Evolution of oesophageal adenocarcinoma from metaplastic columnar epithelium without goblet cells in Barrett's oesophagus

Supported by the Dutch Cancer Society (KWF) and Cancer Research UK (CR-UK). This work was supported by Cancer Research UK (grant number A14895

Gold nanoparticles supported on magnesium oxide for CO oxidation

Au was loaded (1 wt%) on a commercial MgO support by three different methods: double impregnation, liquid-phase reductive deposition and ultrasonication. Samples were characterised by adsorption of N2 at -96°C, temperature-programmed reduction, high-resolution transmission electron microscopy, energy-dispersive X-ray spectroscopy and X-ray diffraction. Upon loading with Au, MgO changed into Mg(OH)2 (the hydroxide was most likely formed by reaction with water, in which the gold precursor was dissolved). The size range for gold nanoparticles was 2-12 nm for the DIM method and 3-15 nm for LPRD and US. The average size of gold particles was 5.4 nm for DIM and larger than 6.5 for the other methods. CO oxidation was used as a test reaction to compare the catalytic activity. The best results were obtained with the DIM method, followed by LPRD and US. This can be explained in terms of the nanoparticle size, well known to determine the catalytic activity of gold catalysts

The Barrett's Gland in Phenotype Space

Barrett's esophagus is characterized by the erosive replacement of esophageal squamous epithelium by a range of metaplastic glandular phenotypes. These glandular phenotypes likely change over time, and their distribution varies along the Barrett's segment. Although much recent work has addressed Barrett's esophagus from the genomic viewpoint-its genotype space-the fact that the phenotype of Barrett's esophagus is nonstatic points to conversion between phenotypes and suggests that Barrett's esophagus also exists in phenotype space. Here we explore this latter concept, investigating the scope of glandular phenotypes in Barrett's esophagus and how they exist in physical and temporal space as well as their evolution and their life history. We conclude that individual Barrett's glands are clonal units; because of this important fact, we propose that it is the Barrett's gland that is the unit of selection in phenotypic and indeed neoplastic progression. Transition between metaplastic phenotypes may be governed by neutral drift akin to niche turnover in normal and dysplastic niches. In consequence, the phenotype of Barrett's glands assumes considerable importance, and we make a strong plea for the integration of the Barrett's gland in both genotype and phenotype space in future work

On Multiview Analysis for Fingerprint Liveness Detection

Fingerprint recognition systems, as any other biometric system, can be subject to attacks, which are usually carried out using artificial fingerprints. Several approaches to discriminate between live and fake fingerprint images have been presented to address this issue. These methods usually rely on the analysis of individual features extracted from the fingerprint images. Such features represent different and complementary views of the object in analysis, and their fusion is likely to improve the classification accuracy. However, very little work in this direction has been reported in the literature. In this work, we present the results of a preliminary investigation on multiview analysis for fingerprint liveness detection. Experimental results show the effectiveness of such approach, which improves previous results in the literatur

MLH1 deficiency leads to deregulated mitochondrial metabolism

The DNA mismatch repair (MMR) pathway is responsible for the repair of base–base mismatches and insertion/deletion loops that arise during DNA replication. MMR deficiency is currently estimated to be present in 15–17% of colorectal cancer cases and 30% of endometrial cancers. MLH1 is one of the key proteins involved in the MMR pathway. Inhibition of a number of mitochondrial genes, including POLG and PINK1 can induce synthetic lethality in MLH1-deficient cells. Here we demonstrate for the first time that loss of MLH1 is associated with a deregulated mitochondrial metabolism, with reduced basal oxygen consumption rate and reduced spare respiratory capacity. Furthermore, MLH1-deficient cells display a significant reduction in activity of the respiratory chain Complex I. As a functional consequence of this perturbed mitochondrial metabolism, MLH1-deficient cells have a reduced anti-oxidant response and show increased sensitivity to reactive oxidative species (ROS)-inducing drugs. Taken together, our results provide evidence for an intrinsic mitochondrial dysfunction in MLH1-deficient cells and a requirement for MLH1 in the regulation of mitochondrial function

The stealth episome: suppression of gene expression on the excised genomic island PPHGI-1 from Pseudomonas syringae pv. phaseolicola

Pseudomonas syringae pv. phaseolicola is the causative agent of halo blight in the common bean, Phaseolus vulgaris. P. syringae pv. phaseolicola race 4 strain 1302A contains the avirulence gene avrPphB (syn. hopAR1), which resides on PPHGI-1, a 106 kb genomic island. Loss of PPHGI-1 from P. syringae pv. phaseolicola 1302A following exposure to the hypersensitive resistance response (HR) leads to the evolution of strains with altered virulence. Here we have used fluorescent protein reporter systems to gain insight into the mobility of PPHGI-1. Confocal imaging of dual-labelled P. syringae pv. phaseolicola 1302A strain, F532 (dsRFP in chromosome and eGFP in PPHGI-1), revealed loss of PPHGI-1::eGFP encoded fluorescence during plant infection and when grown in vitro on extracted leaf apoplastic fluids. Fluorescence-activated cell sorting (FACS) of fluorescent and non-fluorescent PPHGI-1::eGFP F532 populations showed that cells lost fluorescence not only when the GI was deleted, but also when it had excised and was present as a circular episome. In addition to reduced expression of eGFP, quantitative PCR on sub-populations separated by FACS showed that transcription of other genes on PPHGI-1 (avrPphB and xerC) was also greatly reduced in F532 cells harbouring the excised PPHGI-1::eGFP episome. Our results show how virulence determinants located on mobile pathogenicity islands may be hidden from detection by host surveillance systems through the suppression of gene expression in the episomal state

Cell migration leads to spatially distinct but clonally related airway cancer precursors

Background Squamous cell carcinoma of the lung is a common cancer with 95% mortality at 5 years. These cancers arise from preinvasive lesions, which have a natural history of development progressing through increasing severity of dysplasia to carcinoma in situ (CIS), and in some cases, ending in transformation to invasive carcinoma. Synchronous preinvasive lesions identified at autopsy have been previously shown to be clonally related. Methods Using autofluorescence bronchoscopy that allows visual observation of preinvasive lesions within the upper airways, together with molecular profiling of biopsies using gene sequencing and loss-of-heterozygosity analysis from both preinvasive lesions and from intervening normal tissue, we have monitored individual lesions longitudinally and documented their visual, histological and molecular relationship. Results We demonstrate that rather than forming a contiguous field of abnormal tissue, clonal CIS lesions can develop at multiple anatomically discrete sites over time. Further, we demonstrate that patients with CIS in the trachea have invariably had previous lesions that have migrated proximally, and in one case, into the other lung over a period of 12 years. Conclusions Molecular information from these unique biopsies provides for the first time evidence that field cancerisation of the upper airways can occur through cell migration rather than via local contiguous cellular expansion as previously thought. Our findings urge a clinical strategy of ablating high-grade premalignant airway lesions with subsequent attentive surveillance for recurrence in the bronchial tree

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution