Studies on sulphur amino acid metabolising enzymes of trichomonas vaginalis

Methionine--lyase (MGL) from Trichomonas vaginalis has been crystallised and the structure solved by molecular replacement at 2.2 A. The enzyme has a similar overall secondary structure arrangement as the search model, cystathionine -lyase from Escherichia coli, but differs in the active site. In addition to the holoenzyme, the structure of the enzyme in complex with the acetylenic suicide inhibitor L-propargylglycine has also been solved. This has revealed the mechanism of inhibition by this compound. It has also provided insights into the catalytic mechanism of the enzyme and allowed the postulation of a scheme for its action. Particularly, this predicts core roles for active site tyrosine and cysteine residues (111 and 113, respectively). To test the hypothesised mechanism of catalysis, seven site-directed mutants were produced. The activities of the mutants were determined and the structure solved for one of the most interesting. The resulting data confirm the mode of action of L-propargylglycine and also reveal a proton relay which activates the important active site cysteine which mediates much of the enzyme activity. This mechanism is substantially different from that proposed for other members of the same family of enzymes and explains the substrate specificity of MGL. The structure also reveals a potential role for the enzyme. The active site cysteine is positioned ideally to form an internal persulphide with a sulphur atom released from the substrate. This implies a possible role for the enzyme in iron-sulphur cluster formation in an analogous fashion to the enzyme, cysteine desulphurase. Cultivation of the parasite in medium supplemented with L-cysteine has revealed reduced expression of the enzyme. This is the first demonstration of part of the de novo synthesis of cysteine in the T. vaginalis

The burden and impact of vertigo: findings from the REVERT patient registry

Objective: Despite the high prevalence of vertigo globally and an acknowledged, but under-reported, effect on an individual's wellbeing, few studies have evaluated the burden on healthcare systems and society. This study was aimed to quantitatively determine the impact of vertigo on healthcare resource use and work productivity. Methods: The economic burden of vertigo was assessed through a multi-country, non interventional, observational registry of vertigo patients: the Registry to Evaluate the Burden of Disease in Vertigo. Patients included were those with a new diagnosis of Meniere's disease, benign paroxysmal positional vertigo, other vertigo of peripheral vestibular origin, or peripheral vestibular vertigo of unknown origin. Results: A total of 4,294 patients at 618 centers in 13 countries were included during the registry. Of the 4,105 patients analyzed, only half were in employment. Among this working patient population, 69.8% had reduced their workload, 63.3% had lost working days, and 4.6% had changed and 5.7% had quit their jobs, due to vertigo symptoms. Use of healthcare services among patients was high. In the 3 months preceding Visit 1, patients used emergency services 0.4 +/- 0.9 times, primary care consultations 1.6 +/- 1.8 times, and specialist consultations 1.4 +/- 2.0 times (all mean +/- SD). A mean of 2.0 +/- 5.4 days/patient was also spent in hospital due to vertigo. Conclusion: In addition to the negative impact on the patient from a humanistic perspective, vertigo has considerable impact on work productivity and healthcare resource use

Cost-effectiveness of pioglitazone in type 2 diabetes patients with a history of macrovascular disease: a German perspective

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Globalisation, ‘Chinese Walls’ and Industrial Labour

Summaries This article analyses how globalisation — in particular China's integration into global trade and investment flows — has affected industrial labour. It is argued that globalisation has led to discernible pressures as a result of the concentration of world market production in the coastal areas and the heavy reliance on reprocessing exports. These pressures have been mediated by the Chinese institutional structure which includes social rules, the institutional legacy of state socialism and the interests and autonomy of governments. The implications for industrial labour of the combination of the pressures from globalisation and the Chinese institutional structure are examined

Do Trait Emotional Intelligence and Dispositional Mindfulness Have a Complementary Effect on the Children's and Adolescents' Emotional States?

Mindfulness is both a non-judgmental and present-centered awareness, which has been applied to reduce negative emotions. On the other hand, Trait Emotional Intelligence (TEI) is the way of how good people perceive their emotional intelligence abilities (perceiving, expressing, understanding, and regulating emotions), which are involved in people's social functioning. This empirical study was designed to analyze whether dispositional mindfulness (DM) and TEI have a potential combined role for children and adolescent's emotional states. In a sample of primary school students (N = 318), age ranged from 8 to 16 years old (M = 11.25, SD = 2.20), participants filled a TEI measure (ESCQ, Emotional skills and competence questionnaire) and two measures of DM (CAMM, Child and Adolescent Mindfulness Measure and AFQ-Y, Avoidance and Fusion Questionnaire for Youth). Measures selected included: PANAS (Positive affect and negative affect schedule), White Bear Suppression Inventory (a thought suppression inventory), and STAIC (State-Trait Anxiety for Children). Findings pointed out that TEI measures (labeling and expression, understanding, and managing emotions) were positively and significantly related to positive emotional states (especially, positive affect and balance) and negatively with a lower association with state anxiety. However, DM measures were both negatively and strongly associated with negative emotional states (thought suppression, negative affect, and anxiety). Conclusions indicate that a combined effect of both TEI skills and DM based interventions would be more complete than each one separately for better social functioning of children and teenagers

Purification of antibodies to O antigen of Salmonella Typhimurium from human serum by affinity chromatography

AbstractNontyphoidal Salmonellae (NTS) are a common cause of bacteraemia in children and HIV-infected adults in Sub-Saharan Africa. We have previously shown that antibodies play a key role in both bactericidal and cellular mechanisms of immunity to NTS, but found that high concentrations of antibody to Salmonella Typhimurium O antigen (OAg) in the serum of some HIV-infected African adults is associated with impaired killing of NTS. To further investigate the function of antibodies to the OAg of NTS, we developed a method to purify these antibodies from human serum by affinity chromatography. Purified Salmonella Typhimurium OAg was activated with adipic acid dihydrazide (ADH) via two different chemistries before linking to N-hydroxysuccinamide-Sepharose resin: one ADH molecule was introduced per OAg chain on its terminal 3-deoxy-D-manno-octulosonic acid sugar (OAg–ADH), or multiple ADH molecules were attached along the OAg chain after oxidation with sodium periodate (OAgoxADH). Both resulting columns worked well when tested with commercial polyclonal anti-O:4,5 antibodies from rabbit serum. Over 90% of the applied antibodies bound to the resin and 89% of these antibodies were then eluted as detected by ELISA. OAg–ADH was preferred as the method for OAg derivatisation as it does not modify the saccharide chain and can be applied to OAg from different bacteria. Both columns were able to bind OAg-specific antibodies in human serum, but antibody recovery was initially low. Different elution buffers were tested and different amounts of OAg–ADH were linked to the resin to improve the yield. Optimal recovery (51%) was obtained by loading 1mg of activated OAg per ml of resin and eluting with 0.1M glycine, 0.1M NaCl pH2.4. The column matrix could be regenerated following elution with no detectable loss in performance for over ten uses. This method offers the potential to purify antibodies to Salmonella OAg from polyclonal serum following vaccination or natural exposure to Salmonella and so investigate the functionality and diversity of the antibody response to OAg

Charity Retailing in the UK: A Managerial Capabilities Perspective

Nonprofit organizations are venturing into commercial activities due to the intense competition for the limited government funds and declining availability of donor funds for third sector organizations that address social problems. Charity retailing, a popular choice of commercial activity for nonprofit organization, has filled vacant premises in the high streets of the small towns and suburbs of large cities in the UK. Successful charity retail operation requires distinctive capabilities necessary to manage organizations’ resources in commercial environment. Using sixty in-depth elite interviews, we introduce the concept of managerial capabilities for charity retailing. Research propositions and management implications are discussed

Self-maintaining or continuously refreshed? The genetic structure of Euphausia lucens populations in the Benguela upwelling ecosystem

Populations of Euphausia lucens over the shelf of the southern Benguela upwelling region could be self-maintaining. Alternatively, they could be continually refreshed by expatriates from the SW Atlantic that enter the system via South Atlantic Central Water in the south, before developing and then being lost through advection off Namibia. These two hypotheses are investigated here by examining geographic heterogeneity and molecular variation (cox1 and ND1) of the species across its distributional range in the Southern Hemisphere. Comparisons are made with E. vallentini, which is assumed to show panmixia associated with its circumglobal distribution between 50 and 60°S. Phylogenetic analysis with mitochondrial 16S ribosomal RNA and cytochrome oxidase 1 (cox1) confirmed that E. lucens and E. vallentinirepresent sister taxa. Strong geographic structuring of cox1 and ND1 mtDNA genetic variation by ocean basin was recorded in E. lucens, indicating that neritic populations off South Africa are likely self-maintaining. This contrasts with the results for E. vallentini, which appears to occur as a single panmictic population across its distributional range. These differences are likely related to the habitats (neritic, E. lucens; oceanic, E. vallentini) occupied by each species. The results of the neutrality tests are consistent with demographic processes and suggest growth in E. lucens and equilibrium or shrinkage in E. vallentini. Although purifying selection cannot be ruled out in the former, the very few haplotypes recovered from E. vallentini could indicate that any population expansion following a crash is not yet reflected in the relatively slowly evolving mtDNA markers used here. Further work using other methods is recommended.Web of Scienc