26 research outputs found

    An emerging recombinant human enterovirus 71 responsible for the 2008 outbreak of Hand Foot and Mouth Disease in Fuyang city of China

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    Hand, foot and mouth disease (HFMD), a common contagious disease that usually affects children, is normally mild but can have life-threatening manifestations. It can be caused by enteroviruses, particularly Coxsackieviruses and human enterovirus 71 (HEV71) with highly variable clinical manifestations. In the spring of 2008, a large, unprecedented HFMD outbreak in Fuyang city of Anhui province in the central part of southeastern China resulted in a high aggregation of fatal cases. In this study, epidemiologic and clinical investigations, laboratory testing, and genetic analyses were performed to identify the causal pathogen of the outbreak. Of the 6,049 cases reported between 1 March and 9 May of 2008, 3023 (50%) were hospitalized, 353 (5.8%) were severe and 22 (0.36%) were fatal. HEV71 was confirmed as the etiological pathogen of the outbreak. Phylogenetic analyses of entire VP1 capsid protein sequence of 45 Fuyang HEV71 isolates showed that they belong to C4a cluster of the C4 subgenotype. In addition, genetic recombinations were found in the 3D region (RNA-dependent RNA polymerase, a major component of the viral replication complex of the genome) between the Fuyang HEV71 strain and Coxsackievirus A16 (CV-A16), resulting in a recombination virus. In conclusion, an emerging recombinant HEV71 was responsible for the HFMD outbreak in Fuyang City of China, 2008

    Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast

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    Although many prokaryotes have glycolysis alternatives, it\u27s considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism

    General model for retroviral capsid pattern recognition by TRIM5 proteins

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    Permission to archive final published versionRestriction factors are intrinsic cellular defense proteins that have evolved to block microbial infections. Retroviruses such as HIV-1 are restricted by TRIM5 proteins, which recognize the viral capsid shell that surrounds, organizes, and protects the viral genome. TRIM5α uses a SPRY domain to bind capsids with low intrinsic affinity (KD of >1 mM) and therefore requires higher-order assembly into a hexagonal lattice to generate sufficient avidity for productive capsid recognition. TRIMCyp, on the other hand, binds HIV-1 capsids through a cyclophilin A domain, which has a well-defined binding site and higher affinity (KD of ∼10 μM) for isolated capsid subunits. Therefore, it has been argued that TRIMCyp proteins have dispensed with the need for higher-order assembly to function as antiviral factors. Here, we show that, consistent with its high degree of sequence similarity with TRIM5α, the TRIMCyp B-box 2 domain shares the same ability to self-associate and facilitate assembly of a TRIMCyp hexagonal lattice that can wrap about the HIV-1 capsid. We also show that under stringent experimental conditions, TRIMCyp-mediated restriction of HIV-1 is indeed dependent on higher-order assembly. Both forms of TRIM5 therefore use the same mechanism of avidity-driven capsid pattern recognitionYe

    Metal-organic Framework ZIF-67 Functionalized MXene for Enhancing the Fire Safety of Thermoplastic Polyurethanes

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    In this work, a novel functionalization strategy for ZIF-67-modified layered MXene was proposed, aiming at improving the fire safety of thermoplastic polyurethanes (TPU). The ZIF-67@MXene was verified by microscopic morphology, elemental composition, functional group species and crystal structure, and then the successfully prepared ZIF-67@MXene was introduced into the TPU material. When ZIF-67@MXene content was only 0.5 wt%, the peak heat release rate, total heat release rate, peak smoke release rate, total smoke release rate, and CO yield of the TPU/ZIF-67@MXene composites were reduced by 26%, 9%, 50%, and 22%, respectively, compared with the pure TPU. The thermogravimetric tests showed that the residual char of TPU/ZIF-67@MXene composites was the most in all samples. In short, the high-quality carbon layer of TPU/ZIF-67@MXene composites acts as a physical barrier to the transfer of heat and toxic gases, greatly improving the flame retardant properties of the TPU polymer

    Retrogradation properties and in vitro digestibility of wild starch from Castanopsis sclerophylla

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    In order to explore the application of a new starch source isolated from Castanopsis Sclerophylla, the retrogradation properties and in vitro digestibility of C. Sclerophylla starch (CaS) were investigated for the first time in this study. The Chain-length distribution (CLD) of amylopectin from CaS was characterized. The retrogradation behavior of CaS was measured using rapid viscosity analysis (RVA), rheometry, texture profile analysis (TPA), and differential scanning calorimetry (DSC), and the results compared with those of corn starch (CS). Cas amylopectin displays a lower proportion of short chains (A-chains, 13.31%) and higher proportion of long chains (B3-chains, 31.70%) when compared to corn amylopectin. CaS has a high rate of retrogradation, with higher setback, storage modulus (G′), and lower Tan δ values than CS in short-term retrogradation. CaS gels showed increased hardness and released water from starch gels during storage. Compared with CS, native CaS exhibited higher SDS content and lower RS content and estimated glycemic index (eGI) value. Retrogradation greatly increased the RS content in retrograded CaS and was almost five times higher than that obtained for native CaS after 7 days of storage at 4 °C, whereas it was only slightly higher than that in CS. Furthermore, retrogradation significantly decreased the eGI of CaS, indicating a potential application of CaS in functional food

    Knowledge and perceptions of air pollution in Ningbo, China

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    Abstract Background The residents’ knowledge, attitudes and practices related to ambient air pollution and health will help to improve the understanding of environmental protection and make environmental health policies more targeted and effective. This study aimed at knowing the attitudes and behaviors towards ambient air pollution and health. Methods A cross-sectional survey was conducted in Ningbo, China in January 2015. Personal information and questions pertaining to the knowledge, attitudes and practices towards ambient air pollution and health were collected through questionnaire investigations. Descriptive statistics, chi-square tests and multiple unconditional logistic regression analysis were used. Results The questionnaire was completed by 1604 respondents (59.41 % women). The awareness rate was 64.59 % and varied significantly with age, levels of education, and occupation (all p < 0.05). Only 5.80 % of the total participants were satisfied with the air quality in Ningbo in 2014. Most respondents (78.80 %) expressed concern about the possible aggravation of the haze. More than 80 % of participants believed that it will take at least 3-5 years or longer before the air quality is improved. Television and internet resources have replaced books and newspapers as the primary sources for obtaining knowledge about haze and related protective measures. 85.22 % of respondents were concerned about air quality index (AQI). Most of the residents have taken protective measures indoors during haze weather. 48.50 % have worn face masks when going outside, the most frequently type of face masks selected were cotton (39.85 %) or gauze face masks (36.24 %). Age and occupation were the main factors associated with the level of knowledge about air pollution (p < 0.05). Conclusions There were a relatively high knowledge awareness rate, strong health protection consciousness and high enthusiasm for air pollution control among Ningbo residents. The elderly people and less-educated residents are the targetable population for improving environment

    TRIM5α SPRY/coiled-coil interactions optimize avid retroviral capsid recognition

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    <div><p>Restriction factors are important components of intrinsic cellular defense mechanisms against viral pathogens. TRIM5α is a restriction factor that intercepts the incoming capsid cores of retroviruses such as HIV and provides an effective species-specific barrier to retroviral infection. The TRIM5α SPRY domain directly binds the capsid with only very weak, millimolar-level affinity, and productive capsid recognition therefore requires both TRIM5α dimerization and assembly of the dimers into a multivalent hexagonal lattice to promote avid binding. Here, we explore the important unresolved question of whether the SPRY domains are flexibly linked to the TRIM lattice or more precisely positioned to maximize avidity. Biochemical and biophysical experiments indicate that the linker segment connecting the SPRY domain to the coiled-coil domain adopts an α-helical fold, and that this helical portion mediates interactions between the two domains. Targeted mutations were generated to disrupt the putative packing interface without affecting dimerization or higher-order assembly, and we identified mutant proteins that were nevertheless deficient in capsid binding <i>in vitro</i> and restriction activity in cells. Our studies therefore support a model wherein substantial avidity gains during assembly-mediated capsid recognition by TRIM5α come in part from tailored spacing of tethered recognition domains.</p></div

    Dimerization of CC-L2 mutants.

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    <p>Purified mutant proteins were analyzed by using SEC-MALS (size exclusion chromatography coupled with multi-angle light scattering). The solid curves represent the normalized UV absorbance trace (arbitrary units) of eluting components. The dotted curves show the population averaged molecular mass calculated from the measured protein concentration and light scattering data. Dashed gray lines indicate the expected masses of the monomer and dimer species. (A) Wildtype control. (B) D186A. (C) I193A. (D) E197A. The major peak had a substantial trailing edge indicating dissociation into monomers. (E) E201A.</p

    Modeling of SPRY/coiled-coil packing in TRIM5α.

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    <p>(A) Ribbon model of the TRIM5α dimer, which was obtained by combining the crystal structures of the B-box/coiled-coil dimer [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006686#ppat.1006686.ref012" target="_blank">12</a>] and isolated SPRY domain [<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006686#ppat.1006686.ref030" target="_blank">30</a>, <a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1006686#ppat.1006686.ref031" target="_blank">31</a>]. Domains and structural elements are colored as follows: RING, not included in model; B-box 2, orange; coiled-coil, green; L2 linker helix, gray; SPRY, blue. (B) Expanded view of the central region of the antiparallel dimer, in the same orientation as A. Residues selected for mutagenesis in this study are represented by sticks and transluscent spheres. Orange, class I residues; pink, class II residues. (C) Orthogonal view rotated as indicated, with individual residues labeled. The L2 helices are omitted in this panel for clarity. The two subunits are distinguished by an apostrophe. The coiled-coil dimer’s two-fold symmetry axis is indicated by the black oval.</p
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