Photosynthetic traits of freshwater lichens are consistent with the submersion conditions of their habitat

In this study, we compared the photosynthetic performance of epilithic freshwater lichens on siliceous stream rock submerged for: more than 9 (hyper-), 6–9 (meso-) or 3–6 months (sub-hydrophilic lichens). In the dry state, neither variable fluorescence nor respiration activity could be detected. In the wet state, rates of dark respiration (O2 uptake and CO2 production for immerged and in-air samples) were in the lower range of that reported for non-aquatic lichens. With 200 (under water) or 500 mmol.mx2.sx1 photosyntheticallly active photon flux density (PPFD) (aerial), photosynthesis was positive but rates were lower than that published for non-aquatic species. Under intense PPFD (2000 mmol.mx2.sx1, aerial), photo- synthesis increased in sub- but became negative in hyper-hydrophilic species. After hydration, dry samples increased photosystem II (PSII) efficiency, which reached near steady state in <6–7 min. Hyper-hydrophilic lichen took longer than sub-hydrophilic species. A long period of desiccation (4 months) had a negative effect on subsequent PSII photochemistry of hyper- but not of sub-hydrophilic hydrated lichens. When thalli were allowed to dehydrate, all types of lichens lost PSII activity after about 15–20 min. Deactivation was faster in the hyper- than in the sub-hydrophilic species. The metabolic traits presented here are thus consistent with the ecological amplitude of the freshwater lichens studied

DNA hypermethylation in the normal colonic mucosa of patients with colorectal cancer

The CpG-island methylator phenotype (CIMP+) in colorectal cancer (CRC) is characterised by frequent hypermethylation of promoter regions in tumour suppressor genes. Low level methylation of some CpG islands is also seen in the normal colonic mucosa and increases with age; however, it is still unclear what other factors regulate this phenomenon. The first aim of our study was to determine whether the level of promoter methylation is elevated in the normal colonic mucosa of patients with CIMP+ tumours. The second aim was to investigate whether common, functional polymorphisms in genes involved in methyl group metabolism are associated with the level of methylation in this tissue. CpG islands within the ERα, MYOD, P16(INK4A), MLH1, APC, P14(ARF), DAPK and TIMP3 genes were quantitatively evaluated for methylation in normal colonic mucosa from a large series of CRC patients using the MethyLight assay. Genotyping was carried out for polymorphisms in the MTHFR, TS, MS, MTHFD1 and DNMT3b genes. Methylation of ERα and MYOD in normal colonic mucosa increased with age and was higher in female subjects. Methylation of P16(INK4A), MLH1, TIMP3 and DAPK in normal mucosa occurred at a lower level than ERα and MYOD but also increased with age and was significantly higher in patients with CIMP+ tumours. The DNMT3b C46359T polymorphism was associated with significantly less methylation of MYOD and MLH1 and with trends for lower methylation in each of the other CpG islands examined. Our results demonstrate that age, gender and genetic factors can influence the methylation level of CpG islands in gene promoter regions of normal colonic mucosa. Further work is required to determine whether such methylation is associated with the development of CIMP+ CRC

Plant diversity greatly enhances weed suppression in intensively managed grasslands

Weed suppression was investigated in a field experiment across 31 international sites. The study included 15 plant communities at each site, based on two grasses and two legumes, each sown in monoculture and 11 four-species mixtures varying in the relative proportions of the four species. At each site, one grass and one legume species was selected as fast establishing and the other two species were selected for persistence. Average weed biomass in mixtures over the whole experiment was 52% less (95% confidence interval, 30 to 75%) than in the most suppressive monoculture (transgressive suppression). Transgressive suppression of weed biomass persisted over each year for each mixture. Weed biomass was consistently low and relatively similar across all mixtures and years. Average sown species biomass was greater in all mixtures than in any monoculture. The suppressive effect of sown forage species on weeds in mixtures was achieved without any herbicide use. At each site, weed biomass for almost every mixture was lower than the average across the four monocultures. The average proportion of weed biomass in mixtures was less than in the most suppressive monoculture in two thirds of sites. Mixtures outyielded monocultures, and mixture yield comprised far lower weed biomass

Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features

<p>Abstract</p> <p>Background</p> <p>Most previous studies of the CpG island methylator phenotype (CIMP) in colorectal cancer (CRC) have been conducted on a relatively small numbers of CpG sites. In the present study we performed comprehensive DNA methylation profiling of CRC with the aim of characterizing CIMP subgroups.</p> <p>Methods</p> <p>DNA methylation at 1,505 CpG sites in 807 cancer-related genes was evaluated using the Illumina GoldenGate^®methylation array in 28 normal colonic mucosa and 91 consecutive CRC samples. Methylation data was analyzed using unsupervised hierarchical clustering. CIMP subgroups were compared for various clinicopathological and molecular features including patient age, tumor site, microsatellite instability (MSI), methylation at a consensus panel of CpG islands and mutations in <it>BRAF </it>and <it>KRAS</it>.</p> <p>Results</p> <p>A total of 202 CpG sites were differentially methylated between tumor and normal tissue. Unsupervised hierarchical clustering of methylation data from these sites revealed the existence of three CRC subgroups referred to as CIMP-low (CIMP-L, 21% of cases), CIMP-mid (CIMP-M, 14%) and CIMP-high (CIMP-H, 65%). In comparison to CIMP-L tumors, CIMP-H tumors were more often located in the proximal colon and showed more frequent mutation of <it>KRAS </it>and <it>BRAF </it>(<it>P </it>< 0.001).</p> <p>Conclusions</p> <p>Comprehensive DNA methylation profiling identified three CRC subgroups with distinctive clinicopathological and molecular features. This study suggests that both <it>KRAS </it>and <it>BRAF </it>mutations are involved with the CIMP-H pathway of CRC rather than with distinct CIMP subgroups.</p

Molecular markers of response and toxicity to FOLFOX chemotherapy in metastatic colorectal cancer

BACKGROUND: To investigate three genetic alterations (TP53 mutation, Kras mutation and microsatellite instability (MSI)) and three polymorphisms (methylene tetrahydrofolate reductase (MTHFR) C677T, excision repair cross complementing group 1 (ERCC1)-118 and X-ray repair cross complementing group 1 (XRCC1)-399) for their ability to predict response, survival and toxicity to FOLFOX first line chemotherapy in the treatment of metastatic colorectal cancer (mCRC). METHODS: Tumour tissues from 118 mCRC patients who underwent FOLFOX treatment from three successive phase II trials were evaluated for mutations in TP53 (exons 5–8) and Kras (codons 12 and 13) and for MSI using PCR-based analysis. Genotyping for common single nucleotide polymorphisms in the MTHFR (codon 677), ERCC1 (codon 118) and XRCC1 (codon 399) genes was also carried out using PCR techniques. These genetic markers were correlated with clinical response, survival and toxicity to treatment. RESULTS: Patients with the T allele of ERCC1-118 showed significantly worse progression-free survival in univariate analysis (HR 2.62; 95 % CI 1.14–6.02; P 0.02). None of the genetic alterations or polymorphisms showed significant association with clinical response to FOLFOX. The MTHFR, ERCC1 and XRCC1 polymorphisms showed no associations with overall haematological, gastrointestinal or neurological toxicity to FOLFOX, although MTHFR 677 TT genotype patients showed a significantly higher incidence of grade 3 or 4 diarrhoea (26%) compared with CC or CT genotype patients (6%, P 0.02). CONCLUSIONS: The ERCC1-118 and MTHFR C677T polymorphisms were associated with progression and severe diarrhoea