Distribution of macroinvertebrate communities across surface and groundwater habitats in response to hydrological variability

Macroinvertebrate communities are strongly influenced by hydrological variability in surface waters. However, the response of these communities in corresponding groundwater-dependent habitats is not well understood. This study characterised the macroinvertebrate fauna and physicochemical characteristics of a chalk aquifer and its rivers in southern England. Over one year, samples were collected from five paired benthic-hyporheic sites located in perennial or temporary rivers, and a further seven phreatic sites in the surrounding aquifer. The study was preceded by a period of below average rainfall, providing an opportunity to assess the response of macro-invertebrate communities to unseasonal declines in river discharge and groundwater levels. Benthic, hyporheic and phreatic habitats each supported a distinct macroinvertebrate community, with the hyporheic habitat support- ing both epigean taxa and stygofauna. As discharge declined, the composition of these communities changed. In particular, the abundance of the epigean amphipod Gammarus pulex was higher in hyporheic than benthic habitats during periods of low river discharge, suggesting potential refuge-seeking behaviour. Similarly, fluctuations in the abundance and distribution of two stygofauna, Crangonyx subterraneus and Niphargus fontanus, coincided with marked changes in groundwater levels, suggesting that the contraction of available habitat and changes in connectivity also influenced the phreatic community. The variable distribution of macroinvertebrates between these habitats, especially in response to hydrological variability, suggests a dynamic connection between the river and its aquifer. This connection is an important consideration for the assessment and conservation management of both surface and groundwater communities and may help underpin integrated, catchment-based management, especially in river systems with temporary reaches

DNA methylation profiling to assess pathogenicity of BRCA1 unclassified variants in breast cancer

Germline pathogenic mutations in BRCA1 increase risk of developing breast cancer. Screening for mutations in BRCA1 frequently identifies sequence variants of unknown pathogenicity and recent work has aimed to develop methods for determining pathogenicity. We previously observed that tumor DNA methylation can differentiate BRCA1-mutated from BRCA1-wild type tumors. We hypothesized that we could predict pathogenicity of variants based on DNA methylation profiles of tumors that had arisen in carriers of unclassified variants. We selected 150 FFPE breast tumor DNA samples [47 BRCA1 pathogenic mutation carriers, 65 BRCAx (BRCA1-wild type), 38 BRCA1 test variants] and analyzed a subset (n=54) using the Illumina 450K methylation platform, using the remaining samples for bisulphite pyrosequencing validation. Three validated markers (BACH2, C8orf31, and LOC654342) were combined with sequence bioinformatics in a model to predict pathogenicity of 27 variants (independent test set). Predictions were compared with standard multifactorial likelihood analysis. Prediction was consistent for c.5194-12G>A (IVS 19-12 G>A) (P>0.99); 13 variants were considered not pathogenic or likely not pathogenic using both approaches. We conclude that tumor DNA methylation data alone has potential to be used in prediction of BRCA1 variant pathogenicity but is not independent of estrogen receptor status and grade, which are used in current multifactorial models to predict pathogenicity

Stilbenoids remodel the DNA methylation patterns in breast cancer cells and inhibit oncogenic NOTCH signaling through epigenetic regulation of MAML2 transcriptional activity

DNA hypomethylation was previously implicated in cancer progression and metastasis. The purpose of this study was to examine whether stilbenoids, resveratrol and pterostilbene thought to exert anticancer effects, target genes with oncogenic function for de novo methylation and silencing, leading to inactivation of related signaling pathways. Following Illumina 450K, genome-wide DNA methylation analysis reveals that stilbenoids alter DNA methylation patterns in breast cancer cells. On average, 75% of differentially methylated genes have increased methylation, and these genes are enriched for oncogenic functions, including NOTCH signaling pathway. MAML2, a coactivator of NOTCH targets, is methylated at the enhancer region and transcriptionally silenced in response to stilbenoids, possibly explaining the downregulation of NOTCH target genes. The increased DNA methylation at MAML2 enhancer coincides with increased occupancy of repressive histone marks and decrease in activating marks. This condensed chromatin structure is associated with binding of DNMT3B and decreased occupancy of OCT1 transcription factor at MAML2 enhancer, suggesting a role of DNMT3B in increasing methylation of MAML2 after stilbenoid treatment. Our results deliver a novel insight into epigenetic regulation of oncogenic signals in cancer and provide support for epigenetic-targeting strategies as an effective anticancer approach

Epigenome-wide association study reveals decreased average methylation levels years before breast cancer diagnosis

Interest in the potential of DNA methylation in peripheral blood as a biomarker of cancer risk is increasing. We aimed to assess whether epigenome-wide DNA methylation measured in peripheral blood samples obtained before onset of the disease is associated with increased risk of breast cancer. We report on three independent prospective nested case-control studies from the European Prospective Investigation into Cancer and Nutrition (EPIC-Italy; n = 162 matched case-control pairs), the Norwegian Women and Cancer study (NOWAC; n = 168 matched pairs), and the Breakthrough Generations Study (BGS; n = 548 matched pairs). We used the Illumina 450k array to measure methylation in the EPIC and NOWAC cohorts. Whole-genome bisulphite sequencing (WGBS) was performed on the BGS cohort using pooled DNA samples, combined to reach 50× coverage across ~16 million CpG sites in the genome including 450k array CpG sites. Mean β values over all probes were calculated as a measurement for epigenome-wide methylation

Cattle management practices and milk production on mixed smallholder organic pineapple farms in Central Uganda

A longitudinal study to assess animal management practices and milk production was conducted for a period of 12 months on 30 smallholder farms keeping dairy cattle and certified organic pineapple production in Luwero and Kayunga districts, based on questionnaire and on-farm collected data. Farm sizes were 9.3 ± 6.7 acres in tethering system and 4.3 ± 2.6 acres in zero-grazing. Fifty-four percent of the zero-grazing herds had animal housing facilities. All farmers in tethering system kept cows on earthen floors and calves without bedding. Hygiene level in existing farms was low. Majority of calves were fed once a day by restricted suckling (77 %). Seventy-four percent of tethered cows were only fed on natural grass, while cows under zero-grazing system had a more diversified diet but with 82 % feeding mainly Napier grass. Most farms (87 %) used bulls for breeding. Milk production was higher (P < 0.05) in zero-grazing (6.5 L/cow/day) than tethering system, and higher (P < 0.05) for Holstein-Friesian crossbred cows (5.2 L/cow/day) than local breed cows (2.6 L/cow/day). Less than 1 L of milk per farm per day on average was sold. Disease treatments were exclusively for helminths, East Coast fever, and trypanasomiasis. Spraying of ticks and deworming were important control measures of vector-borne diseases. There is potential to develop alternative feed resources for dairy cattle and biorational pesticides for control and treatment of vector-borne diseases

The Surface Waters Acidification Project Palaeolimnology Programme: modern diatom/lake-water chemistry data-set

In 1983, when the Surface Waters Acidification Programme (SWAP) was announced, we were asked to design and implement a palaeolimnology sub-project involving scientists from Sweden, Norway, and the UK. Our aim was to reconstruct the acidification history of a range of sites in the three countries and to identify and evaluate the various alternative causes of lake acidification. The results of the project have been published recently (Battarbee et al. 1990, Renberg and Battarbee 1990). Although a comprehensive range of palaeolimnological methods and approaches was used in the study we recognised diatom analysis as central to the entire project. We consequently committed considerable effort to improving our diatom methodology and we were especially concerned with the pursuit of a common approach to diatom taxonomy and pH reconstruction. This effort centred on the creation and analysis of a large data-set of surface-sediment diatom assemblages and associated environmental variables from 170 sites representing the full range of lake types in the acid-sensitive and acidified regions of the three countries

Intragenic DNA methylation: implications of this epigenetic mechanism for cancer research

Epigenetics is the study of all mechanisms that regulate gene transcription and genome stability that are maintained throughout the cell division, but do not include the DNA sequence itself. The best-studied epigenetic mechanism to date is DNA methylation, where methyl groups are added to the cytosine base within cytosine–guanine dinucleotides (CpG sites). CpGs are frequently clustered in high density (CpG islands (CGIs)) at the promoter of over half of all genes. Current knowledge of transcriptional regulation by DNA methylation centres on its role at the promoter where unmethylated CGIs are present at most actively transcribed genes, whereas hypermethylation of the promoter results in gene repression. Over the last 5 years, research has gradually incorporated a broader understanding that methylation patterns across the gene (so-called intragenic or gene body methylation) may have a role in transcriptional regulation and efficiency. Numerous genome-wide DNA methylation profiling studies now support this notion, although whether DNA methylation patterns are a cause or consequence of other regulatory mechanisms is not yet clear. This review will examine the evidence for the function of intragenic methylation in gene transcription, and discuss the significance of this in carcinogenesis and for the future use of therapies targeted against DNA methylation

Methylation deregulation of miRNA promoters identifies miR124-2 as a survival biomarker in Breast Cancer in very young women

MiRNAs are part of the epigenetic machinery, and are also epigenetically modified by DNA methylation. MiRNAs regulate expression of different genes, so any alteration in their methylation status may affect their expression. We aimed to identify methylation differences in miRNA encoding genes in breast cancer affecting women under 35 years old (BCVY), in order to identify potential biomarkers in these patients. In Illumina Infinium MethylationEPIC BeadChip samples (metEPICVal), we analysed the methylation of 9,961 CpG site regulators of miRNA-encoding genes present in the array. We identified 193 differentially methylated CpG sites in BCVY (p-value < 0.05 and methylation differences ±0.1) that regulated 83 unique miRNA encoding genes. We validated 10 CpG sites using two independent datasets based on Infinium Human Methylation 450k array. We tested gene expression of miRNAs with differential methylation in BCVY in a meta-analysis using The Cancer Genome Atlas (TCGA), Clariom D and Affymetrix datasets. Five miRNAs (miR-9, miR-124-2, miR-184, miR-551b and miR-196a-1) were differently expressed (FDR p-value < 0.01). Finally, only miR-124-2 shows a significantly different gene expression by quantitative real-time PCR. MiR-124-hypomethylation presents significantly better survival rates for older patients as opposed to the worse prognosis observed in BCVY, identifying it as a potential specific survival biomarker in BCVY

Dense, fast, radiation-tolerant Fluoro-Hafnate glass scintillators for electromagnetic calorimeters in high energy physics

Over 200 different compositions of heavy metal fluoride glasses have been produced and evaluated as possible candidates for the active medium in homogeneous electromagnetic calorimeters for high energy particles. Promising glasses, based on mixtures containing hafnium fluoride, have densities of 6 g/cm^3, radiation lengths of 1.6 cm, and good optical transmission from the UV to the IR. Glasses containing the Ce3+ ion are fast scintillators, with properties similar to those of pure cerium fluoride crystal. We have made glasses which have up to 14% of the light yield of CeF3, fast scintillation characterised by typical exponential decay constants of 10 ns and 25 ns, and a temperature dependence of light yield of -0.4%/C over the range -10C to 60C. We have carried out a detailed investigation of the effects of gamma irradiation (up to doses of 6kGy) on the optical transmission, and systematic studies into the role of indium and other elements on radiation tolerance and light yield. Some glasses have shown complete optical annealing of radiation-induced absorbance when exposed to UV light.PPAR

Ixodes ricinus Tick Lipocalins: Identification, Cloning, Phylogenetic Analysis and Biochemical Characterization

BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: Screening a cDNA library in association with RT-PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the salivary glands of the Ixodes ricinus hard tick. A computational in-depth structural analysis confirmed that LIRs belong to the lipocalin family. These proteins were called LIR for "Lipocalin from I. ricinus" and numbered from 1 to 14 (LIR1 to LIR14). According to their percentage identity/similarity, LIR proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57 respectively. In a western blot analysis, all recombinant LIRs appeared as a series of thin bands at 50-70 kDa, suggesting extensive glycosylation, which was experimentally confirmed by treatment with N-glycosidase F. In addition, the in vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed homogeneous expression profiles for certain phylogenetic groups and relatively heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes for a protein that specifically binds leukotriene B4. CONCLUSIONS/SIGNIFICANCE: This work confirms that, regarding their biochemical properties, expression profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more specifically in the Ixodes ricinus species, are segregated into distinct phylogenetic groups suggesting potential distinct function. This was particularly demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP, norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally leukotrienes B4 and C4.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe