Global proteomic and acetylomic analyses reveal how skeletal muscle adapts to high-intensity interval training including adaptations to processes regulating metabolism and contraction.
The central RNA interference protein, human Argonaute-2, releases its target following phosphorylation on a critical loop in the protein, freeing microRNA-bound Argonaute-2 to seek out and repress additional targets.
The midbrain periaqueductal grey is a conserved mediator of elaborate courtship behavior in a range of vertebrate taxa, likely shaping how this behavior diversifies across the tree of life.
Altered coupling of different brain waves during sleep is associated with worse brain features related to Alzheimer’s disease processes and cognitive performance, suggesting that sleep brain waves coupling may contribute to poorer brain and cognitive trajectories in ageing.
Urban wildlife harbor gut bacteria found in humans but missing from rural wildlife, consistent with bacterial transmission from humans to wildlife in cities.
Horizontal cell undergoes amoeboid-like migration in the developing vertebrate retina, a not previously reported migration mode in the central nervous system, that allows them to move within a densely packed tissue without predetermined paths.
Phenotypic heterogeneity at the single-cell level of cellulosomal machinery biosynthesis suggests a division-of-labor strategy as revealed by the nanoscale mechanistic and ecological investigation of in situ structure and distribution of cellulosomes on bacteria while interacting with the cellulosic substrate.
Scenario-invariant representation of physical stability is found in the frontoparietal regions but not the ventral visual pathway (and ImageNet-trained convolutional neural networks), consistent with the hypothesis that computations underlying physical stability may entail forward simulations of what will happen next.
Normal adipogenesis requires de novo DNA methyltransferase 3A (DNMT3A) for proper differentiation and suppression of an age-associated pathogenic inflammatory program.
Prominent transitions between different mental contexts produce a stereotyped brain state shared across internally and externally generated transitions but distinct from minor within-context transitions, potentially reflecting a major flushing and updating of mental models.
Promoter studies identified BMP/Smad signaling as a transcriptional regulator of Ppif gene encoding cyclophilin D, a component of the mitochondrial permeability transition pore, and gain- and loss-of-function experiments determined how such regulation affects osteogenic differentiation.
Single unit recordings in monkeys and biophysical modelling demonstrate that local inhibitory-controlled metastable neural states specify the temporal organization of cognitive functions in frontal areas.
Substrate rigidity modulates genomic stress in the epidermal basal cells of the developing zebrafish embryo and Yap1 and Wwtr1 are required for its survival.
Time-resolved multiomics analysis during Oct4 depletion and recovery reveals concentration-dependent activities of Oct4 in controlling enhancer transcription and chromatin accessibility in mouse embryonic stem cells.
Two-photon functional imaging linked to olfactory preference in Drosophila provides the first understanding of how odors are integrated, transformed, and represented in the lateral horn by an ensemble of higher-order glutamatergic lateral horn neurons.
Advanced machine learning based brain signal decoding of grip-force as a proxy for movement vigor shows Parkinson's disease related performance reduction, suggestive of a loss of cortical vigor encoding in the absence of dopamine.
The sense of smell of female hawkmoths has evolved to find the intense odor of floral nectar sources as well as inconspicuous scents of oviposition sites within a complex olfactory landscape.
Using mass spectrometry to study protein composition of translating ribosomes under unstressed or stress conditions, aspartate aminotransferase 2 (Aat2) is identified as a metabolic enzyme with a moonlighting function in the yeast integrated stress-response pathway.
While performing learned movements at different speeds, motor cortex population activity can be understood based on the need to generate muscle activity via smooth, well-behaved dynamics.
Hybridization not only generates genetic diversity, but this diversity can alter the shape of the fitness landscape, changing which genotypic combinations are favored by natural selection and which accessible genotypic paths lead to novel fitness peaks.
Cryogenic super-resolution microscopy resolves the three-dimensional arrangement of individual fluorescent markers attached to protein complexes with Angstrom precision through their blinking behavior, polarization selection and a classification scheme.
A high-throughput small molecule screen defined compounds that inactivate primary human hepatic stellate cells (HSCs) and led to the identification of nanchangmycin, which regulates intracellular Ca2+ levels and the activity of multiple kinases to control HSC fibrotic activity.
Evidence that enhancer strength determines the extent of random monoallelic gene expression, and that even lineage defining genes thought to be expressed by all cells in a lineage display some degree of random monoallelic expression.
The expression of CD32 in HIV-reservoir cells prevents the binding of specific anti-HIV antibodies conferring resistance to NK cell-mediated death, and gives the cell the potential to proliferate in the presence of immune complexes.
When conducting fear conditioning in mice, cue-elicited activity bursts are primarily a result of nonassociative processes, and freezing behavior remains the best index for associative learning.
Human intracranial electroencephalographic recordings reveal the electrophysiological properties and hierarchical organization of spontaneous neuronal oscillations in the human insula and show that these oscillations are traveling waves, thus providing new insights into intrainsular and interinsular communication.
Partial response electromyography is a useful and reliable measure of action stopping in a stop signal task, supported by psychometric and meta-analytic evidence.
The auditory system adapts to the changing acoustics of reverberant environments by temporally shifting the inhibitory tuning of cortical neurons to reduce the effects of reverberation.
Six- to twelve-month old infants, who have little linguistic or object experience, classify objects by relying on a invariant representation of global shape known as the shape skeleton.
Anatomical and synaptic reconstructions of gustatory axons from the adult Drosophila labellum reveal different classes of gustatory neurons recognizing different taste modalities.
Identification of a novel role for the transcriptional repressor, MAF1, and RNA polymerase III-dependent transcription, in osteoblast differentiation, mineralization, and bone biology.
The treeline follows climate warming with a severe time lag, but migration rates are increasing so that only under ambitious mitigation efforts will 30% of original tundra areas remain in the north in the long run.
Functional imaging (fMRI) across four mammalian species maps the brain areas engaging in burst-suppression activity during anesthesia, and uncovers differences between primates and rodents.
The explanation of why older people show increased behavioral variability despite having decreased neural signal variability lies in the link between the dynamics of the ongoing neural signal and the trial-by-trial variability of neural evoked responses.
Patients with Type 2 diabetes show patterns of neurodegeneration consistent with accelerated brain aging, including impaired cognition and loss of brain volume, which are more severe in those with increased disease duration.
The associations of egg consumption with metabolic markers and of these markers with cardiovascular disease (CVD) risk showed opposite directions, which may partially explain the protective effect of moderate egg consumption on CVD in the Chinese population.
Social-affective features predict the perceived similarity of real-world actions better than, and independently of, visual and action-related features, and are extracted at the final stage of a temporal gradient in the brain.
Despite relative impermeability of the blood-brain barrier for calcitonin gene-related peptide antibodies used in migraine treatment, these antibodies induce certain and highly specific brain effects particularly in the hypothalamus which may be part of the mechanism of their efficacy.
A standardized comparison of contractile force among in vitro muscle tissues across different platforms requires proper normalization with the contractile area and complementary morphological, maturation, and functional analysis to reduce variability and boost a new generation of engineered constructs.
Dcp2 C-terminal domain cis-regulatory elements collaborating with specific activators control decapping enzyme targeting and activation by orchestrating sequential assembly of distinct decapping complexes.
Loss of Dnmt3a in excitatory neurons disrupts synaptic morphology and behavior, and triggers the expansion of H3K27me3 binding, suggestive of increased polycomb repression.
A modified viral strategy reveals that ventral tegmental area dopamine cells receive substantial inputs from local sources, including distributed GABAergic and serotonergic inputs from the midbrain as well as extensive inputs from other midbrain dopamine cells.
4,6-Sulfation of chondroitin sulfate proteoglycans prevents sympathetic nerve regeneration into the infarct after myocardial ischemia/reperfusion, and reducing this sulfation promotes nerve regeneration and decreases arrhythmia susceptibility.
A comprehensive excitatory projectome of the ventro-lateral prefrontal cortex in macaques was generated by using viral tracing integrated with serial two-photon tomography and diffusion tractography, thus providing new evidence of rejecting the monosynaptic connection of inferior fronto-occipital fasciculus in monkeys.
Method NEAdriver employs knowledge from global networks to predict novel cancer driver genes in an individualized manner, which is done by accounting for mutations’ co-occurrence in each tumor genome and rigorous statistical evaluation.
Lead-OR visualizes results derived from microelectrode recordings in anatomical space, together with information derived from patient-specific MRI data, as well as high-resolution atlas resources during deep brain stimulation surgery.
Brucella facilitates its intracellular parasitism by hijacking the host-regulated IRE1α-dependent decay (RIDD)-BLOS1 innate immune defense system through the disassembly of the BLOC-1-related complex that results in the perinuclear trafficking of Brucella-containing vacuoles and enhanced susceptibility to infection.
Although many Apical Ectodermal Ridge signaling components are found in the axolotl limb epidermis, responsiveness to canonical Wnt signaling has shifted to the limb mesenchyme where it regulates mesenchymal Fgf8 expression.
An amino acid dimorphism in HLA-C with an established impact on natural killer cell receptors plays an unexpected and significant role in T cell receptor recognition of HLA-C with relevance for tumor immunity.
Single-cell transcriptomics of the zebrafish ovary identifies both major and minor cell types and provides a valuable resource for researchers interested in reproductive biology, stem cell biology, and aquatic toxicology.
SARS-CoV-2 host-shutoff inhibits innate NK surveillance by suppressing activating ligands, however ADCC provides a potent NK stimulus that is mediated by antibodies targeting Nucleocapsid, ORF3a, and Membrane, with those targeting Spike being significantly weaker.
Selection acting on SARS-CoV-2 variants altering the infectivity profile depends on levels of transmission in the community, and this dependence is used to infer Alpha and Delta variants infectivity profiles.
The functions of seipin in triacylglycerol nucleation and lipid droplet maturation are studied with all-atom and coarse-grained simulations along with cell experiments, providing a novel model for lipid droplet formation.
Live-imaging of Notch-dependent transcription in vivo reveals that cell movements during gastrulation influence transcription levels, and do so downstream of Notch cleavage, illustrating the importance of crosstalk between mechanics and transcription in the context of embryonic development.
Multiple non-redundant features of non-rapid eye movement sleep are altered in schizophrenia and largely independent of waking electrophysiological abnormalities, supporting the promise of neuropsychiatric disease biomarkers based on a precise dissection of the sleep.
Integrative analysis of multi-tissue transcriptomics data of mice subjected to cold, mild warm or room temperature places the thermal adaptation of individual tissues in a whole-organism perspective.
During epigenetic transcriptional memory in budding yeast, histone H3 lysine 4 dimethylation - dependent on Nup1000 and independent of RNA polymerase II - regulates binding of a critical transcription factor and, once established, is mitotically heritable for at least four cell divisions.
Increasing muscle length, rather than increasing stretch amplitude, contributes more to residual force enhancement during submaximal voluntary contractions of the human quadriceps.
In paediatric concussions, there are a multiplicity of ways that brain damage gives rise to symptoms, most of which are missed by conventional statistical approaches and study designs.
The generalizability of CODOP in distinct world regions and its flexibility to reckon with the changing availability of hospital resources makes it a clinically useful tool potentially improving the outcome prediction and the management of COVID-19 hospitalized patients.
A novel mechanism describes how tonic activation of nicotinic acetylcholine receptors can modulate the timing of striatal output by priming feedforward inhibition.
The cryogenic-electron microscopy structure of IL-27 bound to receptors, IL-27Rα and gp130, revealing a three-site assembly mechanism and overall topology and molecular details reminiscent of IL-6 but distinct from related IL-12 and IL-23.
The combination of single-cell analysis and cell fate mapping studies evidenced the presence of AIRE-expressing transit-amplifying thymic epithelial cells, which differentiate into mature medullary thymic epithelial cells expressing tissue-specific antigens.
Individuals within the autism spectrum disorder implicitly outweigh integration (rather than segregating) when performing causal inference and have developed an explicit compensatory mechanism as reflected in choice biases.
Blocking of the function of neurotransmitter receptors by insecticidal peptide toxins resulted in identification of nicotinic acetylcholine receptor subunits through native ligand-binding investigations.
NET-seq analysis of 41 S. cerevisiae transcription regulatory factors uncovers their differential and opposing effects on Pol II transcription elongation and antisense transcription, revealing that wild-type transcription is balanced by the joint impact of many regulators.
Salamanders originate as metamorphosed with a biphasic lifestyle as shown by the palate shape and several non-shape features associated with the vomerine teeth, with diverse ecological types displayed in living species achieved in the Early Cretaceous.
Effective antiestrogens engage a new structural interaction to improve therapeutic antagonism in hormone-resistant breast cancer cells expressing Y537S estrogen receptor alpha.
Molecular analyses and unbiased CRISPR screens reveal that extensive end resection occurs in quiescent cells after inducing DNA double strand breaks, in a manner dependent on DNA-PK.
The essential role of focal adhesion kinase in locally regulating insulin secretion and calcium responses in pancreatic beta cells is identified through the use of the pancreatic slice technique.
Telomere dysfunction in iPSC-derived type II alveolar epithelial cells causes senescence and gene expression changes including Wnt-related changes that GSK3 inhibition can rescue, providing insight into pulmonary fibrosis pathogenesis.
Beyond its well-accepted function in metastasis, non-receptor tyrosine kinase FER also controls ovarian tumor cell proliferation through FER-IRS4-AKT signaling axis, making itself as a promising druggable target for the disease.
Inositol polyphosphate multikinase physically binds to the core subunits of SWI/SNF complex and plays an important role in regulating BRG1 occupancy and BRG-mediated chromatin accessibility in mouse embryonic stem cells.
A comprehensive molecular interrogation of CREB5 interactions identified changes in protein and chromatin interactions of FOXA1 that promoted therapy resistance in prostate cancer cells.
Brief fictive carbon dioxide sensation induced by optogenetics in the female mosquito induces long-lasting arousal and probing, explaining the persistent predatory behavior of this dangerous disease-vectoring insect.
Uphill migrations of lowland plants into warming alpine ecosystems may yield a positive climate feedback by accelerating soil microbial respiration and decreasing soil carbon content.
Comparing humans and mice, the protein composition of central nervous system myelin and the transcriptional profiles of myelin-producing oligodendrocytes are largely similar with respect to abundant structural myelin constituents but show divergent expression of a range of other distinct genes.
Studies of organoid morphogenesis, combined with proteomics and molecular profiling, identify the THBS1-YAP axis as a signalling mechanism that mediates paracrine communication between tumour cells and their wildtype epithelial neighbours.
A genome-wide CRISPR/Cas9 knockout screening approach identified C/EBPδ as transcriptional regulator of the alarmins S100A8 and S100A9 during differentiation of monocytes and inflammatory processes in vivo.
Deciphering the mechanism of action of a large family of natural and synthetic cytotoxic lipids bioactivated by enantiospecific oxidation into protein-reactive species inspires the development of enzyme-specific prodrugs.
Mathematical modelling and large-scale online experiments revealed that learning from others can induce 'smarter' decisions even when most individuals are biased towards adverse risk aversion.
More parent-reported infections in the first year of life were associated with metabolic differences linked with cardiovascular and metabolic disease in adulthood, with observational evidence for inflammation partly mediating this relationship.
Colour-controlled c-di-GMP signalling mediates directional switch of phototaxis via within-a-pole regulation of type IV pili in rod-shaped cyanobacteria Thermosynechococcus vulcanus.
Single-cell time-lapse imaging and optogenetical gene recombination system uncovered that bacteria cells can overcome a deleterious genetic change of antibiotic resistance gene deletion depending on their environmental histories.
A high-resolution approach for monitoring dry mass and the density of that dry mass on a single-cell level is developed and used to reveal that mammalian cells can lose components in mitosis due to lysosomal exocytosis.
Humans are able to generate a complete category of varied objects from just one exemplar shape, identifying and utilizing its most distinctive parts to create a coherent group, even for other observers.
Normalizing Tcf4 expression during early postnatal development improves behavioral outcomes in Pitt-Hopkins syndrome (PTHS) model mice, suggesting that genetic therapies are feasible in individuals with PTHS.
Unique mechanisms of genetic exchange in the important protozoan pathogen Trypanosome cruzi were characterized in detail using genome analyses of hybrid clones at different time points, showing initial tetraploids followed by genome erosion.
Membrane homeostasis in bacteria relies on the controlled degradation of endogenous phospholipids by intracellular phospholipases A, however their structures and catalytic mechanism are still poorly understood.
Together, our multi-tissue single-cell data shows that CD56bright NK cells accumulate in the periventricular brain regions of multiple sclerosis (MS) patients, bringing NK cells back to the spotlight of MS pathology.
The transcriptomes of hematopoietic stem and progenitor cells of human juvenile myelomonocytic leukemia patients and a zebrafish model for Noonan syndrome reveal a common inflammatory response, which may have a causal role in associated myeloproliferative neoplasm.
Analysis of performance on a novel behavioural paradigm investigating active information gathering reveals that subjective cognitive impairment is associated with hyperreactivity to uncertainty and links this mechanism to the affective burden in the condition and heightened insular-hippocampal connectivity.
Repressing astroglial PTBP1 by shRNA or antisense oligonucleotide fails to convert astrocyte to neuron including dopaminergic neuron in a 6-OHDA mouse model of PD.
COV-ID is a highly scalable technology that utilizes a two-step barcoding strategy to detect viral RNAs in saliva samples combining RT-LAMP, PCR, and next generation sequencing.
MDGAs are highly diffusive molecules that alter both neuroligin-1 and AMPA receptor dynamics and function, thereby significantly delaying the differentiation of excitatory post-synapses.
Both the polypeptide and attached O-glycans N-terminal to the A1 domain in von Willebrand factor lower its affinity for its ligand GPIbα on platelets, its stability, and structural dynamics and decrease population of a high-affinity, intermediate state in unfolding.
A novel mouse model which permits tracking of papillomavirus infected cells in mouse stratified epithelia during early infection by means of genetic reporter activation.
Colored surfaces induce gamma oscillations in human early visual cortex that are equally strong for red and green colors when L-M cone contrast is controlled for.
The hippocampal CA1 20–40 Hz rhythm is associated with nonspatial sequence memory processing and may contribute to the role of the hippocampus in processing temporal relationships among events.
Some deleterious mutations co-occurring within a genome can compensate each other, and this affects patterns of polymorphism, particularly in highly polymorphic species.
A medaka mutant revealed that Wnt11 promotes formation of uniquely large protrusions from non-myogenic dorsal dermomyotome cells, which guide the epaxial myotome dorsally to achieve the coverage of the neural tube.
When human participants are able to plan responses in a visuo-spatial working memory task, sensory-like representations of remembered spatial position in early visual and parietal cortex adaptively trade off with motor-like representations of upcoming actions in sensorimotor cortex.
A tissue-wide fluoresence-based screen reveals that not all tissues in an organism (Drosophila) reinforce a hierarchy of codon usage to the same extent, a finding which impacts tissue-specific protein expression and function.
High-resolution blood flow imaging confirms the presence of large, long-living synchronous clusters in renal microcirculation and reveals how vasoactive drugs affect synchronization properties.
In a chemical genetics study, JM03 derived from crotamiton, an inhibitor of trainsient receptor potential vanilloid-4 channels, was identified to extend lifespan and improve oxidative and hypertonic stress resistance in Caenorhabditis elegans via inhibiting OSM-9.
Hematopoietic progenitor cells employ CD47 to engage thymic portal endothelial signal regulatory protein alpha for their transendothelial migration and thymic homing.
The primate caudal area 47/12 is anatomically and functionally connected with the main nodes of the salience network, supporting the role of the ventrolateral prefrontal cortex in all major attention networks.
The Kv3.3 potassium channel subunit is necessary and sufficient to permit presynaptic location and accelerated repolarisation of the presynaptic action potential, thereby conserving resources and enhancing accuracy of timing information on transmission at the calyx of Held excitatory synapse.
The HIV proteins Env and Rev encode helices that overlap in the viral genome but alternate in functional importance so that the non-functional surface of one helix encodes the functional surface of the other.
MorphoGraphX is a user-friendly image processing software primarily aimed at segmenting 3D biological images into cells, quantifying cellular gene expression and growth, and understanding these data in the spatial context of developing organs.
A MRI study of virally infected CNS demonstrates the utility of MRI in detecting the earliest pathological events and studying pathogen-specific T cells at the level of single cell as well as the therapeutic potential of antiviral T cells.
The mechanistic origins of distinct brain malformations associated with different substitutions at α-tubulin residue 409 are examined, revealing disruption of neuronal migration and microtubule regulation by XMAP215 that scales from protein to tissue.
Designer transmembrane peptides precisely control chimeric antigen receptor signaling strength and are insulated from undesired interactions with endogenous receptors.
Late effects of radiation therapy in mice can be prevented by treatment with either senolytics navitoclax or quercetin plus dasatinib or the senostatic metformin.
Rat blood profiles support non-linear aging with distinct trajectory shifts, and these profiles could be used to predict non-overt illness in rats or aging intervention efficacy.
The hypothalamic parasubthalamic nucleus can be subdivided into two distinct populations, one of which decreases food consumption and is necessary for the full appetite-suppressing effects of anorexigenic hormones.
Optogenetic and electrical stimulation of primary visual cortex neurons reveals synaptic and cell-intrinsic mechanisms that underlie neuronal ensemble formation.
A vessel and brain fusion organoid model provides a platform for the study of interactions between neuronal and non-neuronal components during brain development and functioning.
Evidence for a largely unexplored radiation of squamates (lizards, snakes, and amphisbaenians) in the Middle to Late Jurassic is revealed by analyses of morphospace expansion, disparity, and evolutionary rates.
A novel population of adipocytes that play essential roles in adaptive thermogenesis via cell autonomous and non-autonomous effects and regulate systemic glucose metabolism in mice.
Proteolytic cleavage of the extracellular matrix glycoprotein fibrillin-2 by the secreted metalloprotease ADAMTS6 influences skeletal development by modulating fibrillin microfibril abundance and GDF5/BMP signaling, illustrating the crucial role of extracellular matrix proteostatic mechanisms in growth factor regulation during morphogenesis.
Oncoprotein BCL6 confers tumor adaptive resistance to genotoxic stress through the IFN-BCL6-PTEN axis in solid tumors and presents a promising combinational target for chemo-sensitization.
Novel blood pressure devices provide an estimated pulse wave velocity, which is no substitute for measured pulse wave velocity and clinicians should be aware that it only reflects trends derived from representative population samples based on age and blood pressure.
Biochemical approaches and cellular experiments show a novel effect of METTL3 on homologous recombination repair and chemotherapeutic response via the m6A-YTHDC1-dependent regulation of the EGF/RAD51 axis.
Biperiden, but not amisulpride, delays auditory mismatch responses during environmental stability, suggesting a differential sensitivity of auditory statistical learning to muscarinic versus dopaminergic receptor status which could prove useful for developing tests that predict an individual's response to antipsychotic treatment.
The spatial and temporal patterns of eye movements exhibited by humans in virtual reality reveal how they plan paths when navigating in complex, naturalistic environments.
Analytical techniques and computational models reveal novel post-translational modifications on β-myosin heavy chain in the human hearts and highlight their potential as therapeutic targets.
