The Biophysical Basis for Karyopherin-Dependent Ebola Virus VP24 Nuclear Transport.

Nucleocytoplasmic trafficking is a highly regulated process that allows the cell to control the partitioning of proteins and nucleic acids between the cytosolic and nuclear compartments. The Ebola virus minor matrix protein VP24 (eVP24) hijacks this process by binding to a region on the NPI-1 subfamily of karyopherin alpha (KPNA) nuclear importers. This region overlaps with the activated transcription factor STAT1 binding site on KPNAs, preventing STAT1 nuclear localization and activation of antiviral gene transcription.

Cross-sectional and Longitudinal Associations Between Sleep Traits and Work-Related Pay, and Performance.

Study Objective: The aim of the study was to examine cross-sectional and longitudinal relationships between sleep traits and work-related pay, and performance.

Methods: We use data from adult respondents to the UK Household Longitudinal Survey, to relate sleep duration, and sleep quality to work-related pay and two presenteeism measures.

Results: We find short and long sleep durations, as well as poor quality sleep are associated with lower pay, and worse presenteeism; however, only relationships between sleep and presenteeism are robust to inclusion of additional covariates and to using longitudinal methods.

Different relative scalings between transient forces and thermal fluctuations tune regimes of dynamic clustering.

An example system of collective behavior in the presence of active agents is the structural maintenance of chromosome (SMC) protein complexes within the nucleus that create an architecture to facilitate the organization and proper function of the genome. Of the diverse functions these SMC proteins are capable of producing, we focus on the creation of localized clusters of chromatin in the nucleolus through transient cross-links. Large-scale simulations revealed three different dynamic behaviors as a function of timescale: slow cross-linking leads to no clusters, fast cross-linking produces rigid slowly changing clusters, while intermediate timescales produce flexible clusters that mediate gene interaction.

Pattern formation along signaling gradients driven by active droplet behavior of cell swarms.

Gradients of extracellular signals organize cells in tissues. Although there are several models for how gradients can pattern cell behavior, it is not clear how cells react to gradients when the population is undergoing 3D morphogenesis, in which cell-cell and cell-signal interactions are continually changing. cells follow gradients of their nutritional source to feed and maintain their undifferentiated state.

On Discretely Structured Growth Models and Their Moments.

The logistic equation is ubiquitous in applied mathematics as a minimal model of saturating growth. Here, we examine a broad generalisation of the logistic growth model to discretely structured populations, motivated by examples that range from the ageing of individuals in a species to immune cell exhaustion by cancerous tissue. Through exploration of a range of concrete examples and a general analysis of polynomial kinetics, we derive necessary and sufficient conditions for the dependence of the kinetics on structure to result in closed, low-dimensional moment equations that are exact.

Deprivation and general practitioners' working lives: Repeated cross-sectional study.

ObjectivesTo examine how area deprivation affects the working lives of general practitioners (GPs).DesignWe analysed responses to four repeated cross-sectional surveys between 2015 and 2021. We used linear regression to relate the population deprivation ranking of the GP's practice to job pressures, job satisfaction, intentions to quit direct patient care and hours worked.

The association between predisposing, enabling and need factors and oral health care utilization among U.S. working age adults.

Background: Irregular dental visits due to cost-related delays contribute to poor oral health outcomes, dental needs, and emergency service utilization across the life course. The study investigated how predisposing, enabling, and needs factors are associated with cost-related delays in oral health care and postponed dental visits.

Methods: Using secondary data from the 2022 National Health Interview Survey for United States (U.

Proteins with proximal-distal asymmetries in axoneme localisation control flagellum beat frequency.

The 9 + 2 microtubule-based axoneme within motile flagella is well known for its symmetry. However, examples of asymmetric structures and proteins asymmetrically positioned within the 9 + 2 axoneme architecture have been identified. These occur in multiple different organisms, particularly involving the inner or outer dynein arms.

Stroke Incidence and High-Sensitivity C-Reactive Protein Among African Americans: The Jackson Heart Study.

Background: Strokes are a leading cause of death and disability among African Americans in the United States. Biological markers to predict stroke remain elusive; thus, our objective was to investigate whether inflammation, as measured by high-sensitivity C-reactive protein (hs-CRP), was associated with stroke incidence among African Americans enrolled in the Jackson Heart Study (JHS).

Methods: Baseline hs-CRP levels were categorized in quintiles: quintile 1 (0.

Cross-sectional relationships of circadian misalignment and rest-activity rhythms with occupational attainment in UK Biobank participants.

Circadian misalignment and disrupted rest-activity rhythms have been linked to adverse health and educational outcomes, yet few studies have considered their relationships with economic outcomes. We investigate associations between multiple accelerometer-measured circadian misalignment traits (Composite Phase Deviation and the Sleep Regularity Index) and rest-activity rhythm traits (Inter-daily Stability, Intra-daily variability and relative amplitude), with occupational attainment, measured using the average wage paid to an individual's occupation. We use data from 20 356 UK Biobank participants who wore an accelerometer (2013-16), provided employment data for the year they wore the accelerometer, and supplied covariate data at recruitment (2006-10).

HIV risk perception and PrEP uptake among black MSM in Mississippi.

Introduction: Rates for HIV are disproportionately higher for Black men who have sex with men (MSM) compared to other MSM in the U.S. While there is evidence that low perceived risk of HIV infection may increase HIV vulnerability, few studies have examined this relationship among Black MSM in the Southern U.

Different relative scalings between transient forces and thermal fluctuations tune regimes of chromatin organization.

Within the nucleus, structural maintenance of chromosome protein complexes, namely condensin and cohesin, create an architecture to facilitate the organization and proper function of the genome. Condensin, in addition to performing loop extrusion, creates localized clusters of chromatin in the nucleolus through transient crosslinks. Large-scale simulations revealed three different dynamic behaviors as a function of timescale: slow crosslinking leads to no clusters, fast crosslinking produces rigid slowly changing clusters, while intermediate timescales produce flexible clusters that mediate gene interaction.

Interruption of the intratumor CD8 T cell:Treg crosstalk improves the efficacy of PD-1 immunotherapy.

PD-1 blockade unleashes potent antitumor activity in CD8 T cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen the response to immunotherapy. Tumor-Treg inhibition is a promising strategy to improve the efficacy of checkpoint blockade immunotherapy; however, our understanding of the mechanisms supporting tumor-Tregs during PD-1 immunotherapy is incomplete. Here, we show that PD-1 blockade increases tumor-Tregs in mouse models of melanoma and metastatic melanoma patients.

Fipronil Affects Craniofacial and Heart Development in Zebrafish Embryos ().

Fipronil is a broad-spectrum insecticide that has off-target effects in developing vertebrate embryos. In this study, we investigate treatment of zebrafish embryos with fipronil over the course of 5 days and examine the effects on body length, the cardiovascular system, and craniofacial morphology. We found the insecticide caused shorter body length and a decrease in eye size.

Understanding health behaviors that modify the risk for obesity in ADHD.

Objective: Research provides support for the associated risk of inadequate sleep duration, limited physical activity, and excessive media use in attention-deficit/hyperactivity disorder (ADHD) and obesity. The present study aims to (1) examine the association between ADHD and overweight or obese status (OW/OB); (2) comprehensively examine sleep duration, physical activity, and media use as potential moderators of OW/OB; and (3) examine the moderating effects of these health behaviors cross-sectionally by comparing medicated youth with ADHD, unmedicated youth with ADHD, and youth without ADHD.

Methods: Data were acquired from the 2018 and 2019 National Survey of Children's Health, a nationally representative survey of caregivers conducted across the United States.

Male dingo urinary scents code for age class and wild dingoes respond to this information.

Chemical information in canid urine has been implicated in territoriality and influences the spacing of individuals. We identified the key volatile organic compound (VOC) components in dingo (Canis lupus dingo) urine and investigated the potential role of scents in territorial spacing. VOC analysis, using headspace gas chromatography-mass spectrometry (GC-MS), demonstrated that the information in fresh urine from adult male dingoes was sufficient to allow statistical classification into age categories.

Turing Instabilities are Not Enough to Ensure Pattern Formation.

Symmetry-breaking instabilities play an important role in understanding the mechanisms underlying the diversity of patterns observed in nature, such as in Turing's reaction-diffusion theory, which connects cellular signalling and transport with the development of growth and form. Extensive literature focuses on the linear stability analysis of homogeneous equilibria in these systems, culminating in a set of conditions for transport-driven instabilities that are commonly presumed to initiate self-organisation. We demonstrate that a selection of simple, canonical transport models with only mild multistable non-linearities can satisfy the Turing instability conditions while also robustly exhibiting only transient patterns.

Optimal face-to-face coupling for fast self-folding kirigami.

Kirigami-inspired designs can enable self-folding three-dimensional materials from flat, two-dimensional sheets. Hierarchical designs of connected levels increase the diversity of possible target structures, yet they can lead to longer folding times in the presence of fluctuations. Here, we study the effect of rotational coupling between levels on the self-folding of two-level kirigami designs driven by thermal noise in a fluid.

Polymer Modeling Reveals Interplay between Physical Properties of Chromosomal DNA and the Size and Distribution of Condensin-Based Chromatin Loops.

Transient DNA loops occur throughout the genome due to thermal fluctuations of DNA and the function of SMC complex proteins such as condensin and cohesin. Transient crosslinking within and between chromosomes and loop extrusion by SMCs have profound effects on high-order chromatin organization and exhibit specificity in cell type, cell cycle stage, and cellular environment. SMC complexes anchor one end to DNA with the other extending some distance and retracting to form a loop.

NeST: nested hierarchical structure identification in spatial transcriptomic data.

Spatial gene expression in tissue is characterized by regions in which particular genes are enriched or depleted. Frequently, these regions contain nested inside them subregions with distinct expression patterns. Segmentation methods in spatial transcriptomic (ST) data extract disjoint regions maximizing similarity over the greatest number of genes, typically on a particular spatial scale, thus lacking the ability to find region-within-region structure.

VisualPDE: Rapid Interactive Simulations of Partial Differential Equations.

Computing has revolutionised the study of complex nonlinear systems, both by allowing us to solve previously intractable models and through the ability to visualise solutions in different ways. Using ubiquitous computing infrastructure, we provide a means to go one step further in using computers to understand complex models through instantaneous and interactive exploration. This ubiquitous infrastructure has enormous potential in education, outreach and research.

Study on Local-Structure Symmetrization of KXF Crystals Doped with Mn Ions by First-Principles Calculations.

The crystals of Mn-activated fluorides, such as those of the hexafluorometallate family, are widely known for their luminescence properties. The most commonly reported red phosphors are AXF: Mn and BXF: Mn fluorides, where A represents alkali metal ions such as Li, Na, K, Rb, Cs; X=Ti, Si, Ge, Zr, Sn, B = Ba and Zn; and X = Si, Ge, Zr, Sn, and Ti. Their performance is heavily influenced by the local structure around dopant ions.

Interruption of the Intratumor CD8:Treg Crosstalk Improves the Efficacy of PD-1 Immunotherapy.

PD-1 blockade unleashes the potent antitumor activity of CD8 cells but can also promote immunosuppressive T regulatory (Treg) cells, which may worsen response to immunotherapy. Tumor Treg inhibition is a promising strategy to overcome therapeutic resistance; however, the mechanisms supporting tumor Tregs during PD-1 immunotherapy are largely unexplored. Here, we report that PD-1 blockade increases tumor Tregs in mouse models of immunogenic tumors, including melanoma, and metastatic melanoma patients.

The social capital penalty paid by teetotallers.

Social capital is important and helps protect health and reduce loneliness. Governments worldwide are pursuing policies to reduce the amount of alcohol consumed to protect public health but alcohol consumption remains a prevalent feature of social interaction in the UK. Previous studies have identified a strong relationship between alcohol and social capital which varies in direction depending on the dimension of social capital studied.