Electrophysiology pinpoints brain function abnormalities in young people genetically at risk of developing Alzheimer's disease much later in life, supporting theories of initial hyperconnectivity driving eventual profound disconnection.
Acetylcholine, a common modulator in the brain, controls spike-frequency adaptation by specifically attenuating Ether-a-go-go related K+ currents, thereby explaining many cortical network statistical changes often observed in vivo.
The multi-stage model of carcinogenesis requires the incorporation of aging-dependent somatic selection and life history-dependent evolution of species-specific tumor suppressor mechanisms in order to generalize carcinogenesis across tissues and species.
The chromatin remodeler and tumor suppressor SMARCB1 acts to restrict superenhancer function to direct neural differentiation of embryonic stem cells while repressing bivalent gene activity in the pluripotent state.
A characterization of LGN-V1 synaptic transmission properties demonstrates thalamocortical synapses in vivo are weak and unreliable, but biologically constrained models show they efficiently drive cortex.
Expression of a Dravet syndrome-associated mutation in inhibitory neurons disrupts activity of brainstem respiratory neurons and diminishes respiratory behavior in conjunction with seizures and premature death.
An unbiased genetic screen in Drosophila provides evidence for a direct link between glial Ca2+ 25 signaling and classical functions of glia in buffering external K+ as a mechanism to regulate neuronal excitability.
Animal RanBP1 nuclear export and cargo dissociation mechanisms are surprisingly different from yeast, due to mutations of critical residues, leading to greater nuclear transport efficiency and higher energy cost.
During CRISPR adaptation, Cas4 forms a ternary complex with the Cas1-Cas2 spacer integration complex, an interaction that coordinates substrate hand-off following precise, PAM-dependent prespacer processing prior to integration.
In mouse models of Huntington's disease, striatal spiny projection neurons up-regulate dendritic potassium channels, which impairs their normal function, but a zinc finger gene therapy can reverse this deficit.
Biochemical studies revealed novel property of human tumor suppressor PALB2, which significantly contribute into DNA repair in cells and can be targeted for the development of novel anticancer treatment.
Francisella tularensis spreads from cell to cell when macrophages engulf small portions of infected cells upon cell contact, forming distinctive a double membraned endosome containing multiple bacteria per individual vacuole.
L. interrogans utilizes endocytic recycling and vesicular transport systems for transcytosis across endothelial or epithelial barrier in blood vessels or renal tubules, which contributes to spreading and transmission of leptospirosis.
Disconnection of the orbitofrontal cortex from the submedius nucleus but not the mediodorsal thalamus prevented rats to respond adaptively following action-outcome reversal, showing differential involvement of these thalamocortical circuits.
Genomic-profiles and reporters reveal that the three-nucleotide ‘words’ read by the ribosome, codons, have a strong effect on mRNA stability, impacting the homeostatic mRNA and protein levels in human cells.
VIP neurons are a novel class of inferior colliculus stellate neurons that project to long-range auditory and non-auditory targets and integrate inputs from the auditory brainstem and contralateral IC.
Restoration of molecular and morphological symmetry and mechanical integrity following epithelial fusion relies on adaptive changes that are mediated by cytoskeletal tension and Bazooka dependent modulation of fusing interface geometry.
Polyglutamine expansion in mutant huntingtin disrupts a novel transcription-coupled DNA repair complex, providing an undescribed mechanism of neuronal toxicity and degeneration in Huntington's disease.
A multi-phase wrinkling model accounts for the radial and circumferential tension and differential expansion between a uniformly proliferating outer fluid-like layer and an incompressible core that together drive cerebellar folding.
The nutrients available in some tumors and the factors that influence tumor nutrient availability are characterized, which provides insight into the metabolic constraints of the tumor microenvironment.
Parvalbumin positive GABAergic neurons in the ventral zona incerta receive input from somatosensory cortex and enhance sound-induced flight behavior, which underlies a cross-modality facilitation of defensive behavior by somatosensory input.
B cell lymphoma 6 (BCL6) represses fasting gene expression by opposing peroxisome proliferator-activated receptor alpha (PPARa) activity at enhancers, and its ablation protects against steatosis by enhancing fatty acid catabolism.
A transcriptome dataset of nearly 200 genetically identified mouse neuronal cell types revealed that short low-noise homeobox transcription factors and long neuronal effector genes best distinguish neuronal cell types.
Representation of sound lateralisation and intensity by neural population in the rat auditory cortex strongly depends on the brain state suggesting that the neural tuning to lateralisation is not hard-wired.
Single cells from a large heterogeneous population can be identified, isolated and clonally expanded using commonly available microscopy equipment and simple reagents, based solely on visual characteristics.
A subset of EC/VCs have CD4+T cells with resistance specific to R5-tropic HIV infection associated with transcriptional down-regulation of ccr5, a phenotype that appears to be heritable, across multiple generations.
A newfound signaling enzyme that diverged from a protein family ubiquitous in bacteria provides mechanistic insights into how new signaling activity emerges to control distinct cellular function and physiology.
Comprehensive mass spectrometry analysis of human plasma proteome reveals tissue leakage proteins, describes variability between individual plasma proteomes and demonstrates protein transfer across the placenta during pregnancy.
The Notch signaling pathway drives transitions in differentiation capacities during the gradual loss of potency that occurs in the preimplantation mouse embryo before the onset of the first lineage decisions.
At gastrulation, mesoderm arises as a migratory germ layer that will participate to both foetal and placental development through region-dependant adaptation of cytoskeleton composition, cell shape and migration mode.
Liquid-liquid phase separation of tau is demonstrated to be an equilibrium state, stable only within a narrow range near physiological conditions, and thus has the capacity to regulate biological processes.
Estradiol regulates the pre-ovulatory luteinizing hormone surge through hypothalamic anteroventral periventricular kisspeptin neurons and maintains reproductive cyclicity through arcuate kisspeptin neurons in an activational manner.
Sarcoidosis, a granulomatous disease characterized by macrophage and T-cell activation, is found to be associated with increased HIF-1α transcriptional activity, and modulation of HIF-1α regulates inflammatory immune responses.
Analysis of the atypical tryptophan biosynthetic operon of Chlamydia trachomatis revealed the simultaneous regulation of transcriptional initiation and termination by an iron-dependent repressor, expanding known regulatory mechanisms of this pathway.
Invertebrate TRPM2 channels have stable pores but act as chanzymes that hydrolyze their activating ligand ADP ribose (ADPR), whereas vertebrate TRPM2 channels are catalytically dead but undergo pore inactivation.
Mitogen-activated protein kinase phosphatase 1 (DUSP1) deficiency causes early redox imbalance and increased inflammatory response in the cochlea, leading to cell loss and progressive neurosensory hearing loss.
Human mobility drives malaria importation within countries and threatens elimination interventions, but can be measured using new approaches that combine parasite genetics, mobile phone data, travel surveys and models.
Combining parasite genetic and human mobility data can provide detailed information on local and cross-border connectivity, allowing programs to strengthen local and regional coordination for successful elimination of malaria.
Endothelial tightening by augmenting low level Wnt/β-catenin activity in vessels of the mouse subfornical organ, influences neuronal activation in water-deprived mice, linking endothelial barrier properties to neuro-vascular coupling.
Elevating beta-catenin signaling converts endothelial cells in typically fenestrated central nervous system vasculature to a blood-brain barrier (BBB) phenotype and promotes a BBB gene expression program and chromatin landscape.