Implementation of workplace-based smoking cessation support activities and smoking cessation among employees:the Finnish Public Sector Study

We investigated the relationship between implementation of workplace smoking cessation support activities and employee smoking cessation.

An in vitro screen of bacterial lipopolysaccharide biosynthetic enzymes identifies an inhibitor of ADP-heptose biosynthesis

The lipopolysaccharide (LPS)-rich outer membrane of gram-negative bacteria provides a protective barrier that insulates these organisms from the action of numerous antibiotics. Breach of the LPS layer can therefore provide access to the cell interior to otherwise impermeant toxic molecules and can expose vulnerable binding sites for immune system components such as complement. Inhibition of LPS biosynthesis, leading to a truncated LPS molecule, is an alternative strategy for antibacterial drug development in which this vital cellular structure is weakened. A significant challenge for in vitro screens of small molecules for inhibition of LPS biosynthesis is the difficulty in accessing the complex carbohydrate substrates. We have optimized an assay of the enzymes required for LPS heptose biosynthesis that simultaneously surveys five enzyme activities by using commercially available substrates and report its use in a small-molecule screen that identifies an inhibitor of heptose synthesis.

Identification of a general secretory pathway in a human isolate of Burkholderia vietnamiensis (formerly B. cepacia complex genomovar V) that is required for the secretion of hemolysin and phospholipase C activities

Members of the Burkholderia cepacia complex can secrete proteases, lipases, and hemolysins. We report in this study the identification of a general secretory pathway present in a B. vietnamiensis (formerly genomovar V) clinical isolate, which is required for the efficient secretion of phospholipase C and hemolysin activities. Southern blot hybridization experiments revealed that this general secretion pathway is highly conserved among the different genomovars of the B. cepacia complex and is homologous to a similar system described in B. pseudomallei. We also show that this pathway appears not to be necessary for intracellular survival of B. vietnamiensis within Acanthamoeba polyphaga.

PRIMARY STRUCTURES AND BIOLOGICAL-ACTIVITIES OF SUBSTANCE-P-RELATED PEPTIDES FROM THE BRAIN OF THE DOGFISH, SCYLIORHINUS-CANICULA

Two peptides with substance-P-like immunoreactivity were isolated in pure form from an extract of the brain of the elasmobranch fish, Scyliorhinus canicula (european common dogfish). One peptide was identical to scyliorhinin I, previously identified in dogfish intestine, and the second was the undecapeptide Lys-Pro-Arg-Pro-Gly-Gln-Phe-Phe-Gly-Leu-Met-CONH2 which is structurally similar to mammalian substance P Scyliorhinin II or a peptide analogous to mammalian neurokinin A were not detected in the extract. Synthetic dogfish substance P ([Lys1, Arg3, Gly5]substance P) was approximately threefold more potent than mammalian substance P (K(d) = 0.21 +/- 0.11 nM versus K(d)= 0.74 +/- 0.17 nM; mean +/- SD; n = 6) in inhibiting the binding of I-125-labelled substance P to neurokinin (NK1) receptors in rat submandibular gland membranes. The vasodilator action of tachykinins in mammals is mediated primarily through interaction with NK1 receptors. Bolus intravenous injections of [Lys1, Arg3, Gly5]substance P (100 pmol) and scyliorhinin I (100 pmol) produced appreciable (>4 kPa) decreases in arterial blood pressure in the rat whereas intravenous injections of up to 5 nmol of the peptides into conscious, unrestrained dogfish produced no change in arterial blood pressure, pulse amplitude or heart rate. Injections of greater amounts of the peptides (10-50 nmol) produced a slight increase (400-667 Pa) in blood pressure. The data indicate that mammalian-type NK1 tachykinin receptors are not involved in cardiovascular regulation in elasmobranch fish.

Vitamin B-6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration

Vitamin B-6 deficiency causes mild elevation in plasma homocysteine, but the mechanism has not been clearly established. Serine is a substrate in one-carbon metabolism and in the transsulfuration pathway of homocysteine catabolism, and pyridoxal phosphate (PLP) plays a key role as coenzyme for serine hydroxymethyltransferase (SHMT) and enzymes of transsulfuration. In this study we used [H-2(3)]serine as a primary tracer to examine the remethylation pathway in adequately nourished and vitamin B-6-deficient rats pi and 0.1 mg pyridoxine (PN)/kg diet]. [H-2(3)]Leucine and [1-C-13]methionine were also used to examine turnover of protein and methionine pools, respectively, All tracers were injected intraperitoneally as a bolus dose, and then rats were killed (n = 4/time point) after 30, 60 and 120 min. Rats fed the low-PN diet had significantly lower growth and plasma and liver PLP concentrations, reduced liver SHMT activity, greater plasma and liver total homocysteine concentration, and reduced liver S-adenosylmethionine concentration. Hepatic and whole body protein turnover were reduced in vitamin B-6-deficient rats as evidenced by greater isotopic enrichment of [H-2(3)]leucine. Hepatic [H-2(2)]methionine production from [H-2(3)]serine via cytosolic SHMT and the remethylation pathway was reduced by 80.6% in vitamin B-6 deficiency. The deficiency did not significantly reduce hepatic cystathionine-beta-synthase activity, and in vivo hepatic transsulfuration flux shown by production of [H-2(3)]cysteine from the [H-2(3)]serine increased over twofold. In contrast, plasma appearance of [H-2(3)]cysteine was decreased by 89% in vitamin B-6 deficiency. The rate of hepatic homocysteine production shown by the ratio of [1-C-13]homocysteine/[1-C-13]methionine areas under enrichment vs. time curves was not affected by vitamin B-6 deficiency. Overall, these results indicate that vitamin B-6 deficiency substantially affects one-carbon metabolism by impairing both methyl group production for homocysteine remethylation and flux through whole-body transsulfuration.

Novel, antibacterial silicone biomaterials for the prevention of microbial adherence and infection in urinary catheters

P122 93

Functional study of elafin cleaved by Pseudomonas aeruginosa metalloproteinases

Elafin is a 6-kDa innate immune protein present at several epithelial surfaces including the pulmonary epithelium. It is a canonical protease inhibitor of two neutrophil serine proteases [neutrophil elastase (NE) and proteinase 3] with the capacity to covalently bind extracellular matrix proteins by transglutamination. In addition to these properties, elafin also possesses antimicrobial and immunomodulatory activities. The aim of the present study was to investigate the effect of Pseudomonas aeruginosa proteases on elafin function. We found that P aeruginosa PAO1-conditioned medium and two purified Pseudomonas metalloproteases, pseudolysin (elastase) and aeruginolysin (alkaline protease), are able to cleave recombinant elafin. Pseudolysin was shown to inactivate the anti-NE activity of elafin by cleaving its protease-binding loop. Interestingly, antibacterial properties of elafin against PAO1 were found to be unaffected after pseudolysin treatment. In contrast to pseudolysin, aeruginolysin failed to inactivate the inhibitory properties of elafin against NE. Aeruginolysin cleaves elafin at the amino-terminal Lys6-Gly7 peptide bond, resulting in a decreased ability to covalently bind purified fibronectin following transglutaminase activity. In conclusion, this study provides evidence that elafin is susceptible to proteolytic cleavage at alternative sites by P aeruginosa metalloproteinases, which can affect different biological functions of elafin.

A comparison of the haemagglutinating and enzymic activities of Bacteroides fragilis whole cells and outer membrane vesicles

The haemagglutinating and enzymic activities of the obligately anaerobic pathogenic bacterium Bacteroides fragilis were examined. Outer membrane vesicles are released from the surface of B. fragilis. They can be detected by electron microscopy in ultrathin sections and bacterial suspensions after negative staining. Electron microscopy and immunogold labelling with a MAb specific for surface polysaccharide of B. fragilis confirmed that the vesicles carried outer membrane associated epitopes. The haemagglutinating activity of whole cells from populations of B. fragilis strains NCTC9343, BE3 and LS66 enriched by Percoll density gradient centrifugation for a large capsule (LC), electron dense layer (EDL); non-capsulate by light microscopy) and outer membrane vesicles (OMV) which had been purified by centrifugation from EDL-enriched populations were compared using human and horse erythrocytes. The enzymic activity of OMV, LC- and EDL-enriched populations, as detected by the API ZYM kit, was compared for strains NCTC 9343 and BE3. Purified OMV from the strains examined exhibited both haemagglutinating and enzymatic activity. Haemagglutination by the EDL-enriched population was sensitive to treatment with sodium periodate. The LC-enriched population haemagglutinated only after ultrasonic removal of the capsule. This indicates that the LC masks a haemagglutinin. The results suggest a potential role for OMV in the virulence of B. fragilis.

Research activities in the MaRINET project: keeping the European marine energy development facilities at world class level

The MaRINET project aims to build a synergy in the European marine renewable energy development infrastructure network, involving a total of 28 partners across the union. Its scope extends from small to large scale testing, in both tank and field. The main activities of the project are to standardize test procedures, to provide centralized free access for European technology developers, and to innovate for improving test infrastructures and techniques.
This paper presents the work carried in this last part, which focuses on research objectives identified to be current challenges for industrial development. They are distributed in 6 topics. On the one hand are issues that concern directly one of the 3 types of energy scoped in the project: wave, tidal, and offshore wind energy. Two examples are the real time estimation of incident waves, and the measurement of turbulence in tidal flows. On the other hand, collaborative effort is drawn on aspects that are common to those technologies: electrical components, environmental monitoring, and dedicated moorings.

Update on Research Activities in the MaRINET Project

The MaRINET FP7 project aims to build a synergy in the European marine renewable energy development infrastructure network, involving a total of 28 partners across the union. Its scope extends from small to large scale testing, in both tank and field. The main activities of the project are to standardize test procedures, to provide centralized free access for European technology developers, and to innovate for improving test infrastructures and techniques.
Two years to the end of the project, this paper presents an update of the work being carried in this last part. It focuses on research objectives identified to be current challenges for industrial development. They are distributed in 6 topics. On the one hand are issues directly related to one of the 3 types of energy scoped in the project: wave, tidal, and offshore wind. On the other hand, collaborative effort is drawn on aspects that are common to those technologies: electrical components, environmental monitoring, and dedicated moorings.
Theory and validation of new test techniques are presented, for example in the case of non-intrusive wave measurements. This is done in coordination with extensive experimental analysis of the phenomena implying tests, such as nonlinearities in moorings.

Antibacterial Effect of Human Mesenchymal Stem Cells is Mediated in Part from Secretion of the Antimicrobial Peptide LL-37

Recent in vivo studies indicate that mesenchymal stem cells (MSCs) may have beneficial effects in the treatment of sepsis induced by bacterial infection. Administration of MSCs in these studies improved survival and enhanced bacterial clearance. The primary objective of this study was to test the hypothesis that human MSCs possessed intrinsic antimicrobial properties. We studied the effect of human MSCs derived from bone marrow on the bacterial growth of Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus) bacteria. MSCs as well as their conditioned medium (CM) demonstrated marked inhibition of bacterial growth in comparison with control medium or normal human lung fibroblasts (NHLF). Analysis of expression of major antimicrobial peptides indicated that one of the factors responsible for the antimicrobial activity of MSC CM against Gram-negative bacteria was the human cathelicidin antimicrobial peptide, hCAP-18/LL-37. Both m-RNA and protein expression data showed that the expression of LL-37 in MSCs increased after bacterial challenge. Using an in vivo mouse model of E. coli pneumonia, intratracheal administration of MSCs reduced bacterial growth (in colony-forming unit) in the lung homogenates and in the bronchoalveolar lavage (BAL) fluid, and administration of MSCs simultaneously with a neutralizing antibody to LL-37 resulted in a decrease in bacterial clearance. In addition, the BAL itself from MSC-treated mice had a greater antimicrobial activity in comparison with the BAL of phosphate buffered saline (PBS)-treated mice. Human bone marrow-derived MSCs possess direct antimicrobial activity, which is mediated in part by the secretion of human cathelicidin hCAP-18/ LL-37.

Enhanced antimicrobial activities of 1-alkyl-3-methyl imidazolium ionic liquids based on silver or copper containing anions

We have developed a series of 1-alkyl-3-methylimidazolium tetrachlorocuprate(II) and dibromoargentate(I) ionic liquids with enhanced antimicrobial activity when compared with 1-alkyl-3-methylimidazolium chloride ionic liquids. These new ionic liquids proved to be effective against a range of pathogenic bacteria and fungi.

‘5 ways to say your prayers’:The Art and Architecture of Curating People, Place and Creativity in a Post-Conflict Context. The Shed, Galway, Ireland 18th June – 23rd July 2013 Includes: 1. Co-Curation of Exhibition with Peter Mutschler, Director of PS² and 2. Morrow’s individual work as part of the exhibition, entitled ‘Departures & Arrivals: Academic Interactions with the Activities, Artists and Archive of PS² ’

This exhibition profiles the curatorial approach of PS² and the work of creative practitioners who have practiced alongside and with the organisation. PS² is a Belfast-based, voluntary arts organisation that initiates projects inside and outside its project space. It seeks to develop a socio-spatial practice that responds to the post-conflict context of Northern Ireland, with particular focus on active intervention and social interaction between local people, creative practitioners, multidisciplinary groups and theorists.
Morrow has collaborated with PS² since its inception in 2005, acting as curatorial advisor specifically on the projects that occur outside PS² . She regards her involvement as a parallel action to her pedagogical explorations within architectural education.

Morrow's personal contribution to the Exhibition aimed to:
-interrogate PS² spatial projects
-contextualise PS² curatorial practice
-open up the analytical framework and extend to similar local practices

The Shed, Galway, Ireland is a joint Galway City Arts and Harbour Company venture. The exhibition subsequently travelled to DarcSpace Gallery, Dublin (Sept 2013).