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  • Sommer Combs posted an update 2 days, 22 hours ago

    Interactions between the hepatitis B virus core protein (HBc) and host cell proteins are poorly understood, although they may be essential for the propagation of the virus and its pathogenicity. HBc has a C-terminal PDZ (PSD-95, Dlg1, ZO-1)-binding motif (PBM) that is responsible for interactions with host PDZ domain-containing proteins. In this work, we focused on the human protein tyrosine phosphatase non-receptor type 3 (PTPN3) and its interaction with HBc. We solved the crystal structure of the PDZ domain of PTPN3 in complex with the PBM of HBc, revealing a network of interactions specific to class I PDZ domains despite the presence of a C-terminal cysteine in this atypical PBM. We further showed that PTPN3 binds the HBc protein within capsids or as a homodimer. We demonstrate that overexpression of PTPN3 significantly affects HBV infection in HepG2 NTCP cells. Finally, we performed proteomics studies on both sides by pull-down assays and screening of a human PDZ domain library. We identified a pool of human PBM-containing proteins that might interact with PTPN3 in cells and that could be in competition with the HBc PBM during infection, and we also identified potential cellular partners of HBc through PDZ-PBM interactions. This study opens up many avenues of future investigations into the pathophysiology of HBV.High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10-18 and h2 = 0.58, P = 1 × 10-7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs body mass index (- 0.22), waist circumference (- 0.25), triglycerides (- 0.18), fat mass (- 0.23), fasting glucose (- 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (- 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.The number of patients on hemodialysis (HD) is rapidly increasing in China. As an Asian country with a large number of HD patients, understanding the status of Chinese HD patients has a special significance. We reported here the baseline data for China Dialysis Outcomes and Practice Pattern Study Phase 5 (DOPPS5). The DOPPS is an international prospective, observational cohort study. Patients were restricted to the initial sample of patients who participated in China DOPPS5. We summarized the baseline demographic and clinical data of patients. Results were weighted by facility sampling fraction. 1186 patients were initial patients in China DOPPS5. The mean age was 58.7 ± 3.5 years, with 54.6% males. The median dialysis vintage was 3.4 (1.5, 6.3) years. The main assigned primary end-stage kidney disease (ESKD) causes was chronic glomerulonephritis (45.9%), followed by diabetes (19.9%). 17.6% patients had hepatitis B infection, and 10.0% patients had hepatitis C infection. 25.9% patients had a single-pooled Kt/V  3.5 g/dl. 18.8% patients had hemoglobin less then  9 g/dl. 66.5% patients had serum calcium in target range (8.4-10.2 mg/dl), 41.5% patients had serum phosphate in target range (3.5-5.5 mg/dl) and 51.2% patients maintained PTH in 150-600 pg/dl. 88.2% patients used fistula as their vascular access. Meanwhile, there were differences in the demographic, clinical, laboratory, and treatment characteristics among the three cities participated in China DOPPS. We observed a relatively higher albumin level and a higher rate of fistula usage in our patients. But it remains a major challenge to us on the management of CKD-MBD and anemia. This study did not include patients in small cities and remote areas, where the situation of HD patients might be worse than reported.Microvascular disease and rarefaction are key pathological hallmarks of hypertension. The retina uniquely allows direct, non-invasive investigation of the microvasculature. Recently developed optical coherence tomography angiography now allows investigation of the fine retinal capillaries, which may provide a superior marker of overall vascular damage. Androgen Receptor Antagonist libraries This was a prospective cross-sectional study to collect retinal capillary density data on 300 normal eyes from 150 hypertensive adults, and to investigate possible associations with other organ damage markers. The average age of participants was 54 years and there was a greater proportion of males (85; 57%) than females. Multivariate, confounder adjusted linear regression showed that retinal capillary rarefaction in the parafovea was associated with increased pulse wave velocity (β = - 0.4, P = 0.04), log-albumin/creatinine ratio (β = - 0.71, P = 0.003), and with reduced estimated glomerular filtration rate (β = 0.04, P = 0.02). Comparable significant associations were also found for whole-image vascular-density, for foveal vascular-density significant associations were found with pulse wave velocity and estimated glomerular filtration rate only.

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