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Geometric principles of wobble board design for balance training and rehabilitation
Agent-based modelling of the early stages of actin polymerisation required to drive endocytosis in Saccharomyces cerevisiae
Abstract Endocytosis is critical. Its complexity means that many aspects remain poorly understood. We have developed an agent-based model covering key components of actin filament generation in endocytosis in Saccharomyces cerevisiae. The model incorporates realistic values for rates, affinities, concentrations, and mobilities, and reproduces essential features of endocytosis, from the arrival of WASp/Las17 and its inhibitor Sla1 at the membrane up to the burst of actin polymerisation. The model yields relative rates and affinities for interactions that cannot be measured experimentally, and places limitations on plausible scenarios. Specifically, it reveals three novel findings. First, Las17 must form multimeric complexes. Second, de novo F-actin nucleation occurs in two stages, involving the slow formation of linear trimers, followed by rapid polymerisation once an additional actin monomer is positioned at the side of the aligned monomers. Third, competition between SH3 domains and other factors, including actin, is critical to ensure on/off switching. This requires: (1) tandem domains binding to adjacent polyproline sites outcompeting single domains; (2) these tandem domains being weakened in overall affinity through a reduction in avidity by competition with single SH3 domains. We conclude with a pathway that proposes how controlled actin polymerisation occurs, and raises implications for further testing.
Ambulatory physiological measures obtained under naturalistic urban mobility conditions have acceptable reliability
Abstract Ambulatory assessment methods in psychology and clinical neuroscience are powerful research tools for collecting data outside of the laboratory. These methods encompass physiological, behavioral, and self-report measures obtained while individuals navigate in real-world environments, thereby increasing the ecological validity of experimental approaches. Despite the recent increase in applications of ambulatory physiology, data on the reliability of these measures is still limited. To address this issue, twenty-six healthy participants ( N = 15 female, 18–34 years) completed an urban walking route (distance M = 2.2 km, ±SD = 0.11; duration M = 30.8 min, ±SD = 1.34; temperature M = 18.34° degree Celsius, ±SD = 1.19, Range = 16°-21° degrees Celsius) on two separate testing days, while assessing the effect of metabolic state (sated vs. fasted). GPS-location and ambulatory physiological measures (cardiovascular and electrodermal activity) were continuously recorded. The results showed no significant differences in single physiological measures between fasted and sated states. Bootstrapped test-retest reliabilities of single measures and aggregate scores derived via principal component analysis (PCA) were computed. The first principal component (PC#1) accounted for 39–45% of variance across measures. PC#1 scores demonstrated an acceptable test-retest reliability ( r = .60) across testing days, exceeding the reliabilities of most individual measures (heart rate: r = .53, heart rate variability: r = .50, skin conductance level: r = .53, no. of skin conductance responses: r = .28, skin conductance response amplitude: r = .60). Results confirm that ambulatory physiological measures recorded during naturalistic navigation in urban environments exhibit acceptable test-retest reliability, in particular when compound scores across physiological measures are analyzed, a prerequisite for applications in (clinical) psychology and digital health.
Efficacy and safety of taxane plus ramucirumab for advanced gastric cancer after chemotherapy plus nivolumab
Intricate origins of ice mummy’s ink revealed
Analysis of effect of thickness and surface treatment on sound transmission loss characteristics of natural fibres
Abstract Noise pollution, driven by rapid urbanisation and city expansion, has created a growing demand for innovative and bio-degradable sound absorption materials. Traditional solutions such as synthetic acoustic foams are widely used due to their efficiency and low cost but raise environmental concerns because of their non-biodegradable nature. This study explored the use of natural fibres—coir and sponge gourd—as environmentally friendly alternatives for sound insulation. The research focused on the effect of fibre thickness and surface treatment (using sodium hydroxide (NaOH)) on their acoustic performance. The Fourier Transform Infrared Spectroscopy (FTIR) technique was used to understand the effects of the treatment on the functional groups of the fibre. The surface modification of the fibre surface was studied using an optical microscope, Brumauer–Emmet–Teller (BET) analysis and by analysis of Scanning Electron Microscope (SEM) images. An impedance tube setup was used to measure the sound transmission loss for both the untreated and treated fibres. The results showed that increasing the thickness of both coir and sponge gourd fibres improves transmission loss at lower frequencies but reduces effectiveness at higher frequencies. Surface treatment had a material-dependent effect: sponge gourd fibres showed improved transmission loss due to increased surface roughness and airflow resistivity, whereas coir fibres exhibited a decline in performance after treatment. These findings contribute to a better understanding of how natural materials can be optimised for acoustic applications through structural modifications.
Potato, tomato: the roots of the modern tater
A pharmacovigilance study of vortioxetine based on data from the FDA adverse event reporting system
Identification of STAT3 and BIRC5 as anoikis-related biomarkers in psoriasis
The impact of exercise on skeletal muscle proteome of prediabetic subjects analyzed with data independent mass spectrometry
Abstract Physical exercise of even a moderate intensity is beneficial in both the prevention of prediabetes and management of Type 2 diabetes mellitus, as skeletal muscle is a primary tissue responsible for glucose uptake. Exercise-evoked proteomic alterations in muscle of subjects with prediabetes are of great importance for the study of relationships between insulin resistance and exercise. Although data-dependent (DDA) proteomic analysis is a cornerstone of deep proteome profiling employed in the elucidation of skeletal muscle biology, data-independent (DIA) approaches gain popularity in the studies focused on data reproducibility and throughput. We compared various ion-chromatogram libraries assembled with the use of off-line high-pH fractionation (HpH), gas-phase fractionation (GPF) and libraryless DirectDIA in LC/MS/HRMS DIA proteomic analysis of muscle from normoglycemic (NGT) and prediabetic (IGT) subjects after 3 months of supervised, mixed-mode exercise. In our hands, GPF-fractionated, hybrid DDA/DIA libraries yielded the best overall balance between the speed of preparation, data collection and protein identification among tested approaches. Analysis revealed, that despite 3-month exercise intervention skeletal muscle from IGT subjects displayed significant alterations in pathways and molecules relevant to muscle contraction, extracellular matrix composition and protein synthesis as compared to NGT counterparts. In conclusion, our study underlines the importance of the ion library assembly in the DIA analysis of clinical samples and confirms at molecular level changes connected with deficiency of muscle function in the prediabetic state.
Impact of ceftazidime avibactam on colonization by carbapenem resistant Enterobacterales during treatment of related infections
Real time blood detection in CCTV surveillance using attention enhanced InceptionV3
Integrating ecological importance and risk for restoration zoning and ecological water demand in the Shiyang river basin
Invariance of dynamo action in an early-Earth model
Study on the driving mechanisms of spatiotemporal nonstationarity of vegetation dynamics in Heilongjiang Province
Modular arene functionalization by differential 1,2-diborylation
The expression of the tight junction protein and therapeutical target Claudin 18.2 is heterogeneously distributed within esophageal and gastric adenocarcinoma
Abstract Claudin 18.2 (CLDN18.2) is a therapeutically relevant biomarker in esophageal (EAC) -and gastric adenocarcinoma (GAC). Little is known about its heterogeneity within the primary tumor and corresponding metastases and how many biopsies are needed to determine the true CLDN18.2 status of a tumor. CLDN18.2 was assessed in 1,283 patients (822 EAC, 461 GAC), using the antibody clone 43–14 A. Eight virtual endoscopic biopsies were taken from digitized whole tumor blocks. 204 of 822 EAC (24.8%) and 132 of 461 GAC (28,6%) were positive for CLDN18.2. In GAC, CLDN18.2 expression showed a trend towards less invasive growth ( p = 0.02) and less common lymph node metastasis ( p = 0.07) and was more often observed within the EBV-associated subtype ( p = 0.01). When comparing the expression in one biopsy with the whole tissue section, the sensitivity for CLDN18.2 was low (58.8%). The sensitivity increased to a maximum of 76.5% with 6 and 8 biopsies (positive likelihood ratio = 17.8). Discordant expression between primary tumor and corresponding local lymph node metastasis was observed in 18.5%. This study highlights that CLDN18.2 is a heterogeneously expressed biomarker, within the tumor tissue as well as in primary tumor and corresponding lymph node metastasis. In case of CLN18.2-negative results the representativity of the biopsies must be critically assessed and a re-biopsy might be recommendable.
Complementary MR measures of white matter and their relation to cardiovascular health and cognition
Abstract The microstructural and macrostructural integrity of white matter (WM) underpins efficient brain function, and is known to decline with age and vascular burden. Key aspects of WM health include axonal fibre density, myelination, free-water content, and the presence of tissue damage or lesions. Magnetic Resonance Imaging (MRI) offers multiple complementary sequences to non-invasively estimate these properties in vivo. For example, diffusion-weighted imaging (DWI) provides sensitive measures of microstructure, while T1-weighted and T2-weighted MRI can estimate total WM volume and hyper-intensities, and magnetisation transfer imaging (MT) and T1:T2 ratios can indicate myelin content. In this study, we leveraged all of these MRI-derived measures in a large population-based cohort (Cam-CAN) to identify latent WM factors and test how these factors relate to cardiovascular health and cognitive performance. Among 11 commonly-used WM metrics [Fractional Anisotropy (FA); Mean Signal Diffusion (MSD); Mean Signal Kurtosis (MSK); Neurite Density Index (NDI); fibre Orientation Dispersion Index (ODI); Free water volume faction (F iso ); spread of Mean Signal Diffusivity values (MSDvar); Magnetisation Transfer Ratio (MTR); T1:T2 ratio; volume of White Matter Hyper-Intensities (WMHI); White Matter Volume (WMV)], latent factor analysis showed that four factors were needed to explain 89% of the variance, which we interpreted in terms of (1) fibre density/myelination, (2) free-water / tissue damage, (3) fibre-crossing complexity and (4) microstructural complexity. These factors showed distinct effects of age and sex. To test the validity of these factors, we related them to measures of cardiovascular health and cognitive performance. Specifically, we ran path analyses linking (1) cardiovascular factors to the WM factors, and (2) the WM factors to cognitive measures. Even after adjusting for age and sex, we found that a vascular factor related to pulse pressure predicted the WM factor capturing free-water/tissue damage, and that several WM factors made unique predictions for fluid intelligence and processing speed. Our results show that there is both complementary and redundant information across common MR measures of WM, and their underlying latent factors may be useful for pinpointing the differential causes and contributions of white matter health in aging.