Gold(I)-catalysed one-pot synthesis of chromans using allylic alcohols and phenols

A gold(I)-catalysed reaction of allylic alcohols and phenols produces chromans regioselectively via a one-pot Friedel–Crafts allylation/intramolecular hydroalkoxylation sequence. The reaction is mild, practical and tolerant of a wide variety of substituents on the phenol

Gold(I)-Catalysed Direct Thioetherifications Using Allylic Alcohols: an Experimental and Computational Study

A gold(I)-catalysed direct thioetherification reaction between allylic alcohols and thiols is presented. The reaction is generally highly regioselective (S(N)2′). This dehydrative allylation procedure is very mild and atom economical, producing only water as the by-product and avoiding any unnecessary waste/steps associated with installing a leaving or activating group on the substrate. Computational studies are presented to gain insight into the mechanism of the reaction. Calculations indicate that the regioselectivity is under equilibrium control and is ultimately dictated by the thermodynamic stability of the products

Chirality Transfer in Gold(I)-Catalysed Direct Allylic Etherifications of Unactivated Alcohols:Experimental and Computational Study

Gold(I)-catalysed direct allylic etherifications have been successfully carried out with chirality transfer to yield enantioenriched, γ-substituted secondary allylic ethers. Our investigations include a full substrate-scope screen to ascertain substituent effects on the regioselectivity, stereoselectivity and efficiency of chirality transfer, as well as control experiments to elucidate the mechanistic subtleties of the chirality-transfer process. Crucially, addition of molecular sieves was found to be necessary to ensure efficient and general chirality transfer. Computational studies suggest that the efficiency of chirality transfer is linked to the aggregation of the alcohol nucleophile around the reactive π-bound Au–allylic ether complex. With a single alcohol nucleophile, a high degree of chirality transfer is predicted. However, if three alcohols are present, alternative proton transfer chain mechanisms that erode the efficiency of chirality transfer become competitive

Discovery and validation of molecular biomarkers for colorectal adenomas and cancer with application to blood testing

Results: Genome-wide analysis uncovered reproducible gene expression signatures for both adenomas and cancers compared to controls. 386/489 (79%) of the adenoma and 439/529 (83%) of the adenocarcinoma biomarkers were validated in independent tissues. We also identified genes differentially expressed in adenomas compared to cancer. KIAA1199 was selected for further analysis based on consistent up-regulation in neoplasia, previous studies and its interest as an uncharacterized gene. Plasma KIAA1199 RNA levels were significantly higher in patients with either cancer or adenoma (31/ 40) compared to neoplasia-free controls (6/20).This work was co-funded by Flinders University of South Australia and the Commonwealth Scientific and Industrial Research Organisation (CSIRO) of Australia. Drs. Dunne, Molloy and Brown are employed by CSIRO. These funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding was also provided by Clinical Genomics Pty Ltd., a company involved in the discovery and commercialization of biomarkers for colorectal cancer. Drs. LaPointe, Pedersen, Gaur, McEvoy and Thomas are employed by Clinical Genomics Pty Ltd and Prof. Young is a paid consultant of Clinical Genomics Pty Ltd. The funder thus played roles in study design, data collection and analysis, decision to publish, and preparation of the manuscript. Mrs. Pimlott and Dr. Wattchow have nothing to disclose. This work was co-funded by Clinical Genomics Pty Ltd, a company involved in the discovery and commercialization of biomarkers for colorectal cancer. Drs. LaPointe, Pedersen, Gaur, McEvoy and Thomas are employed by Clinical Genomics Pty Ltd. Prof. Young is a paid consultant of Clinical Genomics Pty Ltd. This does not alter the authors’ adherence to all the PLoS ONE policies on sharing data and materials

Colorectal cancer linkage on chromosomes 4q21, 8q13, 12q24, and 15q22

A substantial proportion of familial colorectal cancer (CRC) is not a consequence of known susceptibility loci, such as mismatch repair (MMR) genes, supporting the existence of additional loci. To identify novel CRC loci, we conducted a genome-wide linkage scan in 356 white families with no evidence of defective MMR (i.e., no loss of tumor expression of MMR proteins, no microsatellite instability (MSI)-high tumors, or no evidence of linkage to MMR genes). Families were ascertained via the Colon Cancer Family Registry multi-site NCI-supported consortium (Colon CFR), the City of Hope Comprehensive Cancer Center, and Memorial University of Newfoundland. A total of 1,612 individuals (average 5.0 per family including 2.2 affected) were genotyped using genome-wide single nucleotide polymorphism linkage arrays; parametric and non-parametric linkage analysis used MERLIN in a priori-defined family groups. Five lod scores greater than 3.0 were observed assuming heterogeneity. The greatest were among families with mean age of diagnosis less than 50 years at 4q21.1 (dominant HLOD = 4.51, α = 0.84, 145.40 cM, rs10518142) and among all families at 12q24.32 (dominant HLOD = 3.60, α = 0.48, 285.15 cM, rs952093). Among families with four or more affected individuals and among clinic-based families, a common peak was observed at 15q22.31 (101.40 cM, rs1477798; dominant HLOD = 3.07, α = 0.29; dominant HLOD = 3.03, α = 0.32, respectively). Analysis of families with only two affected individuals yielded a peak at 8q13.2 (recessive HLOD = 3.02, α = 0.51, 132.52 cM, rs1319036). These previously unreported linkage peaks demonstrate the continued utility of family-based data in complex traits and suggest that new CRC risk alleles remain to be elucidated. © 2012 Cicek et al

The capacity of the fecal microbiota from Malawian infants to ferment resistant starch

In Low and Middle-Income Countries (LMIC), weaning is associated with environmentally acquired and inflammation-associated enteric disorders. Dietary intake of high amylose maize starch (HAMS) can promote commensal fermentative bacteria and drive the production of short chain fatty acids (SCFAs). By stabilizing commensal gut microbiology, and stimulating the production of anti-inflammatory metabolites, HAMS supplementation might therefore influence enteric health. However, the extent to which the gut microbiota of LMIC infants are capable of fermenting HAMS is unclear. We assessed the capacity of the fecal microbiota from pre-weaning and weaning Malawian infants to ferment HAMS and produce SCFAs using an in vitro fermentation model. Fecal microbiota from both pre-weaning and weaning infants were able to ferment HAMS, as indicated by an increase in bacterial load and total SCFA concentration, and a reduction in pH. All of these changes were more substantial in the weaning group. Acetate production was observed with both pre-weaning and weaning groups, while propionate production was only observed in the weaning group. HAMS fermentation resulted in significant alterations to the fecal microbial community in the weaning group, with significant increases in levels of Prevotella, Veillonella, and Collinsella associated with propionate production. In conclusion, fecal microbiota from Malawian infants before and during weaning has the capacity to produce acetate through HAMS fermentation, with propionate biosynthetic capability appearing only at weaning. Our results suggest that HAMS supplementation might provide benefit to infants during weaning

CAHM, a long non-coding RNA gene hypermethylated in colorectal neoplasia

Copyright © 2014 Landes Bioscience This is an open-access article licensed under a Creative Commons Attribution 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited. Permission is granted subject to the terms of the License under which the work was published. Please check the License conditions for the work which you wish to reuse. Full and appropriate attribution must be given. This permission does not cover any third party copyrighted material which may appear in the work requested.The CAHM gene (Colorectal Adenocarcinoma HyperMethylated), previously LOC 100526820, is located on chromosome 6, hg19 chr6:163 834 097–163 834 982. It lacks introns, encodes a long non-coding RNA (lncRNA) and is located adjacent to the gene QKI, which encodes an RNA binding protein. Deep bisulphite sequencing of ten colorectal cancer (CRC ) and matched normal tissues demonstrated frequent hypermethylation within the CAHM gene in cancer. A quantitative methylation-specific PCR (qMSP ) was used to characterize additional tissue samples. With a threshold of 5% methylation, the CAHM assay was positive in 2/26 normal colorectal tissues (8%), 17/21 adenomas (81%), and 56/79 CRC samples (71%). A reverse transcriptase-qPCR assay showed that CAHM RNA levels correlated negatively with CAHM % methylation, and therefore CAHM gene expression is typically decreased in CRC . The CAHM qMSP assay was applied to DNA isolated from plasma specimens from 220 colonoscopy-examined patients. Using a threshold of 3 pg methylated genomic DNA per mL plasma, methylated CAHM sequences were detected in the plasma DNA of 40/73 (55%) of CRC patients compared with 3/73 (4%) from subjects with adenomas and 5/74 (7%) from subjects without neoplasia. Both the frequency of detection and the amount of methylated CAHM DNA released into plasma increased with increasing cancer stage. Methylated CAHM DNA shows promise as a plasma biomarker for use in screening for CRC

Analysis of the anti-cancer effects of cincau extract (Premna oblongifolia merr) and other types of non- digestible fibre using faecal fermentation supernatants and Caco-2 cells as a model of the human colon

© 2017 by the authors. Green cincau (Premna oblongifolia Merr) is an Indonesian food plant with a high dietary fibre content. Research has shown that dietary fibre mixtures may be more beneficial for colorectal cancer prevention than a single dietary fibre type. The aim of this study was to investigate the effects of green cincau extract on short chain fatty acid (SCFA) production in anaerobic batch cultures inoculated with human faecal slurries and to compare these to results obtained using different dietary fibre types (pectin, inulin, and cellulose), singly and in combination. Furthermore, fermentation supernatants (FSs) were evaluated in Caco-2 cells for their effect on cell viability, differentiation, and apoptosis. Cincau increased total SCFA concentration by increasing acetate and propionate, but not butyrate concentration. FSs from all dietary fibre sources, including cincau, reduced Caco-2 cell viability. However, the effects of all FSs on cell viability, cell differentiation, and apoptosis were not simply explainable by their butyrate content. In conclusion, products of fermentation of cincau extracts induced cell death, but further work is required to understand the mechanism of action. This study demonstrates for the first time that this Indonesian traditional source of dietary fibre may be protective against colorectal cancer

Behind the Signs - a global review of fish sustainability information schemes

This paper presents the results of a global review of organisations that provide sustainable fisheries information — including ecolabels, recommendation lists and supermarkets — to consumers and supply chain intermediaries. It examined 17 organisations and key supermarkets that communicate on the sustainability of world fisheries and aquaculture products. Certification schemes assess a relatively small number of specific fisheries and indicate sustainability through labels. Recommendation lists cover more species and areas but in less detail. FAO guidelines for fisheries ecolabelling and aquaculture certification constituted the benchmarks with which improving conformance was found. However, significant variation in fisheries’ assessment exists, affecting the accuracy and precision of information and advice provided. Inconsistent approaches and contradictory advice among certification schemes and recommendation lists potentially increase consumer confusion and reduce their credibility. The review identifies seven critical attributes schemes must address — scope, accuracy, independence, precision, transparency, standardisation and cost-effectiveness — and recommends that certification schemes and recommendation lists enhance their consistency and credibility through compliance with these attributes and FAO guidelines. Fish sustainability information schemes play an important role in securing a sustainable future for the oceans. Uptake of this review’s recommendations should reduce consumer confusion and increase confidence in the benefits of sustainable purchasing

Demographic, social cognitive and social ecological predictors of intention and participation in screening for colorectal cancer

Extent: 10p.Background: Previous research points to differences between predictors of intention to screen for colorectal cancer (CRC) and screening behavior, and suggests social ecological factors may influence screening behavior. The aim of this study was to compare the social cognitive and social ecological predictors of intention to screen with predictors of participation. Methods: People aged 50 to 74 years recruited from the electoral roll completed a baseline survey (n = 376) and were subsequently invited to complete an immunochemical faecal occult blood test (iFOBT). Results: Multivariate analyses revealed five predictors of intention to screen and two predictors of participation. Perceived barriers to CRC screening and perceived benefits of CRC screening were the only predictor of both outcomes. There was little support for social ecological factors, but measurement problems may have impacted this finding. Conclusions: This study has confirmed that the predictors of intention to screen for CRC and screening behaviour, although overlapping, are not the same. Research should focus predominantly on those factors shown to predict participation. Perceptions about the barriers to screening and benefits of screening are key predictors of participation, and provide a focus for intervention programs.Tess A Gregory, Carlene Wilson, Amy Duncan, Deborah Turnbull, Stephen R Cole and Graeme Youn