© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.Intercellular communication orchestrates effective immune responses against disease-causing agents. Extracellular vesicles (EVs) are potent mediators of cell-cell communication. EVs carry bioactive molecules, including microRNAs, which modulate gene expression and function in the recipient cell. Here, we show that formation of cognate primary T-B lymphocyte immune contacts promotes transfer of a very restricted set of T-cell EV-microRNAs (mmu-miR20-a-5p, mmu-miR-25-3p, and mmu-miR-155-3p) to the B cell. Transferred EV-microRNAs target key genes that control B-cell function, including pro-apoptotic BIM and the cell cycle regulator PTEN. EV-microRNAs transferred during T-B cognate interactions also promote survival, proliferation, and antibody class switching. Using mouse chimeras with Rab27KO EV-deficient T cells, we demonstrate that the transfer of small EVs is required for germinal center reaction and antibody production in vivo, revealing a mechanism that controls B-cell responses via the transfer of EV-microRNAs of T-cell origin. These findings also provide mechanistic insight into the Griscelli syndrome, associated with a mutation in the Rab27a gene, and might explain antibody defects observed in this pathogenesis and other immune-related and inflammatory disorders. © 2020 The Authors. Published under the terms of the CC BY 4.0 license.The HoBi-like pestivirus (HoBiPeV), currently classified as Pestivirus H species, is a pathogen associated with a broad spectrum of clinical manifestations in ruminants, particularly in cattle. Since HoBiPeV complete genome sequencing data is scarce, in the present study we described five nearly complete new Brazilian HoBiPeV genomes and further perform a more complete genetic and evolutionary characterization with all additional genome sequences available in the GenBank database. Entropy and selection pressure analysis showed the E2 gene, a surface glycoprotein, is the most variable gene, which also displays the greatest number of sites under positive selection. Phylogenetic and Bayesian inference based on complete genome and Npro gene, respectively, from all HoBiPeV sequences available so far, confirms the existence of three main clades (a, b, and c). The abovementioned analysis suggests that this pestivirus species probably emerged in Asia and spread to different regions including Brazil, where only strains belonging to specific genetic group 'a' have been found. The hypothesis of the HoBiPeV introduction in Brazil (between 1,890 and 1,962), formulated based on Bayesian inference, coincides with a period of intensive importation of water buffalo (Bubalus arnee) and indicine cattle (Bos taurus indicus) from Asia to Brazil, suggesting that this could be the origin of the current Brazilian HoBiPeV genetic group 'a'. © 2020 Blackwell Verlag GmbH.Mitochondrial DNA (mtDNA) encodes a subset of the genes which are responsible for oxidative phosphorylation. Pathogenic mutations in the human mtDNA are often heteroplasmic, where wild-type mtDNA species co-exist with the pathogenic mtDNA and a bioenergetic defect is only seen when the pathogenic mtDNA percentage surpasses a threshold for biochemical manifestations. mtDNA segregation during germline development can explain some of the extreme variation in heteroplasmy from one generation to the next. Patients with high heteroplasmy for deleterious mtDNA species will likely suffer from bona-fide mitochondrial diseases, which currently have no cure. Shifting mtDNA heteroplasmy toward the wild-type mtDNA species could provide a therapeutic option to patients. https://www.selleckchem.com/products/alpha-conotoxin-gi.html Mitochondrially targeted engineered nucleases, such as mitoTALENs and mitoZFNs, have been used in vitro in human cells harboring pathogenic patient-derived mtDNA mutations and more recently in vivo in a mouse model of a pathogenic mtDNA point mutation. These gene therapy tools for shifting mtDNA heteroplasmy can also be used in conjunction with other therapies aimed at eliminating and/or preventing the transfer of pathogenic mtDNA from mother to child. © 2020 The Authors.Our previous work indicated exposure of Human liver cell 7702 (HL7702) cells to Microcystin-leucine-arginine (MC-LR) for 24 hours can disrupt insulin (INS) signaling by the hyperphosphorylation of specific proteins. For further exploring the time-dependent effect posed by MC-LR on this pathway, in the current study, HL7702 cells together with mice were exposed to the MC-LR with different concentrations under short-term treatment, and then, protein phosphatase 2A (PP2A) activity and expression of proteins related to INS signaling, as well as the characteristics of their action in the liver, were investigated. The results indicated, in HL7702 cells with 0.5, 1, and 6 hours of treatment by MC-LR, PP2A activity showed an obvious decrease in a time and concentration-dependent manner. While the total protein level of Akt, glycogen synthase kinase 3 (GSK-3), and glycogen synthase remained unchanged, GSK-3 and Akt phosphorylation increased significantly. In livers of mice with 1 hour of intraperitoneal injection with MC-LR, a similar change in these proteins was observed. In addition, the levels of total IRS1 and p-IRS1 at serine sites showed decreasing and increasing trends,respectively, and the hematoxylin and eosin staining showed that liver tissues of mice in the maximum-dose group exhibited obvious hepatocyte degeneration and hemorrhage. Our results further proved that short-term treatment with MC-LR can inhibit PP2A activity and disrupt INS signaling proteins' phosphorylation level, thereby interfering with the INS pathway. Our findings provide a helpful understanding of the toxic effects posed by MC-LR on the glucose metabolism of liver via interference with the INS signaling pathway. © 2020 Wiley Periodicals, Inc.BACKGROUND AND AIMS Fractional lasers have become increasingly popular for treating atrophic scars, but their effectiveness is limited for deeper scars. We developed a novel technique (manual fractional thermal contraction technology, MFTCT) using an ultra-pulse CO2 laser and evaluated its efficacy and safety for treating atrophic facial scars. METHODS A total of 44 patients with atrophic facial scars were treated with MFTCT every 8 weeks for 1-4 times. Overall scar improvement was assessed by photographs taken at baseline and 3 months after the last treatment according to the 4-point global assessment scale (GAS) and ECCA grading scale. Improvements in color, distortion, and texture were assessed by the modified Manchester Scar Scale and scored individually from 1 to 4. Pain degrees and adverse reactions during and after treatment were recorded. RESULTS A total of 44 patients completed the treatment and follow-ups; of them, 89% reported at least 50% overall improvement after the last treatment. The mean ECCA scores fell from 67.