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Mechanisms of concentration control alkali activated fly ash stabilized saline soil in seasonally frozen regions
Limitations of ice cores in reconstructing temperature seasonality
MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis
AbstractThe eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled. A cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate shows a remodelled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and specifically recognises this closed ring. Interestingly, we found that normal helicase loading triggers Mcm4 ATP-hydrolysis, which in turn leads to reorganisation of the MCM2-7 complex and Cdt1 release. However, defective MCM2-7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and complex disassembly. As such we identify Mcm4 as the key ATPase in regulating pre-RC formation. Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysis-dependent remodelling of the helicase.
ATLAS-seq: a microfluidic single-cell TCR screen for antigen-reactive TCRs
Gut microbiota dysbiosis, sarcopenia, osteoporosis and osteosarcopenia in older people: A systematic review protocol
Introduction Sarcopenia and Osteoporosis are two prevalent conditions in the older population and are defined by low strength, muscle quality/volume and low Bone Mineral Density, respectively. When there is a concomitant presence of both, there is a novel musculoskeletal condition called Osteosarcopenia. These conditions adversely affect quality of life and elevate the risk of fractures, disability, and mortality among older individuals. Dysbiosis of the gut microbiota is the impairment of the mutualistic relationship between microorganisms, metabolic products and the host’s immune system. Gut microbiota dysbiosis could be intricately linked to sarcopenia and osteoporosis, shedding light on the complex microbiota-gut-bone-muscle axis. Furthermore, the intestinal microbiota experiences a notable decline in beneficial microorganisms as part of the aging process. The relationship between dysbiosis of the intestinal microbiota in older people and sarcopenia, osteoporosis or osteosarcopenia is still unclear. This review protocol aims to systematically review the literature and compile evidence on the influence of gut microbiota dysbiosis on musculoskeletal function in older people with sarcopenia, osteoporosis or osteosarcopenia. Methods/Analysis This systematic review will analyze observational studies that have investigated the relationship between the effects of gut microbiota dysbiosis and sarcopenia, osteoporosis and osteosarcopenia in older people aged 65 and over. Studies will be retrieved from PubMed/MEDLINE, EMBASE, Scopus, Web of Science and the Cochrane Library. Outcome measures will include body composition for diagnosing osteoporosis and screening for sarcopenia/osteosarcopenia by any criteria. Data synthesis will involve quantitative analysis using summary measures. If sufficient studies, homogeneity and heterogeneity analysis will be performed to conduct Meta-analysis and pooled OR, RR and HR measures will be provided.
Adaptive hip exoskeleton control using heart rate feedback reduces oxygen cost during ecological locomotion
Abstract Despite their potential, exoskeletons have not reached widespread adoption in daily life, partly due to the challenge of seamlessly adapting assistance across various tasks and environments. Task-specific designs, reliance on complex sensing and extensive data-driven training often limit the practicality of the existing control strategies. To address this challenge, we introduce an adaptive control strategy for hip exoskeletons, emphasizing minimal sensing and ease of implementation. Using only insole pressure and heart rate (HR) sensing, the controller modulates assistance across various locomotor tasks. We evaluated this strategy with twelve able-bodied participants in a real-world scenario including level walking, stairs, and inclines. The controller successfully adapted assistance timing and amplitude to different activities. This resulted in effort intensity reductions (measured by oxygen uptake) of up to 12.6% compared to walking with no exoskeleton, and up to 25.5% compared to walking with the exoskeleton in zero-torque mode. Cardiodynamic response of HR, although delayed, proved sufficient for adaptation in tasks lasting longer than around 45 s, and delay-induced limitations primarily affected brief bouts of abrupt change in intensity. However, we found discernible patterns in HR shortly after the onset of such changes that can be exploited to improve responsiveness. Our findings underscore the potential of HR as a promising measure of user effort intensity, encouraging future research to explore its integration into advanced adaptive algorithms.
Two-hit mouse model of heart failure with preserved ejection fraction combining diet-induced obesity and renin-mediated hypertension
Prediction of heavy metal spatial distribution in soils of typical industrial zones utilizing 3D convolutional neural networks
E4F1 coordinates pyruvate metabolism and the activity of the elongator complex to ensure translation fidelity during brain development
AbstractPyruvate metabolism defects lead to severe neuropathies such as the Leigh syndrome (LS) but the molecular mechanisms underlying neuronal cell death remain poorly understood. Here, we unravel a connection between pyruvate metabolism and the regulation of the epitranscriptome that plays an essential role during brain development. Using genetically engineered mouse model and primary neuronal cells, we identify the transcription factor E4F1 as a key coordinator of AcetylCoenzyme A (AcCoA) production by the pyruvate dehydrogenase complex (PDC) and its utilization as an essential co-factor by the Elongator complex to acetylate tRNAs at the wobble position uridine 34 (U34). E4F1-mediated direct transcriptional regulation of Dlat and Elp3, two genes encoding key subunits of the PDC and of the Elongator complex, respectively, ensures proper translation fidelity and cell survival in the central nervous system (CNS) during mouse embryonic development. Furthermore, analysis of PDH-deficient cells highlight a crosstalk linking the PDC to ELP3 expression that is perturbed in LS patients.
Sticky organisms create underwater biological adhesives driven by interactions between EGF- and GlcNAc- containing polysaccharides
Block selection in multiblock partial least squares for modeling genotype-phenotype relations in Saccharomyces
In data-based modeling, correlations between explanatory variables often lead to the formation of distinct gene blocks. This study focuses on identifying influential gene blocks and key variables within these blocks, with a particular application in mind: genotype-phenotype mapping in Saccharomyces. To overcome the challenges of a limited sample size, we use partial least squares (PLS). These gene blocks, which consist of combinations of genes, play a critical role in explaining phenotypic variations. Using partial least squares with multiple blocks, we propose a novel approach, weighted block importance on projection in partial least squares (BwIP-mbPLS), to identify influential gene blocks. Variable importance on projection is used to select significant genes within these blocks. Our study models copper chloride at 0.375mM and melibiose at 2% efficiency and rate in Saccharomyces cerevisiae yeast. Analysis based on silhouette index and total distance within clusters using k-means shows the classification of 5629 genes into 18 gene blocks. Remarkably, BwIP-mbPLS identifies 4 gene blocks on average and significantly improves the prediction of efficiency-based phenotypes. In contrast, traditional block importance in partial least squares projection identifies 6 gene blocks on average and shows comparable or better performance than BIP-mbPLS for rate-based phenotypes. Remarkably, most gene blocks contain fewer than 10 influential genes. Both proposed variants consistently outperform conventional approaches such as partial least squares and multi-block partial least squares in predicting phenotypes. These results highlight the potential of our methods for advancing data-based modeling and genotype-phenotype mapping.
Continuous cell lines derived from the Asian citrus psyllid, Diaphorina citri, harbor viruses and Wolbachia
Molecular dynamics simulations reveal efficient heavy metal ion removal by two-dimensional Cu-THQ metal-organic framework membrane
Fano resonated, ultrathin, flexible and ultrawideband absorption featured nano-metaatom structure with dispersion gap optimized for optical range applications
Engineering spatially-confined conduits to tune nerve self-organization and allodynic responses via YAP-mediated mechanotransduction
Counterintuitive DNA destabilization by monovalent salt at high concentrations due to overcharging
Influence of pre-processing criteria on analysis of accelerometry-based physical activity
Background Accelerometers are widely adopted for physical activity (PA) measurement. Accelerometry data require pre-processing before entering formal statistical analyses. Many pre-processing criteria may influence PA outcomes and the processed sample, impacting results in subsequent statistical analyses. Aim To study the implications of pre-processing criteria for accelerometer data on outputs of interest in physical activity studies. Methods We used the ActiGraph hip-worn accelerometry data from 538 adult Latino participants. We studied four most important domains of pre-processing criteria (wear-time, minimum wear-time, intensity level, and modified bouts). We examined the true sample size in pre-processed data, the moderate-to-vigorous physical activity (MVPA) outcome, and regression coefficients of age and gender predicting MVPA. Results Many pre-processing criteria have minimum impact to the output of interest. However, requirements for minimum wear-time can have high influence on subsequent analyses for MVPA. High requirements for wear-time (e.g., minimum of 5 days with more than 12 hours of wear-time per day) lead to weakened statistical efficiency in estimating the relationship between potential predictors and the MVPA outcome. Intensity levels using vector magnitude triaxial counts yielded drastically different results than those using conventional vertical axis counts. Conclusion Moderate changes in minimum wear-time can yield notably different output data and subsequently influence analyses assessing the impacts of interventions on MVPA behaviors. Processed data using vector magnitude and conventional vertical axis counts are not directly comparable. Sensitivity analyses using alternative pre-processing scenarios are highly recommended to verify the robustness of analyses for accelerometry data.