Estimation of solar prominence magnetic fields based on the reconstructed 3D trajectories of prominence knots

We present an estimation of the lower limits of local magnetic fields in quiescent, activated, and active (surges) promineces, based on reconstructed 3-dimensional (3D) trajectories of individual prominence knots. The 3D trajectories, velocities, tangential and centripetal accelerations of the knots were reconstructed using observational data collected with a single ground-based telescope equipped with a Multi-channel Subtractive Double Pass imaging spectrograph. Lower limits of magnetic fields channeling observed plasma flows were estimated under assumption of the equipartition principle. Assuming approximate electron densities of the plasma n_e = 5*10^{11} cm^{-3} in surges and n_e = 5*10^{10} cm^{-3} in quiescent/activated prominences, we found that the magnetic fields channeling two observed surges range from 16 to 40 Gauss, while in quiescent and activated prominences they were less than 10 Gauss. Our results are consistent with previous detections of weak local magnetic fields in the solar prominences.Comment: 14 pages, 12 figures, 1 tabl

The Genomic Loci of Specific Human tRNA Genes Exhibit Ageing-Related DNA Hypermethylation

Abstract Understanding how the epigenome deteriorates with age and subsequently impacts on biological function may bring unique insights to ageing-related disease mechanisms. As a central cellular apparatus, tRNAs are fundamental to the information flow from DNA to proteins. Whilst only being transcribed from ~46kb ( < 0.002%) of the human genome, their transcripts are the second most abundant in the cell. Furthermore, it is now increasingly recognised that tRNAs and their fragments also have complex regulatory functions. In both their core translational and additional regulatory roles, tRNAs are intimately involved in the control of metabolic processes known to affect ageing. Experimentally DNA methylation can alter tRNA expression, but little is known about the genomic DNA methylation state of tRNAs. Here, we find that the human genomic tRNA loci (610 tRNA genes termed the tRNAome) are enriched for ageing-related DNA hypermethylation. We initially identified DNA hypermethylation of 44 and 21 specific tRNA genes, at study-wide (p < 4.34 × 10 − 9 ) and genome-wide ( p < 4.34 × 10 − 9 ) significance, respectively, in 4,350 MeDIP-seq peripheral blood DNA methylomes (16 - 82 years). This starkly contrasted with 0 hypomethylated at both these significance levels. Further analysing the 21 genome-wide results, we found 3 of these tRNAs to be independent of major changes in cell-type composition (tRNA-iMet-CAT-1-4, tRNA-Ser-AGA-2-6, tRNA-Ile-AAT-4-1). We also excluded the ageing-related changes being due to the inherent CpG density of the tRNAome by permutation analysis (1,000x, Empirical p-value < 1 × 10 − 3 ). We additionally explored 79 tRNA loci in an independent cohort using Fluidigm deep targeted bisulfite-sequencing of pooled DNA (n=190) across a range of 4 timepoints (aged ~4, ~28, ~63, ~78 years). This revealed these ageing changes to be specific to particular isodecoder copies of these tRNA (tRNAs coding for the same amino acid but with sequence body differences) and included replication of 2 of the 3 genome-wide tRNAs. Additionally, this isodecoder-specificity may indicate the potential for regulatory fragment changes with age. In this study we provide the first comprehensive evaluation at the genomic DNA methylation state of the human tRNAome, revealing a discreet and strongly directional hypermethylation with advancing age

The Genomic Loci of Specific Human tRNA Genes Exhibit Ageing-Related DNA Hypermethylation

The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ~46kb (<0.002% genome), is the second most abundant cellular transcript. tRNAs also control metabolic processes known to affect ageing, through core translational and additional regulatory roles. Here, we interrogate the DNA methylation state of the genomic loci of human tRNA. We identify a genomic enrichment for age-related DNA hypermethylation at tRNA loci. Analysis in 4,350 MeDIP-seq peripheral-blood DNA methylomes (16-82 years), identifies 44 and 21 hypermethylating specific tRNAs at study-and genome-wide significance, respectively, contrasting with 0 hypomethylating. Validation and replication (450k array & independent targeted Bisuphite-sequencing) supported the hypermethylation of this functional unit. Tissue-specificity is a significant driver, although the strongest consistent signals, also independent of major cell-type change, occur in tRNA-iMet-CAT-1-4 and tRNA-Ser-AGA-2-6. This study presents a comprehensive evaluation of the genomic DNA methylation state of human tRNA genes and reveals a discreet hypermethylation with advancing age

Integrated transcriptomics and metabolomics reveal signatures of lipid metabolism dysregulation in HepaRG liver cells exposed to PCB 126.

Chemical pollutant exposure is a risk factor contributing to the growing epidemic of non-alcoholic fatty liver disease (NAFLD) affecting human populations that consume a western diet. Although it is recognized that intoxication by chemical pollutants can lead to NAFLD, there is limited information available regarding the mechanism by which typical environmental levels of exposure can contribute to the onset of this disease. Here, we describe the alterations in gene expression profiles and metabolite levels in the human HepaRG liver cell line, a validated model for cellular steatosis, exposed to the polychlorinated biphenyl (PCB) 126, one of the most potent chemical pollutants that can induce NAFLD. Sparse partial least squares classification of the molecular profiles revealed that exposure to PCB 126 provoked a decrease in polyunsaturated fatty acids as well as an increase in sphingolipid levels, concomitant with a decrease in the activity of genes involved in lipid metabolism. This was associated with an increased oxidative stress reflected by marked disturbances in taurine metabolism. A gene ontology analysis showed hallmarks of an activation of the AhR receptor by dioxin-like compounds. These changes in metabolome and transcriptome profiles were observed even at the lowest concentration (100 pM) of PCB 126 tested. A decrease in docosatrienoate levels was the most sensitive biomarker. Overall, our integrated multi-omics analysis provides mechanistic insight into how this class of chemical pollutant can cause NAFLD. Our study lays the foundation for the development of molecular signatures of toxic effects of chemicals causing fatty liver diseases to move away from a chemical risk assessment based on in vivo animal experiments

Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats.

Health effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect. Contrastingly, serum and caecum metabolomics revealed that nicotinamide and tryptophan metabolism were affected, which suggested activation of an oxidative stress response. This was not reflected by gut microbial community composition changes evaluated by shotgun metagenomics. Transcriptomics of the liver showed that 257 genes had their expression changed. Gene functions affected included the regulation of response to steroid hormones and the activation of stress response pathways. Genome-wide DNA methylation analysis of the same liver samples showed that 4,255 CpG sites were differentially methylated. Overall, we demonstrated that in-depth molecular profiling in laboratory animals exposed to low concentrations of pesticides allows the detection of metabolic perturbations that would remain undetected by standard regulatory biochemical measures and which could thus improve the predictability of health risks from exposure to chemical pollutants

Single cell sequencing data identify distinct B cell and fibroblast populations in stricturing Crohn's disease.

Single cell RNA sequencing of human full thickness Crohn's disease (CD) small bowel resection specimens was used to identify potential therapeutic targets for stricturing (S) CD. Using an unbiased approach, 16 cell lineages were assigned within 14,539 sequenced cells from patient-matched SCD and non-stricturing (NSCD) preparations. SCD and NSCD contained identical cell types. Amongst immune cells, B cells and plasma cells were selectively increased in SCD samples. B cell subsets suggested formation of tertiary lymphoid tissue in SCD and compared with NSCD there was an increase in IgG, and a decrease in IgA plasma cells, consistent with their potential role in CD fibrosis. Two Lumican-positive fibroblast subtypes were identified and subclassified based on expression of selectively enriched genes as fibroblast clusters (C) 12 and C9. Cells within these clusters expressed the profibrotic genes Decorin (C12) and JUN (C9). C9 cells expressed ACTA2; ECM genes COL4A1, COL4A2, COL15A1, COL6A3, COL18A1 and ADAMDEC1; LAMB1 and GREM1. GO and KEGG Biological terms showed extracellular matrix and stricture organization associated with C12 and C9, and regulation of WNT pathway genes with C9. Trajectory and differential gene analysis of C12 and C9 identified four sub-clusters. Intra sub-cluster gene analysis detected 13 co-regulated gene modules that aligned along predicted pseudotime trajectories. CXCL14 and ADAMDEC1 were key markers in module 1. Our findings support further investigation of fibroblast heterogeneity and interactions with local and circulating immune cells at earlier time points in fibrosis progression. Breaking these interactions by targeting one or other population may improve therapeutic management for SCD

Coupled-channels analysis of the 16^{{\bf 16}}O+208^{{\bf 208}}Pb fusion barrier distribution

Analyses using simplified coupled-channels models have been unable to describe the shape of the previously measured fusion barrier distribution for the doubly magic $^{16}$O+$^{208}$Pb system. This problem was investigated by re-measuring the fission excitation function for $^{16}$O+$^{208}$Pb with improved accuracy and performing more exact coupled-channels calculations, avoiding the constant-coupling and first-order coupling approximations often used in simplified analyses. Couplings to the single- and 2-phonon states of $^{208}$Pb, correctly taking into account the excitation energy and the phonon character of these states, particle transfers, and the effects of varying the diffuseness of the nuclear potential, were all explored. However, in contrast to other recent analyses of precise fusion data, no satisfactory simultaneous description of the shape of the experimental barrier distribution and the fusion cross-sections for $^{16}$O+$^{208}$Pb was obtained.Comment: RevTex, 29 pages, 7 postscript figures, to appear in PR

Ethnic Variation in Inflammatory Profile in Tuberculosis

PMCID: PMC3701709This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited