The structure of the yeast RSC complex, a member of the SWI/SNF chromatin remodeling family, determined by cryo-electron microscopy, reveals a conserved structural core and the mode of nucleosome engagement.
Layer 5 neuron apical tuft in mouse visual cortex display widespread, highly correlated calcium signals, with a strong and asymmetric coupling to somatic signals, independent of visual stimulation and locomotion.
The ORMDL proteins function to restrain the de novo sphingolipid biosynthetic pathway during myelination, when there is a high demand for sphingolipids to prevent excessive accumulation of metabolic intermediates.
Pleasant touch perception in humans is unaffected by spinothalamic disruption indicating integrated spinal processing of hedonic and discriminative tactile inputs rather than privileged C-tactile-lamina I-spinothalamic projections.
Client protein-driven reversal of endoplasmic reticulum chaperone (BiP) mediated-repression is revealed as a principal component of the regulation of the unfolded protein response transducer IRE1 in cells.
The human cytomegalovirus (HCMV) interactome systematically characterises high-confidence viral-viral and viral-host protein interactions in HCMV-infected cells, facilitating multiple novel insights into HCMV and herpesviral function.
Generation of a premotor/motor neuron comprehensive TEM reconstruction, functional optogenetics, and recurrent network modeling reveals different phase relationships among a subset of Drosophila motor neurons in forward versus backward locomotion.
Electrophysiological and simulation approaches show that a chloride-related longer relaxation of the inhibitory synaptic events partially compensates the early defect in the chloride homeostasis detected in fetal SOD spinal motoneurons.
Self-reactive thymocyte death is most efficient when peptide-presenting cells are phagocytic, and blocking phagocytosis inhibits self-reactive thymocyte death, suggesting that phagocytes play central roles during thymocyte negative selection.
Dark exposure lowers the MMP9 activation threshold, and subsequent light stimulation to an amblyopic eye is sufficient to induce proteolysis at thalamo-cortical synapses in deprived mouse visual cortex.
Human cullin-RING ligases are buffered to a much greater extent than had been previously appreciated, and the roles of ubiquitin chain extension enzymes are far more nuanced at physiological concentrations.
A computer model of human cardiomyocyte was produced and validated on independent datasets, overcoming shortcomings of its predecessors, also yielding broadly relevant insights and results on major ionic currents.
The Timothy syndrome mutation in Cav1.2 gives rise to defects in neuronal differentiation by preventing a developmental switch in channel splicing and elevating calcium signaling in differentiating cells.
The internalization of the angiogenic receptor VEGFR2 expressed in neurons is controlled by ephrinB2 and is required for neuronal dendritic arborization, spine morphogenesis and circuitry development in the hippocampus.
The pseudoenzyme CPT1C is able to sense changes in intracellular malonyl-CoA levels caused by nutrients or energy stress and regulate late endosomes/lysosomes anterograde transport, necessary for proper axon growth.
Identifying FMRP-bound mRNAs in hippocampal CA1 pyramidal neurons reveals cell-type specific regulation of autism-candidate and circadian mRNAs and FMRP-mediated control of memory across the circadian cycle.
Giardia, a multi-ciliated parasitic protist, maintains four different flagellar lengths by balancing flagellar length-independent IFT-mediated assembly with length-dependent kinesin-13 mediated disassembly.
Direct insular recordings in humans reveal that contrary to several prominent models of speech production, it is not engaged in pre-articulatory planning, but in auditory and somatosensory components of speech.
A mechanistic link between TLE3 loss and glucocorticoid receptor-mediated androgen receptor inhibitor resistance supports the rationale to target GR during anti-hormonal treatment in castrate-resistant prostate cancer.
Genomic deletions formed from inter-fork strand annealing associated with a collapsed replication fork are suppressed by the FANCM-related DNA helicase Fml1 in conjunction with its partner proteins Mhf1 and Mhf2.
A human psychopharmacology study reveals that a drug that affects the dopamine and noradrenaline systems enhances people's ability to adapt their learning rate to suit the volatility of the environment.
The conductance-based encoding model creates a new bridge between statistical models and biophysical models of neurons, and infers visually-evoked excitatory and inhibitory synaptic conductances from spike trains in macaque retina.
APOBEC3G, an anti-viral protein with the capability to inhibit HiV-1 infectivity, binds single stranded DNA in multiple physical conformations, enabling complex interactions that allow APOBEC3G to perform multiple diverse functions.
Interactions among parasites in snails create cascading effects on their transmission and highlight that biodiversity has complex, context-dependent and important effects on human schistosomiasis transmission dynamics.
Cell-based high-throughput screening identifies IBT21 as a chemical chaperone, that inhibits ER protein aggregation and prevents the cell death caused by a proteotoxin, the aggregation-prone prion protein.
Unsteady state modeling of blood cell populations reveals that blood loss triggers a cellular clearance delay and a cellular production increase, and modeling provides earlier detection and individualized patient characterization.
Functional hypoconnectivity between ‘social brain’ default mode circuitry and visual association cortex underpins a subtype of autistic toddlers with a strong preference to attend to the non-social visual world.
Cryo-electron microscopy structures, combined with biochemical experiments, show how the E. coli F element-encoded TraR protein regulates transcription initiation by altering RNA polymerase conformation and conformational heterogeneity.
Inspiratory rhythmogenesis is mediated by an emergent mechanism independent of bursts associated with motor output and is modulated by opioids, pointing to strategies for ameliorating opioid-induced respiratory depression.
The gluconeogenic enzyme PCK1 and pyrimidine nucleotide biosynthetic enzyme DHODH drive hypoxic pyrimidine nucleotide biosynthesis and liver metastatic colonization in colorectal cancer, which is therapeutically exploitable by DHODH pharmacologic inhibition.
Telophase reorientation corrects errors in spindle orientation that persist after imprecise initial spindle positioning during early mitosis, and contributes to balancing self-renewal with differentiation during epidermal development.
Parturition gene regulation across multiple cell-types and placental compartments is deciphered at single cell resolution, highlighting the common role of the NFKB pathway in both term and preterm birth.
Quantitative comparison of clathrin-mediated endocytosis in budding and fission yeast identified conserved mechanisms and species-specific adaptations with broad implications that extend from yeast to humans.
Low-field single-sided magnetic resonance diffusion methods detect and measure permeability of sub-micron compartments which likely include cell processes, organelles, and cellular vesicles within ex vivo mouse spinal cords.
Establishing retinal contrast transmission as a novel determinant of mammalian fitness, this research adds functional significance to a prominent exception of nuclear organization, previously described in nocturnal rod photoreceptor cells.
Comprehensive dataset of high-level cognitive assessment in mouse models of neurodegeneration, accompanied by an open-access database/repository to change the paradigm of how cognitive studies in animal models can be shared/re-used.
Text mining of complete EHRs for 14,017 diabetes patients and subsequent clustering led to phenotypically deep clusters, showing distinct glycemic profiles, comorbidities, and SNP association patterns.
The momentary levels of local cortical desynchronization and pupil-linked arousal pose dissociable influences not only on the processing of sensory information but also on human perceptual performance.
Genetic analyses in Drosophila establish the functional hierarchy of the ciliary transition zone module, Dzip1/Fam92/Cby, and reveal tissue specific variations in basal body anchoring pathways in fly ciliated tissues.
The amyloid patterns overlap with the default-mode network, whereas the tau patterns overlap with distinct functional networks and are associated with a loss of anatomical connectivity and multiple cognitive functions.
Sequential phosphorylation of NDEL1 Ser336/Ser332 by DYRK2 and GSK3β is a novel regulatory step for actin dynamics that contributes to the neurite outgrowth and neuronal arborization in the developing brain.
Two new polymorphic structures of recombinant human alpha-synuclein fibrils show striking differences to previous structures, while familial PD mutation sites remain crucial for protofilament interaction and fibril stability.
The structures of Slo1 in complex with b4 imply that the auxiliary beta subunits modulate the channel's gating properties through stabilizing ‘pre-existing’ conformations rather than creating new ones.
A computational model, based on single-cell features like contractility and polarizability, quantitatively describes cellular dynamics from the single cell level up to small cohorts and confluent tissues.
Binding of two macromolecular complexes allows kinetochores to capture force produced by the depolymerising ends of microtubules, allowing chromosomes to be transmitted from a mother cell to its two daughters.
Representational similarity analysis of human functional magnetic resonance imaging data demonstrates that the lateral occipitotemporal cortex represents action knowledge along dimensions that are in accordance with behavioural judgements.
Constraint-based modelling predicts C4 photosynthesis evolves under resource limitation from an ancestral ground state of C3 photosynthesis and attributes divergent metabolic routes in extant C4 subtypes to light.
Intravital imaging with HIV-1 viral-like particle in mouse model reveals a mechanism for HIV-1 uptake by subcapsular sinus macrophages that facilitates HIV-1 spreading tofollicular dendritic and B cells.
Impaired lysosomal acidification results in retention of iron inside lysosomes, triggering functional iron deficiency, dysfunctional mitochondria (especially mtDNA loss), and inflammation in vivo in a mouse model of lysosomal disease.
OCT4 and SOX2 display partially independent activity to regulate chromatin accessibility, and highly dynamic activity of OCT4 is required throughout the cell cycle to maintain pluripotency enhancer accessibility.
Colonisation with resistant Klebsiella pneumoniae in a Cambodian neonatal unit is driven by person-to-person transmission, transmissibility varies by sequence type, and antibiotic consumption generally increases the risk of acquisition.
That early cortical neural progenitor divisions strictly require OCLN isoform expression is a paradigm shift in the functional consideration of this protein best known for promoting between-cell barrier functions.
Computational-driven, imaging-based topological profiles of neurodegeneration differ substantially in different neurodegenerative conditions, suggesting distinct modes of dependence of the pathological spread on the underlying connectivity.
Sepsis-induced long-term muscle weakness was reproduced using a refined murine model, which was accompanied by mitochondrial dysfunction in the absence of sustained atrophy, suggesting the promise of mitochondria-targeted post-sepsis therapies.
Responses to anesthetics differ among individuals and fluctuate stochastically despite constant drug concentration, however, the amount of noise driving transitions between the responsive and the unresponsive state is conserved.
CRISPR genome editing technology can efficiently introduce mutations into lytic and latent HSV genomes to block lytic replication and reactivation of latent herpes simplex virus genome though differential mechanisms.
Notch ligands Jag1 and Dll4 and their effector Ephb2 are required in sinus venosus endocardium for primitive coronary vasculature formation and later for arterial differentiation and maturation of coronary endothelium.