Reversible flow of cholesteryl ester between high-density lipoproteins and triacylglycerol-rich particles is modulated by the fatty acid composition and concentration of triacylglycerols

We determined the influence of fasting (FAST) and feeding (FED) on cholesteryl ester (CE) flow between high-density lipoproteins (HDL) and plasma apoB-lipoprotein and triacylglycerol (TG)-rich emulsions (EM) prepared with TG-fatty acids (FAs). TG-FAs of varying chain lengths and degrees of unsaturation were tested in the presence of a plasma fraction at d > 1.21 g/mL as the source of CE transfer protein. The transfer of CE from HDL to FED was greater than to FAST TG-rich acceptor lipoproteins, 18% and 14%, respectively. However, percent CE transfer from HDL to apoB-containing lipoproteins was similar for FED and FAST HDL. The CE transfer from HDL to EM depended on the EM TG-FA chain length. Furthermore, the chain length of the monounsaturated TG-containing EM showed a significant positive correlation of the CE transfer from HDL to EM (r = 0.81, P < 0.0001) and a negative correlation from EM to HDL (r = -041, P = 0.0088). Regarding the degree of EM TG-FAs unsaturation, among EMs containing C18, the CE transfer was lower from HDL to C18:2 compared to C18:1 and C18:3, 17.7%, 20.7%, and 20%, respectively. However, the CE transfer from EMs to HDL was higher to C18:2 than to C18:1 and C18:3, 83.7%, 51.2%, and 46.3%, respectively. Thus, the EM FA composition was found to be the rate-limiting factor regulating the transfer of CE from HDL. Consequently, the net transfer of CE between HDL and TG-rich particles depends on the specific arrangement of the TG acyl chains in the lipoprotein particle core431211351142FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP95/7662-

Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinant

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Reversible flow of cholesteryl ester between high-density lipoproteins and triacylglycerol-rich particles is modulated by the fatty acid composition and concentration of triacylglycerols

We determined the influence of fasting (FAST) and feeding (FED) on cholesteryl ester (CE) flow between high-density lipoproteins (HDL) and plasma apoB-lipoprotein and triacylglycerol (TG)-rich emulsions (EM) prepared with TG-fatty acids (FAs). TG-FAs of varying chain lengths and degrees of unsaturation were tested in the presence of a plasma fraction at d > 1.21 g/mL as the source of CE transfer protein. The transfer of CE from HDL to FED was greater than to FAST TG-rich acceptor lipoproteins, 18% and 14%, respectively. However, percent CE transfer from HDL to apoB-containing lipoproteins was similar for FED and FAST HDL. The CE transfer from HDL to EM depended on the EM TG-FA chain length. Furthermore, the chain length of the monounsaturated TG-containing EM showed a significant positive correlation of the CE transfer from HDL to EM (r = 0.81, P < 0.0001) and a negative correlation from EM to HDL (r = -041, P = 0.0088). Regarding the degree of EM TG-FAs unsaturation, among EMs containing C18, the CE transfer was lower from HDL to C18:2 compared to C18:1 and C18:3, 17.7%, 20.7%, and 20%, respectively. However, the CE transfer from EMs to HDL was higher to C18:2 than to C18:1 and C18:3, 83.7%, 51.2%, and 46.3%, respectively. Thus, the EM FA composition was found to be the rate-limiting factor regulating the transfer of CE from HDL. Consequently, the net transfer of CE between HDL and TG-rich particles depends on the specific arrangement of the TG acyl chains in the lipoprotein particle core

Cross-transmission of vancomycin-resistant Enterococcus in patients undergoing dialysis and kidney transplant

The objective of this study was to investigate the occurrence of vancomycin-resistant Enterococcus (VRE) cross-transmission between two patient groups (long-term dialysis and kidney transplant patients). Molecular typing, by automated ribotyping with the RiboPrinter Microbial Characterization System (Qualicon, USA), was used to analyze VRE isolates from 31 fecal samples of 320 dialysis patients and 38 fecal samples of 280 kidney transplant patients. Clonal spread of E. faecalis and E. casseliflavus was observed intragroup, but not between the two groups of patients. In turn, transmission of E. gallinarum and E. faecium between the groups was suggested by the finding of vancomycin-resistant isolates belonging to the same ribogroup in both dialysis and transplant patients. The fact that these patients were colonized by VRE from the same ribogroup in the same health care facility provides evidence for cross-transmission and supports the adoption of stringent infection control measures to prevent dissemination of these bacteria

Avaliação das perdas de manga (Mangifera indica L.) no mercado varejista da cidade de Botucatu-SP Mango losses estimate in retail market

O elevado percentual de perdas na comercialização de manga no Brasil faz com que apenas parcela da produção chegue à mesa do consumidor. O presente trabalho determinou, em equipamentos de varejo da cidade de Botucatu - SP, as perdas de manga, suas causas e emitir sugestões para a redução das mesmas. Foram selecionados 22 equipamentos entre supermercados, quitanda/sacolões e feiras livres. O volume estimado de manga comercializada neste município foi 114 t/ano. Verificaram-se as seguintes perdas médias por variedade de manga: 11,5% para 'Tommy Atkins', 12,4% para 'Haden' e 12,7% para as outras variedades. O valor total anual destas perdas no comércio varejista da cidade, em 2007, atingiu R$49.200,00 (US$ 25.231,00), correspondente a 14 toneladas. Os percentuais médios de perda mostram grande semelhança quando comparados a estudos realizados em outras localidades. Os resultados obtidos apontam para a necessidade de melhor gestão de estoques, de exposição da fruta para o consumidor e uso de tecnologia no transporte e armazenagem para a manutenção da qualidade e redução das perdas. Conclui-se também pela necessidade de maiores investimentos em capacitação técnica dos encarregados do setor de frutas e hortaliças.<br>Losses in the mango commercialization process in Brazil has reduced its offer to the consumer. The present study aims at determining these losses in different purchase sites of the retail market, its causes and suggestions for reducing them. Twenty two retail points, including supermarkets, greengroceries and free fair were selected in Botucatu, state of São Paulo, Brazil. The total amount commercialized was 114 ton/year. The following average losses were verified for each mango variety: 'Tommy Atkins' (11, 5%), Haden (12, 4%) and 12, 7% for other varieties. The total loss in retail market reached US$ 25.231, 00 corresponding to 14 tons. The average loss percentage observed is compatible with previous studies running in other cities. The results suggest the need of better management, the exposure of the fruit to the consumer, technology in the transportation of the fruits and most appropriate storage for maintaining the quality and the reduction of losses. The results show the need of higher investment in technical personnel reskilling in fruit and vegetable sector

Discovery of genetic variation on chromosome 5q22 associated with mortality in heart failure.

Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure