6,328 research outputs found

    Regulation and Function of the Caspase-1 in an Inflammatory Microenvironment.

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    The inflammasome is a complex of proteins that has a critical role in mounting an inflammatory response in reply to a harmful stimulus that compromises the homeostatic state of the tissue. The NLRP3 inflammasome, which is found in a wound-like environment, is comprised of three components: the NLRP3, the adaptor protein ASC and caspase-1. Interestingly, although ASC levels do not fluctuate, caspase-1 levels are elevated in both physiological and pathological conditions. Despite the observation that merely raising caspase-1 levels is sufficient to induce inflammation, the crucial question regarding the mechanism governing its expression is unexplored. We found that, in an inflammatory microenvironment, caspase-1 is regulated by NF-κB. Consistent with this association, the inhibition of caspase-1 activity parallels the effects on wound healing caused by the abrogation of NF-κB activation. Surprisingly, not only does inhibition of the NF-κB/caspase-1 axis disrupt the inflammatory phase of the wound-healing program, but it also impairs the stimulation of cutaneous epithelial stem cells of the proliferative phase. These data provide a mechanistic basis for the complex interplay between different phases of the wound-healing response in which the downstream signaling activity of immune cells can kindle the amplification of local stem cells to advance tissue repair

    Evaluating a web-based social anxiety intervention among community users: Analysis of real-world data

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    © Hugh Cameron McCall, Fjola Dogg Helgadottir, Ross G Menzies, Heather D Hadjistavropoulos, Frances S Chen. Background: Social anxiety is both harmful and prevalent. It also currently remains among the most undertreated major mental disorders, due, in part, to socially anxious individuals’ concerns about the stigma and expense of seeking help. The privacy and affordability of computer-aided psychotherapy interventions may render them particularly helpful in addressing these concerns, and they are also highly scalable, but most tend to be only somewhat effective without therapist support. However, a recent evaluation of a new self-guided, 7-module internet-delivered cognitive behavioral therapy intervention called Overcome Social Anxiety found that it was highly effective. Objective: The initial evaluation of Overcome Social Anxiety revealed that it led to significant reductions in symptom severity among university undergraduates. The aim of this study was to extend the results of the initial study and investigate their generalizability by directly evaluating the intervention’s effectiveness among a general community sample. Methods: While signing up for Overcome Social Anxiety, users consented to the usage of their anonymized outcome data for research purposes. Before and after completing the intervention, users completed the Fear of Negative Evaluation Scale (FNE), which we employed as the primary outcome measure. Secondary outcome measures included the Depression Anxiety Stress Scales (DASS) and 2 bespoke questionnaires measuring socially anxious thoughts (Thoughts Questionnaire) and avoidance behaviors (Avoidance Questionnaire). Results: Participants who completed the intervention (102/369, 27.7%) experienced significant reductions in the severity of their symptoms on all measures employed, including FNE (P<.001; Cohen d=1.76), the depression subscale of DASS (P<.001; Cohen d=0.70), the anxiety subscale of DASS (P<.001; Cohen d=0.74), the stress subscale of DASS (P<.001; Cohen d=0.80), the Thoughts Questionnaire (P<.001; Cohen d=1.46), and the Avoidance Questionnaire (P<.001; Cohen d=1.42). Conclusions: Our results provide further evidence that Overcome Social Anxiety reduces the severity of social anxiety symptoms among those who complete it and suggest that its effectiveness extends to the general community. The completion rate is the highest documented for a fully automated intervention for anxiety, depression, or low mood in a real community sample. In addition, our results indicate that Overcome Social Anxiety reduces the severity of symptoms of depression, physiological symptoms of anxiety, and stress in addition to symptoms of social anxiety

    Self-assembly of Microcapsules via Colloidal Bond Hybridization and Anisotropy

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    Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures. Mutually attractive nanoparticles that are deformable due to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles. Furthermore, anisotropic colloids with attractive patches can self-assemble into open lattices and colloidal equivalents of molecules and micelles. However, model systems that combine mutual attraction, anisotropy, and deformability have---to the best of our knowledge---not been realized. Here, we synthesize colloidal particles that combine these three characteristics and obtain self-assembled microcapsules. We propose that mutual attraction and deformability induce directional interactions via colloidal bond hybridization. Our particles contain both mutually attractive and repulsive surface groups that are flexible. Analogous to the simplest chemical bond, where two isotropic orbitals hybridize into the molecular orbital of H2, these flexible groups redistribute upon binding. Via colloidal bond hybridization, isotropic spheres self-assemble into planar monolayers, while anisotropic snowman-like particles self-assemble into hollow monolayer microcapsules. A modest change of the building blocks thus results in a significant leap in the complexity of the self-assembled structures. In other words, these relatively simple building blocks self-assemble into dramatically more complex structures than similar particles that are isotropic or non-deformable
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