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Climate warming may undermine sleep duration and quality in repeated-measure study of 23 million records
Evaluation of the winning technical and tactical actions of the best female table tennis players in the years 1970-2021
A CPC-shelterin-BTR axis regulates mitotic telomere deprotection
Abstract Telomeres prevent ATM activation by sequestering chromosome termini within telomere loops (t-loops). Mitotic arrest promotes telomere linearity and a localized ATM-dependent telomere DNA damage response (DDR) through an unknown mechanism. Using unbiased interactomics, biochemical screening, molecular biology, and super-resolution imaging, we found that mitotic arrest-dependent (MAD) telomere deprotection requires the combined activities of the Chromosome passenger complex (CPC) on shelterin, and the BLM-TOP3A-RMI1/2 (BTR) complex on t-loops. During mitotic arrest, the CPC component Aurora Kinase B (AURKB) phosphorylated both the TRF1 hinge and TRF2 basic domains. Phosphorylation of the TRF1 hinge domain enhances CPC and TRF1 interaction through the CPC Survivin subunit. Meanwhile, phosphorylation of the TRF2 basic domain promotes telomere linearity, activates a telomere DDR dependent on BTR-mediated double Holliday junction dissolution, and leads to mitotic death. We identify that the TRF2 basic domain functions in mitosis-specific telomere protection and reveal a regulatory role for TRF1 in controlling a physiological ATM-dependent telomere DDR. The data demonstrate that MAD telomere deprotection is a sophisticated active mechanism that exposes telomere ends to signal mitotic stress.
U shaped relationship between mean arterial pressure and 28 day mortality in ICU patients with acute myocardial infarction
Transcriptional heterogeneity shapes stress-adaptive responses in yeast
Abstract In response to stress, cells activate signaling pathways that coordinate broad changes in gene expression to enhance cell survival. Remarkably, complex variations in gene expression occur even in isogenic populations and in response to similar signaling inputs. However, the molecular mechanisms underlying this variability and their influence on adaptive cell fate decisions are not fully understood. Here, we use scRNA-seq to longitudinally assess transcriptional dynamics during osmoadaptation in yeast. Our findings reveal highly heterogeneous expression of the osmoresponsive program, which organizes into combinatorial patterns that generate distinct cellular programs. The induction of these programs is favored by global transcriptome repression upon stress. Cells displaying basal expression of the osmoresponsive program are hyper-responsive and resistant to stress. Through a transcription-focused analysis of more than 300 RNA-barcoded deletion mutants, we identify genetic factors that shape the heterogeneity of the osmostress-induced transcriptome, define regulators of stress-related subpopulations and find a link between transcriptional heterogeneity and increased cell fitness. Our findings provide a regulatory map of the complex transcriptional phenotypes underlying osmoadaptation in yeast and highlight the importance of transcriptional heterogeneity in generating distinct adaptive strategies.
Disproportionality analysis of post-marketing safety concerns associated with selumetinib in the FDA adverse event reporting system
A 700-year rupture sequence of great eastern Aleutian earthquakes from tsunami modeling of stratigraphic records
Network pharmacology and experimental validation reveal dexmedetomidine’s protective mechanisms against acute liver injury in mice
Semi-automated IT-scATAC-seq profiles cell-specific chromatin accessibility in differentiation and peripheral blood populations
Abstract Single-cell ATAC-seq (scATAC-seq) enables high-resolution mapping of chromatin accessibility but is often limited by throughput, cost, and equipment requirements. Here, we present indexed Tn5 tagmentation-based scATAC-seq (IT-scATAC-seq), a semi-automated, cost-effective, and scalable approach that leverages indexed Tn5 transposomes and a three-round barcoding strategy. This workflow prepares libraries for up to 10,000 cells in a single day, reduces the per-cell cost to approximately $0.01, and maintains high data quality. Comprehensive benchmarking demonstrates that IT-scATAC-seq achieves robust library complexity, high signal specificity, and improved cost-efficiency compared to existing methods. We apply IT-scATAC-seq to mouse embryonic stem cells, capturing chromatin remodelling during early differentiation, and to human peripheral blood mononuclear cells, resolving cell-type–specific regulatory programs. Here, we show that IT-scATAC-seq provides a robust and efficient approach for high-resolution single-cell epigenomic investigations, balancing scalability, data quality, and accessibility.
Measuring the effect of repetitive stretching on the deformability of human red blood cells using optical tweezers
Habitat openness and squamate color evolution over deep time
Abstract While the ecological roles of colored integument have been extensively studied, what regulates global patterns of color variation remains poorly understood. Here, using a global dataset of 1249 squamates, we evaluate whether and how six key eco-environmental variables and their interactions shaped the evolutionary history of their coloration. We show that only habitat openness consistently associates with brightness evolution, with brighter integuments favored in open habitats, possibly for enhanced heat reflection. Furthermore, brightness evolution rates likely track δ18O (a temperature proxy) changes and increase during global aridification phases, such as those in the Miocene and Pliocene. This trend may be due to the establishment of an arid climate that promoted habitat openness shifts, ultimately inducing adaption to new niches. Our findings suggest that a single environmental variable is associated with color variation in the largest extant tetrapod order.
The facile conversion of waste biomass into few-layer graphene oxide
Abstract Carbon-based materials are highly sought after due to their superior properties, making them valuable for high-performance applications. However, most carbon-based materials are derived from fossil sources, and their synthesis often involves hazardous chemicals. Therefore, it is essential to develop sustainable methods for synthesising these materials from renewable resources, using fewer solvents, catalytic reagents, and generating minimal waste. In this study, few-layer graphene oxide (GO) was directly synthesised from waste biomass, without the formation of an amorphous intermediate, and its use as a fire retardant in two bioplastics was evaluated. Waste birch wood biomass was converted directly into graphitic carbon using manganese nitrate as a catalyst, with varying concentrations (0.003 to 0.1 mol-metal/g-wood) and treatment durations (1 and 2 h). The catalyst was doped through vacuum soaking and mild heating (90 °C), which facilitated the formation of graphitic carbon at relatively lower temperatures (< 1000 °C), eliminating the need for producing amorphous biochar prior to graphitisation. After pyrolysis at 900 °C and 950 °C for 2 h, the sample containing 0.005 mol-metal/g-wood, treated at 950 °C, exhibited the highest degree of graphitisation. This sample was further processed in a planetary ball mill with melamine as a dispersant for 30 min. Characterisation showed a broad absorption peak at 230 nm and the presence of semi-transparent sheets (3–8 layers), indicating the presence of GO. To evaluate its performance as a fire retardant, 2 wt% of the synthesised GO was added to polyamide 11 and wheat gluten bioplastics, which were then subjected to cone calorimeter tests. The results showed a 42% and 33% reduction in the peak heat release rate for polyamide 11 and wheat gluten, respectively, compared to their neat counterparts. The flame retardancy index further indicated that GO had a more significant impact on improving the fire safety of wheat gluten compared to polyamide 11. This study highlights a sustainable method for the preparation of few-layer GO at lower temperatures than contemporary methods, making the process more energy-efficient, environmentally friendly, and cost-effective. Additionally, the effectiveness of few-layer GO as a fire-retardant additive for enhancing the fire safety of bioplastics has been demonstrated.
Entropy scaling for diffusion coefficients in fluid mixtures
Abstract Entropy scaling is a powerful technique that has been used for predicting transport properties of pure components over a wide range of states. However, modeling mixture diffusion coefficients by entropy scaling is an unresolved task. We tackle this issue and present an entropy scaling framework for predicting mixture self-diffusion coefficients as well as mutual diffusion coefficients in a thermodynamically consistent way. The predictions of the mixture diffusion coefficients are made based on information on the self-diffusion coefficients of the pure components and the infinite-dilution diffusion coefficients. This is accomplished using information on the entropy of the mixture, which is taken here from molecular-based equations of state. Examples for the application of the entropy scaling framework for the prediction of diffusion coefficients in mixtures illustrate its performance. It enables predictions over a wide range of temperatures and pressures including gaseous, liquid, supercritical, and metastable states—also for strongly non-ideal mixtures.
Three-quarters of species’ ranges have not been covered by protected areas in global borders
Bacterial Hachiman complex executes DNA cleavage for antiphage defense
Structural basis of gap-filling DNA synthesis in the nucleosome by DNA Polymerase β
Abstract Single-strand breaks (SSBs) are one of the most prevalent forms of DNA damage found in the chromatinized genome and are repaired by single-strand break repair (SSBR) or base excision repair (BER). DNA polymerase beta (Pol β) is the primary enzyme responsible for processing the 1-nt gap intermediate in chromatin during SSBR and BER. To date, the mechanism used by Pol β to process a 1-nt gap in the context of chromatin remains poorly understood. Here, we use biochemical assays and cryogenic electron microscopy (cryo-EM) to determine the kinetic and structural basis of gap-filling DNA synthesis in the nucleosome by Pol β. This work establishes that Pol β uses a global DNA sculpting mechanism for processing 1-nt gaps in the nucleosome during SSBR and BER, providing fundamental insight into DNA repair in chromatin.
Monitoring, modeling, and forecasting long-term changes in coastal seawater quality due to climate change
Histopathology based AI model predicts anti-angiogenic therapy response in renal cancer clinical trial
Abstract Anti-angiogenic (AA) therapy is a cornerstone of metastatic clear cell renal cell carcinoma (ccRCC) treatment, but not everyone responds, and predictive biomarkers are lacking. CD31, a marker of vasculature, is insufficient, and the Angioscore, an RNA-based angiogenesis quantification method, is costly, associated with delays, difficult to standardize, and does not account for tumor heterogeneity. Here, we developed an interpretable deep learning (DL) model that predicts the Angioscore directly from ubiquitous histopathology slides yielding a visual vascular network (H&E DL Angio). H&E DL Angio achieves a strong correlation with the Angioscore across multiple cohorts (spearman correlations of 0.77 and 0.73). Using this approach, we found that angiogenesis inversely correlates with grade and stage and is associated with driver mutation status. Importantly, DL Angio expediently predicts AA response in both a real-world and IMmotion150 trial cohorts, out-performing CD31, and closely approximating the Angioscore (c-index 0.66 vs 0.67) at a fraction of the cost.