DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach

BACKGROUND: Methylation-induced silencing of promoter CpG islands in tumor suppressor genes plays an important role in human carcinogenesis. In colorectal cancer, the CpG island methylator phenotype (CIMP) is defined as widespread and elevated levels of DNA methylation and CIMP+ tumors have distinctive clinicopathological and molecular features. In contrast, the existence of a comparable CIMP subtype in gastric cancer (GC) has not been clearly established. To further investigate this issue, in the present study we performed comprehensive DNA methylation profiling of a well-characterised series of primary GC.

METHODS: The methylation status of 1,421 autosomal CpG sites located within 768 cancer-related genes was investigated using the Illumina GoldenGate Methylation Panel I assay on DNA extracted from 60 gastric tumors and matched tumor-adjacent gastric tissue pairs. Methylation data was analysed using a recursively partitioned mixture model and investigated for associations with clinicopathological and molecular features including age, Helicobacter pylori status, tumor site, patient survival, microsatellite instability and BRAF and KRAS mutations.

RESULTS: A total of 147 genes were differentially methylated between tumor and matched tumor-adjacent gastric tissue, with HOXA5 and hedgehog signalling being the top-ranked gene and signalling pathway, respectively. Unsupervised clustering of methylation data revealed the existence of 6 subgroups under two main clusters, referred to as L (low methylation; 28% of cases) and H (high methylation; 72%). Female patients were over-represented in the H tumor group compared to L group (36% vs 6%; P = 0.024), however no other significant differences in clinicopathological or molecular features were apparent. CpG sites that were hypermethylated in group H were more frequently located in CpG islands and marked for polycomb occupancy.

CONCLUSIONS: High-throughput methylation analysis implicates genes involved in embryonic development and hedgehog signaling in gastric tumorigenesis. GC is comprised of two major methylation subtypes, with the highly methylated group showing some features consistent with a CpG island methylator phenotype.

Chemistry and Mechanism of Alizarin Red S and Methylene Blue Biosorption onto Olive Stone: Equilibrium and Kinetic

The biosorption process of anionic dye Alizarin Red S (ARS) and cationic dye methylene blue (MB) as a function of solution pH, initial concentration and contact time onto olive stone (OS) biomass has been investigated. The main objectives of the current study are to: (i) study the chemistry and the mechanism of ARS and MB biosorption onto olive stone and the type of OS–ARS, MB interactions occurring, (ii) study the biosorption equilibrium and kinetic experimental data required for the design and operation of column reactors. Equilibrium biosorption isotherms and kinetics were also examined. Experimental equilibrium data were fitted to four different isotherms by non-linear regression method, however, the biosorption experimental data for ARS and MB dyes were well interpreted by the Temkin and Langmuir isotherms, respectively. The maximum monolayer adsorption capacity for ARS and MB dyes were 109.0 and 102.6 mg/g, respectively. The kinetic data of the two dyes could be better described by the pseudo second-order model. The data showed that olive stone can be effectively used for removing dyes from wastewater.

The use of a novel compact fluorosensor for in situ monitoring of the photocatalytic destruction of methylene blue dye effluents

The use of TiO 2 photocatalysis for the destruction of dyes such as methylene blue has been extensively reported. One of the challenges faced in both the laboratory and large scale water treatment plants is the fact that the samples have to be removed from the reactor vessel and the catalyst separated prior to analysis being undertaken. In this paper we report the development of a simple fluorimeter instrument and its use in monitoring the photocatalytic destruction of methylene blue dyes in the presence of catalyst suspensions. The results reported show that the instrument provides an effective method for in situ monitoring of the photocatalytic destruction of fluorescent dyes hence allowing more accurate measurement due to the minimisation of sample loss and cross contamination. Furthermore it also provides a method for real time monitoring of the dye pollutant destruction in large scale photocatalytic reactors.

Effect of polyethylenimine, a cell permeabilizer, on the photosensitized destruction of algae by methylene blue and nuclear fast red

The present study reports the effect a cell permeabilizer, polyethylenimine (PEI) has on the photodynamic effect of methylene blue (MB) and nuclear fast red (NFR) in the presence of hydrogen peroxide (H₂O₂). The photosensitized destruction of the algae Chlorella vulgaris under irradiation with visible light is examined. The photodynamic effect was investigated under aerobic and anaerobic conditions. The presence of a permeabilizer during the photosensitized destruction of C. vulgaris does not enhance the activity of the MB, MB/H₂O₂ system or the NFR, NFR/H₂O ₂ system under aerobic conditions. However under anaerobic conditions we have determined that when a cell permeabilizer was added to the MB/H ₂O₂ system, the photosensitized destruction of C. vulgaris proceeded via a combination of Type I and Type II mechanisms. The presence of PEI enforces MB/H₂O₂ to be active toward the destruction of C. vulgaris whether oxygen is present or absent. Under aerobic and anaerobic conditions the activity of NFR was suppressed in the presence of PEI as a result of electrostatic interactions between the photosensitizer and the cell permeabilizer. The decrease in fluorescence recorded is indicative of destruction of the chlorophyll a pigment. 

Photo-dynamic biocidal action of methylene blue and hydrogen peroxide on the cyanobacterium Synechococcus leopoliensis under visible light irradiation

Biofilm growth on stone surfaces is a significant contributing factor to stone biodeterioration. Current market based biocides are hazardous to the environment and to public health. We have investigated the photo-dynamic effect of methylene blue (MB) in the presence of hydrogen peroxide (H₂O₂) on the destruction of the cyanobacterium Synechococcus leopoliensis (S. leopoliensis) under irradiation with visible light. Data presented in this paper illustrate that illumination of S. leopoliensis in the presence of a photosensitiser (MB) and H₂O₂ results in the decomposition of both the cyanobacterium and the photosensitiser. The presence of MB and H₂O₂ affects the viability of the photosensitiser and the cyanobacterium with the fluorescence of both decreasing by 80% over the irradiation time investigated. The photo-dynamic effect was observed under aerobic and anaerobic conditions indicating that oxygen was not necessary for the process. This novel combination could be effective for the remediation of biofilm colonised stone surfaces

Photosensitized destruction of Chlorella vulgaris by methylene blue or nuclear fast red combined with hydrogen peroxide under visible light irradiation

A considerable number of investigations have started to elucidate the essential roles biological agents play in the biodeterioration of stone. Chemical biocides are becoming increasingly banned because of the environmental and health hazards associated with these toxic substances. The present study reports the photodynamic effect of Methylene Blue (MB) and Nuclear Fast Red (NFR) in the presence of hydrogen peroxide (H₂O₂) on the destruction of the algae Chlorella vulgaris (C. vulgaris) under irradiation with visible light. Illumination of C. vulgaris in the presence of MB or NFR combined with H₂O₂ results in the decomposition of both the algal species and the photosensitizer. The photodynamic effect was investigated under aerobic and anaerobic conditions. Differences in mechanism type are reported and are dependent on both the presence and the absence of oxygen. The behavior of each photosensitizer leads to a Type II mechanism and a Type I/Type II combination for MB and NFR, respectively, being concluded. This novel combination could be effective for the remediation of biofilm-colonized stone surfaces.

The impact of climate change on existing and emerging microbial threats across the food chain: an island of Ireland perspective

The Agri-Food and aquaculture industries are vital to the economy of the island of Ireland with a gross annual output that is expected to double in the future. Identifying and understanding the potential influences of the anticipated climate variables on microorganisms that cause foodborne diseases, and their impact on these local industries, are essential. Investigating and monitoring foodborne pathogens and factors that influence their growth, transmission, pathogenesis and survival will facilitate assessment of the stability, security and vulnerability of the continuously evolving and increasing complex local food supply chain.

Holocene landscape intervention and plant food production strategies in island and mainland Southeast Asia

In the areas adjacent to the drowned Pleistocene continent of Sunda – present-day Mainland and Island SE Asia – the Austronesian Hypothesis of a diaspora of rice cultivators from Taiwan ∼4200 years ago has often been linked with the start of farming. Mounting evidence suggests that these developments should not be conflated and that alternative explanations should be considered, including indigenous inception of complex patterns of plant food production and early exchange of plants, animals, technology and genes. We review evidence for widespread forest disturbance in the Early Holocene which may accompany the beginnings of complex food-production. Although often insubstantial, evidence for incipient and developing management of rainforest vegetation and of developing complex relationships with plants is present, and early enough to suggest that during the Early to mid-Holocene this vast region was marked by different approaches to plant food production. The trajectory of the increasingly complex relationships between people and their food organisms was strongly locally contingent and in many cases did not result in the development of agricultural systems that were recognisable as such at the time of early European encounters. Diverse resource management economies in the Sunda and neighbouring regions appear to have accompanied rather than replaced a reliance on hunting and gathering. This, together with evidence for Early Holocene interaction between these neighbours, gives cause for us to question some authors continued adherence to a singular narrative of the Austronesian Hypothesis and the ‘Neolithisation’ of this part of the world. It also leads us to suggest that the forests of this vast region are, to an extent, a cultural artefact.