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The gut microbiome is the largest source of intrinsic non-self-antigens that are continuously sensed by the immune system but typically do not elicit lymphocyte responses. CD4+ T cells are critical to sustain uninterrupted tolerance to microbial antigens and to prevent intestinal inflammation. However, clinical interventions targeting commensal bacteria-specific CD4+ T cells are rare, because only a very limited number of commensal-derived epitopes have been identified. Here, we used a new approach to study epitopes and identify T cell receptors expressed by CD4+Foxp3+ (Treg) cells specific for commensal-derived antigens. Using this approach, we found that antigens from Akkermansia muciniphila reprogram naïve CD4+ T cells to the Treg lineage, expand preexisting microbe specific Tregs, and limit wasting disease in the CD4+ T cell transfer model of colitis. These data suggest that the administration of specific commensal epitopes may help to widen the repertoire of specific Tregs that control intestinal inflammation.Materials exhibiting reversible changes in optical properties upon light irradiation have shown great potential in diverse optoelectronic areas. In particular, the modulation of photochromic behavior on demand for such materials is of fundamental importance, but it remains a formidable challenge. Here, we report a facile and effective strategy to engineer controllable photochromic properties by varying the counterions in a series of zinc complexes consisting of a spirolactam-based photochromic ligand. Colorability and coloration rate can be finely tuned by conveniently changing their counterions. Through utilization of the reversible feature of the metal-ligand coordination bond between Zn2+ and the spirolactam-based ligand, dynamic manipulation of photochromic behavior was achieved. Furthermore, we demonstrated the practical applications of the tunable photochromic properties for these complexes by creating photochromic films and developing multilevel security printing. These findings show opportunities for the development of smart materials with dynamically controllable responsive behavior in advanced optoelectronic applications.Many viruses use their genome as template for self-assembly into an infectious particle. However, this reaction remains elusive because of the transient nature of intermediate structures. To elucidate this process, optical tweezers and acoustic force spectroscopy are used to follow viral assembly in real time. Using Simian virus 40 (SV40) virus-like particles as model system, we reveal a multistep assembly mechanism. Initially, binding of VP1 pentamers to DNA leads to a significantly decreased persistence length. Moreover, the pentamers seem able to stabilize DNA loops. Next, formation of interpentamer interactions results in intermediate structures with reduced contour length. These structures stabilize into objects that permanently decrease the contour length to a degree consistent with DNA compaction in wild-type SV40. These data indicate that a multistep mechanism leads to fully assembled cross-linked SV40 particles. SV40 is studied as drug delivery system. Our insights can help optimize packaging of therapeutic agents in these particles.A key problem in the study of the senses is to describe how sense organs extract perceptual information from the physics of the environment. We previously observed that dynamic touch elicits mechanical waves that propagate throughout the hand. Here, we show that these waves produce an efficient encoding of tactile information. ONO7475 The computation of an optimal encoding of thousands of naturally occurring tactile stimuli yielded a compact lexicon of primitive wave patterns that sparsely represented the entire dataset, enabling touch interactions to be classified with an accuracy exceeding 95%. The primitive tactile patterns reflected the interplay of hand anatomy with wave physics. Notably, similar patterns emerged when we applied efficient encoding criteria to spiking data from populations of simulated tactile afferents. This finding suggests that the biomechanics of the hand enables efficient perceptual processing by effecting a preneuronal compression of tactile information.The obesity rate is rapidly increasing, which has been attributed to lack of exercise and excessive energy intake. Here, we found a previously unidentified explanation, due to lack of maternal exercise. In this study, healthy maternal mice were assigned either to a sedentary lifestyle or to exercise daily, and fetal brown adipose tissue (BAT) development and offspring metabolic health were analyzed. Compared to the sedentary group, maternal exercise enhanced DNA demethylation of Prdm16 promoter and BAT development and prevented obesity of offspring when challenged with a high-energy diet. Apelin, an exerkine, was elevated in both maternal and fetal circulations due to exercise, and maternal administration of apelin mimicked the beneficial effects of exercise on fetal BAT development and offspring metabolic health. Together, maternal exercise enhances thermogenesis and the metabolic health of offspring mice, suggesting that the sedentary lifestyle during pregnancy contributes to the obesity epidemic in modern societies.TUDOR domain-containing proteins (TDRDs) are chiefly responsible for recognizing methyl-lysine/arginine residue. However, how TDRD dysregulation contributes to breast tumorigenesis is poorly understood. Here, we report that TUDOR domain-containing PHF20L1 as a H3K27me2 reader exerts transcriptional repression by recruiting polycomb repressive complex 2 (PRC2) and Mi-2/nucleosome remodeling and deacetylase (NuRD) complex, linking PRC2-mediated methylation and NuRD-mediated deacetylation of H3K27. Furthermore, PHF20L1 was found to serve as a potential MYC and hypoxia-driven oncogene, promoting glycolysis, proliferation, and metastasis of breast cancer cells by directly inhibiting tumor suppressors such as HIC1, KISS1, and BRCA1. PHF20L1 expression was also strongly correlated with higher histologic grades of breast cancer and markedly up-regulated in several cancers. Meanwhile, Phf20l1 deletion not only induces growth retardation and mammary ductal outgrowth delay but also inhibits tumorigenesis in vivo. Our data indicate that PHF20L1 promotes tumorigenesis, supporting the pursuit of PHF20L1 as a target for cancer therapy.
Read More: https://www.selleckchem.com/products/ono-7475.html
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