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In this issue of Cell Stem Cell, An et al. (2020) provide a model to study human X chromosome inactivation. They followed X chromosome activity and traced cellular heterogeneity in naive hESCS, showed that it is caused by incomplete blockade of FGF-signaling, and in doing so isolated cells resembling pre-implantation epiblasts.Large skin wounds in adult mice can heal by regenerating new hair follicles and adipocytes in their center. In this issue of Cell Stem Cell, Abbasi et al. (2020) report how typically scar-forming wound fibroblasts enter a transcriptionally distinct single-cell state of competence during regeneration of new hair follicle mesenchyme.mESCs can self-renew indefinitely in vitro. However, depending on culture conditions some strains are more unstable than others. In this issue of Cell Stem Cell, Skelly et al. (2020) and Ortmann et al. (2020) shed light into the role genetic variation plays in control of ground state pluripotency.Microfabricated and microfluidic devices enable standardized handling, precise spatiotemporal manipulation of cells and liquids, and recapitulation of cellular environments, tissues, and organ-level biology. We asked researchers how these devices can make in vitro experiments more physiologically relevant.Metabolic-associated fatty liver disease (MAFLD) represents a spectrum of disease states ranging from simple steatosis to non-alcoholic steatohepatitis (NASH). Hepatic macrophages, specifically Kupffer cells (KCs), are suggested to play important roles in the pathogenesis of MAFLD through their activation, although the exact roles played by these cells remain unclear. Here, we demonstrated that KCs were reduced in MAFLD being replaced by macrophages originating from the bone marrow. Recruited macrophages existed in two subsets with distinct activation states, either closely resembling homeostatic KCs or lipid-associated macrophages (LAMs) from obese adipose tissue. Hepatic LAMs expressed Osteopontin, a biomarker for patients with NASH, linked with the development of fibrosis. Fitting with this, LAMs were found in regions of the liver with reduced numbers of KCs, characterized by increased Desmin expression. Together, our data highlight considerable heterogeneity within the macrophage pool and suggest a need for more specific macrophage targeting strategies in MAFLD.Mother's milk contains complex microbial communities thought to be important for colonizing a preterm infant's gastrointestinal tract. However, little is known about the microbiota in the preterm mother's milk and factors influencing its composition. We characterized the temporal dynamics of microbial communities in 490 breast milk samples from 86 mothers of preterm infants (born less then 1,250g) over the first 8 weeks postpartum. Highly individualized microbial communities were identified in each mother's milk that changed temporally with notable alterations in predicted microbial functions. However, pre-pregnancy BMI, delivery mode, and antibiotics were associated with changes in these microbial dynamics. Individual classes of antibiotics and their duration of exposure during prenatal and postpartum periods showed unique relationships with microbial taxa abundance and diversity in mother's milk. These results highlight the temporal complexity of the preterm mother's milk microbiota and its relationship with maternal characteristics as well as the importance of discussing antibiotic stewardship for mothers.Planar cell polarity (PCP) organizes the orientation of cellular protrusions and migratory activity within the tissue plane. PCP establishment involves the subcellular polarization of core PCP components. It has been suggested that Wnt gradients could provide a global cue that coordinates local PCP with tissue axes. Here, we dissect the role of Wnt ligands in the orientation of hairs of Drosophila wings, an established system for the study of PCP. We found that PCP was normal in quintuple mutant wings that rely solely on the membrane-tethered Wingless for Wnt signaling, suggesting that a Wnt gradient is not required. We then used a nanobody-based approach to trap Wntless in the endoplasmic reticulum, and hence prevent all Wnt secretion, specifically during the period of PCP establishment. selleck inhibitor PCP was still established. We conclude that, even though Wnt ligands could contribute to PCP, they are not essential, and another global cue must exist for tissue-wide polarization.
Community randomised trials have had mixed success in implementing combination prevention strategies that diagnose 90% of people living with HIV, initiate and retain on antiretroviral therapy (ART) 90% of those diagnosed, and achieve viral load suppression in 90% of those on ART (90-90-90). The Bukoba Combination Prevention Evaluation (BCPE) aimed to achieve 90-90-90 in Bukoba Municipal Council, Tanzania, by scaling up new HIV testing, linkage, and retention interventions.
We did population-based, cross-sectional surveys before and after our community-wide intervention in Bukoba-a mixed urban and rural council of approximately 150 000 residents located on the western shore of Lake Victoria in Tanzania. BCPE interventions were implemented in 11 government-supported health-care facilities throughout Bukoba from Oct 1, 2014, to March 31, 2017, when national ART-eligibility guidelines expanded from CD4 counts of less than 350 cells per μL (Oct 1, 2014-Dec 31, 2015) and 500 or less cells per μL (Jan 1, 2016-Se AIDS Relief.
Despite the universal use of the two-dose trivalent measles-mumps-rubella (MMR) vaccine in the past two decades, outbreaks of these diseases still occur in countries with high vaccine uptake, giving rise to concerns about primary and secondary failure of MMR vaccine components. We aimed to provide seroconversion and waning rate estimates for the measles, mumps, and rubella components of MMR vaccines.
In this systematic review and meta-analysis we searched PubMed (including MEDLINE), Web of Science, and Embase for randomised controlled trials, cohort studies, or longitudinal studies reporting the immunogenicity and persistence of MMR vaccines, published in English from database inception to Dec 31, 2019. Studies were included if they investigated vaccine-induced immunity in healthy individuals who received a trivalent MMR vaccine, including different dosages and timepoints of vaccine administration. Studies featuring coadministration of MMR with other vaccines, maternal immunity to the MMR vaccine, or non-trivalent formulations of the vaccine were excluded.
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