MYOD-1 in normal colonic mucosa - role as a putative biomarker?

Background DNA methylation of promoter-associated CpG islands of certain genes may play a role in the development of colorectal cancer. The MYOD-1 gene which is a muscle differentiation gene has been showed to be significantly methylated in colorectal cancer which, is an age related event. However the role of this gene in the colonic mucosa is not understood and whether methylation occurs in subjects without colon cancer. In this study, we have determined the frequency of methylation of the MYOD-1 gene in normal colonic mucosa and investigated to see if this is associated with established colorectal cancer risk factors primarily ageing. Results We analysed colonic mucosal biopsies in 218 normal individuals and demonstrated that in most individuals promoter hypermethylation was not quantified for MYOD-1. However, promoter hypermethylation increased significantly with age (p < 0.001 using regression analysis) and this was gender independent. We also showed that gene promoter methylation increased positively with an increase in waist to hip (WHR) ratio - the latter is also a known risk factor for colon cancer development. Conclusions Our study suggests that promoter gene hypermethylation of the MYOD-1 gene increases significantly with age in normal individuals and thus may offer potential as a putative biomarker for colorectal cancer.

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammation

Immigration, species radiation and extinction in a highly diverse songbird lineage: white-eyes on Indian Ocean islands

Molecular phylogenetic hypotheses of species-rich lineages in regions where geological history can be reliably inferred may provide insights into the scale of processes driving diversification. Here we sample all extant or recently extinct white-eye (Zosterops) taxa of the southwest Indian Ocean, combined with samples from all principal continental lineages. Results support a high dispersal capability, with at least two independent continental sources for white-eyes of the region. An early (within 1.8 million years ago) expansion into the Indian Ocean may have originated either from Asia or Africa; the three resulting lineages show a disparate distribution consistent with considerable extinction following their arrival. Africa is supported as the origin of a later expansion into the region (within 1.2 million years ago). On two islands, a pair of Zosterops species derived from independent immigrations into the Indian Ocean co-occur or may have formerly co-occurred, providing strong support for their origin by double-island colonization rather than within-island (sympatric or microallopatric) speciation. On Mauritius and La Reunion, phylogenetic placement of sympatric white-eyes allow us to rule out a scenario in which independent within-island speciation occurred on both islands; one of the species pairs must have arisen by double colonization, while the other pair is likely to have arisen by the same mechanism. Long-distance immigration therefore appears to be responsible for much of the region's white-eye diversity. Independent immigrations into the region have resulted in lineages with mutually exclusive distributions and it seems likely that competition with congeneric species, rather than arrival frequency, may limit present-day diversity.

Exploring the land–ocean contrast in convective vigor using islands

Moist convection is well known to be generally more intense over continental than maritime regions, with larger updraft velocities, graupel, and lightning production. This study explores the transition from maritime to continental convection by comparing the trends in Tropical Rainfall Measuring Mission (TRMM) radar and microwave (37 and 85 GHz) observations over islands of increasing size to those simulated by a cloud-resolving model. The observed storms were essentially maritime over islands of <100 km2 and continental over islands >10 000 km2, with a gradual transition in between. Equivalent radar and microwave quantities were simulated from cloud-resolving runs of the Weather Research and Forecasting model via offline radiation codes. The model configuration was idealized, with islands represented by regions of uniform surface heat flux without orography, using a range of initial sounding conditions without strong horizontal winds or aerosols. Simulated storm strength varied with initial sounding, as expected, but also increased sharply with island size in a manner similar to observations. Stronger simulated storms were associated with higher concentrations of large hydrometeors. Although biases varied with different ice microphysical schemes, the trend was similar for all three schemes tested and was also seen in 2D and 3D model configurations. The successful reproduction of the trend with such idealized forcing supports previous suggestions that mesoscale variation in surface heating—rather than any difference in humidity, aerosol, or other aspects of the atmospheric state—is the main reason that convection is more intense over continents and large islands than over oceans. Some dynamical storm aspects, notably the peak rainfall and minimum surface pressure low, were more sensitive to surface forcing than to the atmospheric sounding or ice scheme. Large hydrometeor concentrations and simulated microwave and radar signatures, however, were at least as sensitive to initial humidity levels as to surface forcing and were more sensitive to the ice scheme. Issues with running the TRMM simulator on 2D simulations are discussed, but they appear to be less serious than sensitivities to model microphysics, which were similar in 2D and 3D. This supports the further use of 2D simulations to economically explore modeling uncertainties.

Pathogenicity and other genomic islands in plant pathogenic bacteria

Pathogenicity islands (PAIs) were first described in uropathogenic E. coli. They are now defined as regions of DNA that contain virulence genes and are present in the genome of pathogenic strains, but absent from or only rarely present in non-pathogenic variants of the same or related strains. Other features include a variable G+C content, distinct boundaries from the rest of the genome and the presence of genes related to mobile elements such as insertion sequences, integrases and transposases. Although PAIs have now been described in a wide range of both plant and animal pathogens it has become evident that the general features of PAIs are displayed by a number of regions of DNA with functions other than pathogenicity, such as symbiosis and antibiotic resistance, and the general term genomic islands has been adopted. This review will describe a range of genomic islands in plant pathogenic bacteria including those that carry effector genes, phytotoxins and the type III protein secretion cluster. The review will also consider some medically important bacteria in order to discuss the range, acquisition and stabilization of genomic islands.

The Mesolithic-Neolithic transition in the Channel Islands: maritime and terrrestrial perspectives

This paper investigates the Mesolithic-Neolithic transition in the Channel Islands. It presents a new synthesis of all known evidence from the islands c. 5000-4300 BC, including several new excavations as well as find spot sites that have not previously been collated. It also summarises – in English – a large body of contemporary material from north-west France. The paper presents a new high-resolution sea level model for the region, shedding light on the formation of the Channel Islands from 9000-4000 BC. Through comparison with contemporary sites in mainland France, an argument is made suggesting that incoming migrants from the mainland and the small indigenous population of the islands were both involved in the transition. It is also argued that, as a result of the fact the Channel Islands witnessed a very different trajectory of change to that seen in Britain and Ireland c. 5000-3500 BC, this small group of islands has a great deal to tell us about the arrival of the Neolithic more widely.