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  • York Mahler posted an update 2 weeks, 5 days ago

    Lassa mammarenavirus (LASV) is the etiologic agent of Lassa fever. In endemic regions in West Africa, LASV genetic diversity tends to cluster by geographic area. Seven LASV lineages are recognized, but the role of viral genetic determinants on disease presentation in humans is uncertain. We investigated the geographic structure and distribution of LASV in West Africa. We found strong spatial clustering of LASV populations, with two major east-west and north-south diversity gradients. Analysis of ancestry components indicated that known LASV lineages diverged from an ancestral population that most likely circulated in Nigeria, although alternative locations, such as Togo, cannot be excluded. Extant sequences carrying the largest contribution of this ancestral population include the prototype Pinneo strain, the Togo isolates, and a few viruses isolated in Nigeria. The LASV populations that experienced the strongest drift circulate in Mali and the Ivory Coast. By focusing on sequences form a single LASV sublineage (IIg), we identified an ancestry component possibly associated with protection from a fatal disease outcome. Although the same ancestry component tends to associate with lower viral loads in plasma, the small sample size requires that these results are treated with extreme caution.The pathogenic mechanisms causing type 2 diabetes (T2D) are still poorly understood; a greater awareness of its causation can lead to the development of newer and better antidiabetic drugs. In this study, we used a network-based approach to assess the cellular processes associated with protein-protein interaction subnetworks of glycemic traits-HOMA-β and HOMA-IR. Their subnetworks were further analyzed in terms of their overlap with the differentially expressed genes (DEGs) in pancreatic, muscle, and adipose tissue in diabetics. We found several DEGs in these tissues showing an overlap with the HOMA-β subnetwork, suggesting a role of these tissues in β-cell failure. Many genes in the HOMA-IR subnetwork too showed an overlap with the HOMA-β subnetwork. For understanding the functional theme of these subnetworks, a pathway-to-pathway complementary network analysis was done, which identified various adipose biology-related pathways, containing genes involved in both insulin secretion and action. In conclusion, network analysis of genes showing an association between T2D and its intermediate phenotypic traits suggests their potential role in beta cell failure. These genes enriched the adipo-centric pathways and were expressed in both pancreatic and adipose tissue and, therefore, might be one of the potential targets for future antidiabetic treatment.To better understand heart failure with preserved ejection fraction (HFpEF), we need to better characterize the transition from asymptomatic pre-HFpEF to symptomatic HFpEF. The current emphasis on left ventricular diastolic dysfunction must be redirected to microvascular inflammation and endothelial dysfunction that leads to cardiomyocyte remodeling and enhanced interstitial collagen deposition. A pre-HFpEF patient lacks signs or symptoms of heart failure (HF), has preserved left ventricular ejection fraction (LVEF) with incipient structural changes similar to HFpEF, and possesses elevated biomarkers of cardiac dysfunction. The transition from pre-HFpEF to symptomatic HFpEF also involves left atrial failure, pulmonary hypertension and right ventricular dysfunction, and renal failure. This review focuses on the non-left ventricular mechanisms in this transition, involving the atria, right heart cavities, kidneys, and ultimately the currently accepted driver-systemic inflammation. Impaired atrial function may decrease ventricular hemodynamics and significantly increase left atrial and pulmonary pressure, leading to HF symptoms, irrespective of left ventricle (LV) systolic function. Pulmonary hypertension and low right-ventricular function are associated with the incidence of HF. Interstitial fibrosis in the heart, large arteries, and kidneys is key to the pathophysiology of the cardiorenal syndrome continuum. By understanding each of these processes, we may be able to halt disease progression and eventually extend the time a patient remains in the asymptomatic pre-HFpEF stage.This study aimed to investigate the chemical composition, and evaluate the antioxidant, anti-inflammatory, anti-pyretic, and the analgesic properties of methanol extracts from the leaves of Thymus algeriensis and Thymus fontanesii (Lamiaceae). Thirty-five secondary metabolites were characterized in both extracts using HPLC-PDA-ESI-MS/MS. Phenolic acids, mainly rosmarinic acid and its derivatives, dominated the T. algeriensis extract, while the phenolic diterpene carnosol and the methylated flavonoid salvigenin, prevailed in T. fontanesii extract. Ademetionine supplier Molecular docking study was carried out to estimate the anti-inflammatory potential and the binding affinities of some individual secondary metabolites from both extracts to the main enzymes involved in the inflammation pathway. In vitro enzyme inhibitory assays and in vivo assays were used to investigate the antioxidant and anti-inflammatory activities of the extracts. Results revealed that both studied Thymus species exhibited antioxidant, anti-inflammatory, analgesic, and antipyretic effects. They showed to be a more potent antioxidant than ascorbic acid and more selective against cyclooxygenase (COX-2) than diclofenac and indomethacin. Relatively, the T. fontanesii extract was more potent as COX-2 inhibitor than T. algeriensis. In conclusion, Thymus algeriensis and Thymus fontanesii may be interesting candidates for the treatment of inflammation and oxidative stress-related disorders.A reliable, sensitive and accurate multiple mycotoxin method was developed for the simultaneous determination of 17 mycotoxins in swine, poultry and dairy feeds using stable isotope dilution (13C-ISTD) and (ultra)-high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A simple QuEChERS-based method (quick, easy, cheap, effective, rugged and safe) was developed consisting of soaking with a solution of 1% formic acid followed by extraction with acetonitrile, clean-up with C18 sorbent and finally adding 13C-ISTD before the UHPLC-MS/MS analysis. The chromatographic condition was optimized for separation and detection of the 17 mycotoxins using gradient elution. The method’s performance complied with the SANTE/11813/2017 standard and had mean recovery accuracies in the range 70%-120% and precision testing of % relative standard deviation (RSD) £ 20%. The limit of detection and limit of quantification values ranged from 0.25 to 40.0 ng/g and 0.5 to 100.0 ng/g, respectively. Finally, the method was applied to analyze feed samples, with the results showing that fumonisins, zearalenone, aflatoxin B1 and deoxynivalenol were the most prevalent mycotoxins contaminating the feed samples.

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