterial virulence factor EsxA and the host M cell surface receptor scavenger receptor B1.
Excitatory cortical neurons with a shared developmental lineage are transcriptomically diverse and preferentially connect to each other vertically, across cortical layers, but not laterally within the same layer.
The deubiquitinase USP16 is associated with cytoplasmic precursors of 40S ribosomal subunits and promotes their final maturation by removal of trans-monoubiquitin from RPS27a.
Environmental conditions strongly impact the fitness effects of Hsp90, resulting in the selection of Hsp90 sequences in nature that are robust to a variety of stressful conditions.
A comprehensive compendium of myelin proteins in the peripheral nervous system has been created, alongside a method to address molecular diversity of myelin sheaths in health and disease.
ARL13B regulates cell ciliation and cilia length from within cilia and Sonic hedgehog response from outside of cilia indicating the two processes can be spatially uncoupled.
Full-text analysis of the human brain-imaging literature can predict the spatial distribution of observations in the brain given the description of a subject of study.
Downregulation of mitochondrial activity by immunosuppressive tumor-derived soluble factors leads to systemic unresponsiveness to the PD-1 blockade therapy.
Longitudinal imaging of synapses in the brain shows that sensory deprivation differentially modifies specific synapses within individual neurons across distinct layers of the sensory cortex.
The crucial regulator of brain function, mTOR, signals through distinct macromolecular complexes to control how synaptic vesicles are released from the presynaptic terminal.
Intergroup conflict increases human endogenous oxytocin, which predicts the medial prefrontal activity associated with ingroup pain and propensity to seek revenge upon the outgroup.
Cryo-EM structures reveal how the peptidisc scaffold can adapt to different membrane proteins, establishing it as a universal membrane mimetic to stabilize membrane proteins in solution.
A novel IVDD mechanism that involves p16 is demonstrated and theoretical evidence is provided for effective methods to downregulate p16 and so reverse IVDD.
Demonstrating extreme diversity across crustaceans while contrasting with evolutionary stability in insects, mushroom body homologues further underpin the unity of Pancrustacea and shed new light on arthropod brain evolution.
The crystal structure of neutralizing antibody AR3X in complex with HCV E2 glycoprotein reveals unusual features of antibody recognition in which a conserved epitope is recognized by distinct antibody poses.
The morphology of the inner ear distinguishes major anthropoid clades and enables the proposal of various shared-derived features for apes as a whole, lesser apes, and great apes and humans.
Embryonic lethality associated with deficiency of UBIAD1, which synthesizes a vitamin K2 subtype, results from aberrant ER-associated degradation of the cholesterol biosynthetic enzyme HMG CoA reductase.
LXA4 in lymph nodes is an important resident homeostatic regulator that controls effector T cell functions and egress in the development of adaptive immune responses.
Temperature-sensitive mitochondrial outer membrane proteins used as novel quality control substrates reveal a unique mitochondria-associated degradation pathway consisting of both cytosolic and mitochondrial ubiquitin-proteasome system machinery.
Poly-PR and poly-GR interact with importin β, disrupt importin-cargo loading, and inhibit nuclear import in permeabilized cells in a manner that can be rescued by RNA.
CFTR modulators have potent innate anti-inflammatory properties that can be measured in clinic, both ex vivo and in vitro, which can be used to predict treatment efficacy.
Large scale virtual screening using recently solved structures of Melatonin receptors yield discovery of 10 new high-affinity selective agonists, also revealing novel functional features, including biased signaling at Melatonin receptors.
