Activity

A change in Presenilin (PS)/γ-secretase activity is linked to essential biological events as well as to the progression of many diseases. However, not much is known about how PS/γ-secretase activity is spatiotemporally regulated in cells. One of the limitations is lack of tools to directly monitor dynamic behavior of the PS/γ-secretase in intact/live cells. Here we present successful development and validation of the Förster resonance energy transfer (FRET)-based biosensors that enable quantitative monitoring of endogenous PS/γ-secretase activity in live cells longitudinally on a cell-by-cell basis. Using these FRET biosensors, we uncovered that PS/γ-secretase activity is heterogeneously regulated among live neurons.The massive size of single-cell RNA sequencing datasets often exceeds the capability of current computational analysis methods to solve routine tasks such as detection of cell types. Recently, geometric sketching was introduced as an alternative to uniform subsampling. It selects a subset of cells (the sketch) that evenly cover the transcriptomic space occupied by the original dataset, to accelerate downstream analyses and highlight rare cell types. Here, we propose algorithm Sphetcher that makes use of the thresholding technique to efficiently pick representative cells within spheres (as opposed to the typically used equal-sized boxes) that cover the entire transcriptomic space. We show that the spherical sketch computed by Sphetcher constitutes a more accurate representation of the original transcriptomic landscape. Our optimization scheme allows to include fairness aspects that can encode prior biological or experimental knowledge. We show how a fair sampling can inform the inference of the trajectory of human skeletal muscle myoblast differentiation.Eating disorders are severe mental health conditions, with substantial consequences for health and quality of life. Such disorders are strongly associated with body image concerns. It is important to consider treatments that might enhance our ability to treat such cases. Recently, there has been a growing body of research on self-compassion in relation to such problems. However, we are not yet clear about the extent of such effects, given the range of studies and methodologies used. Therefore, a systematic literature review was carried out using four key databases. Meta-analysis was used to reach conclusions about the size of the effects and moderators. Random-effects meta-analyses were conducted with 59 studies. Higher self-compassion was associated with lower eating pathology, reduced body image concerns, and greater positive body image, with medium to strong effect sizes (respectively, r = -0.34, r = -0.45, r = 0.52). Furthermore, self-compassion interventions for eating pathology and body image were effective, and superior to control groups (respectively, g = 0.58, g = 0.39). These findings support the role of self-compassion in understanding and addressing eating and body image concerns. Self-compassion appears to be an adaptive emotion regulation strategy in eating disorders and body image.Background Vitamin D has important functions outside of bone metabolism. Deficiency has been associated with several adverse outcomes during pregnancy such as preeclampsia and prematurity. Selleckchem Tovorafenib There is an increasing body of literature on this topic with studies performed to date having produced contradictory results. Objective To synthesize the literature about vitamin D deficiency and its association with preeclampsia and prematurity in order to determine if maternal vitamin D insufficiency and/or deficiency during pregnancy is associated with the prevalence of preeclampsia and prematurity. Design A systematic review and meta-analysis of observational and interventional studies. Methods Two independent researchers reviewed the included studies according to PRISMA reporting guidelines. A protocol for this review was registered in PROSPERO with the registration number “CRD42019136318”. Three electronic databases (PubMed, ScienceDirect and Web of Science); were searched in order to identify eligible studies. Observmaturity and vitamin D were only associated when maternal vitamin D concentrations was less then 75 nmol/L. Random-effects meta-analysis found no significant association between vitamin D, preeclampsia and prematurity in either observational or interventional studies. Conclusion Higher vitamin D concentrations during pregnancy could be associated with a decreased risk of preeclampsia and prematurity but statistical significance of associations depends on the study design used. Well-designed clinical trials with vitamin D supplementation are needed in order to better define associations.Introduction Young adults reporting combined alcohol and marijuana use indicate greater frequency of other substances, binge drinking rates, and alcohol-related negative consequences. Emotion regulation (ER) difficulties are linked to alcohol use and abuse, with effects commonly attributed to increased mindfulness and distress tolerance abilities. Evidence is mixed, however, regarding the interactive impact of substance use and mindfulness facets on mental health outcomes. Methods The current study utilized a cross-sectional design to examine mental health outcomes predicted by ER and mindfulness facets in 229 college students across three substance use categories (no use; alcohol/marijuana; illicit use with alcohol/marijuana). Results For participants reporting no substance use, linear stepwise regressions found that Non-Judging was significantly related to reduced anxiety, while Acting with Awareness was related to greater anxiety; for those reporting alcohol/marijuana use only, Non-Judging significantly related to lower stress and anxiety; for those reporting illicit substance use with alcohol/marijuana, Acting with Awareness was related to lower stress. Describing was related to higher distress across groups, and Observing was not significantly related to any aspect of mental health across groups. ER difficulties were positively related to depression, anxiety and stress across substance use groups, with one exception ER difficulty was not significantly associated with depression for no use. Discussion Mindfulness interventions should focus on certain facets, such as Non-Judging, in order to improve psychological functioning across various groups of substance use. Additionally, ER difficulties are closely linked to alcohol, marijuana, and illicit drug use.