Makenna M Morck, Debanjan Bhowmik ... Kathleen M Ruppel
Hypertrophic cardiomyopathy-causing mutations in the light chain-binding region of β-cardiac myosin's lever arm appear to disrupt myosin tail-based autoinhibition, while mutations in the pliant region of the lever arm reduce autoinhibition in the presence of actin and impact myosin’s powerstroke.
A new computational approach for detecting sleep waveforms reveals that the 11–15 Hz sleep 'spindle', a neural rhythm implicated in memory consolidation, co-occurs widely across cortex much more often than previously thought.
Orie T Shafer, Gabrielle J Gutierrez ... Maria de la Paz Fernandez
The most influential clocks within the Drosophila circadian clock neuron network form the fewest synapses within the network, and neurons that do not themselves contain molecular clocks mediate connections between those that do, suggesting a key role in timekeeping.
Distinct surfaces of an interbacterial competition cell wall toxin mediate interactions with different cellular binding partners, resulting in an inherent evolutionary trade-off across the toxin superfamily.
The Toll-like receptor 2-4 genetic modification goat improves effectively resistance against Staphylococcus aureus infection by enhancing autophagy level, and it provides a novel strategy for challenge of S. aureus-caused infections.
Eric N Jimenez-Vazquez, Michael Arad ... José Jalife
Important mechanistic details on Duchenne Muscular Dystrophy arrhythmogenesis are revealed, providing a crucial lead for investigators interested in developing therapeutic solutions for this deadly disease.
Lineage tracing and genetic analysis in zebrafish show that the pseudobranch is a serial homolog of the gills arising from the jaw-forming mandibular arch, thus supporting the model that vertebrate jaws derived from an ancestral mandibular gill.
Marta Matuszewska, Gemma GR Murray ... Lucy A Weinert
The dominant MRSA circulating in European livestock has stably maintained genes associated with resistance to antibiotic treatments over several decades and when it is transmitted to humans it can rapidly acquire genes that allow it to evade human immune responses.
Payel Chatterjee, Agnish Dev Prusty ... Sanjay P Sane
Compensatory head movements in hawkmoths are influenced by the combined feedback from vision and antennal mechanosensory Johnston’s organs, similar to the combined role of vision and halteres in Diptera.
Cystathionine-β-synthase is a novel metabolic regulator of AKT-induced senescence and a potential tumor suppressor in gastric cancer pathogenesis which can be harnessed to target PI3K/AKT-driven cancers.
Opposing activities of ATR kinase and PP4 phosphatase balance phosphorylation of the protein DSB-1 to produce sufficient but not excessive amount of DNA double-strand breaks during meiotic prophase in Caenorhabditis elegans.
Jianhua Zhang, Zachery R Gregorich ... Timothy J Kamp
Investigation of defined extracellular matrix proteins in differentiation of human pluripotent stem cells to cardiomyocytes reveals fibronectin, in addition to soluble factors, is required for cardiogenesis.
Ekaterini Maria Lyras, Karin Zimmermann ... Alexander Mildner
The tongue is a unique barrier organ, which is constantly exposed to environmental pathogens, and therefore is expected to host an immune cell network ensuring local immune defence, which we characterised during development, health, and disease.
An actin-based Brownian Ratchet enables branched actin networks to generate pushing forces, while a capping protein-based Brownian Ratchet provides force feedback that enables these networks to adapt their architecture in response to changing loads.
Pathological TNF-α-producing B cells are involved in the pathological process of polycystic ovary syndrome, and metformin inhibits mTOR phosphorylation, affects metabolic reprogramming, and further inhibits TNF-α expression in pathological B cells.
Kanwal Kayastha, Alexander Katsyv ... Volker Müller
The cryo-EM structural and functional analyses reveals the lactate dehydrogenase/electron-transferring flavoprotein (Ldh-EtfAB) in its enzymatically active form and the geometry of the confurcating flow of two energetically spitted electrons via 2 FAD and 1 [4Fe-4S] cluster to a central FAD.
Intervention of CHI3L1 using anti-CHI3L1 monoclonal antibody or chitinase inhibitor kasugamycin blocks epithelial infection of various SARS-CoV2 variants, suggesting that CHI3L1 is a universal and effective therapeutic target of COVID-19 infection, including recent omicron variants.
Sunwoo Kwon, Berkeley K Fahrenthold ... Jude F Mitchell
V1 damage impairs unconscious following movements of stimulus motion, even after conscious perception has been restored through psychophysical training, thus demonstrating distinct neural pathways for perception and action.
Vladislav Belyy, Iratxe Zuazo-Gaztelu ... Peter Walter
Stress sensors in the membrane of the endoplasmic reticulum respond to the accumulation of unfolded proteins by briefly forming small phosphorylation-competent oligomers and dissolving back into active dimers.
Viktor J Olah, Annie M Goettemoeller ... Matthew JM Rowan
Electrophysiological and genetic analyses reveal a biophysical mechanism in parvalbumin interneurons, uncoupled from changes in gene expression, resulting in reduced cortical inhibition in early-stage Alzheimer's disease.
Henrike Indrischek, Juliane Hammer ... Michael Hiller
Specific evolutionary gene loss signatures indicated an eye-related function for the uncharacterized SERPINE3 gene, which was experimentally confirmed by zebrafish gene knockouts, showing how comparative genomics can provide insights into the function of uncharacterized genes.
Marion Portes, Thomas Mangeat ... Renaud Poincloux
Cutting-edge super-resolution microscopy methods reveal the architecture and dynamics of the sealing zone formed by human osteoclasts and composed of coordinated groups of podosomal cores encircled by adhesion complexes.
Multi-model ensembling projected that the Delta variant would lead to a substantial COVID-19 resurgence in the US, with higher vaccination uptake being a critical factor for limiting transmission and impact between states.
Emily RR Mackie, Andrew S Barrow ... Tatiana P Soares da Costa
The first recently discovered inhibitors of lysine biosynthesis with in planta activity have a dual-target mode of action, which provides proof-of-concept for the development of multi-target ‘resistance-resistant’ herbicides with a novel mode of action.
Excitation of contralesional cortex after stroke suppresses the expression of genes related to plastic neuronal reintegration and accordingly modulates perilesional remodeling and functional network communication at local and global scales.
Comprehensive mutational scanning of the SARS-CoV-2 protease, Mpro, provides functional and structural information to aid in the design of more effective inhibitors against the protease with reduced potential of evolving viral resistance.
Eugene Serebryany, Sourav Chowdhury ... Eugene I Shakhnovich
The human eye lens imports and concentrates within itself a naturally abundant small molecule that inhibits cataract-associated aggregation of an eye lens protein before the aggregates get large enough to scatter light.
A theoretical model combines self-supervised predictive learning with structural inductive biases to reveal how quasi-continuous attractors that perform accurate angular path integration can be learned from experience during development in the Drosophila and potentially other animal models.
A newly identified pattern of circuit assembly shows connectivity between small groups of neurons born in tight time windows from different stem cells, with outputs from one lineage born before inputs from other lineages.
The three-dimensional structure of bacterial biofilms is governed by a buckling-delamination process that is determined by basic physical parameter that allow us to predict and control the biofilm morphology.
In teleost fishes, the independent evolution of electrosensory systems was repeatedly associated with evolutionary changes in brain region scaling that were independent of changes in brain–body allometry.
Andrew Ryan Passer, Shelly Applen Clancey ... Marco A Coelho
A novel form of self-fertility evolved in Cryptococcus depauperatus, a close relative to the human pathogenic Cryptococcus species, in which sexual development is attained by self-signaling of a cognate pheromone and pheromone-receptor pair.
Carrie E Leonard, Jolie Quiros ... Lisa A Taneyhill
Trigeminal nerve deficits observed in familial dysautonomia, which arises from mutations in ELP1, are due to loss of neural crest-derived TrkA nociceptors, while placode-derived TrkB and TrkC neurons are spared.
Nuné Martiros, Vikrant Kapoor ... Venkatesh N Murthy
Real-time imaging of neural activity in behaving mice reveals that the two canonical types of neurons in the olfactory tubercle carry distinct information about learned odor cues, with D1 neurons representing stimulus valence and D2 neurons mainly representing stimulus identity.
Jakub Gemperle, Thomas S Harrison ... Patrick T Caswell
DExCon, LUXon, and DExogron approaches simultaneously block endogenous gene expression and permit tuning of re-expression levels in time and space; proof-of-principle reveals unforeseen differences in protein kinetics, cargo handling, and cell migration regulation between closely related Rab11 family members.
Priscila C Antonello, Thomas F Varley ... Jean Faber
Effectively connected neurons self-organize forming networks with a small-world architecture composed of modules, with most likely few and nearby neurons, integrated by more topologically important and high firing rate neurons.
The underlying neurophysiology of the lateral line system in blind cavefish (Astyanax mexicanus) has evolutionarily converged on elevated afferent neuron activity and partial loss of function in inhibitory efferent neurons, both of which contribute to enhanced sensitivity to flow stimuli.
Novel insights into the molecular mechanisms underlying neurotransmitter release are provided by all-atom molecular dynamics simulations including SNARE proteins, synaptotagmin-1, complexin-1, a vesicle and a flat bilayer.
Ritvija Agrawal, John P Gillies ... Morgan E DeSantis
KASH5 uses an EF-hand domain to directly interact with the light intermediate chain of dynein, promotes processive dynein motility, and facilitates dynein recruitment to the nuclear envelope during prophase I of meiosis.
Gregory S Wirak, Jeremy Florman ... Christopher V Gabel
Comprehensive multi-neuron fluorescence imaging in C. elegans reveals age-associated changes in neuronal activity that include a breakdown of system-wide organization, changes in neuronal frequency dynamics, and a disruption of the balance between excitatory and inhibitory signaling.
James W Antony, America Romero ... Kelly A Bennion
The more semantically related a later experience is to an earlier one (along multiple dimensions), the more likely humans are to think back to and strengthen the memory of the earlier experience and mentally link the two experiences.
Susan M Motch Perrine, M Kathleen Pitirri ... Joan T Richtsmeier
Analysis of 3D reconstructions of chondrocrania of the FgfrcC342Y/+ Crouzon syndrome mouse show the direct effects of this Fgfr2 mutation on embryonic cranial cartilage formation and the indirect effects of chondrocranial morphology on cranial dermal bone development.
Guillaume Ravel, Michel Bergmann ... Simon Labarthe
A new mathematical method has been developed, implemented and validated for the analysis of time-lapse confocal laser scanning microscopy images to characterize the swimming behavior of bacterial swimmers moving in the exogenous matrix of pathogenic biofilms.
Charles N Agoti, Lynette Isabella Ochola-Oyier ... George Githinji
Genomic analysis of initial SARS-CoV-2 waves in Kenya revealed Mombasa City as a key gateway for variants entering Coastal Kenya with onward inter-county transmission highlighting significance of surveillance in major cities for early warning of lineages entering local populations.
The neonatally maturing pituitary harbors an activated stem cell compartment and shows prominent regenerative capacity, as revealed by single-cell transcriptomic profiling and in vitro (organoid) and in vivo (mouse) exploration.
Stefano G Giulieri, Romain Guérillot ... Benjamin P Howden
A large-scale analysis of Staphylococcus aureus within-host evolution based on a comprehensive catalogue of bacterial genetic variation reveals an excess of genome degradation signatures in infecting strains and new genetic loci of clinically relevant adaptation.
Androglobin, a newly identified mammalian globin with a unique modular structure including a protease and calmodulin binding IQ domain within a circularly permuted globin domain, is implicated in murine spermatogenesis.
Laura Medina-Ruiz, Robin Bartolini ... Gerard J Graham
The use of multi-chemokine receptor reporter mice helps to unravel the dynamics of receptor involvement in leukocyte migration in vivo and suggests specificity, rather than redundancy, in receptor use.
In a mouse model of DYT25 dystonia with disruption of striatal neurotransmission by Gnal mutation, the cerebello-thalamic excitability is increased following symptom expression and θ-burst cerebellar stimulations during cholinergic-induced dystonia depress the cerebello-thalamic transmission and reduce the motor symptom severity.
A novel model is presented that reconciles in-cell structure probing data with splicing regulatory elements to predict exon 10 inclusion of the Tau gene with high accuracy for 53 splice altering mutations.
Ramkrishna Mitra, Clare M Adams, Christine M Eischen
The discovery of uncharacterized lncRNAs that regulate cell proliferation/growth across cancer types, including two p53 regulated tumor suppressive lncRNAs, were identified through systematic analyses of multi-omics data and provides a computational framework resource to cancer researchers.
Deny Cabezas-Bratesco, Francisco A Mcgee ... Sebastian E Brauchi
Joint sequence, structure, and phylogenetic analyses identify highly conserved features in transmembrane domains of transient receptor potential (TRP) ion channel proteins that offer a novel explanation for how TRPs could integrate stimuli into cellular signals.
The COVID-19 pandemic reduced participation in a Spanish population-based breast cancer screening program, especially among regular participants, while other outcomes like recall and cancer detection were not negatively affected by the interruption of screening.
Mg2+-dependent JAK1-mediated phosphorylation sensitizes TRPV2 activity and thermo-threshold, which is counterbalanced by PTPN1-mediated dephosphorylation, highlighting a role of phosphorylation homeostasis in setting the basal activity of TRPV2.
Labeling with 13C and 15N in the absence of metabolic engineering enabled the exploration of peptidoglycan metabolism at a very fine level of detail based on kinetic characterization of isotopologues predicted to occur according to known recycling and biosynthesis pathways.
When challenged by energetic stresses triggered by hypoxia and ATP inhibition, plasma membrane PI4P and PIP2 in cells undergo dramatic turnovers that have profound impact on many cellular processes including electrostatic PM targeting of numerous polybasic proteins.
Sarah Lensch, Michael H Herschl ... Lacramioara Bintu
In a synthetic system, spreading of chromatin-mediated silencing to nearby genes depends on distance and can bypass genetic insulators, while reactivation after release of gene targeting is coordinated by insulators and promoters.
A previously unknown calcium channel in human placental trophoblasts provides a calcium source for activating TMEM16F lipid scramblase that flip-flops phospholipids on cell surface, demonstrating a physiological mechanism that helps to understand how lipid dynamics regulates cell fusion.
Inhibiyiton of the lysosomal chloride-proton antiporter ClC-7 by the signaling lipid PI(3,5)P2 is important for lysosomal pH maintenance and is disrupted by a disease-causing gain-of-function mutation.
Carlos-Henrique D Barbosa, Fábio B Canto ... Maria Bellio
Cytotoxic CD4 T lymphocytes are abundantly generated in T. cruzi-infected mice, predominantly infiltrate infected hearts, depend on T-cell intrinsic IL-18R/MyD88 signaling for expansion and their blood frequency correlates with the severity of chronic myocarditis in patients with Chagas disease.
Danielle Holz, Aaron R Hall ... Dimitrios Vavylonis
Computational modeling and single molecule imaging data support frequent disassembly and annealing of newly assembled actin, a process that can underlie structural changes of lamellipodial actin networks.
Phenotypic variants that avoid antibiotic accumulation within clonal bacterial populations are a significant contributor to antibiotic treatment failure and can rely on previously unrecognised survival strategies such as fast growth during drug treatment.
Combined experimental and theoretical analysis identifies a molecular mechanism akin to working memory that enables single cells to perform complex navigation tasks in changing growth factor fields, beyond simple stimulus-response associations.
Feifei Zhang, Margo Chase-Topping ... Mark EJ Woolhouse
In three different regions including the United States, China, and Africa, virus discoveries were strongly associated with GDP and land use, but were less likely to be associated with climate and biodiversity variables than at a global scale.
Spenser S Smith, Daniel Chu ... Richard A Schneider
Multiple levels of gene regulation in the TGFβ signaling pathway mediate the expression of Mmp13, establish species-specific domains of bone resorption, and likely generate evolutionary variation in jaw length.
Chidiebere Akusobi, Bouchra S Benghomari ... Eric J Rubin
PBP-lipo is an essential cell-wall synthesis enzyme in Mycobacterium abscessus that localizes to the septum and whose expression is required for normal cell growth and division, as well as mediating sensitivity to several antibiotics including the β-lactams, ampicillin, and amoxicillin.
Mohammad Ali Salehinejad, Elham Ghanavati ... Michael A Nitsche
The sleep-deprived brain in humans undergoes upscaled intracortical excitability which diminishes induction of LTP-like plasticity via transcranial electrical stimulation while converting the LTD-like to LTP-like plasticity and these physiological changes couple with impaired learning, memory, and attention at behavioral level.
A hydrodynamic model of fish swimming in a channel predicts a critical flow speed for fish to successfully swim against a flow, unveiling a passive mechanism for rheotaxis to emerge without access to any sensory information.
The frequently observed relationship between perceptual performance and correlated variability in sensory cortex can be explained by observers using a decoding strategy that prioritizes generality for many stimuli over precision.
Jonathan E Phillips, Maribel Santos ... Duojia Pan
Genome editing in a close unicellular relative of animals suggests a premetazoan function of the Hippo pathway effector YAP/TAZ/Yorkie in the regulation of cytoskeletal dynamics and multicellular morphogenesis but not proliferation.
Shreya H Dhume, Steven A Connor ... Tabrez J Siddiqui
LRRTM1 and LRRTM2 play multifaceted roles in the molecular organization of neuronal circuits through mediating context-dependent functions in synapse development but independent roles in plasticity and cognition.
Comprehensive proteomic investigation and functional studies unravel an essential role of differentiated glioma cell-secreted fibromodulin (FMOD) in regulating glioblastoma tumor growth by inducing angiogenesis by activating integrin-dependent Notch signaling in endothelial cells, highlighting FMOD as a potential therapeutic target.
A biophysical model of the process by which bacteria transition from the motile planktonic state to the immobilized biofilm state yields testable predictions in terms of two dimensionless parameters, one describing nutrient availability and the other describing cellular dispersal.
HyungGoo R Kim, Dora E Angelaki, Gregory C DeAngelis
Neural recordings from macaque area MT reveal a novel mechanism for detecting moving objects during self-motion, involving neurons with incongruent tuning for depth from motion parallax and binocular disparity cues.
Michaela A Edmond, Andy Hinojo-Perez ... Rene Barro-Soria
Because voltage-gated KCNQ2 channels are central to physiological and pathophysiological events, understanding how disease-causing mutations in different channel regions disrupt function will help future development of mutation-specific antiepileptic therapies.