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Willard Joyner posted an update 6 months ago
Therefore, our results suggest that timing and subsequent differentiation in robust cell-type proportions can emerge from the cooperative behaviour of growing cell populations during development.Stem cells are maintained in specific niches that strictly regulate their proliferation and differentiation for proper tissue regeneration and renewal. Molecular oxygen (O2) is an important component of the niche microenvironment, but little is known about how O2 governs epithelial stem cell (ESC) behavior. Here, we demonstrate that O2 plays a crucial role in regulating the proliferation of ESCs using the continuously growing mouse incisors. We have revealed that slow-cycling cells in the niche are maintained under relatively hypoxic conditions compared with actively proliferating cells, based on the blood vessel distribution and metabolic status. FHD-609 in vivo Mechanistically, we have demonstrated that, during hypoxia, HIF1α upregulation activates the RhoA signal, thereby promoting cortical actomyosin and stabilizing the adherens junction complex, including merlin. This leads to the cytoplasmic retention of YAP/TAZ to attenuate cell proliferation. These results shed light on the biological significance of blood-vessel geometry and the signaling mechanism through microenvironmental O2 to orchestrate ESC behavior, providing a novel molecular basis for the microenvironmental O2-mediated stem cell regulation during tissue development and renewal.Agonist-induced endocytosis is a key regulatory mechanism for controlling the responsiveness of the cell by changing the density of cell surface receptors. In addition to the role of endocytosis in signal termination, endocytosed G protein-coupled receptors (GPCRs) have been found to signal from intracellular compartments of the cell. Arrestins are generally believed to be the master regulators of GPCR endocytosis by binding to both phosphorylated receptors and adaptor protein 2 (AP-2) or clathrin, thus recruiting receptors to clathrin-coated pits to facilitate the internalization process. However, many other functions have been described for arrestins that do not relate to their role in terminating signaling. Additionally, there are now more than 30 examples of GPCRs that internalize independently of arrestins. Here we review the methods, pharmacological tools, and cellular backgrounds used to determine the role of arrestins in receptor internalization, highlighting their advantages and caveats. We also summlternate pathways, and the process appears more diverse than the previously defined “one pathway fits all.”Acute respiratory tract infections (ARIs) are a leading cause of ill-health and death globally. Individual or multiple micronutrients have been shown to modulate immune function and affect the risk and severity of a number of infectious diseases. We systematically reviewed the evidence on the impact of micronutrient supplements to reduce the occurrence of ARIs and shorten the duration of ARI symptoms among adults. Random effects meta-analyses were conducted to estimate the pooled effects of vitamin D, vitamin C, zinc and multiple micronutrient supplementation (MMS) on the occurrence of ARIs and the duration of ARI symptoms. Vitamin D supplementation reduced the risk of ARI (risk ratio (RR)=0.97; 95% CI 0.94 to 1.00; p=0.028) and shortened the duration of symptoms (per cent difference -6% (95% CI -9% to -2%; p=0.003)). The RR of vitamin D to prevent ARI was farther from the null when diagnosis was based on clinical diagnosis or laboratory testing, compared with self-report and when the loading dose was less then 60 000 IU. Vitamin C supplementation reduced the risk of ARIs (RR=0.96; 95% CI 0.93 to 0.99; p=0.01) and shortened the duration of symptoms (per cent difference -9% (95% CI -16% to -2%; p=0.014)). The effect of vitamin C on preventing ARI was stronger among men and in middle-income countries, compared with women and high-income countries, respectively. Zinc supplementation did not reduce the risk of ARIs but shortened the duration of symptoms substantially (per cent difference -47% (95% CI -73% to -21%; p=0.0004)). Our synthesis of global evidence from randomised controlled trials indicates that micronutrient supplements including zinc, vitamins C and D, and multiple micronutrient supplements may be modestly effective in preventing ARIs and improving their clinical course. Further research is warranted to better understand the effectiveness that individual or multiple micronutrients have on SARS-CoV-2 infection and treatment outcomes.
Global health conferences are important platforms for knowledge exchange, decision-making and personal and professional growth for attendees. Neocolonial patterns in global health at large and recent opinion reports indicate that stakeholders from low- and middle-income countries (LMICs) may be under-represented at such conferences. This study aims to describe the factors that impact LMIC representation at global health conferences.
A systematic review of articles reporting factors determining global health conference attendance was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles presenting conference demographics and data on the barriers and/or facilitators to attendance were included. Articles were screened at title and abstract level by four independent reviewers. Eligible articles were read in full text, analysed and evaluated with a risk of bias assessment.
Among 8765 articles screened, 46 articles met inclusion criteria. Thematic analysisns and lower acceptance rates for research presentations. This may be mitigated by relocating conferences to visa-friendly countries, providing travel scholarships and developing mentorship programmes to enable LMIC researchers to participate in global conferences.
Early identification of children at risk of severe febrile illness can optimise referral, admission and treatment decisions, particularly in resource-limited settings. We aimed to identify prognostic clinical and laboratory factors that predict progression to severe disease in febrile children presenting from the community.
We systematically reviewed publications retrieved from MEDLINE, Web of Science and Embase between 31 May 1999 and 30 April 2020, supplemented by hand search of reference lists and consultation with an expert Technical Advisory Panel. Studies evaluating prognostic factors or clinical prediction models in children presenting from the community with febrile illnesses were eligible. The primary outcome was any objective measure of disease severity ascertained within 30 days of enrolment. We calculated unadjusted likelihood ratios (LRs) for comparison of prognostic factors, and compared clinical prediction models using the area under the receiver operating characteristic curves (AUROCs). Risk of bias and applicability of studies were assessed using the Prediction Model Risk of Bias Assessment Tool and the Quality In Prognosis Studies tool.
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