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Associations between physical activity and brain structure in a large community cohort
Abstract Low physical activity (PA) and obesity are dementia risk factors, but it is unclear whether the association between PA and brain health is dependent upon degree of obesity. We aimed to examine the association between PA and brain structure and explore whether it varies by body mass index (BMI). We examined the associations between accelerometer-measured PA and magnetic resonance imaging-measured brain structure using cross-sectional data from a population-based cohort of people in midlife (UK Biobank). Using regression modelling, we explored whether these associations were mediated by BMI or other cardiometabolic risk factors. Complete data were available for 16,725 participants (median age 65 years, 55% women, median BMI 26). Greater PA was positively associated with total brain (β = 3.67, p < 0.0001), grey matter (β = 3.12, p < 0.0001), white matter (β = 0.43, p < 0.0001) and total hippocampal volumes (β = 0.05, p < 0.0001), and inversely associated with white matter hyperintensity volume (β = − 4.6 × 10−5, p < 0.0001). Although there was no interaction between PA and BMI in explaining brain volumes, BMI attenuated the PA-brain volume associations by between 18 and 58%. The PA-brain volume associations were further attenuated by other cardiometabolic risk factors and in the case of grey matter and hippocampal volume, was no longer statistically significant in fully adjusted models. Greater PA is associated with a healthier profile in brain volumes. BMI and cardiometabolic factors mediated the relationship between PA and grey matter and hippocampal volume and partially mediated its relationship with other brain volumes. These results support a mechanistic basis for PA in optimizing cardiometabolic risk for dementia prevention.
Single-cell analyses identify monocyte gene expression profiles that influence HIV-1 reservoir size in acutely treated cohorts
Abstract Eliminating latent HIV-1 is a major goal of AIDS research but host factors determining the size of these reservoirs are poorly understood. Here, we investigate the role of host gene expression on HIV-1 reservoir size during suppressive antiretroviral therapy (ART). Peripheral blood cells of fourteen males initiating ART during acute infection and demonstrating effective viral suppression but varying magnitudes of total HIV-1 DNA were characterized by single-cell RNA sequencing. Differential expression analysis demonstrates increased CD14+ monocyte activity in participants having undetectable HIV-1 reservoirs, with IL1B expression inversely associating with reservoir size. This is validated in another cohort of 38 males comprised of different ancestry and HIV-1 subtypes, and with intact proviral DNA assay (IPDA®) measurements. Modeling interactions show monocyte IL1B expression associates inversely with reservoir size at higher frequencies of central memory CD4+ T cells, linking monocyte IL1B expression to cell types known to be reservoirs for persistent HIV-1. Functional analyses reveal that IL1B activates NF-κB, thereby promoting productive HIV-1 infection while simultaneously suppressing viral spread, suggesting a natural latency reversing activity to deplete the reservoir in ART-treated individuals. Altogether, scRNA-seq analyses reveal that monocyte IL1B expression could decrease HIV-1 proviral reservoirs in individuals initiating ART during acute infection.
Synergistic impact of serum uric acid and ferritin on MAFLD risk: A comprehensive cohort analysis
Super-resolution imaging in whole cells and tissues via DNA-PAINT on a spinning disk confocal with optical photon reassignment
Abstract Single-Molecule Localization Microscopy (SMLM) has traditionally faced challenges to optimize signal-to-noise ratio, penetration depth, field-of-view (FOV), and spatial resolution simultaneously. Here, we show that DNA-PAINT imaging on a Spinning Disk Confocal with Optical Photon Reassignment (SDC-OPR) system overcomes these trade-offs, enabling high-resolution imaging across multiple cellular layers and large FOVs. We demonstrate the system’s capability with DNA origami constructs and biological samples, including nuclear pore complexes, mitochondria, and microtubules, achieving a spatial resolution of 6 nm in the basal plane and sub-10 nm localization precision at depths of 9 µm within a 53 × 53 µm² FOV. Additionally, imaging of the developing Drosophila eye epithelium at depths up to 9 µm with sub-13 nm average localization precision, reveals distinct E-cadherin populations in adherens junctions. Quantitative analysis of Collagen IV deposition in this epithelium indicated an average of 46 ± 27 molecules per secretory vesicle. These results underscore the versatility of DNA-PAINT on an SDC-OPR for advancing super-resolution imaging in complex biological systems.
The balance between integration and segregation drives network dynamics maximizing multistability and metastability
Connectome-driven neural inventory of a complete visual system
Abstract Vision provides animals with detailed information about their surroundings and conveys diverse features such as colour, form and movement across the visual scene. Computing these parallel spatial features requires a large and diverse network of neurons. Consequently, from flies to humans, visual regions in the brain constitute half its volume. These visual regions often have marked structure–function relationships, with neurons organized along spatial maps and with shapes that directly relate to their roles in visual processing. More than a century of anatomical studies have catalogued in detail cell types in fly visual systems 1–3 , and parallel behavioural and physiological experiments have examined the visual capabilities of flies. To unravel the diversity of a complex visual system, careful mapping of the neural architecture matched to tools for targeted exploration of this circuitry is essential. Here we present a connectome of the right optic lobe from a male Drosophila melanogaster acquired using focused ion beam milling and scanning electron microscopy. We established a comprehensive inventory of the visual neurons and developed a computational framework to quantify their anatomy. Together, these data establish a basis for interpreting how the shapes of visual neurons relate to spatial vision. By integrating this analysis with connectivity information, neurotransmitter identity and expert curation, we classified the approximately 53,000 neurons into 732 types. These types are systematically described and about half are newly named. Finally, we share an extensive collection of split-GAL4 lines matched to our neuron-type catalogue. Overall, this comprehensive set of tools and data unlocks new possibilities for systematic investigations of vision in Drosophila and provides a foundation for a deeper understanding of sensory processing.
scMODAL: a general deep learning framework for comprehensive single-cell multi-omics data alignment with feature links
Two dynamical models for male infertility and their stability and sensitivity analysis
A Burning Question
Hexafluorophosphate additive enables durable seawater oxidation at ampere-level current density
Abstract Direct seawater electrolysis at ampere-level current densities, powered by coastal/offshore renewables, is an attractive avenue for sustainable hydrogen production but is undermined by chloride-induced anode degradation. Here we demonstrate the use of hexafluorophosphate (PF₆⁻) as an electrolyte additive to overcome this limitation, achieving prolonged operation for over 5,000 hours at 1 A cm−2 and 2300 hours at 2 A cm−2 using NiFe layered double hydroxide (LDH) as anode. Together with the experimental findings, PF₆⁻ can intercalate into LDH interlayers and adsorb onto the electrode surface under an applied electric field, blocking Cl⁻ and stabilizing Fe to prevent segregation. The constant-potential molecular dynamics simulations further reveal the accumulation of high surface concentrations of PF6 − on the electrode surface that can effectively exclude Cl−, mitigating corrosion. Our work showcases synchronous interlayer and surface engineering by single non-oxygen anion species to enable Cl− rejection and marks a crucial step forward in seawater electrolysis.