311 research outputs found

    Heteromeric TRPV4/TRPC1 channels mediate calcium-sensing receptor-induced relaxations and nitric oxide production in mesenteric arteries: comparative study using wild-type and TRPC1−/- mice

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    We have previously provided pharmacological evidence that stimulation of calcium-sensing receptors (CaSR) induces endothelium-dependent relaxations of rabbit mesenteric arteries through activation of heteromeric TRPV4/TRPC1 channels and nitric oxide (NO) production. The present study further investigates the role of heteromeric TRPV4/TRPC1 channels in these CaSR-induced vascular responses by comparing responses in mesenteric arteries from wild-type (WT) and TRPC1-/- mice. In WT mice, stimulation of CaSR induced endothelium-dependent relaxations of pre-contracted tone and NO generation in endothelial cells (ECs), which were inhibited by the TRPV4 channel blocker RN1734 and the TRPC1 blocking antibody T1E3. In addition, TRPV4 and TRPC1 proteins were colocalised at, or close to, the plasma membrane of endothelial cells (ECs) from WT mice. In contrast, in TRPC1-/- mice, CaSR-mediated vasorelaxations and NO generation were greatly reduced, unaffected by T1E3, but blocked by RN1734. In addition, the TRPV4 agonist GSK1016790A (GSK) induced endothelium-dependent vasorelaxations which were blocked by RN1734 and T1E3 in WT mice, but only by RN1734 in TRPC1-/- mice. Moreover, GSK activated cation channel activity with a 6pS conductance in WT ECs but with a 52 pS conductance in TRPC1-/- ECs. These results indicate that stimulation of CaSR activates heteromeric TRPV4/TRPC1 channels and NO production in ECs, which are responsible for endothelium-dependent vasorelaxations. This study also suggests that heteromeric TRPV4-TRPC1 channels may form the predominant TRPV4-containing channels in mouse mesenteric artery ECs. Together, our data further implicates CaSR-induced pathways and heteromeric TRPV4/TRPC1 channels in the regulation of vascular tone

    Panspermia, Past and Present: Astrophysical and Biophysical Conditions for the Dissemination of Life in Space

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    Astronomically, there are viable mechanisms for distributing organic material throughout the Milky Way. Biologically, the destructive effects of ultraviolet light and cosmic rays means that the majority of organisms arrive broken and dead on a new world. The likelihood of conventional forms of panspermia must therefore be considered low. However, the information content of dam-aged biological molecules might serve to seed new life (necropanspermia).Comment: Accepted for publication in Space Science Review

    The First Magnetic Fields

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    We review current ideas on the origin of galactic and extragalactic magnetic fields. We begin by summarizing observations of magnetic fields at cosmological redshifts and on cosmological scales. These observations translate into constraints on the strength and scale magnetic fields must have during the early stages of galaxy formation in order to seed the galactic dynamo. We examine mechanisms for the generation of magnetic fields that operate prior during inflation and during subsequent phase transitions such as electroweak symmetry breaking and the quark-hadron phase transition. The implications of strong primordial magnetic fields for the reionization epoch as well as the first generation of stars is discussed in detail. The exotic, early-Universe mechanisms are contrasted with astrophysical processes that generate fields after recombination. For example, a Biermann-type battery can operate in a proto-galaxy during the early stages of structure formation. Moreover, magnetic fields in either an early generation of stars or active galactic nuclei can be dispersed into the intergalactic medium.Comment: Accepted for publication in Space Science Reviews. Pdf can be also downloaded from http://canopus.cnu.ac.kr/ryu/cosmic-mag1.pd

    Grain Surface Models and Data for Astrochemistry

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    AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

    Linking Distributive and Procedural Justice to Employee Engagement Through Social Exchange: A Field Study in India

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    Research linking justice perceptions to employee outcomes has referred to social exchange as its central theoretical premise. We tested a conceptual model linking distributive and procedural justice to employee engagement through social exchange mediators, namely, perceived organizational support and psychological contract, among 238 managers and executives from manufacturing and service sector firms in India. Findings suggest that perceived organizational support mediated the relationship between distributive justice and employee engagement, and both perceived organizational support and psychological contract mediated the relationship between procedural justice and employee engagement. Theoretical and practical implications with respect to organizational functions are discussed

    The development and assessment of a scale to measure the experience of an anorexic voice in anorexia nervosa

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    The anorexic voice (AV) is defined as a critical internal dialogue which has been implicated in the development and maintenance of anorexia nervosa (AN). Systematic research to explore this further requires a valid and reliable measurement tool. This study aimed to develop and assess the validity of the Experience of an Anorexic VoicE Questionnaire (EAVE-Q). EAVE-Q items were developed and checked for face and content validity through cognitive interviews with seven individuals diagnosed with AN. Participants with a diagnosis of AN (N = 148) completed the EAVE-Q, sociodemographic questions and measures of mood and quality of life to assess internal consistency and construct 3 validity. Forty-nine participants completed the EAVE-Q twice more to assess test-retest reliability. The EAVE-Q had good face and content validity and good acceptability. Principal axis factoring resulted in an 18-item scale organised into five domains with high internal consistency (α = .70 to α = .85). Domains correlated significantly with eating disorder symptoms, psychological distress and quality of life. The EAVE-Q did not discriminate between participants on the basis of body mass index. Test-retest reliability was moderate. Although the factor structure of the EAVE-Q requires replication in other AN samples, the EAVE-Q is the first measure of a critical internal dialogue in AN. It is hoped that it will aid future research to increase understanding of AN and the continued development of person-centred treatments

    Multiple Determinants of Externalizing Behavior in 5-Year-Olds: A Longitudinal Model

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    In a community sample of 116 children, assessments of parent-child interaction, parent-child attachment, and various parental, child, and contextual characteristics at 15 and 28 months and at age 5 were used to predict externalizing behavior at age 5, as rated by parents and teachers. Hierarchical multiple regression analysis and path analysis yielded a significant longitudinal model for the prediction of age 5 externalizing behavior, with independent contributions from the following predictors: child sex, partner support reported by the caregiver, disorganized infant-parent attachment at 15 months, child anger proneness at 28 months, and one of the two parent-child interaction factors observed at 28 months, namely negative parent-child interactions. The other, i.e., a lack of effective guidance, predicted externalizing problems only in highly anger-prone children. Furthermore, mediated pathways of influence were found for the parent-child interaction at 15 months (via disorganized attachment) and parental ego-resiliency (via negative parent-child interaction at 28 months)

    Insights into Planet Formation from Debris Disks

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