1,551 research outputs found

    Early LQT2 Nonsense Mutation Generates N-Terminally Truncated hERG Channels with Altered Gating Properties by the Reinitiation of Translation

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    Mutations in the human ether-a-go-go-related gene (hERG) result in long QT syndrome type 2 (LQT2). The hERG gene encodes a K+ channel that contributes to the repolarization of the cardiac action potential. We have previously shown that hERG mRNA transcripts that contain premature termination codon mutations are rapidly degraded by nonsense-mediated mRNA decay (NMD). In this study, we identified a LQT2 nonsense mutation, Q81X, which escapes degradation by the reinitiation of translation and generates N-terminally truncated channels. RNA analysis of hERG minigenes revealed equivalent levels of wild-type and Q81X mRNA while the mRNA expressed from minigenes containing the LQT2 frameshift mutation, P141fs+2X, was significantly reduced by NMD. Western blot analysis revealed that Q81X minigenes expressed truncated channels. Q81X channels exhibited decreased tail current levels and increased deactivation kinetics compared to wild-type channels. These results are consistent with the disruption of the N-terminus, which is known to regulate hERG deactivation. Site-specificmutagenesis studies showed that translation of the Q81X transcript is reinitiated atMet124 following premature termination. Q81X co-assembled with hERG to form heteromeric channels that exhibited increased deactivation rates compared to wild-type channels. Mutant channels also generated less outward current and transferred less charge at late phases of repolarization during ventricular action potential clamp. These results provide new mechanistic insight into the prolongation of the QT interval in LQT2 patients. Our findings indicate that the reinitiation of translation may be an important pathogenic mechanism in patients with nonsense and frameshift LQT2 mutations near the 5′ end of the hERG gene

    Why do groups cooperate more than individuals to reduce risks?

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    Previous research has discovered a curious phenomenon: groups cooperate less than individuals in a deterministic prisoner’s dilemma game, but cooperate more than individuals when uncertainty is introduced into the game. We conducted two studies to examine three possible processes that might drive groups to be more cooperative than individuals in reducing risks: group risk concern, group cooperation expectation, and pressure to conform to social norms. We found that ex post guilt aversion and ex-post blame avoidance cause group members to be more risk concerned than individuals under uncertainty. These concerns drive groups to choose the cooperation (and risk-reduction) strategy more frequently than individuals. Groups also have higher cooperation expectations for their corresponding groups than individuals have for their corresponding individuals. We found no evidence of pressure to conform to social norms driving groups to be more cooperative than individuals

    Composition and Expression of Conserved MicroRNA Genes in Diploid Cotton (Gossypium) Species

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    MicroRNAs are ubiquitous in plant genomes but vary greatly in their abundance within and conservation among plant lineages. To gain insight into the evolutionary birth/death dynamics of microRNA families, we sequenced small RNA and 50-end PARE libraries generated from two closely related species of Gossypium. Here, we demonstrate that 33 microRNA families, with similar copy numbers and average evolutionary rates, are conserved in the two congeneric cottons. Analysis of the presence/absence of these microRNA families in other land plants sheds light on their depth of phylogenetic origin and lineage-specific loss/gain. Conserved microRNA families in Gossypium exhibit a striking interspecific asymmetry in expression, potentially connected to relative proximity to neighboring transposable elements. A complex correlated expression pattern of microRNA target genes with their controlling microRNAs indicates that possible functional divergence of conserved microRNA families can also exist even within a single plant genus

    A Thermodynamic Investigation of the Redox Properties of Ceria-Titania Mixed Oxides

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    Ceria-titania solutions with compositions of Ce0.9Ti0.1O2 and Ce0.8Ti0.2O2 were prepared by the citric-acid (Pechini) method and characterized using x-ray diffraction (XRD) for structure, coulometric titration for redox thermodynamics, and water-gas-shift (WGS) reaction rates. Following calcination at 973 K, XRD suggests that the mixed oxides exist as single-phase, fluorite structures, although there was no significant change in the lattice parameter compared to pure ceria. The mixed oxides are shown to be significantly more reducible than bulk ceria, with enthalpies for reoxidation being approximately -500 kJ/mol O2, compared to -760 kJ/mol O2 for bulk ceria. However, WGS rates over 1-wt% Pd supported on ceria, Ce0.8Ti0.2O2, and Ce0.8Zr0.2O2 were nearly the same. For calcination at 1323 K, the mixed oxides separated into ceria and titania phases, as indicated by both the XRD and thermodynamic results

    The Relationship between Resilience and Mental Health: the Mediating Effect of Positive Emotions

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    To investigate the relationship of resilience, positive emotions and mental health, and the relationship of resilience, positive emotion and three sub-dimensions of mental health: self-affirmation, depression and anxiety. In this study, the existing cross-sectional data, select the Beijing Forestry University data as samples. In this study, questionnaire survey a random sample of 199 undergraduate students of Beijing Forestry University, they uniform application three Scale Surveying, PANAS, CD-RISC, GHQ-20. According from the study, (1) resilience, positive mood and general health are related where resilience and positive emotions between the resilience. General psychological health, positive emotions and general mental health?it is positively correlated. (2) Resilience and self-affirmation exists, positive correlation with depression and anxiety, respectively negative correlation. Between positive emotions and self-affirmation the positive correlation with anxiety negative correlation. (3) Part mediating effect of positive emotions exist between resilience and self-affirmation, resilience can be made to self-affirmation prediction coefficient from 0.042 down to 0.036. Therefore, this study concluded that resilience undergraduates can have an impact on mental health through the intermediary variable positive emotions

    The role of supply chain leadership in the learning of sustainable practice: toward an integrated framework

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    AcceptedArticleNOTICE: this is the author’s version of a work that was accepted for publication in Journal of Cleaner Production. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Cleaner Production doi:10.1016/j.jclepro.2014.10.029Sustainable supply chain management (SSCM) is a topic that has become increasingly important in recent years. However, very few papers focus on studying SSCM from both leadership and learning perspectives. In this research, we carry out a content-based literature review on the intersections of Supply Chain leadership, Supply Chain Learning and SSCM; we propose a conceptual framework on how focal companies assuming a leadership role initiate and disseminate sustainable practices in their supply chains. Three types of sustainable supply chain management (SSCM) strategies (i.e., reactive, contributive and proactive) have been identified in this research based on four dimensions of SSCM governance, supply chain learning, supply chain leadership and SSCM performance. It is argued that two new constructs of supply chain learning and supply chain leadership are an integral part of the SSCM conceptual framework developed from the literature and have significant implication to our understanding of SSCM
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