Emission of methane from plants Nisbet, R.E.R; Fisher, R; Nimmo, R.H ...
Proceedings of the Royal Society. B, Biological sciences,
04/2009, Letnik:
276, Številka:
1660
Journal Article
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It has been proposed that plants are capable of producing methane by a novel and unidentified biochemical pathway. Emission of methane with an apparently biological origin was recorded from both ...whole plants and detached leaves. This was the first report of methanogenesis in an aerobic setting, and was estimated to account for 10-45 per cent of the global methane source. Here, we show that plants do not contain a known biochemical pathway to synthesize methane. However, under high UV stress conditions, there may be spontaneous breakdown of plant material, which releases methane. In addition, plants take up and transpire water containing dissolved methane, leading to the observation that methane is released. Together with a new analysis of global methane levels from satellite retrievals, we conclude that plants are not a major source of the global methane production.
MicroRNAs: new players in IBD Kalla, R; Ventham, N T; Kennedy, N A ...
Gut,
03/2015, Letnik:
64, Številka:
3
Journal Article
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MicroRNAs (miRNAs) are small non-coding RNAs, 18-23 nucleotides long, which act as post-transcriptional regulators of gene expression. miRNAs are strongly implicated in the pathogenesis of many ...common diseases, including IBDs. This review aims to outline the history, biogenesis and regulation of miRNAs. The role of miRNAs in the development and regulation of the innate and adaptive immune system is discussed, with a particular focus on mechanisms pertinent to IBD and the potential translational applications.
Epigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 ...newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2 and TXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci; VMP1/microRNA-21 methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within the TXK promoter region negatively correlates with gene expression in whole-blood and CD8
T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression.
Several lines of evidence suggest a role for the multidrug resistance gene (ABCB1/MDR1) and its product, P-glycoprotein 170, in the pathogenesis of inflammatory bowel disease (IBD). In addition, ...P-glycoprotein activity determines bioavailability of many drugs used regularly in many medical specialities, and ABCB/MDR1 variation appears to be a critical pharmacogenetic determinant. We have utilized a gene-wide haplotype tagging approach to further define the identity of germ-line variations in the ABCB1/MDR1 gene contributing to IBD susceptibility. Six haplotype tagging single nucleotide polymorphisms (tSNPs) representing the haplotypic variations of the ABCB1/MDR1 gene were identified initially following the characterization of the haplotype structure of this gene in 24 Centre d'Etude du Polymorphisme Humain Caucasian trios. Genotyping was performed in 249 ulcerative colitis (UC) and 179 Crohn's disease (CD) patients and 260 healthy controls. Using log-likelihood analysis, we observed a highly significant association between the common haplotypes and UC (P=4.22×10−7) but not CD (P=0.22). This significant association was critically dependent on one tSNP, intronic variant rs3789243. All haplotypes with this variant retained a highly significant association (P=3.2×10−7–3.6×10−12), whereas significance was lost when rs3789243 was dropped in systematic haplotypic analysis. The effect of this tSNP was independent of C3435T SNP, previously suggested to be the critical variant in disease susceptibility and drug transport. The association with UC was shown to be strongest with the phenotype of extensive disease (P=1.7×10−7). This ‘candidate gene’ approach provides compelling evidence to support the contribution of the ABCB1/MDR1 gene in determining risk to UC but not to CD and provides new insights into the localization of the critical susceptibility determinants within the gene. In addition, these findings have potentially important implications in the application of pharmacogenetics across a range of common diseases, including HIV, epilepsy and colorectal cancer.
Telomeres, the specialized nucleoprotein structures that comprise the ends of eukaryotic chromosomes, are essential for complete replication, and regulation of their length has been a focus of ...research on tumorigenesis. In the budding yeast Saccharomyces cerevisiae, the protein Rap1p binds to telomeric DNA and functions in the regulation of telomere length. A human telomere protein, hTRF (human TTAGGG repeat factor) binds the telomere sequence in vitro and localizes to telomeres cytologically, but its functions are not yet known. Here we use a genetic screen to identify a telomere protein in fission yeast, Taz1p (telomere-associated in Schizosaccharomyces pombe), that shares homology to the Myb proto-oncogene DNA-binding domain with hTRF. Disruption or deletion of the taz1+ gene causes a massive increase in telomere length. Taz1p is required for the repression of telomere-adjacent gene expression and for normal meiosis or sporulation. It may be a negative regulator of the telomere-replicating enzyme, telomerase, or may protect against activation of telomerase-independent pathways of telomere elongation.
NOD2/caspase recruitment domain (CARD)15 variants are identified in up to 50% of Crohn's disease (CD) patients. Functional variants of toll-like receptor-4 (TLR4) and CD14 genes may also be relevant ...to disease pathophysiology. We aimed to assess the contribution of NOD2/CARD15, TLR4 and CD14 variants in Scottish and Irish CD patients. In all, 612 patients with well-characterised inflammatory bowel disease (252 Scottish CD, 247 Scottish UC, 113 Irish CD) and 304 controls were genotyped for variants of NOD2/CARD15 (1007fsinsC, G908R, R702W, P268S), TLR4 (A299G) and CD14 (T-159C). Genotype-phenotype analyses were performed. Variant 1007fsinsC (P=0.003) and G908R (P=0.008) but not R702W (P=0.269) alleles were more prevalent in Scottish CD (4.7, 1.8 and 7.1%, respectively) than Scottish control (2.3, 0.3 and 5.4%). CD allelic frequencies were lower than the series from Europe (P<0.00001) and North America (P<0.00001) but not Scandinavia (P<0.7). Associations were identified with age at diagnosis (P=0.002), ileal disease (P<0.02), penetrating disease (P=0.04) and inflammatory joint disease (P<0.02). TLR4 and CD14 variants did not differ between CD and controls. In conclusion, we present compelling evidence for genetic heterogeneity within Europe. These NOD2/CARD15 variants have a minor contribution in Scottish and Irish CD patients, consistent with an emerging pattern from Northern Europe.
We infer the elastic thickness of regions of the Moon by performing an admittance analysis on GRAIL gravity and LOLA topography data. Reliable results are generally confined to the lunar farside, ...away from large mare deposits. We find that elastic thickness varies between 13 km and 72 km, with a mean elastic thickness (Te) of 29 km. The highest reliable elastic thicknesses are found to the northwest of South Pole-Aitken (SPA) basin while the lowest elastic thicknesses are found in the equatorial farside and within SPA. Our findings suggest that much of the loading on the Moon must have taken place within the first 200 Myr after lunar magma ocean solidification, though some areas (Te > 40 km) may be recording events as late at 3.5 Ga. We find no correlation between elastic thickness and crater density, crustal thickness, or mean elevation in areas where reliable estimates of elastic thickness can be made, though we do note that regions with the highest crustal thickness and mean elevation are associated with lower elastic thickness values. We also demonstrate that smaller localization windows can lead to systematically lower elastic thickness estimates.
During mitotic prophase, chromosomes frequently adopt a bouquet-like arrangement, with their telomeres clustered close to the nuclear periphery. A dramatic example of this occurs in the fission ...yeast, Schizosaccharomyces pombe, where all telomeres aggregate adjacent to the spindle pole body (SPB). Nuclei then undergo rapid traverses of the cell, known as 'horsetail' movement, which is led by the SPB dragging telomeres and chromosomes behind. This process may initiate or facilitate chromosome pairing before recombination and meiosis. With the aim of identifying components involved in telomere structure and function, we report here the isolation of S. pombe mutants defective in the ability to impose transcriptional silencing on genes placed near telomeres. Two of these mutants, lot2-s17 and lot3-uv3, also display a dramatic lengthening of telomeric repeats. lot3-uv3 carries a mutation in Taz1, a telomere-binding protein containing a Myb-like motif similar to two human telomere-binding proteins. Meiosis is aberrant in these mutant yeast strains, and our analysis demonstrates a decreased association of telomeres with the SPB in mitotic prophase. This results in defective 'horsetail' movement, a significant reduction in recombination, low spore viability and chromosome missegregation through meiosis.
SUMMARY
Anti‐Saccharomyces cerevisiae antibodies (ASCAs) have been proposed as serological markers, which may differentiate Crohn's disease (CD) from ulcerative colitis (UC) and predict disease ...phenotype. Their importance in pathogenesis is unproven. We investigated the relationship between ASCAs, disease phenotype and NOD2/CARD15 genotype in CD and whether ASCAs were related to antibodies to other fungal proteins. Serum from 228 patients 143 CD, 75 UC, 10 with indeterminate colitis (IC) and 78 healthy controls (HC) were assayed for ASCA. Antibodies (IgA, IgG) to other fungal proteins (Fusarium species ATC20334, Mycoprotein) were measured in the same samples using an in‐house enzyme‐linked immunosorbent assay (ELISA) assay. ASCAs were present in 57% of CD, 19% of UC, 30% of IC and 8% of HCs. ASCA‐positive status was a predictor for CD with sensitivity of 57%, specificity of 87%, positive predictive value of 78% and negative predictive value of 68%. ASCA was associated with proximal (gastroduodenal and small bowel involvement) rather than purely colonic disease (P < 0·001) and with a more severe disease phenotype and requirement for surgery over a median follow‐up time of 9 years (P < 0·0001). No associations with NOD2/CARD15 mutations were seen. There was no association between ASCA and antibodies to MP (IgA or IgG). These data implicate ASCA as a specific marker of disease location and progression in CD, emphasizing the heterogeneity within IBD.
The chronic inflammatory bowel diseases Crohn's disease and ulcerative colitis are common causes of gastrointestinal disease in northern Europe, affecting as many as one in 250 people. Although ...mortality is low, morbidity associated with these diseases is substantial. We review the recent advances in the genetics of inflammatory bowel disease, with particular emphasis on the data that have been generated since the discovery of the
CARD15 (NOD2) gene in 2001.
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