88 research outputs found

    Unraveling Controversies Over Civic Honesty Measurement: An Extended Field Replication in China

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    Cohn et al. (2019) conducted a wallet drop experiment in 40 countries to measure civic honesty around the globe, which has received worldwide attention but also sparked controversies over using the email response rate as the sole metric of civic honesty. Relying on the lone measurement may overlook cultural differences in behaviors that demonstrate civic honesty. To investigate this issue, we conducted an extended replication study in China, utilizing email response and wallet recovery to assess civic honesty. We found a significantly higher level of civic honesty in China, as measured by the wallet recovery rate, than reported in the original study, while email response rates remained similar. To resolve the divergent results, we introduce a cultural dimension, individualism versus collectivism, to study civic honesty across diverse cultures. We hypothesize that cultural differences in individualism and collectivism could influence how individuals prioritize actions when handling a lost wallet, such as contacting the wallet owner or safeguarding the wallet. In reanalyzing Cohn et al.\u27s data, we found that email response rates were inversely related to collectivism indices at the country level. However, our replication study in China demonstrated that the likelihood of wallet recovery was positively correlated with collectivism indicators at the provincial level. Consequently, relying solely on email response rates to gauge civic honesty in cross-country comparisons may neglect the vital individualism versus collectivism dimension. Our study not only helps reconcile the controversy surrounding Cohn et al.\u27s influential field experiment but also furnishes a fresh cultural perspective to evaluate civic honesty

    Function of Chick Subcutaneous Adipose Tissue During the Embryonic and Posthatch Period

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    Since excess abdominal fat is one of the main problems in the broiler industry for the development of modern broiler and layer industry, the importance of subcutaneous adipose tissue has been neglected. However, chick subcutaneous adipose tissue appeared earlier than abdominal adipose tissue and more than abdominal adipose tissue. Despite a wealth of data, detailed information is lacking about the development and function of chick subcutaneous adipose tissue during the embryonic and posthatch period. Therefore, the objective of the current study was to determine the developmental changes of adipocyte differentiation, lipid synthesis, lipolysis, fatty acid β-oxidation, and lipid contents from E12 to D9.5. The results showed that subcutaneous adipose tissue was another important energy supply tissue during the posthatch period. In this stage, the mitochondrial copy number and fatty acid β-oxidation level significantly increased. It revealed that chick subcutaneous adipose tissue not only has the function of energy supply by lipidolysis but also performs the same function as brown adipose tissue to some extent, despite that the brown adipose tissue does not exist in birds. In addition, this finding improved the theory of energy supply in the embryonic and posthatch period and might provide theoretical basis on physiological characteristics of lipid metabolism in chicks

    Epigenetic control of translation checkpoint and tumor progression via RUVBL1-EEF1A1 axis

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    Epigenetic dysregulation is reported in multiple cancers including Ewing sarcoma (EwS). However, the epigenetic networks underlying the maintenance of oncogenic signaling and therapeutic response remain unclear. Using a series of epigenetics- and complex-focused CRISPR screens, RUVBL1, the ATPase component of NuA4 histone acetyltransferase complex, is identified to be essential for EwS tumor progression. Suppression of RUVBL1 leads to attenuated tumor growth, loss of histone H4 acetylation, and ablated MYC signaling. Mechanistically, RUVBL1 controls MYC chromatin binding and modulates the MYC-driven EEF1A1 expression and thus protein synthesis. High-density CRISPR gene body scan pinpoints the critical MYC interacting residue in RUVBL1. Finally, this study reveals the synergism between RUVBL1 suppression and pharmacological inhibition of MYC in EwS xenografts and patient-derived samples. These results indicate that the dynamic interplay between chromatin remodelers, oncogenic transcription factors, and protein translation machinery can provide novel opportunities for combination cancer therapy.</p

    Risk of venous thromboembolism with janus kinase inhibitors in inflammatory immune diseases: a systematic review and meta-analysis

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    Objectives: This study aimed to evaluate the risk of venous thrombosis (VTE) associated with Janus kinase (JAK) inhibitors in patients diagnosed with immune-mediated inflammatory diseases.Methods: We conducted a comprehensive search of PUBMED, Cochrane, and Embase databases for randomized controlled trials evaluating venous thromboembolic incidence after administering JAK inhibitors in patients with immune-mediated inflammatory diseases. The studies were screened according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and a meta-analysis was performed.Results: A total of 16 studies, enrolling 17,242 participants, were included in this review. Four approved doses of JAK inhibitors were administered in the included studies. The meta-analysis revealed no significant difference in the incidence of VTE between patients receiving JAK inhibitors, a placebo, or tumor necrosis factor (TNF) inhibitors (RR 0.72, 95% CI (0.33-1.55); RR 0.94, 95%CI (0.33-2.69)). Subgroup analysis showed a lower risk of VTE with lower doses of JAK inhibitors [RR 0.56, 95%CI (0.36-0.88)]. Compared with the higher dose of tofacitinib, the lower dose was associated with a lower risk of pulmonary embolism [RR 0.37, 95%CI (0.18-0.78)].Conclusion: Our meta-analysis of randomized controlled trials observed a potential increase in the risk of VTE in patients with immune-mediated inflammatory diseases treated with JAK inhibitors compared to placebo or tumor necrosis factor inhibitors, though statistical significance was not attained. Notably, a higher risk of pulmonary embolism was observed with high doses of tofacitinib. Our findings provide valuable insights for physicians when evaluating the use of JAK inhibitors for patients with immune-mediated inflammatory diseases.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023382544, identifier CRD4202338254

    The Intracellular Virus-Containing Compartments in Primary Human Macrophages Are Largely Inaccessible to Antibodies and Small Molecules

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    HIV-1 assembly and release occurs at the plasma membrane of human T lymphocytes and model epithelial cell lines, whereas in macrophages intracellular sites of virus assembly or accumulation predominate. The origin of the intracellular virus-containing compartment (VCC) has been controversial. This compartment is enriched in markers of the multivesicular body, and has been described as a modified endosomal compartment. Several studies of this compartment have revealed the presence of small channels connecting to the plasma membrane, suggesting that instead of an endosomal origin the compartment is a modified plasma membrane compartment. If the compartment is accessible to the external environment, this would have important implications for antiviral immune responses and antiviral therapy. We performed a series of experiments designed to determine if the VCC in macrophages was open to the external environment and accessible to antibodies and small molecules. The majority of VCCs were found to be inaccessible to exogenously-applied antibodies to tetraspanins in the absence of membrane permeabilization, while tetraspanin staining was readily observed following membrane permeabilization. Cationized ferritin was utilized to stain the plasma membrane, and revealed that the majority of virus-containing compartments were inaccessible to ferritin. Low molecular weight dextrans could access only a very small percentage of VCCs, and these tended to be more peripheral compartments. We conclude that the VCCs in monocyte-derived human macrophages are heterogeneous, but the majority of VCCs are closed to the external environment

    Rab11-FIP1C and Rab14 Direct Plasma Membrane Sorting and Particle Incorporation of the HIV-1 Envelope Glycoprotein Complex

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    The incorporation of the envelope glycoprotein complex (Env) onto the developing particle is a crucial step in the HIV-1 lifecycle. The long cytoplasmic tail (CT) of Env is required for the incorporation of Env onto HIV particles in T cells and macrophages. Here we identify the Rab11a-FIP1C/RCP protein as an essential cofactor for HIV-1 Env incorporation onto particles in relevant human cells. Depletion of FIP1C reduced Env incorporation in a cytoplasmic tail-dependent manner, and was rescued by replenishment of FIP1C. FIP1C was redistributed out of the endosomal recycling complex to the plasma membrane by wild type Env protein but not by CT-truncated Env. Rab14 was required for HIV-1 Env incorporation, and FIP1C mutants incapable of binding Rab14 failed to rescue Env incorporation. Expression of FIP1C and Rab14 led to an enhancement of Env incorporation, indicating that these trafficking factors are normally limiting for CT-dependent Env incorporation onto particles. These findings support a model for HIV-1 Env incorporation in which specific targeting to the particle assembly microdomain on the plasma membrane is mediated by FIP1C and Rab14. © 2013 Qi et al.Link_to_subscribed_fulltex

    Cyclophilin A-Dependent Restriction of Human Immunodeficiency Virus Type 1 Capsid Mutants for Infection of Nondividing Cells â–¿

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    Among retroviruses, lentiviruses are unusual in their ability to efficiently infect both dividing and nondividing cells, such as activated T cells and macrophages, respectively. Recent studies implicate the viral capsid protein (CA) as a key determinant of cell-cycle-independent infection by human immunodeficiency virus type 1 (HIV-1). We investigated the effects of the host cell protein cyclophilin A (CypA), which binds to HIV-1 CA, on HIV-1 infection of nondividing cells. The HIV-1 CA mutants A92E, T54A, and R132K were impaired for infection of aphidicolin-arrested HeLa cells, but not HOS cells. The mutants synthesized normal quantities of two-long-terminal-repeat circles in arrested HeLa cells, indicating that the mutant preintegration complexes can enter the nuclei of both dividing and nondividing cells. The impaired infectivity of the CA mutants on both dividing and nondividing HeLa cells was relieved by either pharmacological or genetic disruption of the CypA-CA interaction or by RNA interference-mediated depletion of CypA expression in target cells. A second-site suppressor of the CypA-restricted phenotype also restored the ability of CypA-restricted HIV-1 mutants to infect growth-arrested HeLa cells. These results indicate that CypA-restricted mutants are specifically impaired at a step between nuclear import and integration in nondividing HeLa cells. This study reveals a novel target cell-specific restriction of HIV-1 CA mutants in nondividing cells that is dependent on CypA-CA interactions

    Synthesis and sintering of silicon nitride nano-powders via sodium reduction in liquid ammonia

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    Nano-sized silicon nitride powders were synthesized through the reduction of silicon tetrachloride (SiCl4) by sodium in liquid ammonia at around -40 degrees C. The product was in uniform particles of several nanometers, and in the amorphous form. The amorphous structure was stable up to 1200 degrees C and turned to the crystal structure of alpha-Si3N4 at 1300 degrees C, and then to beta-Si3N4 structure when heated at temperatures higher than 1450 degrees C. Via spark plasma sintering (SPS) dense bulks with 97.9% relative density of theoretic value and the grain size of 100-300 nm was successfully fabricated at 1500 degrees C without any sintering additives. (C) 2016 Elsevier Ltd. All rights reserved

    Architectural design and cryogenic synthesis of Si3N4@(TiN-Si3N4) for high conductivity

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    Si3N4@(TiN-Si3N4) composites with heteroshelled structure were designed for enhanced conductivity and successfully synthesized through the simultaneous reduction and in-situ cocoating process in liquid ammonia at around -40 degrees C. The heteroshells were composed of nanosized TiN and Si3N4 particles, which were amorphous with the size ranging from 10 to 40nm. Using spark plasma sintering, dense bulk composite with &gt;98.1% relative density of theoretical value were obtained and their electrical conductivity were increased to an adequate value (6.62 x 10(2) Scm(-1)) for electrical discharge machining by compositing 15 vol% TiN to Si3N4, which is superior to the previous reports. The excellent electric performance could be attributed to the heteroshelled structure which guarantees the conductive network can be formed and kept with minimal TiN content. The nanosized Si3N4 powders in the shells reduce the content of conductive powders and limit the growth of TiN particles.</p
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