117 research outputs found
Perturbation of metabolic pathways mediates the association of air pollutants with asthma and cardiovascular diseases
BACKGROUND: Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and cardiovascular diseases, suggesting the involvement of common altered molecular pathways. OBJECTIVES: The goal was to find intermediate metabolites or metabolic pathways that could be associated with both air pollutants and health outcomes ("meeting-in-the-middle"), thus shedding light on mechanisms and reinforcing causality. METHODS: We applied a statistical approach named 'meet-in-the-middle' to untargeted metabolomics in two independent case-control studies nested in cohorts on adult-onset asthma (AOA) and cardio-cerebrovascular diseases (CCVD). We compared the results to identify both common and disease-specific altered metabolic pathways. RESULTS: A novel finding was a strong association of AOA with ultrafine particles (UFP; odds ratio 1.80 [1.26, 2.55] per increase by 5000âŻparticles/cm3). Further, we have identified several metabolic pathways that potentially mediate the effect of air pollution on health outcomes. Among those, perturbation of Linoleate metabolism pathway was associated with air pollution exposure, AOA and CCVD. CONCLUSIONS: Our results suggest common pathway perturbations may occur as a consequence of chronic exposure to air pollution leading to increased risk for both AOA and CCVD
Prediagnostic plasma concentrations of organochlorines and risk of B-cell non-Hodgkin lymphoma in envirogenomarkers: a nested case-control study
Background: Evidence suggests a largely environmental component to non-Hodgkinâs lymphoma (NHL). Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), DDE and HCB have been repeatedly implicated, but the literature is inconsistent and a causal relationship remains to be determined. Methods: The EnviroGenoMarkers study is nested within two prospective cohorts EPIC-Italy and the Northern Sweden Health and Disease Study. Six PCB congeners, DDE and HCB were measured in blood plasma samples provided at recruitment using gas-chromatography mass spectrometry. During 16 years follow-up 270 incident cases of B-cell NHL (including 76 cases of multiple myeloma) were diagnosed. Cases were matched to 270 healthy controls by centre, age, gender and date of blood collection. Cases were categorised into ordered quartiles of exposure for each POP based on the distribution of exposure in the control population. Logistic regression was applied to assess the association with risk, multivariate and stratified analyses were performed to identify confounders or effect modifiers. Results: The exposures displayed a strong degree of correlation, particularly amongst those PCBs with similar degrees of chlorination. There was no significant difference (pâ90th percentile) the association was null for all POPs Conclusion: We report no evidence that a higher body burden of PCBs, DDE or HCB increased the risk of subsequent NHL diagnosis. Significantly inverse associations were noted for males with a number of the investigated POPs. We hypothesize these unexpected relationships may relate to the subtype composition of our population, effect modification by BMI or other unmeasured confounding. This study provides no additional support for the previously observed role of PCBs, DDE and HCB as risk factors for NHL
Evolving DNA methylation and gene expression markers of B-cell chronic lymphocytic leukemia are present in pre-diagnostic blood samples more than 10Â years prior to diagnosis
An Active Site Aromatic Triad in Escherichia coli DNA Pol IV Coordinates Cell Survival and Mutagenesis in Different DNA Damaging Agents
DinB (DNA Pol IV) is a translesion (TLS) DNA polymerase, which inserts a
nucleotide opposite an otherwise replication-stalling
N2-dG lesion in vitro, and
confers resistance to nitrofurazone (NFZ), a compound that forms these lesions
in vivo. DinB is also known to be part of the cellular
response to alkylation DNA damage. Yet it is not known if DinB active site
residues, in addition to aminoacids involved in DNA synthesis, are critical in
alkylation lesion bypass. It is also unclear which active site aminoacids, if
any, might modulate DinB's bypass fidelity of distinct lesions. Here we
report that along with the classical catalytic residues, an active site
âaromatic triadâ, namely residues F12, F13, and Y79, is critical for
cell survival in the presence of the alkylating agent methyl methanesulfonate
(MMS). Strains expressing dinB alleles with single point
mutations in the aromatic triad survive poorly in MMS. Remarkably, these strains
show fewer MMS- than NFZ-induced mutants, suggesting that the aromatic triad, in
addition to its role in TLS, modulates DinB's accuracy in bypassing
distinct lesions. The high bypass fidelity of prevalent alkylation lesions is
evident even when the DinB active site performs error-prone NFZ-induced lesion
bypass. The analyses carried out with the active site aromatic triad suggest
that the DinB active site residues are poised to proficiently bypass distinctive
DNA lesions, yet they are also malleable so that the accuracy of the bypass is
lesion-dependent
Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation
Dietary acrylamide intake and risk of breast cancer in the UK women's cohort
No studies to date have demonstrated a clear association with breast cancer risk and dietary exposure to acrylamide.Methods:A 217-item food frequency questionnaire was used to estimate dietary acrylamide intake in 33,731 women aged 35-69 years from the UK Women's Cohort Study followed up for a median of 11 years
Novi pogledi na Joakima Stullija (1730-1817), hrvatskog leksikografa, povodom 250. obljetnice roÄenja
EXPOsOMICS is a European Union funded project that aims to develop a novel approach to the assessment of exposure to high priority environmental pollutants, by characterizing the external and the internal components of the exposome. It focuses on air and water contaminants during critical periods of life. To this end, the project centres on 1) exposure assessment at the personal and population levels within existing European short and long-term population studies, exploiting available tools and methods which have been developed for personal exposure monitoring (PEM); and 2) multiple âomicâ technologies for the analysis of biological samples (internal markers of external exposures). The search for the relationships between external exposures and global profiles of molecular features in the same individuals constitutes a novel advancement towards the development of ânext generation exposure assessmentâ for environmental chemicals and their mixtures. The linkage with disease risks opens the way to what are defined here as âexposome-wide association studiesâ (EWAS)
The role of ascorbate in antioxidant protection of biomembranes: Interaction with vitamin E and coenzyme Q
One of the vital roles of ascorbic acid (vitamin C) is to act as an antioxidant to protect cellular components from free radical damage. Ascorbic acid has been shown to scavenge free radicals directly in the aqueous phases of cells and the circulatory system. Ascorbic acid has also been proven to protect membrane and other hydrophobic compartments from such damage by regenerating the antioxidant form of vitamin E. In addition, reduced coenzyme Q, also a resident of hydrophobic compartments, interacts with vitamin E to regenerate its antioxidant form. The mechanism of vitamin C antioxidant function, the myriad of pathologies resulting from its clinical deficiency, and the many health benefits it provides, are reviewed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44796/1/10863_2004_Article_BF00762775.pd
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