The endoplasmic reticulum (ER) and mitochondria are essential intracellular organelles that actively communicate via temporally and spatially formed contacts called mitochondria-associated membranes (MAMs). These mitochondria-ER contacts are not only necessary for the physiological function of the organelles and their coordination with each other, but they also control the intracellular lipid exchange, calcium signaling, cell survival, and homeostasis in cellular metabolism. Growing evidence strongly supports the role of the mitochondria-ER connection in the insulin resistance of peripheral tissues, pancreatic β cell dysfunction, and the consequent development of type 2 diabetes mellitus (T2DM). In this review, we summarize current advances in the understanding of the mitochondria-ER connection and specifically focus on addressing a new perspective of the alterations in mitochondria-ER communication in insulin signaling and β cell maintenance.Caenorhabditis elegans nematodes produce and maintain imprints of attractive chemosensory cues to which they are exposed early in life. Early odor-exposure increases adult chemo-attraction to the same cues. Imprinting is transiently or stably inherited, depending on the number of exposed generations. We show here that the Alanine tRNA (UGC) plays a central role in regulating C. elegans chemo-attraction. Naive worms fed on tRNAAla (UGC) purified from odor-experienced worms, acquire odor-specific imprints. Chemo-attractive responses require the tRNA-modifying Elongator complex sub-units 1 (elpc-1) and 3 (elpc-3) genes. elpc-3 deletions impair chemo-attraction, which is fully restored by wild-type tRNAAla (UGC) feeding. A stably inherited decrease of odor-specific responses ensues from early odor-exposition of elpc-1 deletion mutants. tRNAAla (UGC) may adopt various chemical forms to mediate the cross-talk between innately-programmed and environment-directed chemo-attractive behavior.Persistent neural stem cell (NSC) proliferation is, among others, a hallmark of immaturity in human induced pluripotent stem cell (hiPSC)-based neural models. TGF-β1 is known to regulate NSCs in vivo during embryonic development in rodents. Here we examined the role of TGF-β1 as a potential candidate to promote in vitro differentiation of hiPSCs-derived NSCs and maturation of neuronal progenies. We present that TGF-β1 is specifically present in early phases of human fetal brain development. We applied confocal imaging and electrophysiological assessment in hiPSC-NSC and 3D neural in vitro models and demonstrate that TGF-β1 is a signaling protein, which specifically suppresses proliferation, enhances neuronal and glial differentiation, without effecting neuronal maturation. Moreover, we demonstrate that TGF-β1 is equally efficient in enhancing neuronal differentiation of human NSCs as an artificial synthetic small molecule. The presented approach provides a proof-of-concept to replace artificial small molecules with more physiological signaling factors, which paves the way to improve the physiological relevance of human neural developmental in vitro models.Exposure to fine particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5) is closely correlated with respiratory diseases. Microbiota plays a key role in maintaining body homeostasis including regulation of host immune status and metabolism. this website As reported recently, PM2.5 exposure causes microbiota dysbiosis and thus promotes disease progression. However, whether PM2.5 alters pulmonary microbiota distribution and aggravates bacteria-induced pathogenesis remains unknown. In this study, we used mouse experimental models of PM2.5 exposure combined with Streptococcus pneumonia infection. We characterized the airway microbiota of bronchoalveolar lavage fluid (BALF) by sequencing the 16S rRNA V3-V4 amplicon on the Illumina MiSeq platform, followed by a combination of bioinformatics and statistical analyses. Shannon-diversity index, observed ASVs, and Fisher's diversity index indicated that microbiota richness was significantly decreased in the mice treated with either PM2.5 or pneumococcus when compared with the control group. The genera Streptococcus, Prevotella, Leptotrichia, and Granulicatella were remarkably increased in mice exposed to PM2.5 combined with pneumococcal infection as compared to mice with pneumococcal infection alone. Histopathological examination exhibited that a more pronounced inflammation was present in lungs of mice treated with PM2.5 and pneumococcus than that in mouse groups exposed to either PM2.5 or pneumococcal infection alone. Our results demonstrate that PM2.5 alters the microbiota composition, thereby enhancing susceptibility to pneumococcal infection and exacerbating lung pathogenesis.Trypanosoma cruzi P21 is a protein secreted by the parasite that plays biological roles directly involved in the progression of Chagas disease. The recombinant protein (rP21) demonstrates biological properties, such as binding to CXCR4 receptors in macrophages, chemotactic activity of immune cells, and inhibiting angiogenesis. This study aimed to verify the effects of rP21 interaction with CXCR4 from non-tumoral cells (MCF-10A) and triple-negative breast cancer cells (MDA-MB-231). Our data showed that the MDA-MB-231 cells expressed higher levels of CXCR4 than did the non-tumor cell lines. Besides, cytotoxicity assays using different concentrations of rP21 showed that the recombinant protein was non-toxic and was able to bind to the cell membranes of both cell lineages. In addition, rP21 reduced the migration and invasion of MDA-MB-231 cells by the downregulation of MMP-9 gene expression. In addition, treatment with rP21 blocked the cell cycle, arresting it in the G1 phase, mainly in MDA-MB-231 cells. Finally, rP21 prevents the chemotaxis and proliferation induced by CXCL12. Our data showed that rP21 binds to the CXCR4 receptors in both cells, downregulates CXCR4 gene expression, and decreases the receptors in the cytoplasm of MDA-MB-231 cells, suggesting CXCR4 internalization. This internalization may explain the desensitization of the receptors in these cells. Thus, rP21 prevents migration, invasion, and progression in MDA-MB-231 cells.