Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone

Gold salts and phenylbutazone selectively inhibit the synthesis of PGF_2α and PGE₂ respectively. Lowered production of one prostaglandin species is accompanied by an increased production of the other. Selective inhibition by these drugs was observed in the presence of adrenaline, reduced glutathione and copper sulphate under conditions when most anti-inflammatory compounds inhibited PGE₂ and PGF_2α syntheses equally. It is postulated that selective inhibitors may have a different mode of action and beneficial effects may be related to the endogenous ratio of PGE to PGF required for normal function.     

Soft networks for bridging the gap between research and practice: illuminative evaluation of CHAIN

Objectives To explore the process of knowledge exchange in an informal email network for evidence based health care, to illuminate the value of the service and its critical success factors, and to identify areas for improvement.Design Illuminative evaluation.Setting Targeted email and networking service for UK healthcare practitioners and researchers.Participants 2800 members of a networking service.Main outcome measures Tracking of email messages, interviews with core staff, and a qualitative analysis of messages, postings from focus groups, and invited and unsolicited feedback to the service.Results The informal email network helped to bridge the gap between research and practice by serving as a rich source of information, providing access to members'' experiences, suggestions, and ideas, facilitating cross boundary collaboration, and enabling participation in networking at a variety of levels. Ad hoc groupings and communities of practice emerged spontaneously as members discovered common areas of interest.Conclusion This study illuminated how knowledge for evidence based health care can be targeted, personalised, and made meaningful through informal social processes. Critical success factors include a broad based membership from both the research and service communities; a loose and fluid network structure; tight targeting of messages based on members'' interests; the presence of a strong network identity and culture of reciprocity; and the opportunity for new members to learn through passive participation.     

Oxygen participation in the in vivo and in vitro aging of collagen fibres

We have examined, as a function of oxygen concentration, the in vivo and in vitro aging rates of tendon from animal species with widely differing life-spans. The results suggest that concomitant with the genetically determined aldimine type cross-linking reactions which probably are complete by the time the animal has reached physiological maturity, there is an on-going oxygen-mediated system of reactions which also effectively cross-link the structure. These reactions appear to proceed with their own intrinsic rate dependent only upon oxygen concentration, and independent of the particular species involved. They may not be required by connective tissues, but are an unavoidable consequence of the presence of free oxygen in tissues with a low rate of turnover.     

Molecular evolution of mitochondrial 12S RNA and cytochrome b sequences in the pantherine lineage of Felidae

DNA sequence comparisons of two mitochondrial DNA genes were used to infer phylogenetic relationships among 17 Felidae species, notably 15 in the previously described pantherine lineage. The polymerase chain reaction (PCR) was used to generate sequences of 358 base pairs of the mitochondrial 12S RNA gene and 289 base pairs of the cytochrome b protein coding gene. DNA sequences were compared within and between 17 felid and five nonfelid carnivore species. Evolutionary trees were constructed using phenetic, cladistic, and maximum likelihood algorithms. The combined results suggested several phylogenetic relationships including (1) the recognition of a recently evolved monophyletic genus Panthera consisting of Panthera leo, P. pardus, P. onca, P. uncia, P. tigris, and Neofelis nebulosa; (2) the recent common ancestry of Acinonyx jubatus, the African cheetah, and Puma concolor, the American puma; and (3) two golden cat species, Profelis temmincki and Profelis aurata, are not sister species, and the latter is strongly associated with Caracal caracal. These data add to the growing database of vertebrate mtDNA sequences and, given the relatively recent divergence among the felids represented here (1-10 Myr), allow 12S and cytochrome b sequence evolution to be addressed over a time scale different from those addressed in most work on vertebrate mtDNA.      

The Inhibition of Spores of Bacillus subtilis by Cetrimide Retained on Washed Membrane Filters and on the Washed Spores

Spores of Bacillus subtilis were filtered on membrane filters and then exposed to solutions of cetrimide. The spores, and the membranes themselves, even after being washed retained inhibitory concentrations of cetrimide. This might present a problem in counting bacterial survivors of cetrimide action by a membrane technique. The inhibitory effect of the low cetrimide concentrations retained by the membranes and the spores can be eliminated by washing with a Lubrol–lecithin solution.     

Vangl2-Regulated Polarisation of Second Heart Field-Derived Cells Is Required for Outflow Tract Lengthening during Cardiac Development

Planar cell polarity (PCP) is the mechanism by which cells orient themselves in the plane of an epithelium or during directed cell migration, and is regulated by a highly conserved signalling pathway. Mutations in the PCP gene Vangl2, as well as in other key components of the pathway, cause a spectrum of cardiac outflow tract defects. However, it is unclear why cells within the mesodermal heart tissue require PCP signalling. Using a new conditionally floxed allele we show that Vangl2 is required solely within the second heart field (SHF) to direct normal outflow tract lengthening, a process that is required for septation and normal alignment of the aorta and pulmonary trunk with the ventricular chambers. Analysis of a range of markers of polarised epithelial tissues showed that in the normal heart, undifferentiated SHF cells move from the dorsal pericardial wall into the distal outflow tract where they acquire an epithelial phenotype, before moving proximally where they differentiate into cardiomyocytes. Thus there is a transition zone in the distal outflow tract where SHF cells become more polarised, turn off progenitor markers and start to differentiate to cardiomyocytes. Membrane-bound Vangl2 marks the proximal extent of this transition zone and in the absence of Vangl2, the SHF-derived cells are abnormally polarised and disorganised. The consequent thickening, rather than lengthening, of the outflow wall leads to a shortened outflow tract. Premature down regulation of the SHF-progenitor marker Isl1 in the mutants, and accompanied premature differentiation to cardiomyocytes, suggests that the organisation of the cells within the transition zone is important for maintaining the undifferentiated phenotype. Thus, Vangl2-regulated polarisation and subsequent acquisition of an epithelial phenotype is essential to lengthen the tubular outflow vessel, a process that is essential for on-going cardiac morphogenesis.     

Developmentally regulated expression of the LRRTM gene family during mid-gestation mouse embryogenesis

We have analysed the expression during mid-gestation mouse development of the four member LRRTM gene family which encodes type 1 transmembrane proteins containing 10 extracellular leucine rich repeats and a short intracellular tail. Each family member has a developmentally regulated pattern of expression distinct from all other members. LRRTM1 is expressed in the neural tube, otic vesicle, apical ectodermal ridge, forebrain and midbrain up to a sharp central boundary. LRRTM2 is expressed in a subset of progenitors in the neural tube. LRRTM3 is expressed in a half somite wide stripe in the presomitic mesoderm adjacent to the boundary with the most recently formed somite. Additional expression is seen in the neural tube, forebrain and hindbrain. LRRTM4 is expressed in the limb mesenchyme, neural tube, caudal mesoderm and in three distinct regions of the head. Later expression occurs in a subset of the developing sclerotome. Each family member has a unique expression domain within the neural tube.