Electrophysiological and molecular modeling studies identify a sulfur-aromatic interaction between the hydrophobic channel gate and a nearby methionine residue, termed the "gate latch", which is essential for Orai1 pore opening.
DNA motifs tuned for low affinity binding of BMP-induced pMad/Medea transcription factors function to restrict gene activation to small subsets of the many Drosophila neurons that exhibit active BMP signaling.
Single cell RNA–sequencing and neuroanatomical methods reveal unexpected molecular diversity and highly segregated spatial organization of neuronal cell types within the mouse ventral posterior hypothalamus, including the mammillary nuclei.
A disease-associated polymorphism in a related protein that regulates neurotransmitter release reveals that antiviral protein IFITM3 forms oligomers to rigidify membranes and inhibit virus fusion with cells.
A muscle-derived signaling molecule suppresses excessive accumulation of lipids in the Drosophila adipose tissue by activating the Pi3K/Akt/mTOR signaling cascade in the Drosophila hepatocyte-like cells.
Dot1l and its H3K79 methyltransferase activity are required for thermogenesis, and Dot1l is recruited by Zc3h10 to its targets genes to alter chromatin accessibility to activate the thermogenic gene program.
HemK NTD cotranslational folding starts within the ribosome exit tunnel upon N-terminal helix synthesis and proceeds sequentially through a series of intermediates becoming less dynamic as the nascent chain grows.
The structures of secretory and dimeric IgA reveal pseudosymmetric assemblies of two antibody monomers, in which possible positions of antigen-binding fragments and accessibility to receptor-binding sites are limited.
Glycosylation of flagellins with pseudaminic acid in the bacterial cytoplasm governed by an unknown type of modular glycosyltransferase harboring an N-terminal substrate binding domain and a C-terminal glycosyltransferase domain.
fMRI evidence for distinct hierarchical alterations in intrinsic neural timescales for different positive symptoms of schizophrenia support hierarchical perceptual-inference models of psychosis and suggest local increases in excitation-inhibition ratio.
Closure of the cranial neural tube, which is essential for mammalian development, is driven by spatially and temporally patterned cell remodeling events that require positionally regulated Sonic hedgehog signaling.
Compared to a sensory thalamocortical circuit, the mediodorsal thalamus preferentially innervates prefrontal cortical interneurons, and enhancing excitability of this thalamic structure drives prefrontal activity patterns that are dominated by inhibition.
Targeted optogenetic activation of small ensembles of neurons is sufficient to trigger a behavioral report while recruiting matched network suppression, suggesting exquisite sensitivity despite network mechanisms that maintain sparseness.
The high resolution crystal structure and electrophysiology of a sodium channel complex with cannabidiol, a drug approved for treatment of severe epilepsies, demonstrate the basis for its structural- functional effects.
Cryo-EM structures of the AAA+ ClpXP protease bound to an ssrA degron reveal the mechanism of substrate recognition and show how the machine transitions from recognition to translocation and unfolding.
Tick-derived sequence variation in the fusion glycoprotein of Crimean-Congo hemorrhagic fever virus (CCHFV) drastically impairs infection of mammalian cells, suggesting that certain CCHFV strains undergo purifying selection in mammalian hosts.
Hedgehog acts as a morphogen by regulating proteolytic processing and activation of full-length Ci/Gli transcriptional effectors but can pattern Drosophila wing discs normally in the absence of regulated proteolytic processing.
Linking deep mutational scanning with engineered transcriptional reporters in human cell lines establishes a generalizable method for exploring pharmacogenomics, structure, and function across broad classes of drug receptors.
Similar evolutionary pressures on gene expression between human and chimpanzee populations contribute to the observation that inter-individual gene expression variability is similar across genes in these species.
The sleep-courtship balance in Drosophila males is modulated by yeast/protein availability, and dopaminergic neurons projecting to the protocerebral bridge act downstream of courtship-regulating neurons for male sleep regulation.
New protein labeling strategies unravel the subcellular distribution of neurotransmitter receptor subunits and voltage-gated ion channels in motion-sensing T4/T5 neurons of the Drosophila visual system.
A systematic experimental comparison of prosocial behavior in eight corvid species reveals sex-specific effects of cooperative breeding and colonial nesting, thereby adding important new insights regarding the evolution of prosociality.
The dual control of adiposity and longevity emerges from a latent intestinal feedback loop which simultaneously augments fat loss and shields lifespan from the deleterious effects of continuous fat oxidation.
Fertilizing mouse spermatozoa, characterized by intact CatSper channels, lack of protein tyrosine phosphorylation, and reacted acrosomes, in the female reproductive tract provide molecular insight into sperm selection for successful fertilization.
Confronting different models of chromatin accessibility with temporally resolved transcription profiles favors a scenario where transcription factors actively, rather than passively, drive chromatin from the inaccessible to the accessible state.
Translational evidence indicates APOE2 benefits longevity independent of its protective effects on Alzheimer’s disease, which preserved activity and the metabolism of apoE protein and associated-lipids would be key to understanding.
The principle underlying the appearance of the growth plate, an organ responsible for longitudinal growth, has implications for various cartilage pathologies including growth abnormalities in children, trauma and osteoarthritis.
A novel assay to measure 2-micron stability together with a survey of natural variation among Saccharomyces cerevisiae strains reveals novel means by which yeasts can combat the parasitic 2-micron plasmids.
Cryo-electron microscopic structures of 5-HT3A receptor in complex with first and second generations of clinically used setron reveal the molecular basis for their binding modes and mechanisms of inhibitory action.
Macrophage production of MT1-MMP upon MI contributes to adverse cardiac remodeling and worsened function by promoting EndMT via TGFB, suggesting MT1-MMP inhibition as a therapeutic option for patients with MI.
Animal studies of fatty liver disease over-estimate the benefit of drugs due to publication bias and are confounded by off-target weight loss, illustrating the challenge of successful translational across species.
Caenorhabditis elegans homologs of carboxylesterases that localize to intestinal organelles orchestrate the assembly of modular signaling molecules from building blocks that integrate diverse metabolic pathways.
Left-hander's atypical language brain organization, revealed by task-induced rightward asymmetry, is underpinned at rest by homotopic networks wired for language bilaterally and strong intrinsic connectivity through a large corpus callosum.
Plants and humans use a shared mechanism, the eukaryotic metabolic sensor TARGET OF RAPAMYCIN protein kinase and its substrate, an RNA-binding protein called LARP1, to coordinate post-transcriptional gene expression.
Analyses of human stem cells with distinct GATA6 mutations revealed a spectrum of molecular responses that drive isolated congenital heart disease or the co-occurrence of pancreas and diaphragm malformations.
Development of mouse thymocytes through the pre-TCR checkpoint requires WNK1 kinase signalling via the OXSR1 and STK39 kinases and the SLC12A2 ion co-transporter leading to MYC-dependent cell proliferation.
Administration of dopamine and opioid receptor antagonists resulted in reduced reward anticipation (effort and increased negative facial reactions), but only administration of opioid antagonists resulted in reduced liking (facial reactions).
Spontaneous growth arrest of transformed melanocytes (resulting in benign “moles”) does not result from cell-autonomous oncogene-induced senescence, but can be explained by collective mechanisms used in normal tissue size control.
Aberration correction using 3D microprinting in ultrathin microendoscopes allows two-photon imaging of large neuronal networks with homogeneously high spatial resolution and minimal invasiveness in the deep mouse brain.
Using data for 2566 COVID-19 patients from five hospitals, models are developed to predict for each patient hospitalization and critical care needs, based on demographics, comorbidities, medications, and laboratory findings.
Extensive mass spectrometry-based profiling of polar metabolites within synaptic vesicles that are rapidly isolated either from cultured mouse neurons or directly from mouse brains reveals their neurotransmitter composition.
A coordinated tissue movement during C. elegans central nervous system internalization reveals a novel role for HMR-1/cadherin in maintaining cohesion, and extends the concept of neurulation beyond vertebrates.
The mutual interaction between the basement membrane protein Multiplexin and the phagocytosis receptor Eater expressed by the immune cells drives the formation and maintenance of the hematopoietic tissues in Drosophila.
The growth of multicellular bacterial structures called biofilms generates forces that deform soft material substrates and disrupt epithelial cell layers, potentially mechanically damaging host tissue.
Inhibition of ITGA2-mediated cancer cell-collagen interaction or targeting focal adhesion kinase activity may present an opportunity for therapeutic intervention of metastatic spread in ovarian cancer.
The transcription factor RUNX1 marks a distinct lineage of luminal castration-resistant prostate cells established early during development and enriched in the periurethral region of adult mouse prostate.
The evolving spatial distribution of nuclei between apical and basal surfaces of the developing retinal neuroepithelium is quantitatively described by a nonlinear diffusion equation accounting for crowding within the tissue.
HIV-specific T cells remain detectable for years in HIV-infected individuals on antiretroviral therapy and importantly, mostly (68%) recognize HIV viruses that have the capacity to rebound following treatment interruption.
M2 cortex-dorsolateral striatum circuit is functionally altered in Huntington's disease and, by boosting its activity, we reverse symptoms at behavioral, physiological, and morphological level in symptomatic mice.
Metabolic activity of the methionine/S-adenosylmethionine cycle is sensed and transcriptionally regulated by a nuclear hormone receptor in Caenorhabditis elegans in order to maintain metabolic homeostasis in a tightly controlled regime.
The optogenetic manipulation of hippocampal neuronal circuit activity revealed plastic changes of pyramidal-interneuron connections in behaving animals, which were primarily governed by the firing rate change of postsynaptic interneurons.
Combination of glutaminase inhibitor CB-839 and ASCT2 inhibitor V-9302 showed efficient antitumor effect against glutamine addicted liver cancer cells via glutathione depletion and reactive oxygen species (ROS) induction.
Chemical modifications near the tRNA anticodon and specific mRNA–tRNA pairs combine to control the ribosomal three-nucleotide mRNA reading frame, essential for the sequential addition of amino acids into polypeptide chains.
Hypoplastic left heart syndrome is reflected by reduced proliferative capacity of patient iPSC-derived cardiomyocytes and requires the activity of LRP2/APOB proteins, likely in conjunction with SHH and WNT signaling pathways.
Although human Parkinson's disease is linked to dopamine loss, two distinct mutations in a kinase associated with familial Parkinson's operate downstream, altering excitatory synapses on dopamine-sensing neurons.
Context-dependent optimization of Gli-binding site occupancy, in the presence of Hand2, is critical for modulating tissue-specific transcriptional output within tissues that lack an obvious Hedgehog morphogen gradient.
Cadherin-dependent cell adhesion controls the contralateral migration and clustering of ocular motor subpopulations and is required for the development of functional eye movements driven by those neurons.
Dopaminergic medication dissociates contingent motivation from reward expectation effects on invigoration of movements in PD patients, confirming they are separate processes with different dopaminergic functions.