Mycolactone Diffuses into the Peripheral Blood of Buruli Ulcer Patients - Implications for Diagnosis and Disease Monitoring.

BACKGROUND: Mycobacterium ulcerans, the causative agent of Buruli ulcer (BU), is unique among human pathogens in its capacity to produce a polyketide-derived macrolide called mycolactone, making this molecule an attractive candidate target for diagnosis and disease monitoring. Whether mycolactone diffuses from ulcerated lesions in clinically accessible samples and is modulated by antibiotic therapy remained to be established. METHODOLOGY/PRINCIPAL FINDING: Peripheral blood and ulcer exudates were sampled from patients at various stages of antibiotic therapy in Ghana and Ivory Coast. Total lipids were extracted from serum, white cell pellets and ulcer exudates with organic solvents. The presence of mycolactone in these extracts was then analyzed by a recently published, field-friendly method using thin layer chromatography and fluorescence detection. This approach did not allow us to detect mycolactone accurately, because of a high background due to co-extracted human lipids. We thus used a previously established approach based on high performance liquid chromatography coupled to mass spectrometry. By this means, we could identify structurally intact mycolactone in ulcer exudates and serum of patients, and evaluate the impact of antibiotic treatment on the concentration of mycolactone. CONCLUSIONS/SIGNIFICANCE: Our study provides the proof of concept that assays based on mycolactone detection in serum and ulcer exudates can form the basis of BU diagnostic tests. However, the identification of mycolactone required a technology that is not compatible with field conditions and point-of-care assays for mycolactone detection remain to be worked out. Notably, we found mycolactone in ulcer exudates harvested at the end of antibiotic therapy, suggesting that the toxin is eliminated by BU patients at a slow rate. Our results also indicated that mycolactone titres in the serum may reflect a positive response to antibiotics, a possibility that it will be interesting to examine further through longitudinal studies

How to make a sex chromosome

Sex chromosomes can evolve once recombination is halted between a homologous pair of chromosomes. Owing to detailed studies using key model systems, we have a nuanced understanding and a rich review literature of what happens to sex chromosomes once recombination is arrested. However, three broad questions remain unanswered. First, why do sex chromosomes stop recombining in the first place? Second, how is recombination halted? Finally, why does the spread of recombination suppression, and therefore the rate of sex chromosome divergence, vary so substantially across clades? In this review, we consider each of these three questions in turn to address fundamental questions in the field, summarize our current understanding, and highlight important areas for future work

Adding a third dimension to the edge of a species’ range: altitude and genetic structuring in mountainous landscapes

In addition to the topographical and ecological barriers, other landscape features may also subtly influence the patterns of gene flow and spatial genetic structuring at species’ borders. This paper focuses on the role played by altitudinal gradients that characterize mountainous landscapes. We formulate and test the hypothesis that when the distribution boundaries of plant species intersect mountainous landscapes, altitudinal gradients in ecological conditions may considerably enhance population subdivision and genetic structuring at the regional level. Using amplified fragment length polymorphism markers, we studied genetic diversity and differentiation in a set of 21 peripheral populations of the evergreen shrub Lavandula latifolia Med. (Labiatae) at its southernmost distribution limit in the Betic mountain ranges of southern Spain. Population size and abundance, and within-population genetic diversity, varied predictably with altitude, being highest at middle elevations and declining steadily towards both the upper and lower altitudinal distribution margins. Genetic differentiation tended to follow the opposite trend. These altitudinal patterns result from variation with elevation in the relative influence of gene flow and drift on the distribution of genetic variation. Genetic drift prevails around the upper and lower altitudinal limits, whereas a situation closer to a drift-gene flow equilibrium exists at the center of the altitudinal distribution. Altitudinal variation in the relative influences of gene flow and drift appears as an essential element in the interpretation of regional genetic structuring of L. latifolia at its mountainous distribution edge, and a factor which may influence the evolutionary potential of peripheral populations and the likelihood of local adaptation.Peer reviewe

Strong gene flow and lack of stable population structure in the face of rapid adaptation to local temperature in a spring-spawning salmonid, the European grayling (Thymallus thymallus)

Gene flow has the potential to both constrain and facilitate adaptation to local environmental conditions. The early stages of population divergence can be unstable because of fluctuating levels of gene flow. Investigating temporal variation in gene flow during the initial stages of population divergence can therefore provide insights to the role of gene flow in adaptive evolution. Since the recent colonization of Lake Lesjaskogsvatnet in Norway by European grayling (Thymallus thymallus), local populations have been established in over 20 tributaries. Multiple founder events appear to have resulted in reduced neutral variation. Nevertheless, there is evidence for local adaptation in early life-history traits to different temperature regimes. In this study, microsatellite data from almost a decade of sampling were assessed to infer population structuring and its temporal stability. Several alternative analyses indicated that spatial variation explained 2–3 times more of the divergence in the system than temporal variation. Over all samples and years, there was a significant correlation between genetic and geographic distance. However, decomposed pairwise regression analysis revealed differing patterns of genetic structure among local populations and indicated that migration outweighs genetic drift in the majority of populations. In addition, isolation by distance was observable in only three of the six years, and signals of population bottlenecks were observed in the majority of samples. Combined, the results suggest that habitat-specific adaptation in this system has preceded the development of consistent population substructuring in the face of high levels of gene flow from divergent environments