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.
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.
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.
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..
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.