Biological and biomedical implications of the co-evolution of pathogens and their hosts

Co-evolution between host and pathogen is, in principle, a powerful determinant of the biology and genetics of infection and disease. Yet co-evolution has proven difficult to demonstrate rigorously in practice, and co-evolutionary thinking is only just beginning to inform medical or veterinary research in any meaningful way, even though it can have a major influence on how genetic variation in biomedically important traits is interpreted. Improving our understanding of the biomedical significance of co-evolution will require changing the way in which we look for it, complementing the phenomenological approach traditionally favored by evolutionary biologists with the exploitation of the extensive data becoming available on the molecular biology and molecular genetics of host-pathogen interactions.     

A genome-wide association study identifies colorectal cancer susceptibility loci on chromosomes 10p14 and 8q23.3

To identify colorectal cancer (CRC) susceptibility alleles, we conducted a genome-wide association study. In phase 1, we genotyped 550,163 tagSNPs in 940 familial colorectal tumor cases (627 CRC, 313 high-risk adenoma) and 965 controls. In phase 2, we genotyped 42,708 selected SNPs in 2,873 CRC cases and 2,871 controls. In phase 3, we evaluated 11 SNPs showing association at P < 10(-4) in a joint analysis of phases 1 and 2 in 4,287 CRC cases and 3,743 controls. Two SNPs were taken forward to phase 4 genotyping (10,731 CRC cases and 10,961 controls from eight centers). In addition to the previously reported 8q24, 15q13 and 18q21 CRC risk loci, we identified two previously unreported associations: rs10795668, located at 10p14 (P = 2.5 x 10(-13) overall; P = 6.9 x 10(-12) replication), and rs16892766, at 8q23.3 (P = 3.3 x 10(-18) overall; P = 9.6 x 10(-17) replication), which tags a plausible causative gene, EIF3H. These data provide further evidence for the 'common-disease common-variant' model of CRC predisposition.     

Selection and properties of a mouse L-cell transformant expressing human transferrin receptor

Transferrin receptors are expressed in large quantities on tissues with high requirements for iron such as maturing erythroid cells and placenta. In addition, they are found in abundance on proliferating cells from other normal tissues as well as on a variety of tumours. Recent genetic analysis has shown that structural genes for the transferrin receptor, probably transferrin itself and for p97, a melanoma-associated antigen that exhibits primary sequence homology with transferrin and that can bind ferric iron, each map in man to chromosome 3 (refs 9-12). On this basis it has been suggested that there may be a region on chromosome 3 containing genes involved in Fe transport and that rearrangements in this region of chromosome 3 may in some circumstances be associated with malignant transformation. Furthermore, it is unresolved whether all cell types express structurally identical transferrin receptors. To study these problems, and as an initial step towards cloning the transferrin receptor gene, we describe here the derivation of mouse L-cell transformants expressing the human transferrin receptor.     

Bootstrap Replacement to Validate the Influence of the Economic Cycle on the Structure and the Accuracy Level of Business Failure Prediction Models

The aim of this study was to answer the question of how the economic cycle affects the stability and efficiency of business failure prediction models, using bootstrap replacement method for validation. We analyse 2228 Spanish small and medium‐sized enterprises for the period 2001–2009, and divide it into three different phases of the economic cycle (growth, crisis, recession). We find that the structure and the ability of business failure prediction models are different according to the economic cycle. These findings are relevant for the debate on the most suitable financial ratios when developing business failure prediction models and to pose their accuracy level in these prediction models. Copyright © 2015 John Wiley & Sons, Ltd.     

Spatial distribution of ichthyofauna in the northern Alboran Sea (western Mediterranean)

This study describes the four main demersal fish assemblages identified along the continental shelf and slope (30–800 m depth) of the northern Alboran Sea (western Mediterranean), based on the analysis of the MEDITS (International bottom trawl survey in the Mediterranean) 12-year data series. We collected 186 fish species belonging to three classes, 24 orders and 69 families. Taxonomically, the order Perciformes was the most diverse, represented by 18 families and 58 species. Each assemblage had particular characteristics of abundance, biomass, mean fish weight and species richness. The geographical differences associated with the distribution of some species occurred within shelf assemblages. The middle slope was characterised by the highest similarity between samples, probably due to its lower environmental variability compared to that of the other assemblages.     

An anaerobic mitochondrion that produces hydrogen

Hydrogenosomes are organelles that produce ATP and hydrogen, and are found in various unrelated eukaryotes, such as anaerobic flagellates, chytridiomycete fungi and ciliates. Although all of these organelles generate hydrogen, the hydrogenosomes from these organisms are structurally and metabolically quite different, just like mitochondria where large differences also exist. These differences have led to a continuing debate about the evolutionary origin of hydrogenosomes. Here we show that the hydrogenosomes of the anaerobic ciliate Nyctotherus ovalis, which thrives in the hindgut of cockroaches, have retained a rudimentary genome encoding components of a mitochondrial electron transport chain. Phylogenetic analyses reveal that those proteins cluster with their homologues from aerobic ciliates. In addition, several nucleus-encoded components of the mitochondrial proteome, such as pyruvate dehydrogenase and complex II, were identified. The N. ovalis hydrogenosome is sensitive to inhibitors of mitochondrial complex I and produces succinate as a major metabolic end product--biochemical traits typical of anaerobic mitochondria. The production of hydrogen, together with the presence of a genome encoding respiratory chain components, and biochemical features characteristic of anaerobic mitochondria, identify the N. ovalis organelle as a missing link between mitochondria and hydrogenosomes.