102 research outputs found

    Human APOBEC3 proteins can inhibit xenotropic murine leukemia virus-related virus infectivity

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    AbstractXenotropic murine leukemia virus-related virus (XMRV) is a novel retrovirus, related to murine leukemia virus (MLV), that has been implicated in human disease. If XMRV is indeed able to replicate in humans, then one might predict that XMRV would have developed resistance to human innate antiviral resistance factors such as APOBEC3G (hA3G). In fact, we observed that XMRV and MLV are both highly sensitive to inhibition by hA3G and equally resistant to inhibition by murine APOBEC3. While several human prostate cancer cell lines were found to lack hA3G, stable expression of physiological levels of hA3G rendered these cells refractory to XMRV replication. Few human tissues fail to express hA3G, and we therefore hypothesize that XMRV replicates in one or more hA3G-negative reservoir tissues and/or that human XMRV infections are likely to be rare and potentially of zoonotic origin

    Reducing the Resource Acquisition Costs for Returnee Entrepreneurs: Role of Chinese National Science Parks

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    Purpose: The purpose of this paper is to empirically explore the mechanisms through which Chinese National Science Parks' (NSPs) services facilitate returnee entrepreneurs' (REs) acquisition of resources for their new ventures. Resource acquisition is crucial for new ventures, but it inevitably leads to significant costs increase. Although the NSPs offer various services to REs to reduce these costs, they still struggle to find the right mix of services. Design/methodology/approach: From the transaction cost's perspective, an exploratory multiple-case study was conducted with data collected from six NSPs in China. Findings: The results reveal that four types of NSP services (mentoring and training, social event, promotion of REs and accreditation of resource holders (RHs)) have both individual and joint effects on reducing REs' resource acquisition costs. Specifically, the “accreditation of RHs” service directly helps REs reduce search costs. The combination of “accreditation of RHs”, “promotion of REs” and “social event” services help REs and RHs to establish guanxi. Further, guanxi, working along with the “mentoring and training” service, helps REs to reduce contracting, monitoring and enforcement costs. Originality/value: This study is among the first to explore the matching mechanisms between science parks’ services and entrepreneurs' cost reduction. This helps reconcile the inconsistent findings on science parks' effect by explaining why some NSPs are able to provide strong support to REs while others are less successful. In addition, the findings are useful for NSPs to develop the right mix of tailored services for REs. Finally, REs will find this study useful to evaluate which NSP is a more suitable location for their new ventures

    Effectiveness of Shuxuening injection in coronary heart disease: a systematic review and meta-analysis

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    Background: Coronary heart disease (CHD) poses a serious threat to public health, and the current medical management still faces significant challenges. Reliable evidence on the efficacy of Shuxuening injection (SXNI) in CHD is still lacking, even though it is widely used in China.Purpose: To evaluate the efficacy of SXNI combination therapy in treating CHD.Methods: A systematic search of eight databases was conducted to identify relevant randomized controlled trials (RCTs) from the inception of each database until June 2023. ROB 2.0, RevMan 5.4, and Stata 15.1 were used for quality evaluation and data analysis. The Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the quality of evidence.Results: A total of 3,779 participants from 39 studies were included. The results showed SXNI combination therapy increased the clinical efficacy and decreased the frequency and duration of angina. Furthermore, SXNI combination therapy improved cardiac function of patients by decreasing LVEDD, and increased CI, CO, and LVEF. It also improved blood lipid profiles by increasing HDL, decreasing TC, TG, and LDL. The thrombosis factors of patients were also improved by decreasing FIB, PV, HCT, and HS. Moreover, SXNI combination therapy was superior to the conventional treatment in improving CRP levels, increasing ECG efficacy and BNP. However, due to the limited safety information, reliable safety conclusions could not be drawn. Furthermore, the levels of evidence ranged from very low to moderate due to publication bias and heterogeneity.Conclusion: SXNI can effectively improve angina symptoms, clinical efficacy, cardiac function, blood lipid indicators, and thrombosis factors of patients with CHD. However, more multi-center and large-sample studies are needed to confirm the conclusions due to the limitations of this study.Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=399606; Identifier: CRD42023433292

    Collective forest tenure reform and forest conditions: evidence from the social-ecological system in Southwest China

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    China’s recent collective forest tenure reform (CFTR) aims to improve forest conditions by devolution of forest management rights from community collectives to individual households. Studies reveal substantial local variation in CFTR implementation, but the ecological effects and underlying mechanism have received little attention. Our study focused on community-managed forests and household-managed forests in four communities located in the mountains of Southwest China. The objective was to investigate the relationship between CFTR and forest conditions at the local scale. We employed a combination of remote sensing technology, field forest observations and socioeconomic surveys to gather data for analysis. The results showed that the forest cover change trends of collective forests and household forests in each community were consistent from 1994 to 2014. There was no significant relationship between CFTR implementation and local-level differences in species diversity and soil fertility in forests. The aboveground biomass of collective forests was significantly higher than that of household forests. Differentiated access and use, low compensation amounts, and loose payment terms jointly affected CFTR’s effectiveness to improve local-scale forest conditions in the study area. Attempts to formalize forest tenure rights must be flexible enough and adapted to the local environment so that changes induced by the CFTR can improve local access to forest resources and its benefits

    Identification of Interferon-Stimulated Genes with Antiretroviral Activity

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    SummaryInterferons (IFNs) exert their anti-viral effects by inducing the expression of hundreds of IFN-stimulated genes (ISGs). The activity of known ISGs is insufficient to account for the antiretroviral effects of IFN, suggesting that ISGs with antiretroviral activity are yet to be described. We constructed an arrayed library of ISGs from rhesus macaques and tested the ability of hundreds of individual macaque and human ISGs to inhibit early and late replication steps for 11 members of the retroviridae from various host species. These screens uncovered numerous ISGs with antiretroviral activity at both the early and late stages of virus replication. Detailed analyses of two antiretroviral ISGs indicate that indoleamine 2,3-dioxygenase 1 (IDO1) can inhibit retroviral replication by metabolite depletion while tripartite motif-56 (TRIM56) accentuates ISG induction by IFNα and inhibits the expression of late HIV-1 genes. Overall, these studies reveal numerous host proteins that mediate the antiretroviral activity of IFNs

    Wafer-scale heterogeneous integration InP on trenched Si with a bubble-free interface

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    Heterogeneous integration of compound semiconductors on a Si platform leads to advanced device applications in the field of Si photonics and high frequency electronics. However, the unavoidable bubbles formed at the bonding interface are detrimental for achieving a high yield of dissimilar semiconductor integration by the direct wafer bonding technology. In this work, lateral outgassing surface trenches (LOTs) are introduced to efficiently inhibit the bubbles. It is found that the chemical reactions in InP-Si bonding are similar to those in Si-Si bonding, and the generated gas can escape via the LOTs. The outgassing efficiency is dominated by LOTs\u27 spacing, and moreover, the relationship between bubble formation and the LOT\u27s structure is well described by a thermodynamic model. With the method explored in this work, a 2-in. bubble-free crystalline InP thin film integrated on the Si substrate with LOTs is obtained by the ion-slicing and wafer bonding technology. The quantum well active region grown on this Si-based InP film shows a superior photoemission efficiency, and it is found to be 65% as compared to its bulk counterpart

    Longitudinal variation in SARS-CoV-2 antibody levels and emergence of viral variants:a serological analysis

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    BACKGROUND: Serological assays are being used to monitor antibody responses in individuals who had SARS-CoV-2 infection and those who received a COVID-19 vaccine. We aimed to determine whether such assays can predict neutralising antibody titres as antibody levels wane and viral variants emerge. METHODS: We measured antibody levels in serum samples from a cohort of 112 participants with SARS-CoV-2 infection using ten high-throughput serological tests and functional neutralisation assays. Serum samples were taken at baseline and at up to four subsequent visits. We assessed the effects of time and spike protein sequence variation on the performance and predictive value of the various assays. We did correlation analyses for individual timepoints using non-parametric Spearman correlation, and differences between timepoints were determined by use of a two-tailed Wilcoxon matched-pairs signed rank test. FINDINGS: Neutralising antibody titres decreased over the first few months post-infection but stabilised thereafter, at about 30% of the level observed shortly after infection. Serological assays commonly used to measure antibodies against SARS-CoV-2 displayed a range of sensitivities that declined to varying extents over time. Quantitative measurements generated by serological assays based on the spike protein were better at predicting neutralising antibody titres than those based on nucleocapsid, but performance was variable, and manufacturer positivity thresholds were not able to predict the presence or absence of detectable neutralising activity. Although we observed some deterioration in correlation between serological measurements and functional neutralisation activity, some assays maintained an ability to predict neutralising titres, even against variants of concern. INTERPRETATION: The ability of high-throughput serological assays to predict neutralising antibody titres is likely to be crucial for evaluation of immunity at the population scale. These data can facilitate the selection of the most suitable assays as surrogates of functional neutralising activity and suggest that such measurements might be useful in clinical practice. FUNDING: US National Institutes of Health and National Health Service Research Scotland BioResource

    Clathrin Facilitates the Morphogenesis of Retrovirus Particles

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    The morphogenesis of retroviral particles is driven by Gag and GagPol proteins that provide the major structural component and enzymatic activities required for particle assembly and maturation. In addition, a number of cellular proteins are found in retrovirus particles; some of these are important for viral replication, but many lack a known functional role. One such protein is clathrin, which is assumed to be passively incorporated into virions due to its abundance at the plasma membrane. We found that clathrin is not only exceptionally abundant in highly purified HIV-1 particles but is recruited with high specificity. In particular, the HIV-1 Pol protein was absolutely required for clathrin incorporation and point mutations in reverse transcriptase or integrase domains of Pol could abolish incorporation. Clathrin was also specifically incorporated into other retrovirus particles, including members of the lentivirus (simian immunodeficiency virus, SIVmac), gammaretrovirus (murine leukemia virus, MLV) and betaretrovirus (Mason-Pfizer monkey virus, M-PMV) genera. However, unlike HIV-1, these other retroviruses recruited clathrin primarily using peptide motifs in their respective Gag proteins that mimicked motifs found in cellular clathrin adaptors. Perturbation of clathrin incorporation into these retroviruses, via mutagenesis of viral proteins, siRNA based clathrin depletion or adaptor protein (AP180) induced clathrin sequestration, had a range of effects on the accuracy of particle morphogenesis. These effects varied according to which retrovirus was examined, and included Gag and/or Pol protein destabilization, inhibition of particle assembly and reduction in virion infectivity. For each retrovirus examined, clathrin incorporation appeared to be important for optimal replication. These data indicate that a number of retroviruses employ clathrin to facilitate the accurate morphogenesis of infectious particles. We propose a model in which clathrin contributes to the spatial organization of Gag and Pol proteins, and thereby regulates proteolytic processing of virion components during particle assembly
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