Community perceptions of a malaria vaccine in the Kintampo districts of Ghana.

BACKGROUND: Malaria remains the leading cause of morbidity and mortality in sub-Saharan Africa despite tools currently available for its control. Making malaria vaccine available for routine use will be a major hallmark, but its acceptance by community members and health professionals within the health system could pose considerable challenge as has been found with the introduction of polio vaccinations in parts of West Africa. Some of these challenges may not be expected since decisions people make are many a time driven by a complex myriad of perceptions. This paper reports knowledge and perceptions of community members in the Kintampo area of Ghana where malaria vaccine trials have been ongoing as part of the drive for the first-ever licensed malaria vaccine in the near future. METHODS: Both qualitative and quantitative methods were used in the data collection processes. Women and men whose children were or were not involved in the malaria vaccine trial were invited to participate in focus group discussions (FGDs). Respondents, made up of heads of religious groupings in the study area, health care providers, traditional healers and traditional birth attendants, were also invited to participate in in-depth interviews (IDIs). A cross-sectional survey was conducted in communities where the malaria vaccine trial (Mal 047RTS,S) was carried out. In total, 12 FGDs, 15 IDIs and 466 household head interviews were conducted. RESULTS: Knowledge about vaccines was widespread among participants. Respondents would like their children to be vaccinated against all childhood illnesses including malaria. Knowledge of the long existing routine vaccines was relatively high among respondents compared to hepatitis B and Haemophilus influenza type B vaccines that were introduced more recently in 2002. There was no clear religious belief or sociocultural practice that will serve as a possible barrier to the acceptance of a malaria vaccine. CONCLUSION: With the assumption that a malaria vaccine will be as efficacious as other EPI vaccines, community members in Central Ghana will accept and prefer malaria vaccine to malaria drugs as a malaria control tool. Beliefs and cultural practices as barriers to the acceptance of malaria vaccine were virtually unknown in the communities surveyed

Co-assortment in integron-associated gene cassette assemblages in environmental DNA samples

<p>Abstract</p> <p>Background</p> <p>It has been shown that integron-associated gene cassettes exist largely in tandem arrays of variable size, ranging from antibiotic resistance arrays of three to five cassettes up to arrays of more than 100 cassettes associated with the vibrios. Further, the ecology of the integron/gene cassette system has been investigated by showing that very many different cassettes are present in even small environmental samples. In this study, we seek to extend the ecological perspective on the integron/gene cassette system by investigating the way in which this diverse cassette metagenome is apportioned amongst prokaryote lineages in a natural environment.</p> <p>Results</p> <p>We used a combination of PCR-based techniques applied to environmental DNA samples and ecological analytical techniques to establish co-assortment within cassette populations, then establishing the relationship between this co-assortment and genomic structures. We then assessed the distribution of gene cassettes within the environment and found that the majority of gene cassettes existed in large co-assorting groups.</p> <p>Conclusions</p> <p>Our results suggested that the gene cassette diversity of a relatively pristine sampling environment was structured into co-assorting groups, predominantly containing large numbers of cassettes per group. These co-assorting groups consisted of different gene cassettes in stoichiometric relationship. Conservatively, we then attributed co-assorting cassettes to the gene cassette complements of single prokaryote lineages and by implication, to large integron-associated arrays. The prevalence of large arrays in the environment raises new questions about the assembly, maintenance and utility of large cassette arrays in prokaryote populations.</p

Predictability of evolutionary trajectories in fitness landscapes

Experimental studies on enzyme evolution show that only a small fraction of all possible mutation trajectories are accessible to evolution. However, these experiments deal with individual enzymes and explore a tiny part of the fitness landscape. We report an exhaustive analysis of fitness landscapes constructed with an off-lattice model of protein folding where fitness is equated with robustness to misfolding. This model mimics the essential features of the interactions between amino acids, is consistent with the key paradigms of protein folding and reproduces the universal distribution of evolutionary rates among orthologous proteins. We introduce mean path divergence as a quantitative measure of the degree to which the starting and ending points determine the path of evolution in fitness landscapes. Global measures of landscape roughness are good predictors of path divergence in all studied landscapes: the mean path divergence is greater in smooth landscapes than in rough ones. The model-derived and experimental landscapes are significantly smoother than random landscapes and resemble additive landscapes perturbed with moderate amounts of noise; thus, these landscapes are substantially robust to mutation. The model landscapes show a deficit of suboptimal peaks even compared with noisy additive landscapes with similar overall roughness. We suggest that smoothness and the substantial deficit of peaks in the fitness landscapes of protein evolution are fundamental consequences of the physics of protein folding.Comment: 14 pages, 7 figure

Gene cassette transcription in a large integron-associated array

<p>Abstract</p> <p>Background</p> <p>The integron/gene cassette system is a diverse and effective adaptive resource for prokaryotes. Short cassette arrays, with less than 10 cassettes adjacent to an integron, provide this resource through the expression of cassette-associated genes by an integron-borne promoter. However, the advantage provided by large arrays containing hundreds of cassettes is less obvious. In this work, using the 116-cassette array of <it>Vibrio </it>sp. DAT722 as a model, we investigated the theory that the majority of genes contained within large cassette arrays are widely expressed by intra-array promoters in addition to the integron-borne promoter.</p> <p>Results</p> <p>We demonstrated that the majority of the cassette-associated genes in the subject array were expressed. We further showed that cassette expression was conditional and that the conditionality varied across the array. We finally showed that this expression was mediated by a diversity of cassette-borne promoters within the array capable of responding to environmental stressors.</p> <p>Conclusions</p> <p>Widespread expression within large gene cassette arrays could provide an adaptive advantage to the host in proportion to the size of the array. Our findings explained the existence and maintenance of large cassette arrays within many prokaryotes. Further, we suggested that repeated rearrangement of cassettes containing genes and/or promoters within large arrays could result in the assembly of operon-like groups of co-expressed cassettes within an array. These findings add to our understanding of the adaptive repertoire of the integron/gene cassette system in prokaryotes and consequently, the evolutionary impact of this system.</p

An experimental test of non-local realism

Most working scientists hold fast to the concept of 'realism' - a viewpoint according to which an external reality exists independent of observation. But quantum physics has shattered some of our cornerstone beliefs. According to Bell's theorem, any theory that is based on the joint assumption of realism and locality (meaning that local events cannot be affected by actions in space-like separated regions) is at variance with certain quantum predictions. Experiments with entangled pairs of particles have amply confirmed these quantum predictions, thus rendering local realistic theories untenable. Maintaining realism as a fundamental concept would therefore necessitate the introduction of 'spooky' actions that defy locality. Here we show by both theory and experiment that a broad and rather reasonable class of such non-local realistic theories is incompatible with experimentally observable quantum correlations. In the experiment, we measure previously untested correlations between two entangled photons, and show that these correlations violate an inequality proposed by Leggett for non-local realistic theories. Our result suggests that giving up the concept of locality is not sufficient to be consistent with quantum experiments, unless certain intuitive features of realism are abandoned.Comment: Minor corrections to the manuscript, the final inequality and all its conclusions do not change; description of corrections (Corrigendum) added as new Appendix III; Appendix II replaced by a shorter derivatio

Entangled Mechanical Oscillators

Hallmarks of quantum mechanics include superposition and entanglement. In the context of large complex systems, these features should lead to situations like Schrodinger's cat, which exists in a superposition of alive and dead states entangled with a radioactive nucleus. Such situations are not observed in nature. This may simply be due to our inability to sufficiently isolate the system of interest from the surrounding environment -- a technical limitation. Another possibility is some as-of-yet undiscovered mechanism that prevents the formation of macroscopic entangled states. Such a limitation might depend on the number of elementary constituents in the system or on the types of degrees of freedom that are entangled. One system ubiquitous to nature where entanglement has not been previously demonstrated is distinct mechanical oscillators. Here we demonstrate deterministic entanglement of separated mechanical oscillators, consisting of the vibrational states of two pairs of atomic ions held in different locations. We also demonstrate entanglement of the internal states of an atomic ion with a distant mechanical oscillator.Comment: 7 pages, 2 figure

The Epstein-Barr Virus G-Protein-Coupled Receptor Contributes to Immune Evasion by Targeting MHC Class I Molecules for Degradation

Epstein-Barr virus (EBV) is a human herpesvirus that persists as a largely subclinical infection in the vast majority of adults worldwide. Recent evidence indicates that an important component of the persistence strategy involves active interference with the MHC class I antigen processing pathway during the lytic replication cycle. We have now identified a novel role for the lytic cycle gene, BILF1, which encodes a glycoprotein with the properties of a constitutive signaling G-protein-coupled receptor (GPCR). BILF1 reduced the levels of MHC class I at the cell surface and inhibited CD8+ T cell recognition of endogenous target antigens. The underlying mechanism involves physical association of BILF1 with MHC class I molecules, an increased turnover from the cell surface, and enhanced degradation via lysosomal proteases. The BILF1 protein of the closely related CeHV15 c1-herpesvirus of the Rhesus Old World primate (80% amino acid sequence identity) downregulated surface MHC class I similarly to EBV BILF1. Amongst the human herpesviruses, the GPCR encoded by the ORF74 of the KSHV c2-herpesvirus is most closely related to EBV BILF1 (15% amino acid sequence identity) but did not affect levels of surface MHC class I. An engineered mutant of BILF1 that was unable to activate G protein signaling pathways retained the ability to downregulate MHC class I, indicating that the immune-modulating and GPCR-signaling properties are two distinct functions of BILF1. These findings extend our understanding of the normal biology of an important human pathogen. The discovery of a third EBV lytic cycle gene that cooperates to interfere with MHC class I antigen processing underscores the importance of the need for EBV to be able to evade CD8+ T cell responses during the lytic replication cycle, at a time when such a large number of potential viral targets are expressed

The pathophysiology of malarial anaemia: where have all the red cells gone?

Malarial anaemia is an enormous public health problem in endemic areas and occurs predominantly in children in the first 3 years of life. Anaemia is due to both a great increase in clearance of uninfected cells and a failure of an adequate bone marrow response. Odhiambo, Stoute and colleagues show how the age distribution of malarial anaemia and the haemolysis of red blood cells may be linked by an age-dependent increase in the capacity of red blood cells to inactivate complement components absorbed or deposited directly on to the surface of the red blood cell. In this commentary, we discuss what has been established about the role of complement deposition on the surface of red blood cells in the pathology of malarial anaemia, how genetic polymorphisms of the complement control proteins influence the outcome of malaria infection and how the findings of Odhiambo, Stoute and colleagues and others shed light on the puzzling age distribution of different syndromes of severe malaria

No Detectable Fertility Benefit from a Single Additional Mating in Wild Stalk-Eyed Flies

Background: Multiple mating by female insects is widespread, and the explanation(s) for repeated mating by females has been the subject of much discussion. Females may profit from mating multiply through direct material benefits that increase their own reproductive output, or indirect genetic benefits that increase offspring fitness. One particular direct benefit that has attracted significant attention is that of fertility assurance, as females often need to mate multiply to achieve high fertility. This hypothesis has never been tested in a wild insect population.Methodology/Principal Findings: Female Malaysian stalk-eyed flies (Teleopsis dalmanni) mate repeatedly during their lifetime, and have been shown to be sperm limited under both laboratory and field conditions. Here we ask whether receiving an additional mating alleviates sperm limitation in wild females. In our experiment one group of females received a single additional mating, while a control group received an interrupted, and therefore unsuccessful, mating. Females that received an additional mating did not lay more fertilised eggs in total, nor did they lay proportionately more fertilised eggs. Female fertility declined significantly through time, demonstrating that females were sperm limited. However, receipt of an additional mating did not significantly alter the rate of this decline.Conclusions/Significance: Our data suggest that the fertility consequences of a single additional mating were small. We discuss this effect (or lack thereof), and suggest that it is likely to be attributed to small ejaculate size, a high proportion of failed copulations, and the presence of X-linked meiotic drive in this species