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The phenotypes were not rescued by expression of a palmitoylation-deficient CKAP4 mutant. These results suggest that CKAP4 plays a role in maintaining mitochondrial functions through the binding to VDAC2 at ER-mitochondria contact sites and that palmitoylation is required for this novel function of CKAP4.This article has an associated First Person interview with the first author of the paper.Vaccinia-related kinase 3 (VRK3) has been reported to be a negative regulator of ERK (ERK1 and ERK2; also known as MAPK3 and MAPK1, respectively) that protects cells from persistent ERK activation and inhibits ERK-dependent apoptosis. Here we report that the E3 ubiquitin-protein ligase RNF144a promotes the degradation of VRK3 via polyubiquitylation and thus affects VRK3-mediated ERK activity. Under oxidative stress, VRK3 migrates from the nucleus to the cytoplasm, which increases its chance of interacting with RNF144a, thereby promoting the degradation of VRK3. Overexpression of RNF144a increases ERK activity via downregulation of VRK3 and promotes ERK-dependent apoptosis. In contrast, depletion of RNF144a increases the protein level of VRK3 and protects cells from excessive ERK activity. These findings suggest that VRK3 protects cells by suppressing oxidative stress-induced ERK, and that RNF144a sensitively regulates this process.<br /><br /> Accurate measurement of compliance with COVID-19 guidance is important for public health policy and communications. Responses to surveys, however, are susceptible to psychological biases, including framing effects and social desirability. Our aim was to measure the effects of these biases on estimates of compliance with public health guidance (eg, hand-washing, social distancing).<br /><br /> We conducted two online experiments (n=1800) and varied whether questions were framed positively or negatively (eg, 'I always wash my hands…' vs 'I don't always wash my hands…'). We also varied the degree to which anonymity was assured, via a 'list' experiment.<br /><br /> Reported compliance, despite being generally high, was reduced by negatively framing questions and increasing anonymity using a list experiment technique. Effect sizes were large compliance estimates diminished by up to 17% points and 10% points, respectively.<br /><br /> Estimates of compliance with COVID-19 guidance vary substantially with how the question is asked. Standard tracking surveys tend to pose questions in ways that lead to higher estimates than alternative approaches. Experimental tests of these surveys offer public health officials greater insight into the range of likely compliance estimates to better inform policy and communications.<br /><br />Estimates of compliance with COVID-19 guidance vary substantially with how the question is asked. Standard tracking surveys tend to pose questions in ways that lead to higher estimates than alternative approaches. Experimental tests of these surveys offer public health officials greater insight into the range of likely compliance estimates to better inform policy and communications.<br /><br /> Since the first case of COVID-19 was recorded in California, the geospatial distribution of disease cases has fluctuated over time. Given documented racial disparities in other parts of the country, longitudinal convergence of COVID-19 rates around race groups warrants assessment.<br /><br /> County-level cases for COVID-19 were collected from the Johns Hopkins University, and racial distributions were collected from the American Community Survey. Pearson's correlation coefficients were computed for each day since COVID-19 was first reported in California, and the longitudinal distribution of each race-specific set of correlation coefficients was assessed for stationarity, linear trend and exponential trend.<br /><br /> Earlier in the outbreak, the distribution of COVID-19 was most highly correlated with Asian American communities; after approximately 100days, the distribution of COVID-19 most closely resembled that of African American communities. For every day in this dataset, the county-level distribution of COVID-19 was negatively correlated with the distribution of White American communities in California.<br /><br /> The geospatial distribution of COVID-19 in California has increasingly resembled that of African American communities within the state. Further study should be conducted to characterise potentially disproportionate impacts of the COVID-19 pandemic across race groups.<br /><br />The geospatial distribution of COVID-19 in California has increasingly resembled that of African American communities within the state. Further study should be conducted to characterise potentially disproportionate impacts of the COVID-19 pandemic across race groups.<br /><br /> Uterine fibroids (UFs) are the most common form of sex steroid hormone-dependent benign tumours that grow in the walls of the uterus. Several observational studies have examined the association between obesity and the risk of UFs, but findings are inconsistent. The objective of this systematic review and meta-analysis is to further examine the association of obesity with the risk/prevalence of UFs.<br /><br /> A literature search was performed in three databases (PubMed, EMBASE and Web of Science) from 1 January 1992 to 30 May 2020. We used random-effect models to calculate the pooled ORs with corresponding 95% CIs. Additionally, we performed a dose-response meta-analysis to analyse the effect of body mass index (BMI), weight change since age 18, waist-to-hip ratio and waist circumference on the risk/prevalence of UFs.<br /><br /> A total of 22 articles, covering 24 studies including 325899 participants and 19593 cases, were selected based on our inclusion criteria. We found a positive association between obesity and the risk/prevalence of UFs (OR, 1.19; 95% CI, 1.09 to 1.29). Among participants with the highest BMI, the pooled OR was 1.19 (1.09 to 1.31) when compared to participants with normal BMI. For weight change since age 18, the pooled OR (95% CI) of UFs was 1.26 (1.12 to 1.42) among the highest change group when compared with no change. Additionally, our meta-analysis indicated the relationship of BMI with risk of UFs to be an inverse J-shaped pattern.<br /><br /> The results of this meta-analysis suggest that obesity may increase the risk/prevalence of UFs, and the association is non-linear.<br /><br />The results of this meta-analysis suggest that obesity may increase the risk/prevalence of UFs, and the association is non-linear.Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed too late for effective therapy. The classic strategy for early detection biomarker advancement consists of initial retrospective phases of discovery and validation with tissue samples taken from individuals diagnosed with disease, compared with controls. Using this approach, we previously reported the discovery of a blood biomarker panel consisting of thrombospondin-2 (THBS2) and CA19-9 that together could discriminate resectable stage I and IIa PDAC as well as stages III and IV PDAC, with c-statistic values in the range of 0.96 to 0.97 in two phase II studies. We now report that in two studies of blood samples prospectively collected from 1 to 15 years prior to a PDAC diagnosis (Mayo Clinic and PLCO cohorts), THBS2 and/or CA19-9 failed to discriminate cases from healthy controls at the AUC = 0.8 needed. We conclude that PDAC progression may be heterogeneous and for some individuals can be more rapid than generally appreciated. It is important that PDAC early-detection studies incorporate high-risk, prospective prediagnostic cohorts into discovery and validation studies. PREVENTION RELEVANCE A blood biomarker panel of THBS2 and CA19-9 detects early stages of pancreatic ductal adenocarcinoma at diagnosis, but not when tested across a population up to 1 year earlier. Our findings suggest serial sampling over time, using prospectively collected samples for biomarker discovery, and more frequent screening of high-risk individuals.<br /><br /> To identify characteristics of people with undiagnosed type 2 diabetes (T2D) among adults in Germany.<br /><br /> The study population comprised participants aged 40-79 years of the German Health Interview and Examination Survey for Adults 2008-2011. Glycemic status was categorized as undiagnosed T2D (glycated hemoglobin A1c (HbA1c) ≥48 mmol/mol (6.5%), n=135), diagnosed T2D (n=518) and normoglycemia (HbA1c&lt;48 mmol/mol (6.5%), n=4451). Multinomial logistic regression models including glycemic status as the outcome variable and sociodemographic characteristics, living alone, diabetes risk factors and healthcare services utilization as independent variables were used to identify factors associated with undiagnosed T2D compared with normoglycemia and diagnosed T2D. Odds ratios (ORs) and 95% confidence intervals (CIs) are reported as measure of association between the outcome and independent variables.<br /><br /> The prevalence of undiagnosed T2D was 2.9% (95% CI 2.2% to 3.9%) at an overall prevalence of 12.3% (11.0% to 13.6%) and communication strategy on diabetes mellitus in Germany.<br /><br />Apart from major known risk factors of diabetes, characteristics specific to undiagnosed diabetes among adults in Germany will serve to inform the national education and communication strategy on diabetes mellitus in Germany.<br /><br /> Loss-of-function mutations in tRNA methyltransferase 10 homologue A (<br /><br /> ), a tRNA methyltransferase, have recently been described as a monogenic cause of early-onset diabetes with microcephaly, epilepsy and intellectual disability.<br /><br /> We report a Chinese young patient who was diagnosed with diabetes mellitus as a result of a <br /><br /> mutation.<br /><br /> A homozygous mutation c.496-1G&gt;A in <br /><br /> was identified using targeted next-generation sequencing and confirmed by PCR/Sanger sequencing. In addition to being diagnosed with diabetes, the patient also has microcephaly and intellectual deficiency. The diabetes was due to marked insulin resistance and responded very well to metformin treatment.<br /><br /> Our case is the first report in the Asian population. It adds to current knowledge of <br /><br /> related with young-onset non-insulin-dependent diabetes and confirms the a single previous report of insulin resistance in this syndrome. Genomic testing should be considered in children with non-insulin-dependent diabetes with intellectual disability and microcephaly. A clear genetic diagnosis is helpful for early detection and treatment addressing insulin resistance.<br /><br />Our case is the first report in the Asian population. It adds to current knowledge of TRMT10A related with young-onset non-insulin-dependent diabetes and confirms the a single previous report of insulin resistance in this syndrome. Genomic testing should be considered in children with non-insulin-dependent diabetes with intellectual disability and microcephaly. A clear genetic diagnosis is helpful for early detection and treatment addressing insulin resistance.Diatoms are an abundant group of microalgae, known for their ability to form an intricate cell wall made of silica. Silicon levels in seawater are in the micromolar range, making it a challenge for diatoms to supply the rapid intracellular silicification process with the needed flux of soluble silicon. [https://www.selleckchem.com/products/chloroquine-phosphate.html Autophagy inhibitor] Here, we use three-dimensional cryo-electron microscopy and spectroscopy to quantitatively analyze, at submicrometer spatial resolution and sensitivity in the millimolar range, intracellular silicon in diatom cells. Our results show that the internal silicon concentration inside the cell is ~150 mM in average, three orders of magnitude higher than the external environment. The cellular silicon content is not compartmentalized, but rather unevenly distributed throughout the cell. Unexpectedly, under silicon starvation, the internal silicon pool is not depleted, reminiscent of a constitutive metabolite. Our spatially resolved approach to analyze intracellular silicon opens avenues to investigate this homeostatic trait of diatoms.