Collagen V Promotes Fibroblast Contractility, And Adhesion Formation, And Stability

Ehlers-Danlos syndrome, classical type, (cEDS) is a hereditary connective tissue disorder causing excessive elasticity and fragility of the connective tissue and problems with wound healing. Most cases of cEDS are caused by haploinsufficiency for collagen V. Collagen V regulates collagen fibril diameter. In cEDS fibroblast migration is impaired and integrin expression is altered. The effects of collagen V on collagen gel ultrastructure and how it alters its mechanical properties were measured using scanning electron microscopy (SEM) and rheology respectively. Fibroblast contractility and adhesion dynamics were investigated to better understand the role of fibroblast disfunction in wound healing in cEDS. To quantify these, traction force microscopy (TFM) and time lapse imaging were used. Collagen V decreased fibril diameter and curvature, and increased gel stiffness, indicating that the fibrils themselves were likely stiffer. Cells cultured on collagen V were more contractile and adhesions assembled faster

The role of GABA-ergic interneurons in CA1 and dentate gyrus for sequence learning

posterThe hippocampus (HPP) is widely accepted as a structure that supports spatial memory. Current interest is focused on temporal processing for sequences of events. It has been demonstrated that HPP lesions disrupt acquisition of a spatial temporal sequence in an 8-arm maze (DeCoteau & Kesner, 2000). •HPP subregions have been indicated to be critical in spatial temporal sequence processing. The CA1 region has been shown to play a critical role in temporal information processing and CA1 principal cell lesions impair acquisition of 8-arm radial maze sequences (Rolls & Kesner, 2006; Weeden et al, 2009). The dentate gyrus (DG) is also an important region in the processing of new spatial information, but granule cell lesion studies indicate that principal cells are not a necessary component in the learning of sequential events (Weeden et al, 2009). •Interneurons exhibit inhibitory control over the excitatory principal cells of HPP (Freund & Buzáki, 1996). Their role in temporal processing for spatial locations has yet to be identified. Electrophysiological recording investigations indicate that CA1 and DG interneurons display differential patterns of activation when engaged in identical tasks, such as novel environment exploration (Nitz & McNaughton, 2004). These divergent patterns suggest unique roles for interneurons of different subregions. Within the HPP, inhibitory interneurons exclusively express Substance P receptors (SPR). SPRs have a high affinity for a peptidase-resistant Substance P analog conjugated to the neurotoxin saporin (SSP-Saporin), which allows for selective neurotoxic lesions of inhibitory interneurons that spare surrounding excitatory principal cells (Martin & Sloviter, 2001). The present study aims to determine the level of influence HPP interneurons of the CA1 and DG subregions exert on acquisition of spatial temporal sequences compared to excitatory principal cells. We predict that CA1 interneuron lesion subjects but not DG lesion subjects will make more errors during acquisition of sequence information compared to controls

A Holistic Approach to Estimating the Influence of Good Practices on Student Outcomes at Liberal Arts and non-Liberal Arts Institutions

Many higher education administrators and researchers have considered certain “good practices” of institutions as an instrumental way to improve student outcomes. Chickering and Gamson’s (1987) seven principles of good practice has been particularly salient in defining these practices. Often, prior studies only select some of the seven principles for their analysis. Even studies that consider several principles of good practice on student outcomes typically examine the net effect of each principle instead of assessing how these principles holistically influence student out-comes. Using structural equation modeling, we test a basic conceptual framework where we in-vestigate the contribution of the seven principles on a global measure of good practices (GP), as well as the influence of GP on a multitude of student outcomes. We further test whether liberal arts colleges promote an institutional ethos of good practices as compared to non-liberal arts col-leges. Overall, the majority (but not all) of the principles affect GP. Moreover, we find partial evidence that liberal arts colleges foster an institutional ethos of good practices. Although a commitment to foster good practices may create a supportive environment that influences student outcomes, this commitment may lead to unintended consequences for those with little exposure to these good practices

Polymerizing actin regulates myosin-independent mechanosensing by modulating actin elasticity and flow fluctuation

The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has stronger contribution than Arp2/3. Interestingly, we report a four-fold reduction in traction of cells when both Arp2/3 and myosin were inhibited, compared to cells with only myosin inhibition, while there was only a slight reduction in F-actin flow speed in those cells. We show that the conventional rigid-actin-based clutch model is insufficient to explain this force-flow behavior and requires the inclusion of F-actin’s own elasticity into consideration. Our model prediction suggests that Arp2/3 and formin modulate stiffness sensing via stiffening F-actin network with stronger effect from formin. Analysis of F-actin flow reveals stiffness-dependent fluctuation frequency in the flow speed, which is predictable only via the model considering actin elasticity. Our data and model provide a potential role of the polymerizing actin and its elasticity in myosin-independent mechanosensing

Low Shear in Short-Term Impacts Endothelial Cell Traction and Alignment in Long-Term

Within the vascular system, endothelial cells (ECs) are exposed to fluid shear stress (FSS), a mechanical force exerted by blood flow that is critical for regulating cellular tension and maintaining vascular homeostasis. The way ECs react to FSS varies significantly; while high, laminar FSS supports vasodilation and suppresses inflammation, low or disturbed FSS can lead to endothelial dysfunction and increase the risk of cardiovascular diseases. Yet, the adaptation of ECs to dynamically varying FSS remains poorly understood. This study focuses on the dynamic responses of ECs to brief periods of low FSS, examining its impact on endothelial traction—a measure of cellular tension that plays a crucial role in how endothelial cells respond to mechanical stimuli. By integrating traction force microscopy (TFM) with a custom-built flow chamber, we analyzed how human umbilical vein endothelial cells (HUVECs) adjust their traction in response to shifts from low to high shear stress. We discovered that initial exposure to low FSS prompts a marked increase in traction force, which continues to rise over 10 hours before slowly decreasing. In contrast, immediate exposure to high FSS causes a quick spike in traction followed by a swift reduction, revealing distinct patterns of traction behavior under different shear conditions. Importantly, the direction of traction forces and the resulting cellular alignment under these conditions indicate that the initial shear experience dictates long-term endothelial behavior. Our findings shed light on the critical influence of short-lived low-shear stress experiences in shaping endothelial function, indicating that early exposure to low FSS results in enduring changes in endothelial contractility and alignment, with significant consequences for vascular health and the development of cardiovascular diseases

Myosin-independent stiffness sensing by fibroblasts is regulated by the viscoelasticity of flowing actin

The stiffness of the extracellular matrix induces differential tension within integrin-based adhesions, triggering differential mechanoresponses. However, it has been unclear if the stiffness-dependent differential tension is induced solely by myosin activity. Here, we report that in the absence of myosin contractility, 3T3 fibroblasts still transmit stiffness-dependent differential levels of traction. This myosin-independent differential traction is regulated by polymerizing actin assisted by actin nucleators Arp2/3 and formin where formin has a stronger contribution than Arp2/3 to both traction and actin flow. Intriguingly, despite only slight changes in F-actin flow speed observed in cells with the combined inhibition of Arp2/3 and myosin compared to cells with sole myosin inhibition, they show a 4-times reduction in traction than cells with myosin-only inhibition. Our analyses indicate that traditional models based on rigid F-actin are inadequate for capturing such dramatic force reduction with similar actin flow. Instead, incorporating the F-actin network’s viscoelastic properties is crucial. Our new model including the F-actin viscoelasticity reveals that Arp2/3 and formin enhance stiffness sensitivity by mechanically reinforcing the F-actin network, thereby facilitating more effective transmission of flow-induced forces. This model is validated by cell stiffness measurement with atomic force microscopy and experimental observation of model-predicted stiffness-dependent actin flow fluctuation

The analysis of facial beauty: an emerging area of research in pattern analysis

Much research presented recently supports the idea that the human perception of attractiveness is data-driven and largely irrespective of the perceiver. This suggests using pattern analysis techniques for beauty analysis. Several scientific papers on this subject are appearing in image processing, computer vision and pattern analysis contexts, or use techniques of these areas. In this paper, we will survey the recent studies on automatic analysis of facial beauty, and discuss research lines and practical application

Acute erythemal ultraviolet radiation causes systemic immunosuppression in the absence of increased 25-hydroxyvitamin D-(3) levels in male mice

Extent: 12p.Vitamin D is synthesised by ultraviolet (UV) irradiation of skin and is hypothesized to be a direct mediator of the immunosuppression that occurs following UV radiation (UVR) exposure. Both UVR and vitamin D drive immune responses towards tolerance by ultimately increasing the suppressive activities of regulatory T cells. To examine a role for UVR-induced vitamin D, vitamin D₃-deficient mice were established by dietary vitamin D₃ restriction. In comparison to vitamin D₃-replete mice, vitamin D₃-deficient mice had significantly reduced serum levels of 25-hydroxyvitamin D₃ (25(OH)D₃, <20 nmol.L⁻¹) and 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃, <20 pmol.L⁻¹). Following either acute erythemal UVR, or chronic sub-erythemal UVR (8 exposures over 4 weeks) treatment, serum 25(OH)D₃ levels significantly increased in vitamin D₃-deficient female but not male mice. To determine if UVR-induced vitamin D was a mediator of UVR-induced systemic immunosuppression, responses were measured in mice that were able (female) or unable (male) to increase systemic levels of 25(OH)D₃ after UVR. Erythemal UVR (≥4 kJ/m²) suppressed contact hypersensitivity responses (T helper type-1 or -17), aspects of allergic airway disease (T helper type-2) and also the in vivo priming capacity of bone marrow-derived dendritic cells to a similar degree in female and male vitamin D₃-deficient mice. Thus, in male mice, UVR-induced 25(OH)D₃ is not essential for mediating the immunosuppressive effects of erythemal UVR.Shelley Gorman, Naomi M. Scott, Daryl H. W. Tan, Clare E. Weeden, Robert C. Tuckey, Jacqueline L. Bisley, Michele A. Grimbaldeston, Prue H. Har

Patterns of isozyme variation in relation to population size, isolation, and phytogeographic history in royal catchfly

The distribution of genetic variation within and among plant populations is influenced by both contemporary and historical factors. I used isozyme analysis of band phenotypes to examine genetic structure in the rare prairie forb Silene regia. Relationships between current-day population size, isolation, and phenotypic variation were assessed for 18 populations in two regions with differing postglacial history. Western populations from unglaciated southern Missouri and Arkansas were more genetically diverse based on the Shannon-Weaver index (H) and a polymorphic index than were more eastern populations. These differences may be due to loss of variation with repeated founding of new populations in previously glaciated sites in Indiana and Ohio. Within the western region, population size was not significantly correlated with genetic variation. In the east, size was correlated with Shannon-Weaver diversity. There was no relationship between variation and isolation in either region, but eastern populations were slightly more differentiated. Greater among-population differentiation and the demonstrated connection between population size and variation in the eastern sites may reflect lower levels of interpopulation gene flow in the fragmented remnant prairies of Indiana and Ohio