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Tectonic–astronomical interactions in shaping late Paleozoic climate and organic carbon burial
Evaluation of the protective efficacy of a user seal check for N95 respirators through quantitative fit testing in an ambulance crew
Trans-eQTL mapping prioritises USP18 as a negative regulator of interferon response at a lupus risk locus
Abstract Although genome-wide association studies have provided valuable insights into the genetic basis of complex traits and diseases, translating these findings to causal genes and their downstream mechanisms remains challenging. We performed trans expression quantitative trait locus (trans-eQTL) meta-analysis in 3734 lymphoblastoid cell line samples, identifying four robust loci that replicated in an independent multi-ethnic dataset of 682 individuals. The trans-eQTL signal at the ubiquitin specific peptidase 18 (USP18) locus colocalised with a GWAS signal for systemic lupus erythematosus (SLE). USP18 is a known negative regulator of interferon signalling and the SLE risk allele increased the expression of 50 interferon-inducible genes, suggesting that the risk allele impairs USP18’s ability to effectively limit the interferon response. Intriguingly, the USP18 trans-eQTL signal would not have been discovered in a meta-analysis of up to 43,301 whole blood samples, reaffirming the importance of capturing context-specific genetic effects for GWAS interpretation.
Systematic metabolomic study on the plasma and urine of a mouse model of Alport syndrome
Arabidopsis response to the apocarotenoid zaxinone involves interference with strigolactone signaling via binding to DWARF14
Perovskite engineering for efficient oxygen evolution reaction through iron and silver doping
Chiral recognition via symmetry-dependent luminescence in zero-dimensional hybrid copper halides
Time-restricted eating improves quality of life, heart rate, and mitochondrial function in patients with postural orthostatic tachycardia syndrome. An open-label pilot study
Abstract Postural orthostatic tachycardia syndrome (POTS) is characterized by an abnormal increase in heart rate upon standing, leading to symptoms such as dizziness, fatigue, and rapid heart rate. Time-restricted eating (TRE), which limits caloric intake to an 8–10 h daily window, has been shown to decrease inflammation and improve immune, autonomic, and mitochondrial function, as well as cardiometabolic parameters. This single arm pilot study evaluated the effects of TRE on quality of life (QOL), heart rate, and mitochondrial function in 20 participants with POTS (≥ 30 bpm increase in upright heart rate) and a baseline dietary window of ≥ 12 h. Following a 2-week baseline monitoring period, participants underwent a 12-week TRE intervention. Pre- and post-intervention assessments included QOL questionnaires, a 10-minute stand test, and plasma mitochondrial analysis. TRE significantly reduced heart rate increase upon standing (mean decrease: 11 bpm, p < 0.001) and improved QOL metrics, as assessed by the Malmö POTS Symptom Score Survey (MAPS) and the General Health Questionnaire Short Form-36 (SF-36). Notable improvements include POTS symptom severity (p < 0.0001), physical functioning (p = 0.02), and energy/fatigue (p < 0.01). Additionally TRE increased mitochondrial-derived ATP production. These findings suggest TRE as a promising lifestyle intervention to improve QOL, heart rate, and mitochondrial function in POTS patients.
Stratified wind from a super-Eddington X-ray binary is slower than expected
Abstract Accretion disks in strong gravity ubiquitously produce winds, seen as blueshifted absorption lines in the X-ray band of both stellar mass X-ray binaries (black holes and neutron stars)1–4 and supermassive black holes5. Some of the most powerful winds (termed Eddington winds) are expected to arise from systems in which radiation pressure is sufficient to unbind material from the inner disk (L ≳ L Edd). These winds should be extremely fast and carry a large amount of kinetic power, which, when associated with supermassive black holes, would make them a prime contender for the feedback mechanism linking the growth of those black holes with their host galaxies6. Here we show the XRISM Resolve spectrum of the galactic neutron star X-ray binary, GX 13+1, which reveals one of the densest winds ever seen in absorption lines. This Compton-thick wind significantly attenuates the flux, making it appear faint, although it is intrinsically more luminous than usual (L ≳ L Edd). However, the wind is extremely slow, more consistent with the predictions of thermal-radiative winds launched by X-ray irradiation of the outer disk than with the expected Eddington wind driven by radiation pressure from the inner disk. This puts new constraints on the origin of winds from bright accretion flows in binaries, but also highlights the very different origin required for the ultrafast (v ~ 0.3c) winds seen in recent Resolve observations of a supermassive black hole at a similarly high Eddington ratio7.
Left-handed DNA for efficient highly multiplexed imaging at single-protein resolution
Abstract Multiplexed super-resolution microscopy enables spatial proteomics at single-protein resolution, but current methods often depend on secondary labels, complicating implementation and limiting throughput. We introduce a streamlined approach that combines speed-optimized DNA-PAINT sequences with their mirror-image analogs (left-handed DNA), enabling rapid and efficient 12-plex imaging. Validated on synthetic and cellular benchmarks, our method maps dense neuronal interactomes in 3D with 15 nm spatial resolution across a 200 × 200 µm2 field of view.
Transformer-enhanced vertebrae segmentation and anatomical variation recognition from CT images
Iron and oxygen vacancies co-modulated adsorption evolution and lattice oxygen dual-path mechanism for water oxidation
Robust optimization of uncertain E-commerce closed-loop supply chain networks under carbon policies
Identification of a RAB32-LRMDA-Commander membrane trafficking complex reveals the molecular mechanism of human oculocutaneous albinism type 7
Abstract The endosomal Commander assembly associates with the sorting nexin-17 (SNX17) cargo adaptor to regulate cell surface recycling of internalised integral proteins including integrins and lipoprotein receptors. Here, we identify leucine rich melanocyte differentiation associated (LRMDA) as a Commander binding protein. We reveal that LRMDA and SNX17 share a common mechanism of Commander association, and that LRMDA simultaneously associates with Commander and active RAB32, establishing distinct RAB32-LRMDA-Commander and SNX17-Commander assemblies. Functional analysis in melanocytes reveals distinct roles for RAB32-LRMDA-Commander and SNX17-Commander in melanosome biogenesis. We reveal how LRMDA mutations, causative for oculocutaneous albinism type 7, a hypopigmentation disorder accompanied by poor visual acuity, uncouple RAB32 and Commander binding thereby establishing the mechanistic basis of this disease. Our discovery of this alternative Commander assembly highlights the plasticity of Commander function in human pigmentation and extends the Commander function beyond the SNX17-mediated regulation of cell surface proteome.
Evaluation of agar dilution as an alternative method for antimicrobial susceptibility testing and tentative ECOFF determination for Arcobacter butzleri
Multicenter evaluation of label-free quantification in human plasma on a high dynamic range benchmark set
Abstract Human plasma is routinely collected during clinical care and constitutes a rich source of biomarkers for diagnostics and patient stratification. Liquid chromatography-mass spectrometry (LC-MS)-based proteomics is a key method for plasma biomarker discovery, but the high dynamic range of plasma proteins poses significant challenges for MS analysis and data processing. To benchmark the quantitative performance of neat plasma analysis, we introduce a multispecies sample set based on a human tryptic plasma digest containing varying low level spike-ins of yeast and E. coli tryptic proteome digests, termed PYE. By analysing the sample set on state-of-the-art LC-MS platforms across twelve different sites in data-dependent (DDA) and data-independent acquisition (DIA) modes, we provide a data resource comprising a total of 1116 individual LC-MS runs. Centralized data analysis shows that DIA methods outperform DDA-based approaches regarding identifications, data completeness, accuracy, and precision. DIA achieves excellent technical reproducibility, as demonstrated by coefficients of variation (CVs) between 3.3% and 9.8% at protein level. Comparative analysis of different setups clearly shows a high overlap in identified proteins and proves that accurate and precise quantitative measurements are feasible across multiple sites, even in a complex matrix such as plasma, using state-of-the-art instrumentation. The collected dataset, including the PYE sample set and strategy presented, serves as a valuable resource for optimizing the accuracy and reproducibility of LC-MS and bioinformatic workflows for clinical plasma proteome analysis.
A multidimensional analysis of the risk of infection with Ehrlichia canis among urban dogs in Iquitos, Peru
Monitoring changes in vitamin D levels during the COVID-19 pandemic with routinely-collected laboratory data
Abstract Vitamin D is critical for bone health and immune function, but the COVID-19 pandemic, characterized by lockdowns and reduced outdoor activity, raised concerns about potential declines in vitamin D levels due to dietary changes and limited sunlight exposure. In this study, we analyzed routinely-collected laboratory data ( N = 292,187 patients) from a large laboratory chain in Bavaria, Germany, to assess changes in vitamin D levels before (March 2018 to February 2020) and during (March 2020 to February 2022) the pandemic. Different statistical approaches (i.e., descriptive statistics, propensity score matching, and a causal forest) were used to evaluate confounder-adjusted changes in vitamin D levels and deficiency rates. Mean vitamin D levels decreased significantly from 26.7 μ g/l pre-pandemic to 26.0 μ g/l during the pandemic ( p -value < 0.001), with a corresponding increase in deficiency rates from 31.2% to 35.2% ( p -value < 0.001). Across all statistical approaches, the decline in mean levels and the increase in deficiency rates were particularly pronounced among elderly women. These findings highlight the importance of public health strategies to monitor and improve vitamin D status, especially during periods of restricted outdoor activity.