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© 2020, Nascimento et al.We report that mouse hypothalamic stem/progenitor cells produce multiple pancreatic, gastrointestinal and hypothalamic peptides in addition to exosomes. Through cell sorting and selection according to insulin promoter activity, we generated a subpopulation(s) of these cells which formed 3D spherical structure with combined features of hypothalamic neurospheres and pancreatic islets. Through testing streptozotocin-induced pancreatic islet disruption and fatal diabetes, we found that peripheral implantation of these spheres in mice led to remarkable improvements in general health and survival in addition to a moderate antidiabetic effect, and notably these pro-survival versus metabolic effects were dissociable to a significant extent. Mechanistically, secretion of exosomes by these spheres was essential for enhancing survival while production of insulin was important for the antidiabetic effect. In summary, hypothalamic neural stem/progenitor cells comprise subpopulations with multifaceted secretion, and their derived hypothalamic islets can be implanted peripherally to enhance general health and survival together with an antidiabetic benefit. © 2020, Tang et al.Polypyrimidine tract-binding protein 1 (PTBP1) is a RNA-binding protein (RBP) expressed throughout B cell development. Deletion of Ptbp1 in mouse pro-B cells results in upregulation of PTBP2 and normal B cell development. We show that PTBP2 compensates for PTBP1 in B cell ontogeny as deletion of both Ptbp1 and Ptbp2 results in a complete block at the pro-B cell stage and a lack of mature B cells. In pro-B cells PTBP1 ensures precise synchronisation of the activity of cyclin dependent kinases at distinct stages of the cell cycle, suppresses S-phase entry and promotes progression into mitosis. PTBP1 controls mRNA abundance and alternative splicing of important cell cycle regulators including CYCLIN-D2, c-MYC, p107 and CDC25B. Our results reveal a previously unrecognised mechanism mediated by a RBP that is essential for B cell ontogeny and integrates transcriptional and post-translational determinants of progression through the cell cycle. © 2020, Monzón-Casanova et al.We reveal a novel mechanism that explains how preparatory activity can evolve in motor-related cortical areas without prematurely inducing movement. The smooth eye movement region of the frontal eye fields (FEFSEM) is a critical node in the neural circuit controlling smooth pursuit eye movement. Preparatory activity evolves in the monkey FEFSEM during fixation in parallel with an objective measure of visual-motor gain. We propose that the use of FEFSEM output as a gain signal rather than a movement command allows for preparation to progress in pursuit without causing movement. We also show that preparatory modulation of firing rate in FEFSEM predicts movement, providing evidence against the 'movement-null' space hypothesis as an explanation of how preparatory activity can progress without movement. Finally, there is a partial reorganization of FEFSEM population activity between preparation and movement that would allow for a directionally non-specific component of preparatory visual-motor gain enhancement in pursuit. © 2020, Darlington and Lisberger.The diverse repertoire of T-cell receptors (TCR) plays a key role in the adaptive immune response to infections. Using TCR alpha and beta repertoire sequencing for T-cell subsets, as well as single-cell RNAseq and TCRseq, we track the concentrations and phenotypes of individual T-cell clones in response to primary and secondary yellow fever immunization - the model for acute infection in humans - showing their large diversity. We confirm the secondary response is an order of magnitude weaker, albeit ∼10 days faster than the primary one. Estimating the fraction of the T-cell response directed against the single immunodominant epitope, we identify the sequence features of TCRs that define the high precursor frequency of the two major TCR motifs specific for this particular epitope. We also show the consistency of clonal expansion dynamics between bulk alpha and beta repertoires, using a new methodology to reconstruct alpha-beta pairings from clonal trajectories. © 2020, Minervina et al.To implement effective stewardship in food animal production, it is essential that producers and veterinarians are aware of preventive interventions to reduce illness in livestock. Systematic reviews and meta-analyses (SR/MA) provide transparent, replicable, and quality-assessed overviews. At present, it is unknown how many SR/MA evaluate preventive antibiotic use or management practices aimed at reducing disease risk in animal agriculture. Further, the quality of existing reviews is unknown. Selleckchem Elamipretide Our aim was to identify reviews investigating these topics and to provide an assessment of their quality. Thirty-eight relevant reviews were identified. Quality assessment was based on the AMSTAR 2 framework for the critical appraisal of systematic reviews. The quality of most of the reviews captured was classified as critically low (84.2%, n = 32/38), and only a small percentage of the evaluated reviews did not contain critical weaknesses (7.9%, n = 3/38). Particularly, a small number of reviews reported the development of an a priori protocol (15.8%, n = 6/38), and few reviews stated that key review steps were conducted in duplicate (study selection/screening 26.3%, n = 10/38; data extraction 15.8%, n = 6/38). The development of high-quality reviews summarizing evidence on approaches to antibiotic reduction is essential, and thus greater adherence to quality conduct guidelines for synthesis research is crucial.A systematic review and network meta-analysis (NMA) were conducted to address the question, 'What is the efficacy of litter management strategies to reduce morbidity, mortality, condemnation at slaughter, or total antibiotic use in broilers?' Eligible studies were clinical trials published in English evaluating the efficacy of litter management in broilers on morbidity, condemnations at slaughter, mortality, or total antibiotic use. Multiple databases and two conference proceedings were searched for relevant literature. After relevance screening and data extraction, there were 50 trials evaluating litter type, 22 trials evaluating litter additives, 10 trials comparing fresh to re-used litter, and six trials evaluating floor type. NMAs were conducted for mortality (61 trials) and for the presence or absence of footpad lesions (15 trials). There were no differences in mortality among the litter types, floor types, or additives. For footpad lesions, peat moss appeared beneficial compared to straw, based on a small number of comparisons.

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