Ubiquity and Diversity of Human-Associated Demodex Mites

Demodex mites are a group of hair follicle and sebaceous gland-dwelling species. The species of these mites found on humans are arguably the animals with which we have the most intimate interactions. Yet, their prevalence and diversity have been poorly explored. Here we use a new molecular method to assess the occurrence of Demodex mites on humans. In addition, we use the 18S rRNA gene (18S rDNA) to assess the genetic diversity and evolutionary history of Demodex lineages. Within our samples, 100% of people over 18 years of age appear to host at least one Demodex species, suggesting that Demodex mites may be universal associates of adult humans. A phylogenetic analysis of 18S rDNA reveals intraspecific structure within one of the two named human-associated Demodex species, D. brevis. The D. brevis clade is geographically structured, suggesting that new lineages are likely to be discovered as humans from additional geographic regions are sampled.     

Experimental demonstration of the antiherbivore effects of silica in grasses: impacts on foliage digestibility and vole growth rates

The impact of plant-based factors on the population dynamics of mammalian herbivores has been the subject of much debate in ecology, but the role of antiherbivore defences in grasses has received relatively little attention. Silica has been proposed as the primary defence in grasses and is thought to lead to increased abrasiveness of foliage so deterring feeding, as well as reducing foliage digestibility and herbivore performance. However, at present there is little direct experimental evidence to support these ideas. In this study, we tested the effects of manipulating silica levels on the abrasiveness of grasses and on the feeding preference and growth performance of field voles, specialist grass-feeding herbivores. Elevated silica levels did increase the abrasiveness of grasses and deterred feeding by voles. We also demonstrated, for the first time, that silica reduced the growth rates of both juvenile and mature female voles by reducing the nitrogen they could absorb from the foliage. Furthermore, we found that vole feeding leads to increased levels of silica in leaves, suggesting a dynamic feedback between grasses and their herbivores. We propose that silica induction due to vole grazing reduces vole performance and hence could contribute to cyclic dynamics in vole populations.     

Impacts of silica-based defences in grasses on the feeding preferences of sheep

Grasses, which dominate many terrestrial ecosystems, sustain high densities of grazing mammals, so are of great economic and ecological importance. Traditionally, grasses are thought to be adapted to tolerate grazing rather than defend against it; however, silica deposited in the leaves of grasses has recently been shown to act as a feeding deterrent to invertebrate herbivores and small mammals. This study assesses whether silica is effective as a feeding deterrent to larger mammalian herbivores. We assess the impact of manipulated silica levels in five grass species on the feeding preferences of sheep both within and between grass species.Sheep feeding behaviour was driven by between-species differences in palatability. Hence, within a single species silica addition did not cause significant changes in feeding preference. However, there were significant differences in both the feeding preferences and bite rates between grass species, and these differences were much more marked when the grasses had been exposed to high levels of silica. The impacts that silica had on preference were least pronounced in palatable species (e.g. Poa annua) compared with less-palatable species (e.g. Brachypodium pinnatum and Festuca ovina). Sheep fed for longer, took more bites and had a higher bite rate on the grass species with the lowest leaf silica concentrations, namely P. annua.Sheep were less affected by silica defences than smaller, non-ruminant herbivores, but the changes in species preference rankings caused by silica suggest it may lead to changes in sward composition. Further, in species that are already relatively low in palatability, silica-induced reductions in bite rate could potentially reduce forage intake rates, with consequences for sheep performance.     

The gut flora as a forgotten organ

The intestinal microflora is a positive health asset that crucially influences the normal structural and functional development of the mucosal immune system. Mucosal immune responses to resident intestinal microflora require precise control and an immunosensory capacity for distinguishing commensal from pathogenic bacteria. In genetically susceptible individuals, some components of the flora can become a liability and contribute to the pathogenesis of various intestinal disorders, including inflammatory bowel diseases. It follows that manipulation of the flora to enhance the beneficial components represents a promising therapeutic strategy. The flora has a collective metabolic activity equal to a virtual organ within an organ, and the mechanisms underlying the conditioning influence of the bacteria on mucosal homeostasis and immune responses are beginning to be unravelled. An improved understanding of this hidden organ will reveal secrets that are relevant to human health and to several infectious, inflammatory and neoplastic disease processes.     

Control of BRCA2 cellular and clinical functions by a nuclear partner, PALB2

BRCA2 mutations predispose carriers to breast and ovarian cancer and can also cause other cancers and Fanconi anemia. BRCA2 acts as a "caretaker" of genome integrity by enabling homologous recombination (HR)-based, error-free DNA double-strand break repair (DSBR) and intra-S phase DNA damage checkpoint control. Described here is the identification of PALB2, a BRCA2 binding protein. PALB2 colocalizes with BRCA2 in nuclear foci, promotes its localization and stability in key nuclear structures (e.g., chromatin and nuclear matrix), and enables its recombinational repair and checkpoint functions. In addition, multiple, germline BRCA2 missense mutations identified in breast cancer patients but of heretofore unknown biological/clinical consequence appear to disrupt PALB2 binding and disable BRCA2 HR/DSBR function. Thus, PALB2 licenses key cellular biochemical properties of BRCA2 and ensures its tumor suppression function.     

A comparison of primary oesophageal squamous epithelial cells with HET‐1A in organotypic culture

Background Information. Carcinoma of the oesophagus is the sixth leading cause of cancer death in the western world and is associated with a 5‐year survival of less than 15%. Recent evidence suggests that stromal—epithelial interactions are fundamental in carcinogenesis. The advent of co‐culture techniques permits the investigation of cross‐talk between the stroma and epithelium in a physiological setting. We have characterized a histologically representative oesophageal organotypic model and have used it to compare the most commonly used squamous oesophageal cell line, HET‐1A, with primary oesophageal squamous cells for use in studies of the oesophageal epithelium in vitro. Results. When grown in an organotypic culture with normal fibroblasts, the oesophageal carcinoma cell lines OE21 (squamous) and OE19 (adenocarcinoma) morphologically resembled the tumour of origin with evidence of stromal invasion and mucus production, respectively. However, HET‐1A cells, which were derived from normal squamous oesophageal cells, appeared dysplastic and failed to display evidence of squamous differentiation. By comparison with primary oesophageal epithelial cells, the HET‐1A cells were highly proliferative and did not express the epithelial markers E‐cadherin or CK5/6 (casein kinase 5/6), or the stratified epithelial marker ΔNp63, but did express the mesenchymal markers vimentin and N‐cadherin. Conclusion. Studies of epithelial carcinogenesis will benefit from culture systems which allow manipulation of the stromal and epithelial layers independently. We have developed an organotypic culture using primary oesophageal squamous cells and fibroblasts in which a stratified epithelium with a proliferative basal layer that stains strongly for ΔNp63 develops. This model will be suitable for the study of the molecular events in the development of Barrett's oesophagus. The most commonly used normal oesophageal squamous cell line, HET‐1A, does not have the characteristics of normal oesophageal squamous cells and should not be used in models of the normal oesophageal epithelium. Until more representative cell lines are available, future studies in oesophageal cancer will be reliant on the availability and manipulation of primary tissue.