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Mechanical forces, actin filament turnover, and adhesion to the extracellular environment regulate lamellipodial protrusions. Computational and mathematical models at the continuum level have been used to investigate the molecular clutch mechanism, calculating the stress profile through the lamellipodium and around focal adhesions. However, the forces and deformations of individual actin filaments have not been considered while interactions between actin networks and actin bundles is not easily accounted with such methods. We develop a filament-level model of a lamellipodial actin network undergoing retrograde flow using 3D Brownian dynamics. Retrograde flow is promoted in simulations by pushing forces from the leading edge (due to actin polymerization), pulling forces (due to molecular motors), and opposed by viscous drag in cytoplasm and focal adhesions. Simulated networks have densities similar to measurements in prior electron micrographs. Connectivity between individual actin segments is maintained by permanent and dynamic crosslinkers. Remodeling of the network occurs via the addition of single actin filaments near the leading edge and via filament bond severing. We investigated how several parameters affect the stress distribution, network deformation and retrograde flow speed. The model captures the decrease in retrograde flow upon increase of focal adhesion strength. The stress profile changes from compression to extension across the leading edge, with regions of filament bending around focal adhesions. The model reproduces the observed reduction in retrograde flow speed upon exposure to cytochalasin D, which halts actin polymerization. Changes in crosslinker concentration and dynamics, as well as in the orientation pattern of newly added filaments demonstrate the model’s ability to generate bundles of filaments perpendicular (actin arcs) or parallel (microspikes) to the protruding direction.

Blood flow metrics obtained with four-dimensional (4D) flow phase contrast (PC) magnetic resonance imaging (MRI) can be of great value in clinical and experimental cerebrovascular analysis. However, limitations in both quantitative and qualitative analyses can result from errors inherent to PC MRI. One method that excels in creating low-error, physics-based, velocity fields is computational fluid dynamics (CFD). Augmentation of cerebral 4D flow MRI data with CFD-informed neural networks may provide a method to produce highly accurate physiological flow fields. In this preliminary study, the potential utility of such a method was demonstrated by using high resolution patient-specific CFD data to train a convolutional neural network, and then using the trained network to enhance MRI-derived velocity fields in cerebral blood vessel data sets. Through testing on simulated images, phantom data, and cerebrovascular 4D flow data from 20 patients, the trained network successfully de-noised flow images, decreased velocity error, and enhanced near-vessel-wall velocity quantification and visualization. Such image enhancement can improve experimental and clinical qualitative and quantitative cerebrovascular PC MRI analysis.

Polarized exocytosis induced by local Cdc42 GTPase activity results in membrane flows that deplete low-mobility membrane-associated proteins. A reaction-diffusion particle model comprising Cdc42 positive feedback activation, hydrolysis by GTPase-activating proteins (GAPs), and flow-induced displacement by exo/endocytosis shows that flow-induced depletion of low mobility GAPs promotes polarization. We modified Cdc42 mobility in Schizosaccharomyces pombe by replacing its prenylation site with 1, 2 or 3 repeats of the Rit C-terminal membrane-binding domain (ritC), yielding alleles with progressively lower mobility and increased flow-coupling. While Cdc42-1ritC cells are viable and polarized, Cdc42-2ritC polarize poorly and Cdc42-3ritC are inviable, in agreement with model’s predictions. Deletion of Cdc42 GAPs restores viability to Cdc42-3ritC cells, verifying the model’s prediction that GAP deletion increases Cdc42 activity at the expense of polarization. Our work demonstrates how membrane flows are an integral part of Cdc42-driven pattern formation and require Cdc42-GTP to turn over faster than the surface on which it forms. Yeast cells exhibit polarized cell growth due in part to the asymmetric activity of the small GTPase Cdc42, which regulates polarized membrane secretion that causes flows that redistribute membrane-associated molecules. Here, modeling and experiments show that membrane flow itself impacts the distribution of Cdc42, which requires fast mobility in order to maintain its polarization.

This study investigates how different conditioning model specifications affect the stability of marginal and subgroup achievement distributions in large-scale assessments. Through both a simulation and an empirical example reflecting typical operational designs, we examine the robustness of these distributions under alternative latent regression models. We compare parameter estimates obtained from generating parameters with aggregated estimates derived from plausible values. Our findings show that marginal and subgroup achievement distributions are consistently stable and well-recovered across several specifications, aligning with established results from linear regression and multiple imputation. These results provide practical guidance for methodological practice and strengthen the interpretation of large-scale assessment outcomes, bridging technical rigor with applied research needs.

Force transmission at integrin-based adhesions is important for cell migration and mechanosensing. Talin is an essential focal adhesion (FA) protein that links F-actin to integrins. F-actin constantly moves on FAs, yet how Talin simultaneously maintains the connection to F-actin and transmits forces to integrins remains unclear. Here we show a critical role of dynamic Talin unfolding in force transmission. Using single-molecule speckle microscopy, we found that the majority of Talin are bound only to either F-actin or the substrate, whereas 4.1% of Talin is linked to both structures via elastic transient clutch. By reconstituting Talin knockdown cells with Talin chimeric mutants, in which the Talin rod subdomains are replaced with the stretchable β-spectrin repeats, we show that the stretchable property is critical for force transmission. Simulations suggest that unfolding of the Talin rod subdomains increases in the linkage duration and work at FAs. This study elucidates a force transmission mechanism, in which stochastic molecular stretching bridges two cellular structures moving at different speeds. Focal adhesion proteins transmit intracellular forces to the extracellular matrix (ECM). Here, the authors show a force transmission by elastic transient clutch of Talin between ECM and constantly flowing F-actin at focal adhesions.

Background Robust coordination of surface and volume changes is critical for cell integrity. Few studies have elucidated the plasma membrane (PM) remodeling events during drastic cell surface and volume alteration, especially regarding PM sensing and its subsequent rearrangements. Results In this article, using fission yeast protoplasts, we reveal a Ca 2+ -dependent mechanism for membrane addition that ensures PM integrity and allows its expansion during acute hypoosmotic cell swelling. We show that MscS-like mechanosensitive channels activated by PM tension control extracellular Ca 2+ influx, which triggers potential direct lipid transfer at endoplasmic reticulum (ER)-PM contact sites by conserved extended-synaptotagmins and accelerates exocytosis, enabling PM expansion necessary for osmotic equilibrium. Defects in any of these key events result in rapid protoplast rupture upon severe hypotonic shock. Our numerical simulations of such hypoosmotic PM expansion further propose a cellular strategy that combines instantaneous non-vesicular lipid transfer with bulk exocytic membrane delivery to maintain PM integrity for dramatic cell surface/volume adaptation. Conclusions We propose a cellular strategy that combines instantaneous non-vesicular lipid transfer with bulk exocytic membrane delivery to maintain PM integrity for dramatic cell surface/volume adaptation.

Food insecurity remains a crucial issue across the globe, including in developed countries. In this study, we examined the relationship between food insecurity and student math achievement globally. We used novel, student-level data from about half a million students in 65 countries that participated in the Program for International Student Assessment (PISA) 2022. We applied three-level hierarchical linear regression models to analyze the data. Without an exception across countries, we found a consistent relationship between food insecurity and student achievement which remains robust after accounting for student and school demographics and socioeconomic status. Students who experience the most severe food insecurity fall behind their food-secure counterparts by approximately two academic years. This substantial achievement gap necessitates profound policy response on a global scale.

This paper scrutinizes the increasing trend of using international large-scale assessment (ILSA) data for causal inferences in educational research, arguing that such inferences are often tenuous. We explore the complexities of causality within ILSAs, highlighting the methodological constraints that challenge the validity of causal claims derived from these datasets. The analysis begins with an overview of causality in relation to ILSAs, followed by an examination of randomized control trials and quasi-experimental designs. We juxtapose two quasi-experimental studies demonstrating potential against three studies using ILSA data, revealing significant limitations in causal inference. The discussion addresses the ethical and epistemological challenges in applying quasi-experimental designs to ILSAs, emphasizing the difficulty in achieving robust causal inference. The paper concludes by suggesting a framework for critically evaluating quasi-experimental designs using ILSAs, advocating for a cautious approach in employing these data for causal inferences. We call for a reevaluation of methodologies and conceptual frameworks in comparative education, underscoring the need for a multifaceted approach that combines statistical rigor with an understanding of educational contexts and theoretical foundations.

Aneurysm rupture has been suggested to be related to aneurysm geometry, morphology, and complex flow activity; therefore, understanding aneurysm-specific hemodynamics is crucial. 4D Flow MRI has been shown to be a feasible tool for assessing hemodynamics in intracranial aneurysms with high spatial resolution. However, it requires averaging over multiple heartbeats and cannot account for cycle-to-cycle hemodynamics variations. This study aimed to assess cycle-to-cycle flow dynamics variations in a patient-specific intracranial aneurysm model using tomographic particle image velocimetry (tomo-PIV) at a high image rate under pulsatile flow conditions. Time-resolved and time-averaged velocity flow fields within the aneurysm sac and estimations of wall shear stress (WSS) were compared with those from 4D Flow MRI. A one-way ANOVA showed a significant difference between cardiac cycles (p value < 0.0001); however, differences were not significant after PIV temporal and spatial resolution was matched to that of MRI (p value 0.9727). This comparison showed the spatial resolution to be the main contributor to assess cycle-to-cycle variability. Furthermore, the comparison with 4D Flow MRI between velocity components, streamlines, and estimated WSS showed good qualitative and quantitative agreement. This study showed the feasibility of patient-specific in-vitro experiments using tomo-PIV to assess 4D Flow MRI with high repeatability in the measurements.

In this paper, we explore the association between a major result of food insecurity, hunger, and academic achievement internationally. Specifically, using data from the Trends in Mathematics and Science Study (TIMSS) 2019, we examined the association between students who go to school hungry and their achievement in eighth-grade math. Within this analysis, we also study the achievement gap between food-insecure students and their peers and assess if that gap is confounded by socioeconomic status, peer effect, and teacher quality.