The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: A longitudinal analysis

Background/Aims: Although there have been a few reports regarding the effect of basal core promoter (BCP) double mutations (A1762T and G1764A) on hepatitis B viral loads, the association remains uncertain. We aim to determine the association after controlling for HBeAg - a strong confounding factor.Methods: We selected randomly 190 individuals from a Chinese cohort of 2258 subjects for cross-sectional analysis and 56 of the 190 for longitudinal analysis of viral loads.Results: In multivariable analysis of the cross-sectional data, BCP double mutations are significantly associated with lower viral loads in HBeAg positive subjects but no difference was found in anti-HBe positive subjects. Triple mutations at nucleotide (nt) 1753, 1762 and 1764 and mutations between nt 1809 and 1817, precore stop mutation (nt 1896) and genotype are not associated with viral loads in either HBeAg or anti-HBe positive subjects. Analysis of the longitudinal data yielded similar results to the cross-sectional data. Viral loads differ significantly between individuals infected with wild-type and BCP double mutations prior to HBeAg seroconversion but this difference is lost after seroconversion.Conclusions: BCP double mutations are associated with lower viral loads in HBeAg positive individuals but have no effect on the viral loads of anti-HBe positive individuals. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

Maternal mental health and well-being during the COVID-19 pandemic in Beijing, China

Background: The aim of this study is to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on breastfeeding women and to identify predictors of maternal mental health and coping. Methods: Mothers aged ≥ 18 years with a breast-fed infant ≤ 18 months of age during the COVID-19 pandemic in Beijing, China, completed a questionnaire. Descriptive analysis of lockdown consequences was performed and predictors of these outcomes were examined using stepwise linear regression. Results: Of 2233 participants, 29.9%, 20.0% and 34.7% felt down, lonely, and worried, respectively, during the lockdown; however, 85.3% felt able to cope. Poorer maternal mental health was predicted by maternal (younger age, higher education) and infant (older age, lower gestation) characteristics, and social circumstances (husband unemployed or working from home, receiving advice from family, having enough space for the baby, living close to a park or green space). Conversely, better maternal mental health was predicted by higher income, employment requiring higher qualifications, more personal space at home, shopping or walking > once/week and lack of impact of COVID-19 on job or income. Mothers with higher education, more bedrooms, fair division of household chores and attending an online mother and baby group > once/week reported better coping. Conclusion: The findings highlight maternal characteristics and circumstances that predict poorer mental health and reduced coping which could be used to target interventions in any future public health emergencies requiring social restrictions

Polymorphisms of two neuroendocrine–correlated genes associated with body weight and reproductive traits in Jinghai yellow chicken

In this study, insulin-like growth factor binding protein 2 (IGFBP-2) and signal transducers activators of transcription 5b (STAT5b) gene were studied as candidate gene associated with body weight and reproductive traits of the Jinghai Yellow chicken. Single nucleotide polymorphisms (SNPs) of the IGFBP-2 and STAT5b genes were examined in both Jinghai Yellow chicken and three reference chicken populations by PCR-SSCP. Two SNPs (T3746TG and CC3753TT) were detected in the IGFBP-2 gene. One SNP (C8066T) was observed in the STAT5b gene. For primer 1, the general linear model analysis showed that Jinghai yellow chickens with FF genotypes had significant effect on hatch weight, egg weight at 300 days and body weight at 300 days than those of the EF genotype and had significant effect on body weight at 8 weeks of age than those of the EE genotype (P < 0.05). For primer 2, Jinghai yellow chickens with CT genotype had significant effect on hatch weight and age at first egg than CC genotype and TT genotype respectively (P < 0.05). SNPs in both IGFBP-2 and STAT5b genes had significant effect on body weight and reproductive traits of the Jinghai yellow chicken than those with either SNP alone. These SNPs may be served as a potential genetic marker for growth and reproduction traits evaluation of the Jinghai yellow chicken.Key words: Jinghai Yellow chicken, IGFBP-2 gene, STAT5b gene, economic traits, polymorphism

Isolation and Purification of Sesquiterpene Lactones from Ixeris sonchifolia (Bunge) Hance by High-Speed Counter- Current Chromatography and Semi-Preparative High Performance Liquid Chromatography

Purpose: To isolate and purify sesquiterpene lactones from Ixeris sonchifolia (Bunge) Hance by highspeed counter-current chromatography (HSCCC).Methods: I. sonchifolia was extracted with water and then loaded on a glass column (10 ~ 1500 cm containing 3000g D101 macroporous resin) where various concentrations of aqueous ethanol (0, 10, 30, 50, and 95 %) were used to elute the column successively. The 50 % ethanol fraction was  purified by HSCCC using a solvent system comprised of ethyl acetate: n-butanol: methanol: water (4: 6: 1: 20, v/v), and semi-preparative high performance liquid chromatography (HPLC). The chemical structures of thecomponents obtained were further confirmed by high-resolution mass spectroscopy (MS) and nuclear magnetic resonance spectroscopy (NMR).Results: Three compounds, including ixerin Z1 (0.7 mg), ixerin Z (11.4 mg), and 11, 13α-dihydroixerin Z (8.2 mg), with purity of 96.2, 98.2, and 98.4 %, respectively, were obtained from 200 mg each of the 50 % ethanol fraction.Conclusion: HSCCC is a rapid and effective method for isolating and purifying sesquiterpene lactones from I. sonchifolia.Keywords: Sesquiterpene lactones, High-speed counter-current chromatography, Ixeris sonchifolia, Ixerin, 13α-Dihydroixeri

A conserved arginine residue is critical for stabilizing the N2 FeS cluster in mitochondrial complex I.

Respiratory complex I (NADH:ubiquinone oxidoreductase), the first enzyme of the electron-transport chain, captures the free energy released by NADH oxidation and ubiquinone reduction to translocate protons across an energy-transducing membrane and drive ATP synthesis during oxidative phosphorylation. The cofactor that transfers the electrons directly to ubiquinone is an iron-sulfur cluster (N2) located in the NDUFS2/NUCM subunit. A nearby arginine residue (R121), which forms part of the second coordination sphere of the N2 cluster, is known to be posttranslationally dimethylated but its functional and structural significance are not known. Here, we show that mutations of this arginine residue (R121M/K) abolish the quinone-reductase activity, concomitant with disappearance of the N2 signature from the electron paramagnetic resonance (EPR) spectrum. Analysis of the cryo-EM structure of NDUFS2-R121M complex I at 3.7 Å resolution identified the absence of the cubane N2 cluster as the cause of the dysfunction, within an otherwise intact enzyme. The mutation further induced localized disorder in nearby elements of the quinone-binding site, consistent with the close connections between the cluster and substrate-binding regions. Our results demonstrate that R121 is required for the formation and/or stability of the N2 cluster and highlight the importance of structural analyses for mechanistic interpretation of biochemical and spectroscopic data on complex I variants

Octopaminergic neurons have multiple targets in Drosophila larval mushroom body calyx and can modulate behavioral odor discrimination.

Discrimination of sensory signals is essential for an organism to form and retrieve memories of relevance in a given behavioral context. Sensory representations are modified dynamically by changes in behavioral state, facilitating context-dependent selection of behavior, through signals carried by noradrenergic input in mammals, or octopamine (OA) in insects. To understand the circuit mechanisms of this signaling, we characterized the function of two OA neurons, sVUM1 neurons, that originate in the subesophageal zone (SEZ) and target the input region of the memory center, the mushroom body (MB) calyx, in larval Drosophila We found that sVUM1 neurons target multiple neurons, including olfactory projection neurons (PNs), the inhibitory neuron APL, and a pair of extrinsic output neurons, but relatively few mushroom body intrinsic neurons, Kenyon cells. PN terminals carried the OA receptor Oamb, a Drosophila α1-adrenergic receptor ortholog. Using an odor discrimination learning paradigm, we showed that optogenetic activation of OA neurons compromised discrimination of similar odors but not learning ability. Our results suggest that sVUM1 neurons modify odor representations via multiple extrinsic inputs at the sensory input area to the MB olfactory learning circuit.MRC studentship, UK Genetics Society Summer scholarship, BBSRC DTP summer placement, Isaac Newton Trust