Efficacy model for antibody-mediated pre-erythrocytic malaria vaccines

Antibodies to the pre-erythrocytic antigens, circumsporozoite protein (CSP), thrombospondin-related adhesive protein (TRAP) and liver-stage antigen 1, have been measured in field studies of semi-immune adults and shown to correlate with protection from Plasmodium falciparum infection. A mathematical model is formulated to estimate the probability of sporozoite infection as a function of antibody titres to multiple pre-erythrocytic antigens. The variation in antibody titres from field data was used to estimate the relationship between the probability of P. falciparum infection per infectious mosquito bite and antibody titre. Using this relationship, we predict the effect of vaccinations that boost baseline CSP or TRAP antibody titres. Assuming the estimated relationship applies to vaccine-induced antibody titres, then single-component CSP or TRAP antibody-mediated pre-erythrocytic vaccines are likely to provide partial protection from infection, with vaccine efficacy of approximately 50 per cent depending on the magnitude of the vaccine-induced boost to antibody titres. It is possible that the addition of a TRAP component to a CSP-based vaccine such as RTS,S would provide an increase in infection-blocking efficacy of approximately 25 per cent should the problem of immunological interference between antigens be overcome.     

Extent of invasion of Tasmanian native vegetation by the exotic bumblebee Bombus terrestris (Apoidea: Apidae)

Abstract Observations of the large earth bumblebee, Bombus terrestris (L.), in native vegetation were collated to determine the extent to which this exotic species has invaded Tasmanian native vegetation during the first 9 years after its introduction. The range of B. terrestris now encompasses all of Tasmania's major vegetation types, altitudes from sea level to 1260m a.s.L, and the entire breadth of annual precipitation in the state from more than 3200 mm to less than 600 mm. Observations of workers carrying pollen, together with the presence of large numbers of bumblebees at many localities across this range indicate that colonies are frequently established in native vegetation. Evidence that colonies are often successful was obtained from repeated observations of the species during more than 1 year at particular sites. Unequivocal evidence of colonies was obtained from six National Parks, including four of the five in the Tasmanian Wilderness World Heritage Area (WHA). Indeed, the species has been present in the WHA for at least as long as it has in the city of Hobart, where it was first recorded. In southwestern Tasmania, evidence of colonies was obtained up to 40km from gardens, 61 km from small towns and 93 km from large towns. Hence, contrary to previous suggestions, the species is established in the most remote parts of Tasmania and is not dependent on introduced garden plants. Given their strong record of invasion, it is likely that B. terrestris will form feral populations on the mainland of Australia and in many other parts of the world if introduced. Because of their likely negative impacts on native animals and plants, and potential to enhance seed production in weeds, the spread of bumblebees should be avoided.     

A systems interpretation for observations of bird V-formations

Birds in V formations are frequently observed and two main hypotheses have emerged to explain this particular geometry: (i) it offers aerodynamic advantages and (ii) it is used to improve visual communication. Both explanations require a bird to track its predecessor. However, most V-formations observed in nature are small and the distribution of wing-tip spacings has a large variation. This suggests that tracking the lateral position of the preceding bird is a difficult task. Control theorists, when trying to control platoons of vehicles, also noted that predecessor following is difficult. In this paper, we apply a result from systems theory to explain the observations of bird V-formations. The strength of this result is that it does not rely on the details of the bird flight model. Thus we claim that formation flight is inherently difficult for birds.     

ABC Transporters in Saccharomyces cerevisiae and Their Interactors: New Technology Advances the Biology of the ABCC (MRP) Subfamily

Summary: Members of the ATP-binding cassette (ABC) transporter superfamily exist in bacteria, fungi, plants, and animals and play key roles in the efflux of xenobiotic compounds, physiological substrates, and toxic intracellular metabolites. Based on sequence relatedness, mammalian ABC proteins have been divided into seven subfamilies, ABC subfamily A (ABCA) to ABCG. This review focuses on recent advances in our understanding of ABC transporters in the model organism Saccharomyces cerevisiae. We propose a revised unified nomenclature for the six yeast ABC subfamilies to reflect the current mammalian designations ABCA to ABCG. In addition, we specifically review the well-studied yeast ABCC subfamily (formerly designated the MRP/CFTR subfamily), which includes six members (Ycf1p, Bpt1p, Ybt1p/Bat1p, Nft1p, Vmr1p, and Yor1p). We focus on Ycf1p, the best-characterized yeast ABCC transporter. Ycf1p is located in the vacuolar membrane in yeast and functions in a manner analogous to that of the human multidrug resistance-related protein (MRP1, also called ABCC1), mediating the transport of glutathione-conjugated toxic compounds. We review what is known about Ycf1p substrates, trafficking, processing, posttranslational modifications, regulation, and interactors. Finally, we discuss a powerful new yeast two-hybrid technology called integrated membrane yeast two-hybrid (iMYTH) technology, which was designed to identify interactors of membrane proteins. iMYTH technology has successfully identified novel interactors of Ycf1p and promises to be an invaluable tool in future efforts to comprehensively define the yeast ABC interactome.     

Male inclusion in randomized controlled trials of lifestyle weight loss interventions

The prevalence of obesity is similar for men (32.2%) and women (35.5%). It has been assumed that lifestyle weight loss interventions have been developed and tested in predominately female samples, but this has not been systematically investigated. The aim of this review was to investigate total and ethnic male inclusion in randomized controlled trials of lifestyle interventions. PUBMED, MEDLINE, and PSYCHINFO were searched for randomized controlled trials of lifestyle weight loss interventions (N = 244 studies with a total of 95,207 participants) published in the last 10 years (1999-2009). A trial must be in English, included weight loss as an outcome, and tested a dietary, exercise, and/or other behavioral intervention for weight loss. Results revealed samples were on average 27% male vs. 73% female (P < 0.001). Trials recruiting a diseased sample included a larger proportion of males than those not targeting a disease (35% vs. 21%; P < 0.001). About 32% of trials used exclusively female samples, whereas only 5% used exclusively male samples (P < 0.001). No studies in the past 10 years specifically targeted minority males. Ethnic males identified composed 1.8% of total participants in US studies. Only 24% of studies that underrepresented males provided a reason. Males, especially ethnic males, are underrepresented in lifestyle weight loss trials.