Perivascular Expression and Potent Vasoconstrictor Effect of Dynorphin A in Cerebral Arteries

BACKGROUND: Numerous literary data indicate that dynorphin A (DYN-A) has a significant impact on cerebral circulation, especially under pathophysiological conditions, but its potential direct influence on the tone of cerebral vessels is obscure. The aim of the present study was threefold: 1) to clarify if DYN-A is present in cerebral vessels, 2) to determine if it exerts any direct effect on cerebrovascular tone, and if so, 3) to analyze the role of κ-opiate receptors in mediating the effect. METHODOLOGY/PRINCIPAL FINDINGS: Immunohistochemical analysis revealed the expression of DYN-A in perivascular nerves of rat pial arteries as well as in both rat and human intraparenchymal vessels of the cerebral cortex. In isolated rat basilar and middle cerebral arteries (BAs and MCAs) DYN-A (1-13) and DYN-A (1-17) but not DYN-A (1-8) or dynorphin B (DYN-B) induced strong vasoconstriction in micromolar concentrations. The maximal effects, compared to a reference contraction induced by 124 mM K(+), were 115±6% and 104±10% in BAs and 113±3% and 125±9% in MCAs for 10 µM of DYN-A (1-13) and DYN-A (1-17), respectively. The vasoconstrictor effects of DYN-A (1-13) could be inhibited but not abolished by both the κ-opiate receptor antagonist nor-Binaltorphimine dihydrochloride (NORBI) and blockade of G(i/o)-protein mediated signaling by pertussis toxin. Finally, des-Tyr(1) DYN-A (2-13), which reportedly fails to activate κ-opiate receptors, induced vasoconstriction of 45±11% in BAs and 50±5% in MCAs at 10 µM, which effects were resistant to NORBI. CONCLUSION/SIGNIFICANCE: DYN-A is present in rat and human cerebral perivascular nerves and induces sustained contraction of rat cerebral arteries. This vasoconstrictor effect is only partly mediated by κ-opiate receptors and heterotrimeric G(i/o)-proteins. To our knowledge our present findings are the first to indicate that DYN-A has a direct cerebral vasoconstrictor effect and that a dynorphin-induced vascular action may be, at least in part, independent of κ-opiate receptors

An exploratory cluster randomised trial of a university halls of residence based social norms marketing campaign to reduce alcohol consumption among 1st year students

<p>Aims: This exploratory trial examines the feasibility of implementing a social norms marketing campaign to reduce student drinking in universities in Wales, and evaluating it using cluster randomised trial methodology.</p> <p>Methods: Fifty residence halls in 4 universities in Wales were randomly assigned to intervention or control arms. Web and paper surveys were distributed to students within these halls (n = 3800), assessing exposure/contamination, recall of and evaluative responses to intervention messages, perceived drinking norms and personal drinking behaviour. Measures included the Drinking Norms Rating Form, the Daily Drinking Questionnaire and AUDIT-C.</p> <p>Results: A response rate of 15% (n = 554) was achieved, varying substantially between sites. Intervention posters were seen by 80% and 43% of students in intervention and control halls respectively, with most remaining materials seen by a minority in both groups. Intervention messages were rated as credible and relevant by little more than half of students, though fewer felt they would influence their behaviour, with lighter drinkers more likely to perceive messages as credible. No differences in perceived norms were observed between intervention and control groups. Students reporting having seen intervention materials reported lower descriptive and injunctive norms than those who did not.</p> <p>Conclusions: Attention is needed to enhancing exposure, credibility and perceived relevance of intervention messages, particularly among heavier drinkers, before definitive evaluation can be recommended. A definitive evaluation would need to consider how it would achieve sufficient response rates, whilst hall-level cluster randomisation appears subject to a significant degree of contamination.</p&gt

Observation of Coherent Elastic Neutrino-Nucleus Scattering

The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross-section is the largest by far of all low-energy neutrino couplings. This mode of interaction provides new opportunities to study neutrino properties, and leads to a miniaturization of detector size, with potential technological applications. We observe this process at a 6.7-sigma confidence level, using a low-background, 14.6-kg CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source (SNS) at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the Standard Model for this process, are observed in high signal-to-background conditions. Improved constraints on non-standard neutrino interactions with quarks are derived from this initial dataset

A formally verified compiler back-end

This article describes the development and formal verification (proof of semantic preservation) of a compiler back-end from Cminor (a simple imperative intermediate language) to PowerPC assembly code, using the Coq proof assistant both for programming the compiler and for proving its correctness. Such a verified compiler is useful in the context of formal methods applied to the certification of critical software: the verification of the compiler guarantees that the safety properties proved on the source code hold for the executable compiled code as well

Dalitz Plot Analysis of Ds to K+K-pi+

We perform a Dalitz plot analysis of the decay Ds to K+K-pi+ with the CLEO-c data set of 586/pb of e+e- collisions accumulated at sqrt(s) = 4.17 GeV. This corresponds to about 0.57 million D_s+D_s(*)- pairs from which we select 14400 candidates with a background of roughly 15%. In contrast to previous measurements we find good agreement with our data only by including an additional f_0(1370)pi+ contribution. We measure the magnitude, phase, and fit fraction of K*(892) K+, phi(1020)pi+, K0*(1430)K+, f_0(980)pi+, f_0(1710)pi+, and f_0(1370)pi+ contributions and limit the possible contributions of other KK and Kpi resonances that could appear in this decay.Comment: 21 Pages,available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR