Can primaquine therapy for vivax malaria be improved?

The incidence and range of endemic malaria caused by Plasmodium vivax has expanded during the past 30 years. This parasite forms hypnozoites in the liver, creating a persistent reservoir of infection. Primaquine (PQ), introduced 50 years ago, is the only drug available to eliminate hypnozoites. However, lengthy treatment courses and follow-up periods are not conducive to assessing the effectiveness of this drug in preventing relapses. Resistance to standard therapy could be widespread. Studies are urgently needed to gauge this problem and to determine the safety, tolerability and efficacy of shorter courses and higher doses of PQ.     

Can museum egg specimens be used for proteomic analyses?

Background  

Mass spectrometry and proteomic analyses have become powerful tools for the analysis of proteins and peptides. Investigation of proteins contained in the various layers of the avian eggshell has focused entirely on domesticated species. It has been widely assumed that this existing research can inform the study of wild bird species despite the fact that the vast majority of the diversity in avian species (~95%) exists outside the Orders to which domestic and poultry species belong. Museum collections offer a potentially valuable source of material for studying composition of wild avian eggshell matrix proteins. We used museum and fresh eggshells of common quails Coturnix coturnix to compare the protein composition of their organic matrices. Four eggs of domestic chickens were analysed simultaneously as a control for comparison to the fresh and museum quail eggs. The determination of the proteins was carried out using enzymatic cleavage followed by high-performance mass spectrometry.     

Can a reductionist be a pluralist?

Pluralism is often put forth as a counter-position to reductionism. In this essay, I argue that reductionism and pluralism are in fact consistent. I propose that there are several potential goals for reductions and that the proper form of a reduction should be considered in tandem with the goal that it aims to achieve. This insight provides a basis for clarifying what version(s) of reductionism are currently defended, for explicating the notion of a fundamental level of explanation, and for showing how one can be both a reductionist and a pluralist.     

Can intraspecific brood parasitism be detected using egg morphology only?

Intraspecific brood parasites lay their eggs in the nests of conspecifics. There are a number of methods for detecting intraspecific brood parasitism (IBP) in birds based on egg morphology. Here we test Eadie's (1989) method, which calculates the Euclidean distances between eggs in a given clutch in a three-dimensional space (weight, length and width). A parasitised clutch is predicted to contain an egg (or eggs) that is significantly different from the clutch's other eggs. Data from three species were analysed. Our captive zebra finch Taeniopygia guttata clutches did not include any instances of IBP, the wild jackdaw Corvus monedula data were unlikely to contain any, and for the goldeneye Bucephala clangula data set we had an observational estimate of IBP. We simulated IBP in the zebra finch, jackdaw and goldeneye data to test whether the method reliably detects an experimentally 'parasitised' clutch. We show that the distributions of the test statistics greatly overlap in 'parasitised' and unmodified clutches, and are dependent on the clutch size. We therefore conclude that the method can only be used with caution, after calibrating it for a given population.     

Can estimates of antimalarial efficacy from field studies be improved?

Monitoring therapeutic efficacy of antimalarial drugs is important because treatment failure rates are the primary basis for changing antimalarial treatment policy. An important aspect of efficacy studies is the use of PCR genotyping to distinguish recrudescent from new infections. The conclusions reached using this technique might be misleading if there is insufficient parasite diversity or a non-uniform haplotype frequency distribution in the study area. Statistical techniques can be used to overcome this problem, but only when data describing the haplotype frequency distribution are available. Therefore, assessing haplotype frequency and distribution should form an integral part of all studies investigating the therapeutic efficacy of antimalarial treatment regimes.     

Can asthma control be improved by understanding the patient's perspective?

Background

Clinical trials show that asthma can be controlled in the majority of patients, but poorly controlled asthma still imposes a considerable burden. The level of asthma control achieved reflects the behaviour of both healthcare professionals and patients. A key challenge for healthcare professionals is to help patients to engage in self-management behaviours with optimal adherence to appropriate treatment. These issues are particularly relevant in primary care, where most asthma is managed. An international panel of experts invited by the International Primary Care Respiratory Group considered the evidence and discussed the implications for primary care practice.

Discussion

Causes of poor control Clinical factors such as exposure to triggers and concomitant rhinitis are important but so are patient behavioural factors. Behaviours such as smoking and nonadherence may reduce the efficacy of treatment and patients' perceptions influence these behaviours. Perceptual barriers to adherence include doubting the need for treatment when symptoms are absent and concerns about potential adverse effects. Under-treatment may also be related to patients' underestimation of the significance of symptoms, and lack of awareness of achievable control. Implications Three key implications for healthcare professionals emerged from the debate. First, the need for simple tools to assess asthma control. Two approaches considered were the monitoring of biometric markers of control and questionnaires to record patient-reported outcomes. Second, to understand the reasons for poor control for individual patients, identifying both clinical (e.g. rhinitis) and behavioural factors (e.g. smoking and nonadherence to treatment). Third was the need to incorporate, within asthma review, an assessment of patient perspectives including their goals and aspirations and to elicit their beliefs and concerns about asthma and its treatment. This can be used as a basis for agreement between the healthcare professional and patient on a predefined target regarding asthma control and a treatment plan to achieve this.

Summary

Optimum review of asthma is essential to improve control. A key priority is the development of simple and effective tools for identifying poor control for individual patients coupled with a tailored approach to treatment to enable patients to set and achieve realistic goals for asthma control.     

Can polymorphism be maintained by selection favouring an intermediate optimum phenotype?

Populations of Drosophila melanogaster containing the special chromosome, M-5, were subjected to artificial selection to canalise scutellar bristle phenotype at four bristles. At the end of the experiment allele frequencies at three enzyme loci were measured. In the selected population, these frequencies were found to have diverged from their starting values less than would have been predicted on the basis of random genetic drift. This was not found in control populations or in populations selected for low bristle number.     

Can models of density-dependent habitat selection be applied for trap-building predators?

Density-dependent habitat selection theory was mainly tested on active foragers and therefore its applicability to trap-building predators is poorly understood. The high sensitivity of trap-building predators to changes in their physical environment, combined with their limited movement capability, can lead to habitat specialization, reducing their utilization of alternative habitats. We studied density-dependent habitat selection in two pit-building antlions, differing in their habitat utilization spectrum. The habitat generalist, Myrmeleon hyalinus, inhabits and performs equally well in both sand- and loess-derived soils, although preferring the former, more productive coarse-grained soils. In contrast, the habitat specialist, Cueta lineosa, only inhabits fine-grained soils such as loess, while showing reduced foraging performance in coarse-grained sandy soils. We allowed larvae to select between these two soils, while manipulating con-specific density and initial stocking position. Irrespective of the initial stocking position, the number of M. hyalinus pits in the sand was positively correlated with the number of con-specific pits in the loess, implying that this species is a density-dependent habitat selector. Furthermore, these patterns of density-dependence were consistent with the expectations of ideal pre-emptive distribution (i.e., strong non-linearity in the distribution of antlions between soils with increased total density), suggesting that interference competition largely dictates habitat selection in this species. In contrast, the habitat specialist showed constant habitat selectivity, as neither con-specific density nor initial stocking positions influenced its habitat preference. Although mainly tested on active foragers, habitat selection theory can be applicable for trap-building predators, demonstrating how mechanisms operating at the individual level influence spatial distribution patterns.     

Can zebrafish be used as a model to study the neurodevelopmental causes of autism?

The zebrafish has proven to be an excellent model for analyzing issues of vertebrate development. In this review we ask whether the zebrafish is a viable model for analyzing the neurodevelopmental causes of autism. In developing an answer to this question three topics are considered. First, the general attributes of zebrafish as a model are discussed, including low cost maintenance, rapid life cycle and the multitude of techniques available. These techniques include large-scale genetic screens, targeted loss and gain of function methods, and embryological assays. Second, we consider the conservation of zebrafish and mammalian brain development, structure and function. Third, we discuss the impressive use of zebrafish as a model for human disease, and suggest several strategies by which zebrafish could be used to dissect the genetic basis for autism. We conclude that the zebrafish system could be used to make important contributions to understanding autistic disorders.     

Can a cell be assembled from its constituents?

To date, available are a provisional list of the minimal set of genes required for the functioning and multiplication of a living cell under maximally favorable conditions, methods for the complete chemical synthesis of the minimal genome, and cell-free systems for carrying out all the biochemical reactions comprising the genome replication and expression. The most serious problem that remains on the way to creating an artificial living cell is the need to meet two apparently incompatible requirements: separation of the biochemical reactions from the environment, and exchange between the environment and the cell. A solution to this problem can be provided by molecular colonies (other names: nanocolonies, polonies), which form when RNA or DNA is replicated in a solid medium having pores of a nanometer size. Molecular colonies might also have served as a pre-cellular form of compartmentalization in the RNA World.     

Can a collapse of global civilization be avoided?

Environmental problems have contributed to numerous collapses of civilizations in the past. Now, for the first time, a global collapse appears likely. Overpopulation, overconsumption by the rich and poor choices of technologies are major drivers; dramatic cultural change provides the main hope of averting calamity.     

Will genomic selection be a practical method for plant breeding?

Background

Genomic selection or genome-wide selection (GS) has been highlighted as a new approach for marker-assisted selection (MAS) in recent years. GS is a form of MAS that selects favourable individuals based on genomic estimated breeding values. Previous studies have suggested the utility of GS, especially for capturing small-effect quantitative trait loci, but GS has not become a popular methodology in the field of plant breeding, possibly because there is insufficient information available on GS for practical use.

Scope

In this review, GS is discussed from a practical breeding viewpoint. Statistical approaches employed in GS are briefly described, before the recent progress in GS studies is surveyed. GS practices in plant breeding are then reviewed before future prospects are discussed.

Conclusions

Statistical concepts used in GS are discussed with genetic models and variance decomposition, heritability, breeding value and linear model. Recent progress in GS studies is reviewed with a focus on empirical studies. For the practice of GS in plant breeding, several specific points are discussed including linkage disequilibrium, feature of populations and genotyped markers and breeding scheme. Currently, GS is not perfect, but it is a potent, attractive and valuable approach for plant breeding. This method will be integrated into many practical breeding programmes in the near future with further advances and the maturing of its theory.Key words: Genomic selection, plant breeding, marker assisted selection, genetic model, linkage disequilibrium     

Variable selection on Eurosta's gall size,III: Can an evolutionary response to selection be detected?

Standard quantitative genetic theory predicts that when a trait is exposed to selection, the between-generation change in the phenotypic mean, Δz?_i, will be equal to the product of the trait's heritability and the selection differential, h²S. By extension, this theory implies that if a number of replicate populations are exposed to varying intensities of selection, the between-generation changes in means should covary with the selection differential applied. This relationship offers an opportunity for a statistical test to detect evolutionary change when selection is measured in replicate populations. If an evolutionary response to phenotypic selection occurs, the regression of over S_i, where i indicates population, will have a positive slope. This statistical test was applied to data on the insect Eurosta solidaginis (Diptera: Tephritidae). The larvae of this fly induce galls on the stems of the host plant, Solidago altissima (Asteraceae). Previous work has shown that gall size is a heritable trait of the insect. Further, size-dependent attack on Eurosta larvae by parasitoids selects for larger gall size (Weis and Abrahamson, 1986). Long-term data on phenotypic selection in 16 populations across 5 generations were analyzed for selection response. Apparent upward evolutionary responses were seen in 2 of the 4 between-generation transitions. However, no response was seen when the analysis was applied to the cumulative change in gall size. Examination of the data suggested that some of the change in mean gall size was a developmental response to spatial and temporal variation in the environment. Non-linear developmental effects of environment, when combined with non-linear fitness functions, can induce a spurious selection response; these non-linear relationships can account for the apparent evolutionary change gall size found in the by-generation analysis. Thus, there is no reliable evidence for evolutionary change in Eurosta's gall size over the generations studied. Stasis of gall size in the face of ongoing selection may be due to counterbalancing selection on the gallmaker imposed by host plant resistance.