A bacterial tRNA gene set rapidly evolves, compensating the loss of one tRNA type by large duplication events that increase the gene copy number of a second, different tRNA type.
Priscilla S-W Yeung, Christopher E Ing ... Murali Prakriya
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.
Anthony JE Berndt, Katerina M Othonos ... Douglas W Allan
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.
A conceptual and unifying framework with a critical appraisal of lipid hijacking by microbes cycling between an arthropod vector and a mammalian host is explored.
Laura E Mickelsen, William F Flynn ... Alexander C Jackson
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.
Sleep-related hemodynamic signals are much larger than those in the awake brain, so it is crucial to monitor the arousal state during studies of spontaneous activity.
Damien Lemoine, Sarah Mondoloni ... Alexandre Mourot
A photoswitchable pore blocker was covalently attached to a cysteine-substituted glutamate delta 2 receptor, to provide optical control of its ion channel function.
The same host–virus interactions can evolve multiple times in nature, due to the high effective mutation rate of viruses, and provide interesting systems of study.
Lumen formation by single epithelial cells depends on FGF-signalling-dependent expression of a spectraplakin, which can be functionally replaced by Tau.
Experimental and modelling analyses suggest a non-linear scaling relationship between IFT velocity and ciliary length that can be accounted for by limitation of the motors.
Yiska Weisblum, Fabian Schmidt ... Paul D Bieniasz
SARS-CoV-2 spike variants that resist neutralization by therapeutic antibodies or convalescent plasma can be generated in the laboratory and exist at low frequency in natural populations.
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.
Patterns of antibiotic use and the connectivity between wards are independently associated with the incidence of antimicrobial-resistant infections in hospital networks.
Lower malaria prevalence in females does not appear to be due to lower rates of infection but rather due to faster clearance of asymptomatic infections.
Arpan C Ghosh, Sudhir Gopal Tattikota ... Norbert Perrimon
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.
A mouse model of retinal degeneration reveals a common mechanism for axonal degeneration and photoreceptor cell death and identifies SARM1 as a therapeutic candidate for retinopathies.
Marija Liutkute, Manisankar Maiti ... Marina V Rodnina
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.
Daniel J Millman, Gabriel Koch Ocker ... Saskia EJ de Vries
Measurements of visual response to motion of different contrasts along with network modeling reveals a microcircuit in superficial layers of cortex that regulates the gain regime.
Samuel J Modlin, Derek Conkle-Gutierrez ... Faramarz Valafar
Fully assembled DNA methylomes from phylogeographically diverse clinical Mycobacterium tuberculosis complex isolates reveals 'intercellular mosaic methylation' as a source of epigenetic diversity.
Sonya Kumar Bharathkar, Benjamin W Parker ... Beth M Stadtmueller
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.
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.
Thuy-Lan V Lite, Robert A Grant ... Michael T Laub
A generalizable approach to understanding the logic of molecular recognition reveals the contributions of individual residues to the specificity of protein-protein interactions.
Silvia Ardissone, Nicolas Kint, Patrick H Viollier
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.
Nicole L Nuckolls, Anthony C Mok ... Sarah E Zanders
The Wtf4 antidote protein assembles with the Wtf4 poison protein and promotes the transportation of the assembled proteins to the vacuole for sequestration or destruction.
Kenneth Wengler, Andrew T Goldberg ... Guillermo Horga
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.
Stefanie Hampel, Katharina Eichler ... Andrew M Seeds
Anatomically and physiologically distinct subpopulations of mechanosensory neurons on the fruit fly antennae elicit both common and distinct behavioral responses.
Eric R Brooks, Mohammed Tarek Islam ... Jennifer A Zallen
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.
Inhibiting IRE1α decreases tumor cell proliferation and migration in hepatocellular carcinoma, therefore components of this ER-stress pathway may be therapeutically relevant for liver cancer.
Henry WP Dalgleish, Lloyd E Russell ... Michael Häusser
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.
Arghya Mukherjee, Navdeep Bajwa ... Michael M Halassa
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.
An integrative structural biology approach provides refined models of the KCNQ1-KCNE1 channel complex, which propose a new mechanism to explain how KCNE1 modulates KCNQ1 channel activation.
Recent examples demonstrate that already the transcriptional activity at lncRNA genes does have an important function on gene regulation, while the produced non-coding RNA might be dispensable.
İbrahim Avşar Ilik, Michal Malszycki ... Tuğçe Aktaş
Re-characterization of the targets of a commonly used nuclear speckle marker unexpectedly leads to the discovery of the elusive core of the nuclear speckles.
A new tool that allows specific subpopulations of telomerase RNAs in vivo forces a thorough revision of the telomerase maturation pathway and suggests a new function for Mex67.
Monitoring the formation of two distinct arrangements in early amyloid-ß aggregation by mass spectrometry and ion mobility allows determination of the effect of potential drug candidates.
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.
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.
Thomas Zhihao Luo, Adrian Gopnik Bondy ... Carlos D Brody
Techniques are presented to facilitate widespread and standardized chronic use of Neuropixels probes for high-yield, long-term neural recording in freely moving animals.
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.
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.
A chromatin remodeling factor cooperates with Wnt signaling pathway to transcribe erythropoietin in the adult liver, inducing its secretion and a dramatic erythropoiesis in the spleen.
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.
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.
Harvie P Portugaliza, Shinya Miyazaki ... Alfred Cortés
Treatment of malaria parasites with the frontline antimalarial drug artemisinin can increase the proportion of parasites that convert into transmission forms.
Amir Rattner, Chantelle E Terrillion ... Jeremy Nathans
A mouse mutant in which nearly all dentate gyrus granule cells fail to develop provides a new window on the role of the dentate gyrus in spatial learning and memory.
Jamie C Little, Elisa Garcia-Garcia ... Daniel Kalderon
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.
Genetic analyses using the fruit fly illustrate how neuronal system couples germline stem cell increase to an external cue, which is mating, through stem cell niche signaling.
Correlative imaging of the heart at multiple spatial scales has the potential to revolutionize the way we understand deficiencies in congenital heart disease.
The fidelity of 3D visual object representations, choice-related activity, and experience-dependent sensorimotor associations are functionally linked in the caudal intraparietal area.
The physical interaction network encoded in the multi-domain protein native structure handles the trade-off between the fast, stable folding and the efficient, reliable function.
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.
Nicole K Littlejohn, Nicolas Seban ... Supriya Srinivasan
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.
Slug chloroplasts avoid damage to photosynthesis by maintaining an oxidized electron transfer chain with the help of oxygen-sensitive electron acceptors.
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.
Catarina Albergaria, N Tatiana Silva ... Megan R Carey
Cannabinoid receptors modulate cerebellar learning, not through direct effects on synaptic plasticity, but as a secondary consequence of their modulation of behavioral state.
The synthesis capability of some amino acids is lost during the insect evolution, and hymenopteran parasitoids can make up for these deficiencies by altering free amino acid concentrations in host.
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.
Antonietta Franco, Xiawei Dang ... Gerald W Dorn II
A trial of mitofusin activation shows neuron regeneration and phenotype reversal in vitro and in vivo in experimental Charcot–Marie–Tooth disease type 2A caused by mitofusin 2 mutations.
Posterior parietal cortex encodes errors in a task-dependent manner while a large array of frontal regions predict subsequent behavioral changes in response to ambiguous errors.
Mitsuru Shinohara, Takahisa Kanekiyo ... Guojun Bu
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.
Dennis Segebarth, Matthias Griebel ... Robert Blum
A comparison of different bioimage analysis pipelines reveals how deep learning can be used for automatized and reliable analysis of fluorescent features in biological datasets.
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.
Laura Alonso-Herranz, Álvaro Sahún-Español ... Mercedes Ricote
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.
Loïc Labache, Bernard Mazoyer ... Nathalie Tzourio-Mazoyer
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.
Enrico Sandro Colizzi, Renske MA Vroomans, Roeland MH Merks
Selection for undifferentiated multicellularity emerges in an evolutionary cell-based model because a collective of cells performs chemotaxis better than single cells in a noisy environment.
Danae E Zamboulis, Chavaunne T Thorpe ... Peter D Clegg
Phase-specific mechanical and proteomic analyses reveal how tendon responds to its mechanical environment during postnatal development to meet functional requirements.
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.
Pedrum Mohammadi-Shemirani, Michael Chong ... Guillaume Paré
Long-term increased testosterone improved body composition and bone density, but lowered HDL and raised risks of hypertension, androgenic alopecia, prostate cancer, and spinal stenosis in males.
Henry H Le, Chester JJ Wrobel ... Frank C Schroeder
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.
Harriet Hunter, Dana de Gracia Hahn ... Jake P Mann
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.
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.
Arun Sharma, Lauren K Wasson ... Pediatric Cardiac Genomics Consortium
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.
M Regina Scarpin, Samuel Leiboff, Jacob O Brunkard
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.
Maria M Diehl, Jorge M Iravedra-Garcia ... Gregory J Quirk
Projections from the prelimbic prefrontal cortex targeting the ventral striatum or the basolateral amygdala bidirectionally regulate platform-mediated active avoidance in rats.
A theory predicts whether diffusion or direct transport establishes a more precise morphogen profile, and this prediction explains data from a wide variety of morphogens in two different organisms.
Immune cell motility and vascular response are imaged in vivo and label free in the CNS for the first time, using high-resolution phase-contrast adaptive optics retinal imaging.
Robert Köchl, Lesley Vanes ... Victor LJ Tybulewicz
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.
Timothy J Duerr, Ester Comellas ... James R Monaghan
Whole mount 3D visualization of macromolecule synthesis with light sheet fluorescence microscopy enables quantitative, multiscale analysis at the organ, cellular, and molecular levels of organization.
Jorge Luis Galeano Niño, Sophie V Pageon ... Maté Biro
Killer T cells swarm around tumour targets by accelerating the recruitment of distant T cells, which upon arrival and target engagement augment the chemotactic signal in a positive feedback loop.
Rolando Ruiz-Vega, Chi-Fen Chen ... Arthur D Lander
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.
Sebastian Korb, Sebastian J Götzendorfer ... Giorgia Silani
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).
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.
Biochemical and genetic approaches uncover a chromatin remodeler for PRDM9 binding and the parallel local epigenetic modification of cytosines in mouse spermatocytes.
Dihia Moussaoui, James P Robblee ... Anne Houdusse
The structure of full-length myosin A provides some hints about its atypical mechanism, and reveals that the light chain PfELC is a target to block malaria pathogenesis.
The Reissner fiber in the cerebrospinal fluid is required for a signal integrated by developing sensory neurons and modulated by catecholamines to control the embryo posterior axis morphogenesis.
Lynne Chantranupong, Jessica L Saulnier ... Bernardo L Sabatini
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.
Dominique Förster, Thomas O Helmbrecht ... Herwig Baier
The retinotectal map in zebrafish exhibits location-specific, functional specializations to match prey object movement in the visual field during the hunting sequence.
Boran Hao, Shahabeddin Sotudian ... Ioannis Ch Paschalidis
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.
Social dominance has opposing effects on behavior following stress in male vs. female mice indicating an important role in sex differences in the stress response.
The polo-like kinase (Plk1) phophorylates the C. elegans lamin LMN-1 to promote timely lamina disassembly, which is essential for the merging of the parental chromosomes at the beginning of life.
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.
Inhibition of bacterial protein synthesis by an antimicrobial peptide apidaecin triggers translation arrest at the stop codons, ribosome queuing and pervasive stop codon readthrough.
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.
An unusual molecular mechanism has been revealed based on ultrastable histidine cluster co-aggregation underlying feedback control of an ancient cell communication pathway.
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.
A control system model of cerebellar patients' movements provides insight into the cerebellum's role in reaching and informs a virtual reality intervention to improve patient reaches.
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.
Rui Tang, Christopher W Murray ... Monte M Winslow
A novel reporter system that employs cell surface antigen-nanobody pairing enables physical interaction-dependent labeling and functional modification between diverse cell types.
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.
Lynda S Ostedgaard, Margaret P Price ... Michael J Welsh
Submucosal glands are critical for two key respiratory host defenses, bactericidal activity and mucociliary transport, in an animal model that has lungs like humans.
The sex-specificity of a transcription factor required for sexual differentiation of a neural circuit is regulated by a novel post-transcriptional mechanism.
Michelle M Lissner, Katherine Cumnock ... David Schneider
Illustrating the impact of host metabolism on infection outcome, loss of the aryl hydrocarbon receptor in radioresistant cells leads to heme-mediated kidney toxicity during malaria.
Joanna A Warren, Shuntai Zhou ... Nilu Goonetilleke
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.
Precise spatiotemporal optogenetic activation of ERK and AKT signaling pathways reveals neural repair mechanisms of the peripheral and central nervous systems in live Drosophila larvae.
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.
Cryo-electron tomography reveals the structure and arrangement of the VP40 matrix protein lattice that mediates the formation of Ebola and Marburg virus particles.
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.
Igor Gridchyn, Philipp Schoenenberger ... Jozsef Csicsvari
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.
Sara Fernández-García, Sara Conde-Berriozabal ... Mercè Masana
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.
Gabrielle E Giese, Melissa D Walker ... Albertha JM Walhout
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.
GAS5 is related to osteoporosis by regulating the differentiation of bone marrow stromal cells that acts as a promising treatment target for osteoporosis.
Kelsey H Elliott, Xiaoting Chen ... Samantha A Brugmann
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.
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.
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.
The terminal selector-type transcription factor UNC-3/Ebf partially modifies the suite of its target genes at different life stages to establish and maintain the identity of C. elegans motor neurons.
The HOXA9 reporter and genetic screens facilitated the functional interrogation of the HOXA9 regulome and advanced our understanding of the molecular regulation network in HOXA9-driven leukemia.
A novel, overlapping, putatively functional gene in SARS-CoV-2, ORF3d, is absent from close relatives of SARS-CoV-2 and may have contributed to the biology, emergence, or spread of the virus.
John P Grogan, Timothy R Sandhu ... Sanjay G Manohar
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.
