Rebecca N Lawrence

The Pseudomonas aeruginosa quorum-sensing signal molecule, N-(3-oxododecanoyl)-L-homoserine lactone, inhibits porcine arterial smooth muscle contraction

The Pseudomonas aeruginosa quorum sensing molecule N‐(3‐oxododecanoyl)‐L‐homoserine lactone (OdDHL) has been shown to suppress cytokine production in macrophages. We have examined the effect of OdDHL and related compounds on constrictor tone of porcine blood vessels. OdDHL (1–30 μM) caused a concentration‐dependent inhibition of U46619‐induced contractions of the coronary artery through a largely endothelium‐independent mechanism, but was markedly less effective in the pulmonary artery. Quantitively similar effects to those produced by OdDHL were observed with N‐(3‐oxododecanoyl)‐L‐homocysteine thiolactone, a thiolactone derivative, while N‐3‐oxododecanamide, a lactone‐free acyl analogue, possessed 1/3rd the potency as a vasorelaxant. Neither N‐butanoyl‐L‐homoserine lactone nor L‐homoserine lactone (up to 30 μM) were active. Our findings indicate that OdDHL inhibits vasoconstrictor tone of both pulmonary and coronary blood vessels from the pig. The vasorelaxant action of OdDHL appears to be primarily determined by the N‐acyl chain length, with a minor contribution by the homoserine lactone moiety.

Differential role of vasoactive prostanoids in porcine and human isolated pulmonary arteries in response to endothelium-dependent relaxants

1 The pig is increasingly being used in medical research, both as a model of the human cardiovascular system, and as a possible source of organs for xenotransplantation. However, little is known about the comparative functions of the vascular endothelium between porcine and human arteries. We have therefore compared the effects of two endothelium‐dependent vasorelaxants, acetylcholine (ACh) and the Ca2+‐ATPase inhibitor, cyclopiazonic acid (CPA) on the porcine and human isolated pulmonary artery using isometric tension recording. 2 ACh and CPA produced endothelium‐dependent relaxations of both the human and porcine pulmonary arteries. 3 In the porcine pulmonary artery, the cyclo‐oxygenase inhibitor, flurbiprofen had no effect on relaxations to ACh (Emax: control 67.8±8.8% versus 72.4±9.5% (n = 11)) or CPA (Emax: control 79.6±5.0% versus 94.0±10.6% (n = 7)). The nitric oxide synthase inhibitor, l‐NAME converted relaxations to both ACh and CPA into contractile responses (maximum response: ACh 30.0±11.1% (n = 10); CPA 80.4±26.2% (n = 8) of U46619‐induced tone). These contractile responses in the presence of l‐NAME were abolished by flurbiprofen. 4 In the human pulmonary artery, l‐NAME and flurbiprofen partly attenuated relaxations to ACh (Emax: control: 45.1±12.1%; flurbiprofen: 33.4±13.5%; l‐NAME: 10.1±7.2%) and CPA (Emax: control: 78.1±5.5%; flurbiprofen: 69.6±7.2%; l‐NAME 37.9±10.7% of U46619‐induced tone). These responses were abolished by the combination of both inhibitors. 5 We have demonstrated that while the release of nitric oxide is important in responses to endothelium‐dependent vasorelaxants in both human and porcine pulmonary arteries, in the human arteries, there is an important role for vasorelaxant prostanoids whilst in the porcine arteries, vasoconstrictor prostanoids are released.

Altmetrics as a means of assessing scholarly output

Career progression for scientists involves an assessment of their contribution to their field and a prediction of their future potential. Traditional measures, such as the impact factor of the journal that a researcher publishes in, may not be an appropriate or accurate means of assessing the overall output of an individual. The development of altmetrics offers the potential for fuller assessments of a researchers output based on both their traditional and non‐traditional scholarly outputs. New tools should make it easier to include non‐traditional outputs such as data, software and contributions to peer review in the evaluation of early‐ and mid‐career researchers.

Towards an open science publishing platform

The way science and research is done is rapidly becoming more open and collaborative. The traditional way of publishing new findings in journals is becoming increasingly outdated and no longer serves the needs of much of science. Whilst preprints can bring significant benefits of removing delay and selection, they do not go far enough if simply implemented alongside the existing journal system. We propose that we need a new approach, an Open Science Platform, that takes the benefits of preprints but adds formal, invited, and transparent post-publication peer review. This bypasses the problems of the current journal system and, in doing so, moves the evaluation of research and researchers away from the journal-based Impact Factor and towards a fairer system of article-based qualitative and quantitative indicators. In the long term, it should be irrelevant where a researcher publishes their findings. What is important is that research is shared and made available without delay within a framework that encourages quality standards and requires all players in the research community to work as collaborators.

New opportunities in Asia: a focus on India and China.

A focus on IBCs Drug Discovery Technology held in Mumbai, India, on 18-20 October 2004.

James Gimzewski discusses the potential of nanobiotechnology

Abstract James Gimzewski, California NanoSystems Institute, Department of Chemistry and Biochemistry, 607 Charles E. Young Drive East, Box 951569, University of California, Los Angeles, CA 90095, USA. Tel.: 1 310 794 7514; fax: +1-310-206-4038; e-mail: gim@chem.ucla.edu

Endothelium-dependent Relaxation in Response to Ethanol in the Porcine Isolated Pulmonary Artery

Many drugs cannot be dissolved in distilled water and so other solvents such as ethanol, dimethylsulphoxide and methanol are used. Because very little is known about the direct effects of these three solvents on the cardiovascular system, we have examined their effects on isolated pulmonary and coronary arteries from the pig.

Data exchange standards to support and acknowledge peer-review activity

Peer review is used to evaluate research, including publications, scientific awards, and grant proposals, and there is a continuum of at least six approaches to review from completely closed, double‐blind review to fully‐open and citable peer review. It is getting harder to find suitable experts to serve as reviewers so publishers and others are experimenting with methods to incentivize researcher participation, with a growing interest in enabling citation of peer‐review activity as a component. A Working Group on Peer Review Service, facilitated by CASRAI, was created to develop a data model and citation standard for peer‐review activity that can be used to support both existing and new review models. Standardized citation structures for reviews can enable the inclusion of peer‐review activity in personal recognition and evaluation, as well the ability to refer to reviews as part of the scholarly literature.

Sir Chris Evans divulges his experiences as an entrepreneur

Abstract Sir Christopher co-founded Merlin Biosciences in 1996 and is widely regarded as one of the most successful biotechnology entrepreneurs in the UK. Sir Christopher has founded a number of high-technology companies, three of which [Chiroscience Group (now merged with Celltech and Medeva), Celsis International and Toad] are now publicly listed. Evans was appointed OBE for services to biotechnology in 1995 and has been actively involved in many of the UK Governments biotechnology initiatives. He is also an active member of The Prime Ministers Council for Science and Technology and holds Professorships at the Universities of Exeter, Liverpool, Manchester and Imperial College in the UK, where he regularly lectures. He has been awarded seven Doctor of Science degrees and has over 100 scientific publications and patents. In addition, he regularly gives ‘informal’ lectures to schools, colleges and key regional assemblies to promote the awareness of science and the importance of high-technology SMEs. Evans was knighted in the New Years Honours List 2001.