Golgins are an abundant class of peripheral membrane proteins of the Golgi. These very long (50–400 nm) rod‐like proteins initially capture cognate transport vesicles, thus enabling subsequent SNARE‐mediated membrane fusion. Here, we explore the hypothesis that in addition to serving as vesicle tethers, Golgins may also possess the capacity to phase separate and, thereby, contribute to the internal organization of the Golgi. GM130 is the most abundant Golgin at the cis Golgi. Remarkably, overexpressed GM130 forms liquid droplets in cells analogous to those described for numerous intrinsically disordered proteins with low complexity sequences, even though GM130 is neither low in complexity nor intrinsically disordered. Virtually pure recombinant GM130 also phase‐separates into dynamic, liquid‐like droplets in close to physiological buffers and at concentrations similar to its estimated local concentration at the cis Golgi.
Background The prevalence of obesity and diabetes in Samoa, like many other Pacific Island nations, has reached epidemic proportions. Although the etiology of these conditions can be largely attributed to the rapidly changing economic and nutritional environment, a recently identified genetic variant, rs373863828 (CREB 3 regulatory factor, CREBRF: c.1370G>A p.[R457Q]) is associated with increased odds of obesity, but paradoxically, decreased odds of diabetes. Objective The overarching goal of the Soifua Manuia (Good Health) study was to precisely characterize the association of the CREBRF variant with metabolic (body composition and glucose homeostasis) and behavioral traits (dietary intake, physical activity, sleep, and weight control behaviors) that influence energy homeostasis in 500 adults. Methods A cohort of adult Samoans who participated in a genome-wide association study of adiposity in Samoa in 2010 was followed up, based on the presence or absence of the CREBRF variant, between August 2017 and March 2019. Over a period of 7-10 days, each participant completed the main study protocol, which consisted of anthropometric measurements (weight, height, circumferences, and skinfolds), body composition assessment (bioelectrical impedance and dual-energy x-ray absorptiometry), point-of-care glycated hemoglobin measurement, a fasting blood draw and oral glucose tolerance test, urine collection, blood pressure measurement, hand grip strength measurement, objective physical activity and sleep apnea monitoring, and questionnaire measures (eg, health interview, cigarette and alcohol use, food frequency questionnaire, socioeconomic position, stress, social support, food and water insecurity, sleep, body image, and dietary preferences). In January 2019, a subsample of the study participants (n=118) completed a buttock fat biopsy procedure to collect subcutaneous adipose tissue samples. Results Enrollment of 519 participants was completed in March 2019. Data analyses are ongoing, with results expected in 2020 and 2021. Conclusions While the genetic variant rs373863828, in CREBRF, has the largest known effect size of any identified common obesity gene, very little is currently understood about the mechanisms by which it confers increased odds of obesity but paradoxically lowered odds of type 2 diabetes. The results of this study will provide insights into how the gene functions on a whole-body level, which could provide novel targets to prevent or treat obesity, diabetes, and associated metabolic disorders. This study represents the human arm of a comprehensive and integrated approach involving humans as well as preclinical models that will provide novel insights into metabolic disease. International Registered Report Identifier (IRRID) RR1-10.2196/17329
Dedicated to Prof. R. Heiner Schirmer, whose knowledge and kindness continue to inspire The examination of the complex cell biology of the human malaria parasite Plasmodium falciparum usually relies on the time-consuming generation of transgenic parasites. Here, metabolic labeling and click chemistry are employed as a fast transfection-independent method for the microscopic examination of protein S-palmitoylation, an important post-translational modification during the asexual intraerythrocytic replication of P. falciparum. Applying various microscopy approaches such as confocal, single-molecule switching, and electron microscopy, differences in the extent of labeling within the different asexual developmental stages of P. falciparum and the host erythrocytes over time are observed.
Summary Background Samoa is a Pacific Island country facing one of the highest burdens of non-communicable disease globally. Methods In this study, we apply a cascade-of-care approach to understand gaps in the awareness, treatment, and control cascade of diabetes and hypertension in a cross-sectional, convenience sample of 703 young, high-risk Samoan adults (29.5-50.9 years). Findings Non-communicable diseases were prevalent in the study sample: 19.5% (95% CI: 16.6%-22.7%) of participants had diabetes; 47.6% (95% CI: 43.7%-51.4%) presented with pre-diabetes or diabetes; 31.0% (95% CI: 27.5%-34.6%) had hypertension; and nearly 90% (95% CI: 86.7%-91.5%) had overweight or obesity. Among those with diabetes and hypertension, only 20.5% (95% CI: 13.9%-28.4%) and 11.8% (95% CI: 7.8%-16.9%) of participants were aware of their condition, respectively. Only 0.8% (95% CI: 0.0%-4.2%) of all participants with diabetes had achieved glycemic control; only 2.8% (95% CI: 1.1%-6.1%) of those with hypertension achieved control. Interpretation We found a significant burden of diabetes and hypertension in Samoa, exceeding the recent prevalence estimates of other low- to middle-income countries by nearly two-fold. A severe unmet need in both detection and subsequent control and monitoring of these chronic conditions exists. Our results suggest that the initial diagnosis and surveillance stage in the cascade of care for chronic conditions should be a major focus of primary care efforts; national screening campaigns and programs that leverage village and district nurses to deliver community-based primary care may significantly impact gap closure in the NCD cascade. Funding This study was supported by the U.S. National Institutes of Health R01HL140570 (PIs: McGarvey and DeLany); AR was supported by NIH FIC D43TW010540; HK and AR-C were supported by the Minority Health and Health Disparities International Research Training (MHIRT) Program at Brown University, NIH Grant # 5T37MD008655.
To evaluate the impact of instillation angle and nozzle tip geometry on crosscontamination risk of multidose ocular solution bottles. Methods: Pseudomonas aeruginosa solution was passed exclusively on the outside of the nozzle to simulate contamination on the exterior of topical agents. Three drops were administered from angles of 90°and 45°from bottles with either a round or sharp tip geometry, and the cultures were examined for growth. Two-hundred sixteen cultures from nine lubricant eyedrop brands currently existing in the Brazilian market were assessed for bacterial growth. Results: After seven days, bacterial contamination was detected in 53.7% of cultures when drops were administered at 90°and in 70.4% of cultures at 45°. Eyedrops collected from a rounded nozzle tip and an instillation angle of 90°transmitted bacteria in 69.4% of cases, whereas those administered from a sharp tip transmitted bacteria in only 22.2% of cases (P = 0.001). At an instillation angle of 45°, contamination was identified in 83.3% of bottles with a rounded tip geometry and in only eight of 18 bottles (44.4%) from those with a sharp nozzle geometry (P = 0.005). Conclusions: Adjusting the instillation angle of eyedrop solutions to 90°, as well as using a nozzle geometry that prevents flow of the solution to the side of the bottle, significantly reduced contamination rates. Translational Relevance: Standardizing drop bottles and adjusting delivery angle shows promise in reducing contamination rates and may critically impact the quality of care for patients requiring topical therapeutic agents.
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