An African origin for the intimate association between humans and Helicobacter pylori

Infection of the stomach by Helicobacter pylori is ubiquitous among humans. However, although H. pylori strains from different geographic areas are associated with clear phylogeographic differentiation, the age of an association between these bacteria with humans remains highly controversial. Here we show, using sequences from a large data set of bacterial strains that, as in humans, genetic diversity in H. pylori decreases with geographic distance from east Africa, the cradle of modern humans. We also observe similar clines of genetic isolation by distance (IBD) for both H. pylori and its human host at a worldwide scale. Like humans, simulations indicate that H. pylori seems to have spread from east Africa around 58,000 yr ago. Even at more restricted geographic scales, where IBD tends to become blurred, principal component clines in H. pylori from Europe strongly resemble the classical clines for Europeans described by Cavalli-Sforza and colleagues. Taken together, our results establish that anatomically modern humans were already infected by H. pylori before their migrations from Africa and demonstrate that H. pylori has remained intimately associated with their human host populations ever since.     

A mutation in APP protects against Alzheimer's disease and age-related cognitive decline

The prevalence of dementia in the Western world in people over the age of 60 has been estimated to be greater than 5%, about two-thirds of which are due to Alzheimer's disease. The age-specific prevalence of Alzheimer's disease nearly doubles every 5 years after age 65, leading to a prevalence of greater than 25% in those over the age of 90 (ref. 3). Here, to search for low-frequency variants in the amyloid-β precursor protein (APP) gene with a significant effect on the risk of Alzheimer's disease, we studied coding variants in APP in a set of whole-genome sequence data from 1,795 Icelanders. We found a coding mutation (A673T) in the APP gene that protects against Alzheimer's disease and cognitive decline in the elderly without Alzheimer's disease. This substitution is adjacent to the aspartyl protease β-site in APP, and results in an approximately 40% reduction in the formation of amyloidogenic peptides in vitro. The strong protective effect of the A673T substitution against Alzheimer's disease provides proof of principle for the hypothesis that reducing the β-cleavage of APP may protect against the disease. Furthermore, as the A673T allele also protects against cognitive decline in the elderly without Alzheimer's disease, the two may be mediated through the same or similar mechanisms.     

Diverse mechanisms of feeding and movement in Cyclorrhaphan larvae (Diptera)

Direct observation, filmed behaviour and morphological analysis were used to investigate mechanisms of larval feeding and movement in 20 species of Cyclorrhapha (Diptera). Feeding mechanisms refer to techniques of gathering food close to the pharynx entrance prior to sucking it in. A total of 12 mechanisms were recorded. Contrasting mechanisms were associated with saprophagy, phytophagy, mycophagy and zoophagy. Larvae had role-specific, compartmentalised bodies. The rear compartment grips substrates enabling the front ones to scan for food by sweeping from side to side or up and down. The front compartments extend or lunge to gather food or grip substrates during locomotion. Lower cyclorrhaphans had more disparate mechanisms than higher cyclorrhaphans. In the latter, the size, shape and movements of the thorax, pseudocephalon and head skeleton are diverse. Influences on this diversity are food quality and access conditions at development sites. Movement capabilities and functions were established for many components.     

Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes

Epidemics of drug-resistant bacteria emerge worldwide, even as resistant strains frequently have reduced fitness compared to their drug-susceptible counterparts. Data from model systems suggest that the fitness cost of antimicrobial resistance can be reduced by compensatory mutations; however, there is limited evidence that compensatory evolution has any significant role in the success of drug-resistant bacteria in human populations. Here we describe a set of compensatory mutations in the RNA polymerase genes of rifampicin-resistant M. tuberculosis, the etiologic agent of human tuberculosis (TB). M. tuberculosis strains harboring these compensatory mutations showed a high competitive fitness in vitro. Moreover, these mutations were associated with high fitness in vivo, as determined by examining their relative clinical frequency across patient populations. Of note, in countries with the world's highest incidence of multidrug-resistant (MDR) TB, more than 30% of MDR clinical isolates had this form of mutation. Our findings support a role for compensatory evolution in the global epidemics of MDR TB.     

Common sequence variants on 20q11.22 confer melanoma susceptibility

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.75 (1.53, 2.01), with evidence for stronger association in early-onset cases.     

Improving knowledge of the cyclorrhaphan larva (Diptera)

A significant factor in the evolution of the Cyclorrhapha (Diptera), the most biodiverse of higher dipteran taxa, is the larva. The larva also has wide-ranging trophic and environmental relationships, including positive and negative impacts on human health and wealth. Despite its importance, the larva is neglected and a low proportion of species are known in this stage. In this paper, factors contributing to larval neglect are reviewed, including: poor attitudes leading to cycles of neglect and shallow treatment; taxonomy that uses adult not larval stages; lack of material in collections; rearing barriers, and presumptions of morphological similarity suggesting that characters will be problematic to acquire and analyse. Neglect is pervasive and affects many subjects; those considered here are: species inventories and rarity assessments for biodiversity and conservation, in which larvae are usually ignored although they can be more cost-effective to sample and a richer source of environmental data; determining larval feeding modes where controversies due to conflicting evidence persist unresolved; and reliance on a limited pool of increasingly old publications whose data are repeated rather than tested and updated with new research. In an attempt to reinvigorate interest, which is the main aim of this paper, poorly assessed larval features possibly significant to cyclorrhaphan diversification are also considered. These include: change facilitated by independently evolvable modules; rapid change enabled by labile trophic morphology; shifts between saprophagy and phytophagy due to opportunities provided by angiosperm evolution; and enhanced adaptive potential resulting in derived more than basal taxa developing adaptations that enable access to new and little used resources. Apart from the need to rear more larvae, a major conclusion from this review is that knowledge will improve when the movement capabilities of larvae are used to inform morphological and taxonomic analyses.     

On the history of the Euclidean Steiner tree problem

The history of the Euclidean Steiner tree problem, which is the problem of constructing a shortest possible network interconnecting a set of given points in the Euclidean plane, goes back to Gergonne in the early nineteenth century. We present a detailed account of the mathematical contributions of some of the earliest papers on the Euclidean Steiner tree problem. Furthermore, we link these initial contributions with results from the recent literature on the problem.