Evaluation of an alternative transport initiative in Perth, Western Australia 2000-2004

Issue addressed: Perth Western Australia, has the highest proportion of per capita car ownership in Australia. Despite the various health, environmental and traffic-related benefits, the uptake of alternative forms of transportation such as walking, cycling and public transport are low.Methods: In response to a growing reliance on motorised transport, the Department for Planning and Infrastructure's (DPI's) Cycling Unit conducts an annual Bike to Work Breakfast to promote cycling as a viable form of transport to work. During this event a short cross sectional survey is distributed to assess the usual cycling behaviours of attendees. Topical issues relating to cycling are also investigated.Results: Results from the 2004 survey indicated that the majority of respondents cycled at least 2-3 times per week (85%) to improve fitness (88%), for enjoyment (70%) and because it was a cost effective means of transport (45%). Most of the respondents (92%) supported the need for more cycle friendly infrastructure such as advanced stop lines at intersections and safety measures such as wearing cycle helmets (85%). These findings were consistent with results from similar surveys conducted between 2000 and 2003.Conclusions: The DPI's Bike to Work Breakfast is a popular event within the cycling calendar that provides the opportunity to gain a snapshot of cycling behaviours and attitudes of cyclists. Prior consultation with the evaluators in the developed of the survey instrument has the potential to investigate barriers and enablers to cycling on a regular basis. Age and gender differences could also be explored

Computational design-of-experiment unveils the conformational reaction coordinate of GH125 α-mannosidases

Conformational analysis of enzyme-catalyzed mannoside hydrolysis has revealed two predominant conformational itineraries through B 2,5 or 3H 4 transitionstate (TS) conformations. A prominent unassigned catalytic itinerary is that of exo-1,6-α-mannosidases belonging to CAZy family 125. A published complex of Clostridium perfringens GH125 enzyme with a nonhydrolyzable 1,6-α-thiomannoside substrate mimic bound across the active site revealed an undistorted 4 C 1 conformation and provided no insight into the catalytic pathway of this enzyme. We show through a purely computational approach (QM/MM metadynamics) that sulfur-for-oxygen substitution in the glycosidic linkage fundamentally alters the energetically accessible conformational space of a thiomannoside when bound within the GH12S active site. Modeling of the conformational free energy landscape (FEL) of a thioglycoside strongly favors a mechanistically uninformative 4 C 1 conformation within the GH125 enzyme active site, but the FEL of corresponding O-glycoside substrate reveals a preference for a Michaelis complex in an oS 2 conformation (consistent with catalysis through a B 2,5 TS). This prediction was tested experimentally by determination of the 3D X-ray structure of the pseudo-Michaelis complex of an inactive (D220N) variant of C. perfringens GH125 enzyme in complex with 1,6-α-mannobiose. This complex revealed unambiguous distortion of the -1 subsite mannoside to an oS 2 conformation, matching that predicted by theory and supporting an oS 2 → B 2,5 → 1S 5 conformational itinerary for GH125 α-mannosidases. This work highlights the power of the QM/MM approach and identified shortcomings in the use of nonhydrolyzable substrate analogues for conformational analysis of enzymebound species

Dantu blood group erythrocytes form large Plasmodium falciparum rosettes less commonly

Dantu erythrocytes, which express a hybrid glycophorin B/A protein, are protective against severe malaria. Recent studies have shown that Dantu impairs Plasmodium falciparum invasion by increasing erythrocyte membrane tension, but its effects on pathological host–parasite adhesion interactions such as rosetting, the binding of uninfected erythrocytes to P. falciparum–infected erythrocytes, have not been investigated previously. The expression of several putative host rosetting receptors—including glycophorin A (GYPA), glycophorin C (GYPC), complement receptor 1 (CR1), and band 3, which complexes with GYPA to form the Wrightb blood group antigen—are altered on Dantu erythrocytes. Here, we compare receptor expression, and rosetting at both 1 hour and 48 hours after mixing with mature trophozoite-stage Kenyan laboratory–adapted P. falciparum strain 11019 parasites in Dantu and non-Dantu erythrocytes. Dantu erythrocytes showed lower staining for GYPA and CR1, and greater staining for band 3, as observed previously, whereas Wrightb and GYPC staining did not vary significantly. No significant between-genotype differences in rosetting were seen after 1 hour, but the percentage of large rosettes was significantly less in both Dantu heterozygous (mean, 16.4%; standard error of the mean [SEM], 3.2) and homozygous donors (mean, 15.4%; SEM, 1.4) compared with non-Dantu erythrocytes (mean, 32.9%; SEM, 7.1; one-way analysis of variance, P = 0.025) after 48 hours. We also found positive correlations between erythrocyte mean corpuscular volume (MCV), the percentage of large rosettes (Spearman’s rs = 0.5970, P = 0.0043), and mean rosette size (rs = 0.5206, P = 0.0155). Impaired rosetting resulting from altered erythrocyte membrane receptor expression and reduced MCV might add to the protective effect of Dantu against severe malaria

Distortion of mannoimidazole supports a B 2,5 boat transition state for the family GH125 α-1,6-mannosidase from Clostridium perfringens

Enzyme transition-state mimics can act as powerful inhibitors and allow structural studies that report on the conformation of the transition-state. Here, mannoimidazole, a mimic of the transition state of mannosidase catalyzed hydrolysis of mannosides, is shown to bind in a B2,5 conformation on the Clostridium perfringens GH125 α-1,6-mannosidase, providing additional evidence of a OS2-B2,5-1S5 conformational itinerary for enzymes of this family

Mannosidase mechanism : at the intersection of conformation and catalysis

Mannosidases are a diverse group of enzymes that are important in the biological processing of mannose-containing polysaccharides and complex glycoconjugates. They are found in 12 of the >160 sequence-based glycosidase families. We discuss evidence that nature has evolved a small set of common mechanisms that unite almost all of these mannosidase families. Broadly, mannosidases (and the closely related rhamnosidases) perform catalysis through just two conformations of the oxocarbenium ion-like transition state: a B2,5 (or enantiomeric 2,5B) boat and a 3H4 half-chair. This extends to a new family (GT108) of GDPMan-dependent β-1,2-mannosyltransferases/phosphorylases that perform mannosyl transfer through a boat conformation as well as some mannosidases that are metalloenzymes and require divalent cations for catalysis. Yet, among this commonality lies diversity. New evidence shows that one unique family (GH99) of mannosidases use an unusual mechanism involving anchimeric assistance via a 1,2-anhydro sugar (epoxide) intermediate

The Role of Biosecurity in the Control of Campylobacter: A Qualitative Study of the Attitudes and Perceptions of UK Broiler Farm Workers

Campylobacter is the leading cause of human bacterial diarrhoeal disease worldwide, with poultry meat products contributing to a large proportion of cases. Due to the ubiquitous presence of Campylobacter in the poultry farm environment, biosecurity is the main area for intervention to prevent colonisation of commercial broiler chicken flocks. However, research has repeatedly demonstrated that farmers' uptake of biosecurity recommendations is often poor. This study explored farmers' attitudes towards biosecurity and identified barriers to effective implementation of biosecurity protocols. Semi-structured interviews were conducted with 1–3 members of staff on each of 16 broiler farms; 6 owned by, and 10 contracted to, 3 different UK poultry integrators. In total, 28 interviewees participated, including farm owners, managers, and workers, with a range of industry experience. Thematic analysis of the interviews revealed high levels of recognition amongst broiler farmers of the importance of Campylobacter and the responsibility of the whole farm-to-fork chain within the poultry industry to reduce Campylobacter contamination of chicken meat for the benefit of public health. Participants' self-reported awareness and implementation of biosecurity has improved significantly following the industry-wide focus on Campylobacter control. However, there are frustrations with the industry's approach to tackling Campylobacter and the heavy burden of responsibility that has been put on interventions at the farm-level. There was also scepticism amongst participants as to the effectiveness of current biosecurity measures in the reduction of Campylobacter. Nevertheless, the interviewees' recognition of the benefit of improved biosecurity on broiler health and welfare and other important targets, such as reducing antimicrobial usage, leaves a legacy of which the UK broiler industry can be proud. There is scope for further farmer education about the evidence supporting biosecurity interventions, particularly in the control of Campylobacter, and a need to establish more effective channels of communication. Furthermore, to give all players within the industry agency and investment in industry targets, contributions from all levels should be permitted in the design of future biosecurity interventions. Biosecurity compliance may be improved through collaborative efforts, such as participatory and co-design practises, to facilitate knowledge co-creation and exchange

Risk of Adverse Cognitive or Behavioral Conditions and Psychiatric Disorders: Evidence Report

In April 2010, President Obama declared a space pioneering goal for the United States in general and NASA in particular. "Fifty years after the creation of NASA, our goal is no longer just a destination to reach. Our goal is the capacity for people to work and learn and operate and live safely beyond the Earth for extended periods of time, ultimately in ways that are more sustainable and even indefinite." Thus NASA's Strategic Objective 1.1 emerged as "expand human presence into the solar system and to the surface of Mars to advance exploration, science, innovation, benefits to humanity, and international collaboration" (NASA 2015b). Any space flight, be it of long or short duration, occurs in an extreme environment that has unique stressors. Even with excellent selection methods, the potential for behavioral problems among space flight crews remain a threat to mission success. Assessment of factors that are related to behavioral health can help minimize the chances of distress and, thus, reduce the likelihood of adverse cognitive or behavioral conditions and psychiatric disorders arising within a crew. Similarly, countermeasures that focus on prevention and treatment can mitigate the cognitive or behavioral conditions that, should they arise, would impact mission success. Given the general consensus that longer duration, isolation, and confined missions have a greater risk for behavioral health ensuring crew behavioral health over the long term is essential. Risk, which within the context of this report is assessed with respect to behavioral health and performance, is addressed to deter development of cognitive and behavioral degradations or psychiatric conditions in space flight and analog populations, and to monitor, detect, and treat early risk factors, predictors and other contributing factors. Based on space flight and analog evidence, the average incidence rate of an adverse behavioral health event occurring during a space mission is relatively low for the current conditions. While mood and anxiety disturbances have occurred, no behavioral emergencies have been reported to date in space flight. Anecdotal and empirical evidence indicate that the likelihood of an adverse cognitive or behavioral condition or psychiatric disorder occurring greatly increases with the length of a mission. Further, while cognitive, behavioral, or psychiatric conditions might not immediately and directly threaten mission success, such conditions can, and do, adversely impact individual and crew health, welfare, and performance