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The present findings suggest that the IL is a key brain region for conditioned safety memory. Because anxiety disorder patients are often not capable to use safety cues to inhibit unnecessary fear responses, the present findings are of clinical relevance and could potentially contribute to therapy optimization.Retreating subduction zones such as the Lesser Antilles, Gibraltar and Scotia have been migrating towards the Atlantic Ocean by cutting their way through the oceanic crust. This spontaneously retreating subduction is enabled by the development of faults at the edges of the slab, but the physical mechanisms controlling fault propagation and direction remain unknown. Here, using 3D numerical subduction models we show that oceanic lithosphere recycling is mainly controlled by the intensity of strain-induced weakening of fractures forming at the edges of the slab. Intense strain-induced weakening causes predominantly brittle fault propagation and slab narrowing until detachment. Without weakening, preponderantly ductile slab edge propagation occurs, which causes slab widening. This rheological control is not affected by the proximity of non-weakened passive continental margins. Natural examples suggest that slab edges follow convergent paths that could be controlled by fractures weakening due to deep water penetration into the oceanic lithosphere.As the overlap between heart disease and cancer patients increases as cancer-specific mortality is decreasing and the surviving population is aging, it is necessary to identify cancer patients who are at an increased risk of death from heart disease. The purpose of this study is to identify cancer patients at highest risk of fatal heart disease compared to the general population and other cancer patients at risk of death during the study time period. Here we report that 394,849 of the&nbsp;7,529,481 cancer patients studied died of heart disease. The heart disease-specific mortality rate is 10.61/10,000-person years, and the&nbsp;standardized mortality ratio (SMR) of fatal heart disease is 2.24 (95% CI 2.23-2.25). Compared to other cancer patients, patients who are older, male, African American, and unmarried are at a greatest risk of fatal heart disease. For almost all cancer survivors, the risk of fatal heart disease increases with time.C-terminal binding protein 2 (CtBP2) is elevated in epithelial ovarian cancer, especially in the aggressive and highly lethal subtype, high-grade serous ovarian cancer (HGSOC). However, whether HGSOC tumor progression is dependent on CtBP2 or its paralog CtBP1, is not well understood. Here we report that CtBP1/2 repress HGSOC cell apoptosis through silencing of death receptors (DRs) 4/5. CtBP1 or 2 knockdown upregulated DR4/5 expression, and triggered autonomous apoptosis via caspase 8 activation, but dependent on cell-type context. Activation of DR4/5 by CtBP1/2 loss also sensitized HGSOC cell susceptibility to the proapoptotic DR4/5 ligand TRAIL. Consistent with its function as transcription corepressor, CtBP1/2 bound to the promoter regions of DR4/5 and repressed DR4/5 expression, presumably through recruitment to a repressive transcription regulatory complex. We also found that CtBP1 and 2 were both required for repression of DR4/5. Collectively, this study identifies CtBP1 and 2 as potent repressors of DR4/5 expression and activity, and supports the targeting of CtBP as a promising therapeutic strategy for HGSOC.Decision confidence reflects our ability to evaluate the quality of decisions and guides subsequent behavior. Experiments on confidence reports have almost exclusively focused on two-alternative decision-making. [https://www.selleckchem.com/ selleck products] In this realm, the leading theory is that confidence reflects the probability that a decision is correct (the posterior probability of the chosen option). There is, however, another possibility, namely that people are less confident if the best two options are closer to each other in posterior probability, regardless of how probable they are in absolute terms. This possibility has not previously been considered because in two-alternative decisions, it reduces to the leading theory. Here, we test this alternative theory in a three-alternative visual categorization task. We found that confidence reports are best explained by the difference between the posterior probabilities of the best and the next-best options, rather than by the posterior probability of the chosen (best) option alone, or by the overall uncertainty (entropy) of the posterior distribution. Our results upend the leading notion of decision confidence and instead suggest that confidence reflects the observer's subjective probability that they made the best possible decision.Ulcerative colitis (UC) is a chronic and etiologically refractory inflammatory gut disorder. Although berberine, an isoquinoline alkaloid, has been revealed to exert protective effects on experimental colitis, the underlying molecular mechanism in chronic intestinal inflammation remains ill-defined. This study was designed to uncover the therapeutic efficacy and immunomodulatory role of berberine in chronic UC. Therapeutic effects of oral administration of berberine were investigated in dextran sodium sulfate (DSS)-induced murine chronic UC and the underlying mechanisms were further identified by si-OSMR transfection in human intestinal stromal cells. Berberine significantly attenuated the experimental symptoms and gut inflammation of chronic UC. Berberine treatment could also maintain the intestinal barrier function and rectify tissue fibrosis. In accordance with infiltrations of antigen-presenting cells (APCs), innate lymphoid cells (ILCs), and activated NK cells in colonic lamina propria, increased expression of OSM and OSMR were observed in the inflamed tissue of chronic UC, which were decreased following berberine treatment. Moreover, berberine inhibited the overactivation of human intestinal stromal cells through OSM-mediated JAK-STAT pathway, which was obviously blocked upon siRNA targeting OSMR. The research provided an infusive mechanism of berberine and illustrated that OSM and OSMR intervention might function as the potential target in chronic UC.