Association of high sensitive C-reactive protein (hsCRP) with established cardiovascular risk factors in the Indian population

Introduction Inflammation, the key regulator of C-reactive protein (CRP) synthesis, plays a pivotal role in atherothrombotic cardiovascular disease. Methods High sensitivity CRP (hsCRP) analysis was carried out in randomly selected 600 individuals from the sentinel surveillance study in Indian industrial population (SSIP). The hsCRP was measured quantitatively by turbid metric test using kits from SPINREACT, Spain. We analyzed the association between hsCRP and traditional CVD risk factors in this sub-sample. Results Complete risk factor data and CRP levels were available from 581/600 individuals. One half (51.2%) of the study subjects were males. Mean age of the study group was 39.2 ± 11.2 years. The Pearson correlation coefficients were in the range of 0.12 for SBP (p = 0.004) to 0.55 for BMI (p < 0.001). The linear regression coefficients ranged from 0.01 for SBP, PG and TC (p < 0.001) to 0.55 for logeTAG (p < 0.001) after adjustment for age, sex and education. The mean of logehsCRP significantly increased (P < 0.001) from individuals with ≤1 risk factors (-0.50) to individuals with three or more risk factors (0.60). In the multivariate model, the odds ratios for elevated CRP (CRP ≥ 2.6 mg/dl) were significantly elevated only in females in comparison to males (1.63, 95% CI; 1.02-2.58), overweight individuals in comparison to normal weight individuals (3.90, 95% CI; 2.34-6.44, p < 0.001), and abdominal obese individuals (1.62, 95% CI; 1.02-2.60, p = 0.04) in comparison to non-obese individuals. Conclusion Clinical measurements of adiposity (body mass index and abdominal obesity) correlate well and can be surrogate for systemic inflammatory state of individuals

Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins.

This is a freely-available open access publication. Please cite the published version which is available via the DOI link in this record.Asthma is the most common chronic inflammatory disorder in children. The aetiology of asthma pathology is complex and highly heterogeneous, involving the interplay between genetic and environmental risk factors that is hypothesized to involve epigenetic processes. Our aim was to explore whether methylomic variation in early childhood is associated with discordance for asthma symptoms within monozygotic (MZ) twin pairs recruited from the Environmental Risk (E-Risk) longitudinal twin study. We also aimed to identify differences in DNA methylation that are associated with asthma that develops in childhood and persists into early adulthood as these may represent useful prognostic biomarkers. RESULTS: We examined genome-wide patterns of DNA methylation in buccal cell samples collected from 37 MZ twin pairs discordant for asthma at age 10. DNA methylation at individual CpG sites demonstrated significant variability within discordant MZ twin pairs with the top-ranked nominally significant differentially methylated position (DMP) located in the HGSNAT gene. We stratified our analysis by assessing DNA methylation differences in a sub-group of MZ twin pairs who remained persistently discordant for asthma at age 18. The top-ranked nominally significant DMP associated with persisting asthma is located in the vicinity of the HLX gene, which has been previously implicated in childhood asthma. CONCLUSIONS: We identified DNA methylation differences associated with childhood asthma in peripheral DNA samples from discordant MZ twin pairs. Our data suggest that differences in DNA methylation associated with childhood asthma which persists into early adulthood are distinct from those associated with asthma which remits.Medical Research Council (MRC)National Institute of Child Health and Development (NICHD)American Asthma FoundationMRC Centenary Awar

Bioavailability of iodine in the UK-Peak District environment and its human bioaccessibility: an assessment of the causes of historical goitre in this area

Iodine is an essential micronutrient for human health. Its deficiency causes a number of functional and developmental abnormalities such as goitre. The limestone region of Derbyshire, UK was goitre-endemic until it declined from the 1930s and the reason for this has escaped a conclusive explanation. The present study investigates the cause(s) of goitre in the UK-Peak District area through an assessment of iodine in terms of its environmental mobility, bioavailability, uptake into the food chain and human bioaccessibility. The goitre-endemic limestone area is compared with the background millstone grit area of the UK-Peak District. The findings of this study show that ‘total’ environmental iodine is not linked to goitre in the limestone area, but the governing factors include iodine mobility, bioavailability and bioaccessibility. Compared with the millstone grit area, higher soil pH and calcium content of the limestone area restrict iodine mobility in this area, also soil organic carbon in the limestone area is influential in binding the iodine to the soil. Higher calcium content in the limestone area is an important factor in terms of strongly fixing the iodine to the soil. Higher iodine bioaccessibility in the millstone grit than the limestone area suggests that its oral bioaccessibility is restricted in the limestone area. Iodine taken up by plant roots is transported freely into the aerial plant parts in the millstone grit area unlike the limestone area, thus providing higher iodine into the human food chain in the millstone grit area through grazing animals unlike the goitre-prevalent limestone area

An “In-Depth” Description of the Small Non-coding RNA Population of Schistosoma japonicum Schistosomulum

Parasitic flatworms of the genus Schistosoma are the causative agents of schistosomiasis, which afflicts more than 200 million people yearly in tropical regions of South America, Asia and Africa. A promising approach to the control of this and many other diseases involves the application of our understanding of small non-coding RNA function to the design of safe and effective means of treatment. In a previous study, we identified five conserved miRNAs from the adult stage of Schistosoma japonicum. Here, we applied Illumina Solexa high-throughput sequencing methods (deep sequencing) to investigate the small RNAs expressed in S. japonicum schistosomulum (3 weeks post-infection). This has allowed us to examine over four million sequence reads including both frequently and infrequently represented members of the RNA population. Thus we have identified 20 conserved miRNA families that have orthologs in well-studied model organisms and 16 miRNA that appear to be specific to Schistosoma. We have also observed minor amounts of heterogeneity in both 3′ and 5′ terminal positions of some miRNA as well as RNA fragments resulting from the processing of miRNA precursor. An investigation of the genomic arrangement of the 36 identified miRNA revealed that seven were tightly linked in two clusters. We also identified members of the small RNA population whose structure indicates that they are part of an endogenously derived RNA silencing pathway, as evidenced by their extensive complementarities with retrotransposon and retrovirus-related Pol polyprotein from transposon

Targeted Destruction of Photosensitive Retinal Ganglion Cells with a Saporin Conjugate Alters the Effects of Light on Mouse Circadian Rhythms

Non-image related responses to light, such as the synchronization of circadian rhythms to the day/night cycle, are mediated by classical rod/cone photoreceptors and by a small subset of retinal ganglion cells that are intrinsically photosensitive, expressing the photopigment, melanopsin. This raises the possibility that the melanopsin cells may be serving as a conduit for photic information detected by the rods and/or cones. To test this idea, we developed a specific immunotoxin consisting of an anti-melanopsin antibody conjugated to the ribosome-inactivating protein, saporin. Intravitreal injection of this immunotoxin results in targeted destruction of melanopsin cells. We find that the specific loss of these cells in the adult mouse retina alters the effects of light on circadian rhythms. In particular, the photosensitivity of the circadian system is significantly attenuated. A subset of animals becomes non-responsive to the light/dark cycle, a characteristic previously observed in mice lacking rods, cones, and functional melanopsin cells. Mice lacking melanopsin cells are also unable to show light induced negative masking, a phenomenon known to be mediated by such cells, but both visual cliff and light/dark preference responses are normal. These data suggest that cells containing melanopsin do indeed function as a conduit for rod and/or cone information for certain non-image forming visual responses. Furthermore, we have developed a technique to specifically ablate melanopsin cells in the fully developed adult retina. This approach can be applied to any species subject to the existence of appropriate anti-melanopsin antibodies

Sequence Relationships among C. elegans, D. melanogaster and Human microRNAs Highlight the Extensive Conservation of microRNAs in Biology

microRNAs act in a prevalent and conserved post-transcriptional gene regulatory mechanism that impacts development, homeostasis and disease, yet biological functions for the vast majority of miRNAs remain unknown. Given the power of invertebrate genetics to promote rapid evaluation of miRNA function, recently expanded miRNA identifications (miRBase 10.1), and the importance of assessing potential functional redundancies within and between species, we evaluated miRNA sequence relationships by 5′ end match and overall homology criteria to compile a snapshot overview of miRNA families within the C. elegans and D. melanogaster genomes that includes their identified human counterparts. This compilation expands literature documentation of both the number of families and the number of family members, within and between nematode and fly models, and highlights sequences conserved between species pairs or among nematodes, flies and humans. Themes that emerge include the substantial potential for functional redundancy of miRNA sequences within species (84/139 C. elegans miRNAs and 70/152 D. melanogaster miRNAs share significant homology with other miRNAs encoded by their respective genomes), and the striking extent to which miRNAs are conserved across species—over half (73/139) C. elegans miRNAs share sequence homology with miRNAs encoded also in both fly and human genomes. This summary analysis of mature miRNA sequence relationships provides a quickly accessible resource that should facilitate functional and evolutionary analyses of miRNAs and miRNA families

The ERI-6/7 Helicase Acts at the First Stage of an siRNA Amplification Pathway That Targets Recent Gene Duplications

Endogenous small interfering RNAs (siRNAs) are a class of naturally occuring regulatory RNAs found in fungi, plants, and animals. Some endogenous siRNAs are required to silence transposons or function in chromosome segregation; however, the specific roles of most endogenous siRNAs are unclear. The helicase gene eri-6/7 was identified in the nematode Caenorhabditis elegans by the enhanced response to exogenous double-stranded RNAs (dsRNAs) of the null mutant. eri-6/7 encodes a helicase homologous to small RNA factors Armitage in Drosophila, SDE3 in Arabidopsis, and Mov10 in humans. Here we show that eri-6/7 mutations cause the loss of 26-nucleotide (nt) endogenous siRNAs derived from genes and pseudogenes in oocytes and embryos, as well as deficiencies in somatic 22-nucleotide secondary siRNAs corresponding to the same loci. About 80 genes are eri-6/7 targets that generate the embryonic endogenous siRNAs that silence the corresponding mRNAs. These 80 genes share extensive nucleotide sequence homology and are poorly conserved, suggesting a role for these endogenous siRNAs in silencing of and thereby directing the fate of recently acquired, duplicated genes. Unlike most endogenous siRNAs in C. elegans, eri-6/7–dependent siRNAs require Dicer. We identify that the eri-6/7–dependent siRNAs have a passenger strand that is ∼19 nt and is inset by ∼3–4 nts from both ends of the 26 nt guide siRNA, suggesting non-canonical Dicer processing. Mutations in the Argonaute ERGO-1, which associates with eri-6/7–dependent 26 nt siRNAs, cause passenger strand stabilization, indicating that ERGO-1 is required to separate the siRNA duplex, presumably through endonucleolytic cleavage of the passenger strand. Thus, like several other siRNA–associated Argonautes with a conserved RNaseH motif, ERGO-1 appears to be required for siRNA maturation