Tumor Necrosis Factor-α Contributes to Ischemia- and Reperfusion-Induced Endothelial Activation in Isolated Hearts

During myocardial reperfusion, polymorphonuclear neutrophil (PMN) adhesion involving the intercellular adhesion molecule-1 (ICAM-1) may lead to aggravation and prolongation of reperfusion injury. We studied the role of early tumor necrosis factor-α (TNF-α) cleavage and nuclear factor-κB (NF-κB) activation on ICAM-1 expression and venular adhesion of PMN in isolated hearts after ischemia (15 minutes) and reperfusion (30 to 480 minutes). NF-κB activation (electromobility shift assay) was found after 30 minutes of reperfusion and up to 240 minutes. ICAM-1 mRNA, assessed by Northern blot, increased during the same interval. Functional effect of newly synthesized adhesion molecules was found by quantification (in situ fluorescence microscopy) of PMN, given as bolus after ischemia, which became adherent to small coronary venules (10 to 50 mm in diameter). After 480 minutes of reperfusion, ICAM-1–dependent PMN adhesion increased 2.5-fold compared with PMN adhesion obtained during acute reperfusion. To study the influence of NF-κB on PMN adhesion, we inhibited NF-κB activation by transfection of NF-κB decoy oligonucleotides into isolated hearts using HJV-liposomes. Decoy NF-κB but not control oligonucleotides blocked ICAM-1 upregulation and inhibited the subacute increase in PMN adhesion. Similar effects were obtained using BB 1101 (10 μg), an inhibitor of TNF-α cleavage enzyme. These data suggest that ischemia and reperfusion in isolated hearts cause liberation of TNF-α, activation of NF-κB, and upregulation of ICAM-1, an adhesion molecule involved in inflammatory response after ischemia and reperfusion

Author Correction: Early pregnancy ultrasound measurements and prediction of first trimester pregnancy loss: A logistic model (Scientific Reports, (2020), 10, 1, (1545), 10.1038/s41598-020-58114-3)

The original version of this Article contained an error in the spelling of the author Patricia J. Goedecke which was incorrectly given as Patricia J. Goeske. The original Article has been corrected

Galois theory and commutators

We prove that the relative commutator with respect to a subvariety of a variety of Omega-groups introduced by the first author can be described in terms of categorical Galois theory. This extends the known correspondence between the Froehlich-Lue and the Janelidze-Kelly notions of central extension. As an example outside the context of Omega-groups we study the reflection of the category of loops to the category of groups where we obtain an interpretation of the associator as a relative commutator.Comment: 14 page

Total daily energy expenditure in black and white, lean and obese South African women.

Background/Objectives:In South Africa (SA), the prevalence of obesity in women is 56%, with black women being most at risk (62%). Studies in the United States have demonstrated ethnic differences in resting (REE) and total daily energy expenditure (TDEE) between African American (AA) and their white counterparts. We investigated whether differences in EE exist in black and white SA women, explaining, in part, the ethnic obesity prevalence differences.Subjects/Methods:We measured REE, TDEE and physical activity EE (PAEE) in lean (BMI 30 kg m(-2)) SA women (N=44, 30+/-6 year). REE, TDEE, PAEE and total awake EE were measured during a 21 h stay in a respiration chamber.Results:Black and white subjects within obese and lean groups were not significantly different for age, mass, BMI and % body fat. However, fat-free mass (kg FFM) was consistently lower in the black women (P<0.01) in both weight groups. After adjusting EE measurements for differences in FFM, REE was not significantly different for either body weight or ethnicity, although 24 h TDEE (kJ) was significantly greater in the obese women (P<0.01) and white women (P<0.05). Total awake non-PAEE was not significantly different for either groups, while total awake time was only significantly lower for the lean groups (P<0.01). Total PAEE (kJ min(-1)) was significantly lower in the lean (P<0.001) and black groups (P<0.01).Conclusions:In this sample of matched, lean and obese, black and white SA women, differences in TDEE were largely explained by ethnic differences in PAEE, and were not as a result of ethnic differences in REE.European Journal of Clinical Nutrition advance online publication, 13 February 2008; doi:10.1038/ejcn.2008.8

Glucocorticoids associate with cardiometabolic risk factors in black South Africans

Circulating glucocorticoids are associated with metabolic syndrome and related cardiometabolic risk factors in non-Africans. This study investigated these associations in Africans, whose metabolic phenotype reportedly differs from Europeans. Adiposity, blood pressure, glycaemia, insulin resistance, and lipid profile, were measured in 316 African men and 788 African women living in Soweto, Johannesburg. The 2009 harmonized criteria were used to define metabolic syndrome. Serum glucocorticoids were measured using liquid chromatography-mass spectrometry. Cortisol was associated with greater odds presenting with metabolic syndrome (odds ratio (95% CI) =1.50 (1.04, 2.17) and higher systolic (beta coefficient, β (95% CI) =0.04 (0.01, 0.08)) and diastolic (0.05 (0.02, 0.09)) blood pressure, but higher HDL (0.10 (0.02, 0.19)) and lower LDL (−0.14 (−0.24, −0.03)) cholesterol concentrations, in the combined sample of men and women. In contrast, corticosterone was only associated with higher insulin sensitivity (Matsuda index; 0.22 (0.03, 0.41)), but this was not independent of BMI. Sex-specific associations were observed, such that both cortisol and corticosterone were associated with higher fasting glucose (standardized β (95% CI): 0.24 (0.12, 0.36) for cortisol and 0.12 (0.01, 0.23) for corticosterone) and HbA1c (0.13 (0.01, 0.25) for cortisol and 0.12 (0.01, 0.24) for corticosterone) in men only, but lower HbA1c (0.10 (−0.20, −0.01) for cortisol and −0.09 (−0.18, −0.03) for corticosterone) in women only. Our study reports for the first time that associations between circulating glucocorticoid concentrations and key cardiometabolic risk factors exhibit both glucocorticoid- and sex-specificity in Africans

The Impact II, a Very High-Resolution Quadrupole Time-of-Flight Instrument (QTOF) for Deep Shotgun Proteomics

Hybrid quadrupole time-of-flight (QTOF) mass spectrometry is one of the two major principles used in proteomics. Although based on simple fundamentals, it has over the last decades greatly evolved in terms of achievable resolution, mass accuracy, and dynamic range. The Bruker impact platform of QTOF instruments takes advantage of these developments and here we develop and evaluate the impact II for shotgun proteomics applications. Adaption of our heated liquid chromatography system achieved very narrow peptide elution peaks. The impact II is equipped with a new collision cell with both axial and radial ion ejection, more than doubling ion extraction at high tandem MS frequencies. The new reflectron and detector improve resolving power compared with the previous model up to 80%, i.e. to 40,000 at m/z 1222. We analyzed the ion current from the inlet capillary and found very high transmission (>80%) up to the collision cell. Simulation and measurement indicated 60% transfer into the flight tube. We adapted MaxQuant for QTOF data, improving absolute average mass deviations to better than 1.45 ppm. More than 4800 proteins can be identified in a single run of HeLa digest in a 90 min gradient. The workflow achieved high technical reproducibility (R2 > 0.99) and accurate fold change determination in spike-in experiments in complex mixtures. Using label-free quantification we rapidly quantified haploid against diploid yeast and characterized overall proteome differences in mouse cell lines originating from different tissues. Finally, after high pH reversed-phase fractionation we identified 9515 proteins in a triplicate measurement of HeLa peptide mixture and 11,257 proteins in single measurements of cerebellum-the highest proteome coverage reported with a QTOF instrument so far

Circulating and Adipose Tissue Fatty Acid Composition in Black South African Women with Obesity: A Cross-Sectional Study

Background and Aims: During positive energy balance, excess lipid storage in subcutaneous adipose tissue (SAT) is associated with increased lipolysis. Elevated circulating fatty acid (FA) concentrations from both SAT lipolysis and dietary fat intake may result in visceral adipose tissue (VAT) accumulation, impairment of glucose metabolism, altogether increasing obesity-associated metabolic risks. We aimed to test the hypothesis that FA composition of red blood cell total phospholipids (RBC-TPL) and SAT is associated with body fat centralisation (VAT/SAT ratio) and insulin sensitivity (SI) in black South African women with obesity. Methods: Participants’ (n = 41) body fat composition and distribution, SI, and RBC-TPL, abdominal and gluteal SAT (gSAT) FA composition (gas-liquid chromatography) were measured. Results: RBC-TPL contained higher proportions of saturated fatty acids (SFAs) than SAT (p < 0.001), which were associated with lower SI (p < 0.05). Mono-unsaturated fatty acids (MUFAs) and stearoyl-CoA desaturase-1 (SCD1)-16 were lower, while poly-unsaturated fatty acids (PUFAs), and delta-5 and delta-6 desaturase indices were higher in RBC-TPL than SAT (p < 0.001). Interestingly, FA profiles differed between SAT depots with higher SFAs and lower MUFAs, SCD1-16 and SCD1-18 indices in abdominal compared to gluteal SAT (p < 0.01). In both SAT depots, higher SFAs and lower PUFAs (n-3 and n-6) correlated with lower VAT/SAT ratio; and lower PUFAs (n-3 and n-6) and higher total MUFA correlated with higher SI. Conclusion: Our findings confirm the relationships between the FA composition of RBC-TPL and SAT and metabolic risk in black women with obesity, which are dependent on both the FA class, and the tissue type/blood compartment in which they are distributed

Exercise intervention alters HDL subclass distribution and function in obese women

Background Obesity is associated with a change in high-density lipoprotein (HDL) function and subclass. Exercise training reduces cardiovascular risk in obese patients. We aimed to explore the effect of an exercise training stimulus on HDL functionality and subclass in obese women. Methods Thirty-two obese black South African women were randomly assigned to exercise (combined aerobic and resistance exercise) or control (no exercise) conditions for 12-weeks. Pre- and post-testing included venous blood sampling for analysis of lipid profile and HDL functionality, by measuring cellular cholesterol efflux capacity, reduction in endothelial vascular cell adhesion molecule (VCAM) expression (anti-inflammatory function), paraoxonase (PON) (antioxidative function) and platelet activating factor acetylhydrolase (PAF-AH) activities (anti-thrombotic function). PON-1 and PAF-AH expression were determined in serum and in isolated HDL using Western blotting. Levels of large, intermediate and small HDL subclasses were measured using the Lipoprint® system. Results Exercise training resulted in a decrease in body mass index (− 1.0 ± 0.5% vs + 1.2 ± 0.6%, p = 0.010), PON activity (− 8.7 ± 2.4% vs + 1.1 ± 3.0%, p = 0.021), PAF-AH serum expression (− 22.1 ± 8.0% vs + 16.9 ± 9.8, p = 0.002), and the distribution of small HDL subclasses (− 10.1 ± 5.4% vs + 15.7 ± 6.6%, p = 0.004) compared to controls. Exercise did not alter HDL cellular cholesterol efflux capacity and anti-inflammatory function. Conclusions These results demonstrate the potential for exercise training to modify HDL subclass distribution and HDL function in obese women. Trial registration Clinical trials number: PACTR201711002789113