evere infection with COVID-19 has been linked to immune dysregulation, including impaired or delayed production of type I and type III interferons 1-5 , marked lymphopenia [6][7][8][9][10] and a paradoxical increase in pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 1,4,6,[11][12][13] . Alteration of T cell compartments include increases in effector and activated CD4 and CD8 T cells [14][15][16][17] , CD8 + T cells contribute to survival in patients with COVID-19 and hematologic cancer

Two experiments were designed to assess the importance of maternal nutrition in the later stages of gestation on reproductive performance of beef females and on the growth and survival of their calves. In experiment 1, 59 Hereford first-calf heifers were assigned to one of two levels of dietary energy (high [HI which was 100% of the recommended level of prepartum energy or low [L] which was 65% of the N.R.C. [1970] recommended level) 100 days prior to predicted calving. After calving both groups were fed N.R.C. (1970) recommended levels of energy and protein.Heifers fed the H ration gained 36.1 kg during the 100-day prepartum period while the heifers on the L ration lost 5.8 kilograms. The heifers restricted in energy prepartum had lighter calves at birth but the calves were born with the same degree of calving difficulty as calves of adequately fed dams. More calves from nutritionally deprived heifers died at or near birth and the surviving calves were lighter at weaning. There was a tendency for a higher percentage of adequately-fed heifers to show estrus by 40 days postpartum.In experiment 2, 43 second-calf cows were allotted, 100 days prepartum, to a restricted intake ration of approximately 50% of the N.R.C. (1970) recommended level of energy for cows during gestation. Thirty days prior to predicted calving, one group of cows (H) was t

PURPOSE: A causal biomarker for acute respiratory distress syndrome (ARDS) could fuel precision therapy options. Plasma angiopoietin-2 (ANG2), a vascular permeability marker, is a strong candidate based on experimental and observational evidence. We used genetic causal inference methods – Mendelian Randomization and mediation – to infer potential effects of plasma ANG2. METHODS: We genotyped 703 septic subjects, measured ICU admission plasma ANG2, and performed a quantitative trait loci (QTL) analysis to determine variants in the ANGPT2 gene associated with plasma ANG2 (p < 0.005). We then used linear regression and post-estimation analysis to genetically predict plasma ANG2 and tested genetically-predicted ANG2 for ARDS association using logistic regression. We estimated the proportion of the genetic effect explained by plasma ANG2 using mediation analysis. RESULTS: Plasma ANG2 was strongly associated with ARDS (OR 1.59 (95% CI 1.35, 1.88) per log). Five ANGPT2 variants were associated with ANG2 in European ancestry subjects (n=404). Rs2442608C, the most extreme cis QTL (coefficient 0.22, 95% CI 0.09 – 0.36, p=0.001), was associated with higher ARDS risk: adjusted OR 1.38 (95% CI 1.01, 1.87), p=0.042. No significant QTL were identified in African ancestry subjects. Genetically-predicted plasma ANG2 was associated with ARDS risk: adjusted OR 2.25 (95% CI 1.06 – 4.78), p=0.035. Plasma ANG2 mediated 34% of the rs2442608C - ARDS risk. CONCLUSIONS: In septic European ancestry subjects, the strongest ANG2-determining ANGPT2 genetic variant associates with higher ARDS risk. Plasma ANG2 may be a causal factor in ARDS development. Strategies to reduce plasma ANG2 warrant testing to prevent or treat sepsis-associated ARDS.

Highlights d APOL1 risk variant (RV) is associated with increased sepsis incidence and severity d Mice with endothelial-specific RV APOL1 expression have increased sepsis severity d RV APOL1 interferes with mitophagy, leading to cytosolic release of mitochondrial DNA d Deletion or inhibition of NLRP3 and STING protects against RV APOL1-induced defects

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