MiR-409-3p regulates angiogenesis, white to brown adipose tissue transition, and insulin resistance through MAP4K3 and ZEB1 signaling pathways.

Endothelial cells (ECs) within the microvasculature of brown adipose tissue (BAT) are important in regulating the plasticity of adipocytes in response to increased metabolic demand by modulating the angiogenic response. However, the mechanism of EC-adipocyte crosstalk during this process is not completely understood. We used RNA sequencing to profile microRNAs derived from BAT ECs of obese mice and identified an anti-angiogenic microRNA, miR-409-3p. MiR-409-3p overexpres- sion inhibited EC angiogenic properties; whereas, its inhibition had the opposite effects. Mechanistic studies revealed that miR-409-3p targets ZEB1 and MAP4K3. Knockdown of ZEB1/MAP4K3 phenocopied the angiogenic effects of miR-409-3p. Adipocytes co-cultured with conditioned media from ECs deficient in miR-409-3p showed increased expression of BAT markers, UCP1 and CIDEA. We identified a pro-angiogenic growth factor, placental growth factor (PLGF), released from ECs in response to miR-409-3p inhibition. Deficiency of ZEB1 or MAP4K3 blocked the release of PLGF from ECs and PLGF stimulation of 3T3-L1 adipocytes increased UCP1 expression in a miR-409-3p dependent manner. MiR-409-3p neutraliza- tion improved BAT angiogenesis, glucose and insulin tolerance, and energy expenditure in mice with diet-induced obesity. These findings establish miR-409-3p as a critical regulator of EC-BAT crosstalk by modulating a ZEB1-MAP4K3-PLGF signaling axis, providing new insights for therapeutic intervention in obesity

COVID-19: booster(s) vs. hospitalization and Intensive Care Unit admission.

OBJECTIVE: As the pandemic continues, different vaccine protocols have been implemented to maintain the protection of vaccines and to provide protection against new variants. The aim of this study was to assess hospitalized patients' vaccination status and document the efficacy of boosters. PATIENTS AND METHODS: The patients that were hospitalized due to COVID-19 were enrolled from 28 hospitals in Turkey for five months from September 2021. 5,331 confirmed COVID-19 patients from collaborating centers were randomly enrolled to understand/estimate the distribution of vaccination status in hospitalized patients and to compare the efficacy of vaccination/booster protocols. RESULTS: 2,779 men and 2,552 women of which 2,408 (45.2%) were admitted to Intensive Care Units participated in this study. It was found that the highest risk reduction for all age groups was found in groups that received 4 doses. Four doses of vaccination for every 3.7 people under 50 years of age, for every 5.7 people in the 50-64 age group, and for every 4.3 people over 65 years of age will prevent 1 patient from being admitted to intensive care. Regardless of the type of vaccine, it was found that the risk of ICU hospitalization decreased in those who were vaccinated compared to those who were not vaccinated. Regardless of the type of vaccine, the ICU risk was found to decrease 1.25-fold in those who received 1 or 2 doses of vaccine, 1.18-fold in those who received 3 doses, and 3.26-fold in those who received 4 doses. CONCLUSIONS: The results suggested that the addition of a fourth dose is more effective in preventing intensive unit care even in disadvantaged

COVID-19: booster(s) vs. hospitalization and Intensive Care Unit admission

OBJECTIVE: As the pandemic continues, different vaccine protocols have been implemented to maintain the protection of vaccines and to provide protection against new variants. The aim of this study was to assess hospitalized patients’ vaccination status and document the efficacy of boosters. PATIENTS AND METHODS: The patients that were hospitalized due to COVID-19 were enrolled from 28 hospitals in Turkey for five months from September 2021. 5,331 confirmed COVID-19 patients from collaborating centers were randomly enrolled to understand/estimate the distribution of vaccination status in hospitalized patients and to compare the efficacy of vaccination/booster protocols. RESULTS: 2,779 men and 2,552 women of which 2,408 (45.2%) were admitted to Intensive Care Units participated in this study. It was found that the highest risk reduction for all age groups was found in groups that received 4 doses. Four doses of vaccination for every 3.7 people under 50 years of age, for every 5.7 people in the 50-64 age group, and for every 4.3 people over 65 years of age will prevent 1 patient from being admitted to intensive care. Regardless of the type of vaccine, it was found that the risk of ICU hospitalization decreased in those who were vaccinated compared to those who were not vaccinated. Regardless of the type of vaccine, the ICU risk was found to decrease 1.25-fold in those who received 1 or 2 doses of vaccine, 1.18-fold in those who received 3 doses, and 3.26-fold in those who received 4 doses. CONCLUSIONS: The results suggested that the addition of a fourth dose is more effective in preventing intensive unit care even in disadvantaged groups

Reproducibility of fluorescent expression from engineered biological constructs in E. coli

We present results of the first large-scale interlaboratory study carried out in synthetic biology, as part of the 2014 and 2015 International Genetically Engineered Machine (iGEM) competitions. Participants at 88 institutions around the world measured fluorescence from three engineered constitutive constructs in E. coli. Few participants were able to measure absolute fluorescence, so data was analyzed in terms of ratios. Precision was strongly related to fluorescent strength, ranging from 1.54-fold standard deviation for the ratio between strong promoters to 5.75-fold for the ratio between the strongest and weakest promoter, and while host strain did not affect expression ratios, choice of instrument did. This result shows that high quantitative precision and reproducibility of results is possible, while at the same time indicating areas needing improved laboratory practices