Tumor suppressor PALB2 maintains redox and mitochondrial homeostasis in the brain and cooperates with ATG7/autophagy to suppress neurodegeneration

The PALB2 tumor suppressor plays key roles in DNA repair and has been implicated in redox homeostasis. Autophagy maintains mitochondrial quality, mitigates oxidative stress and suppresses neurodegeneration. Here we show that Palb2 deletion in the mouse brain leads to mild motor deficits and that co-deletion of Palb2 with the essential autophagy gene Atg7 accelerates and exacerbates neurodegeneration induced by ATG7 loss. Palb2 deletion leads to elevated DNA damage, oxidative stress and mitochondrial markers, especially in Purkinje cells, and co-deletion of Palb2 and Atg7 results in accelerated Purkinje cell loss. Further analyses suggest that the accelerated Purkinje cell loss and severe neurodegeneration in the double deletion mice are due to excessive oxidative stress and mitochondrial dysfunction, rather than DNA damage, and partially dependent on p53 activity. Our studies uncover a role of PALB2 in mitochondrial homeostasis and a cooperation between PALB2 and ATG7/autophagy in maintaining redox and mitochondrial homeostasis essential for neuronal survival.     

The persistent circulation of enterovirus 71 in People's Republic of China: causing emerging nationwide epidemics since 2008

Emerging epidemics of hand-foot-and-mouth disease (HFMD) associated with enterovirus 71 (EV71) has become a serious concern in mainland China. It caused 126 and 353 fatalities in 2008 and 2009, respectively. The epidemiologic and pathogenic data of the outbreak collected from national laboratory network and notifiable disease surveillance system. To understand the virological evolution of this emerging outbreak, 326 VP1 gene sequences of EV71 detected in China from 1987 to 2009 were collected for genetic analyses. Evidence from both traditional and molecular epidemiology confirmed that the recent HFMD outbreak was an emerging one caused by EV71 of subgenotype C4. This emerging HFMD outbreak is associated with EV71 of subgenotype C4, circulating persistently in mainland China since 1998, but not attributed to the importation of new genotype. Originating from 1992, subgenotype C4 has been the predominant genotype since 1998 in mainland China, with an evolutionary rate of 4.6∼4.8×10⁻³ nucleotide substitutions/site/year. The phylogenetic analysis revealed that the majority of the virus during this epidemic was the most recent descendant of subgenotype C4 (clade C4a). It suggests that the evolution might be one of the potential reasons for this native virus to cause the emerging outbreak in China. However, strong negative selective pressure on VP1 protein of EV71 suggested that immune escape might not be the evolving strategy of EV71, predicting a light future for vaccine development. Nonetheless, long-term antigenic and genetic surveillance is still necessary for further understanding.     

Rapid identification of lettuce seed germination mutants by bulked segregant analysis and whole genome sequencing

Lettuce (Lactuca sativa) seeds exhibit thermoinhibition, or failure to complete germination when imbibed at warm temperatures. Chemical mutagenesis was employed to develop lettuce lines that exhibit germination thermotolerance. Two independent thermotolerant lettuce seed mutant lines, TG01 and TG10, were generated through ethyl methanesulfonate mutagenesis. Genetic and physiological analyses indicated that these two mutations were allelic and recessive. To identify the causal gene(s), we applied bulked segregant analysis by whole genome sequencing. For each mutant, bulked DNA samples of segregating thermotolerant (mutant) seeds were sequenced and analyzed for homozygous single‐nucleotide polymorphisms. Two independent candidate mutations were identified at different physical positions in the zeaxanthin epoxidase gene (ABSCISIC ACID DEFICIENT 1/ZEAXANTHIN EPOXIDASE, or ABA1/ZEP) in TG01 and TG10. The mutation in TG01 caused an amino acid replacement, whereas the mutation in TG10 resulted in alternative mRNA splicing. Endogenous abscisic acid contents were reduced in both mutants, and expression of the ABA1 gene from wild‐type lettuce under its own promoter fully complemented the TG01 mutant. Conventional genetic mapping confirmed that the causal mutations were located near the ZEP/ABA1 gene, but the bulked segregant whole genome sequencing approach more efficiently identified the specific gene responsible for the phenotype.     

Pre-Existing HCV Variants Resistant to DAAs and Their Sensitivity to PegIFN/RBV in Chinese HCV Genotype 1b Patients

BackgroundThe efficacy of direct-acting antiviral agents (DAAs) could be attenuated by the presence of resistance-associated variants (RAVs). The aim of this study was to investigate the natural prevalence of RAVs among Chinese HCV genotype 1b patients and analyze the efficacy of pegylated interferon (PegIFN)/ribavirin (RBV) therapy in patients with and without RAVs at baseline.MethodsDirect sequencing of the HCV NS3, NS5A and NS5B regions was performed in baseline serum samples of 117 DAAs-naïve subjects infected with HCV genotype 1b. The efficacy of PegIFN/RBV therapy in patients with and without RAVs at baseline was analyzed by comparing the response rates between patients with RAVs and patients with wild type virus.ResultsThe incidence of RAVs was 8.00% (8/100) in the NS3 region (T54S, n = 1, 1.00%; R117H, n = 5, 5.00%; S122T, n = 1, 1.00%; S174F, n = 1, 1.00%), 29.91% (32/107) in the NS5A region (L28M, n = 12, 11.21%; R30Q, n = 10, 9.35%; L31M, n = 1, 0.93%; P58S, n = 4, 3.74%; Y93H, n = 8, 7.48%) and 98.15% (106/108) in the NS5B region (L159F, n = 1, 0.93%; C316N, n = 103, 95.37%; A421V, n = 6, 5.56%). The response rates to PegIFN/RBV treatment did not differ between patients with or without RAVs in the NS5A region.ConclusionsPre-existing RAVs, including key RAVs, were detected in Chinese DAAs-naïve patients infected with HCV genotype 1b. IFN-based therapy could be a good option for patients with RAVs, especially key RAVs, at baseline.     

Melatonin protects against defects induced by malathion during porcine oocyte maturation

Malathion (MAL) is a common organophosphorus pesticide and affects both animal and human reproduction. However, the mechanisms regarding how MAL affects the mammalian oocyte quality and how to prevent it have not been fully investigated. In this study, we used porcine oocyte as a model and proved that MAL impaired porcine oocyte quality in a dose-dependent manner during maturation. MAL decreased the first polar body extrusion, disrupted spindle assembly and chromosome alignment, impaired cortical granules (CGs) distribution, and increased reactive oxygen species (ROS) level in oocytes. RNA-seq analysis showed that MAL exposure altered the expression of 2,917 genes in the porcine maturated oocytes and most genes were related to ROS, the lipid droplet process, and the energy supplement. Nevertheless, these defects could be remarkably ameliorated by adding melatonin (MLT) into the oocyte maturation medium. MLT increased oocyte maturation rate and decreased the abnormities of spindle assembly, CGs distribution and ROS accumulation in MAL-exposed porcine oocytes. More important, MLT upregulated the expression of genes related to lipid droplet metabolism (PPARγ and PLIN2), decreased lipid droplet size and lipid peroxidation in MAL-exposed porcine oocytes. Finally, we found that MLT increased the blastocysts formation and the cell numbers of blastocysts in MAL-exposed porcine oocytes after parthenogenetic activation, which was mediated by reduction of ROS levels and maintaining lipid droplet metabolism. Taken together, our results revealed that MLT had a protective action against MAL-induced deterioration of porcine oocyte quality.     

Structural and Stereochemical Studies of Hydroxyanthraquinone Derivatives from the Endophytic Fungus Coniothyrium sp

Four known hydroxyanthraquinones ( 1–4 ) together with four new derivatives having a tetralone moiety, namely coniothyrinones A–D ( 5–8 ), were isolated from the culture of Coniothyrium sp., an endophytic fungus isolated from Salsola oppostifolia from Gomera in the Canary Islands. The structures of the new compounds were elucidated by detailed spectroscopic analysis and comparison with reported data. The absolute configurations of coniothyrinones A ( 5 ), B ( 6 ), and D ( 8 ) were determined by TDDFT calculations of CD spectra, allowing the determination of the absolute configuration of coniothyrinone C ( 7 ) as well. Coniothyrinones A ( 5 ), B ( 6 ), and D ( 8 ) could be used as ECD reference compounds in the determination of absolute configuration for related tetralone derivatives. This is the first report of anthraquinones and derivatives from an isolate of the genus Coniothyrium sp. These compounds showed inhibitory effects against the fungus Microbotryum violaceum, the alga Chlorella fusca, and the bacteria Escherichia coli and Bacillus megaterium. Chirality 25:141–148, 2013. © 2012 Wiley Periodicals, Inc.     

Hollow CuS Nanoboxes as Li‐Free Cathode for High‐Rate and Long‐Life Lithium Metal Batteries

Transition metal sulfides hold promising potentials as Li‐free conversion‐type cathode materials for high energy density lithium metal batteries. However, the practical deployment of these materials is hampered by their poor rate capability and short cycling life. In this work, the authors take the advantage of hollow structure of CuS nanoboxes to accommodate the volume expansion and facilitate the ion diffusion during discharge–charge processes. As a result, the hollow CuS nanoboxes achieve excellent rate performance (≈371 mAh g^?1 at 20 C) and ultra‐long cycle life (>1000 cycles). The structure and valence evolution of the CuS nanobox cathode are identified by scanning electron microscopy, transmission electron microscopy, and X‐ray photoelectron spectroscopy. Furthermore, the lithium storage mechanism is revealed by galvanostatic intermittent titration technique and operando Raman spectroscopy for the initial charge–discharge process and the following reversible processes. These results suggest that the hollow CuS nanobox material is a promising candidate as a low‐cost Li‐free cathode material for high‐rate and long‐life lithium metal batteries.     

Binding mechanism of maltol with catalase investigated by spectroscopy,molecular docking,and enzyme activity assay

Maltol is a flavor additive that is widely used in the daily diet of humans, and its biosafety attention is concomitantly increasing. Catalase (CAT) is an antioxidant enzyme to maintain homeostasis in the tissue's environment of human body and protect cells from oxidative damages. The adverse effects of maltol to CAT activity within mouse hepatocytes as well as the structural and functional changes of CAT on molecular level were investigated by multiple spectroscopy techniques, enzyme activity experiments, and molecular docking. Results suggested that when the maltol concentrations reached to 8 × 10^?5 mol L^?1, the viability of hepatocytes decreased to 93%, and CAT activity was stimulated by maltol to 111% than the control group after exposure for 24 hours. Changes in CAT activity on molecular level were consistent with those on cellular level. The fluorescence quenching of CAT by maltol was static with the forming of maltol‐CAT complex. Moreover, ultraviolet‐visible (UV‐visible) absorption, synchronous fluorescence, and circular dichroism (CD) spectra reflected that the presence of maltol caused conformational change of CAT and made the CAT molecule skeleton loose and increased α‐helix of CAT. Maltol mainly bound with CAT through hydrogen bond, and binding site that is near the heme ring in the enzyme activity center did not interact with its main amino acid residues. This study explores the combination between maltol and CAT, providing references for evaluating health damages caused by maltol.     

Length-weight relationships of eight fish species from the Hailang river,China

The present study reports the length-weight relationships (LWRs) for eight fish species sampled in Hailang River, a left-bank tributary of the Mudan River in Northeast China. The fishes were collected from April to October bimonthly 2017 by electrofishing (fishing 2 kilometers along the river and within 5 meters from the bank) and netting (drift gillnet: mesh size 2 cm × 3 cm; 200 m net length). The specimens were weighed (nearest 0.1 g) and measured (nearest 0.1 cm) in the laboratory. This study provides an update in maximum lengths for five species.