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Gender and racial/ethnic differences in the associations of urinary phthalate metabolites with markers of diabetes risk: national health and nutrition examination survey 2001–2008
Background
Phthalates are ubiquitous endocrine disrupting chemicals associated with diabetes. Although women and minorities are more likely to be exposed to phthalates, no prior studies have examined phthalate exposure and markers of diabetes risk evaluating effect modification by gender and race/ethnicity.
Methods
We analyzed CDC data for 8 urinary phthalate metabolites from 3,083 non-diabetic, non-pregnant participants aged 12- < 80 years in the National Health and Nutrition Examination Survey (NHANES) 2001–2008. We used median regression to assess the associations between urinary phthalate metabolites and fasting blood glucose (FBG), fasting insulin and Homeostatic Model Assessment of insulin resistance (HOMA-IR), controlling for urinary creatinine as well as several sociodemographic and behavioral factors. Stratified analyses were conducted to compare the gender- and race/ethnicity-specific patterns for the associations.
Results
Urinary levels of several phthalate metabolites, including MBzP, MnBP, MiBP, MCPP and ∑DEHP showed significant positive associations with FBG, fasting insulin and HOMA-IR. No clear difference was noted between men and women. Mexican-Americans and non-Hispanic blacks had stronger dose–response relationships for MnBP, MiBP, MCPP and ∑DEHP compared to non-Hispanic whites. For example, the highest quartile of MiBP relative to its lowest quartile showed a median FBG increase of 5.82 mg/dL (95% CI: 3.77, 7.87) in Mexican-Americans, 3.63 mg/dL (95% CI: 1.23, 6.03) in blacks and 1.79 mg/dL (95% CI: -0.29, 3.87) in whites.
Conclusions
The findings suggest that certain populations may be more vulnerable to phthalates with respect to disturbances in glucose homeostasis. Whether endocrine disrupting chemicals contribute to gender and racial/ethnic differences in diabetes risk will be an important area for further study.
Journal Article
MARTs and MARylation in the Cytosol: Biological Functions, Mechanisms of Action, and Therapeutic Potential
Mono(ADP-ribosyl)ation (MARylation) is a regulatory post-translational modification of proteins that controls their functions through a variety of mechanisms. MARylation is catalyzed by mono(ADP-ribosyl) transferase (MART) enzymes, a subclass of the poly(ADP-ribosyl) polymerase (PARP) family of enzymes. Although the role of PARPs and poly(ADP-ribosyl)ation (PARylation) in cellular pathways, such as DNA repair and transcription, is well studied, the role of MARylation and MARTs (i.e., the PARP ‘monoenzymes’) are not well understood. Moreover, compared to PARPs, the development of MART-targeted therapeutics is in its infancy. Recent studies are beginning to shed light on the structural features, catalytic targets, and biological functions of MARTs. The development of new technologies to study MARTs have uncovered essential roles for these enzymes in the regulation of cellular processes, such as RNA metabolism, cellular transport, focal adhesion, and stress responses. These insights have increased our understanding of the biological functions of MARTs in cancers, neuronal development, and immune responses. Furthermore, several novel inhibitors of MARTs have been developed and are nearing clinical utility. In this review, we summarize the biological functions and molecular mechanisms of MARTs and MARylation, as well as recent advances in technology that have enabled detection and inhibition of their activity. We emphasize PARP-7, which is at the forefront of the MART subfamily with respect to understanding its biological roles and the development of therapeutically useful inhibitors. Collectively, the available studies reveal a growing understanding of the biochemistry, chemical biology, physiology, and pathology of MARTs.
Journal Article
Urinary Phthalate Metabolite Concentrations and Diabetes among Women in the National Health and Nutrition Examination Survey (NHANES) 2001-2008
Background: Previous studies have shown that women have higher urinary concentrations of several phthalate metabolites than do men, possibly because of a higher use of personal care products. Few studies have evaluated the association between phthalate metabolites, diabetes, and diabetesrelated risk factors among women. Objective: We explored the association between urinary phthalate metabolite concentrations and diabetes among women who participated in a cross-sectional study. Methods: We used urinary concentrations of phthalate metabolites, analyzed by the Centers for Disease Control and Prevention, and self-reported diabetes of 2,350 women between 20 and 79 years of age who participated in the NHANES (2001-2008). We used multiple logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) and adjusted for urinary creatinine, sociodemographic characteristics, dietary factors, and body size. A secondary analysis was conducted for women who did not have diabetes to evaluate the association between phthalate metabolite concentrations and fasting blood glucose (FBG), homeostasis model assessmentestimated insulin resistance, and glycosylated hemoglobin A1c. Results: After adjusting for potential confounders, women with higher levels of mono-n-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono-(3-carboxypropyl) phthalate (MCPP), and three di-(2-ethylhexyl) phthalate metabolites (∑DEHP) had an increased odds of diabetes compared with women with the lowest levels of these phthalates. Women in the highest quartile for MBzP and MiBP had almost twice the odds of diabetes [OR = 1.96 (95% CI: 1.11, 3.47) and OR = 1.95 (95% CI: 0.99, 3.85), respectively] compared with women in the lowest quartile. Nonmonotonic, positive associations were found for MnBP and ∑DEHP, whereas MCPP appeared to have a threshold effect. Certain phthalate metabolites were positively associated with FBG and insulin resistance. Discussion: Urinary levels of several phthalates were associated with prevalent diabetes. Future prospective studies are needed to further explore these associations to determine whether phthalate exposure can alter glucose metabolism and increase the risk of insulin resistance and diabetes.
Journal Article
A nuclear-targeted effector of Rhizophagus irregularis interferes with histone 2B mono-ubiquitination to promote arbuscular mycorrhisation
• Arguably, symbiotic arbuscular mycorrhizal (AM) fungi have the broadest host range of all fungi, being able to intracellularly colonise root cells in the vast majority of all land plants. This raises the question how AM fungi effectively deal with the immune systems of such a widely diverse range of plants.
• Here, we studied the role of a nuclear-localisation signal-containing effector from Rhizophagus irregularis, called Nuclear Localised Effector1 (RiNLE1), that is highly and specifically expressed in arbuscules.
• We showed that RiNLE1 is able to translocate to the host nucleus where it interacts with the plant core nucleosome protein histone 2B (H2B). RiNLE1 is able to impair the mono-ubiquitination of H2B, which results in the suppression of defence-related gene expression and enhanced colonisation levels.
• This study highlights a novel mechanism by which AM fungi can effectively control plant epigenetic modifications through direct interaction with a core nucleosome component. Homologues of RiNLE1 are found in a range of fungi that establish intimate interactions with plants, suggesting that this type of effector may be more widely recruited to manipulate host defence responses.
Journal Article
Association of Exposure to Phthalates with Endometriosis and Uterine Leiomyomata: Findings from NHANES, 1999-2004
BACKGROUND: Phthalates are ubiquitous chemicals used in consumer products. Some phthalates are reproductive toxicants in experimental animals, but human data are limited. OBJECTIVE: We conducted a cross-sectional study of urinary phthalate metabolite concentrations in relation to self-reported history of endometriosis and uterine leiomyomata among 1,227 women 20-54 years of age from three cycles of the National Health and Nutrition Examination Survey (NHANES), 1999-2004. METHODS: We examined four phthalate metabolites: mono(2-ethylhexyl) phthalate (MEHP), monobutyl phthalate (MBP), monoethyl phthalate and monobenzyl phthalate (MBzP). From the last two NHANES cycles, we also examined mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP). We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: Eighty-seven (7%) and 151 (12%) women reported diagnoses of endometriosis and leiomyomata, respectively, lhe ORs comparing the highest versus lowest three quartiles of urinary MBP were 1.36 (95% CI, 0.77-2.41) for endometriosis, 1.56 (95% CI, 0.93-2.61) for leiomyomata, and 1.71 (95% CI, 1.07-2.75) for both conditions combined. The corresponding ORs for MEHP were 0.44 (95% CI, 0.19-1.02) for endometriosis, 0.63 (95% CI, 0.35-1.12) for leiomyomata, and 0.59 (95% CI, 0.37-0.95) for both conditions combined. Findings for MEHHP and MEOHP agreed with findings for MEHP with respect to endometriosis only. We observed null associations for and MBzP. Associations were similar when we excluded women diagnosed > 7 years before their NHANES evaluation. CONCLUSION: The positive associations for MBP and inverse associations for MEHP in relation to endometriosis and leiomyomata warrant investigation in prospective studies.
Journal Article
Fat and vitamin intakes during pregnancy have stronger relations with a proinflammatory maternal microbiota than does carbohydrate intake
Background Although diet is known to have a major modulatory influence on gut microbiota, knowledge of the specific roles of particular vitamins, minerals, and other nutrients is limited. Modulation of the composition of the microbiota in pregnant women is especially important as maternal microbes are transferred during delivery and initiate the colonization process in the infant. We studied the associations between intake of specific dietary nutrients during pregnancy and gut microbiota composition. Methods Utilizing the Norwegian NoMIC cohort, we examined the relations between intakes of 28 dietary macro- and micronutrients during pregnancy, derived from food frequency questionnaires administered to 60 women in the second trimester, and observed taxonomic differences in their gut microbiota four days after delivery (assessed through Illumina 16S rRNA amplicon analysis). Results Higher dietary intakes of fat-soluble vitamins, especially vitamin D, were associated with reduced microbial alpha diversity (p value <0.001). Furthermore, using recently developed statistical methodology, we discovered that the variations in fat-soluble vitamins, saturated and mono-unsaturated fat, and cholesterol intake, were associated with changes in phyla composition. Specifically, vitamin D, mono-unsaturated fat, cholesterol, and retinol were associated with relative increases in Proteobacteria, which is a phylum known to encompass multiple pathogens and to have pro-inflammatory properties. In contrast, saturated fat, vitamin E, and protein were associated with relative decreases in Proteobacteria. Conclusions The results in this article indicate that fats and fat-soluble vitamins are among the most potent dietary modulators of gut microbiota in mothers. The shifts in microbiota due to diet need to be further studied alongside gut microbiota changes during pregnancy to better understand the impact on infant gut microbiota.
Journal Article
Preparation of Tough, Binder‐Free, and Self‐Supporting LiFePO4 Cathode by Using Mono‐Dispersed Ultra‐Long Single‐Walled Carbon Nanotubes for High‐Rate Performance Li‐Ion Battery
Low‐contents/absence of non‐electrochemical activity binders, conductive additives, and current collectors are a concern for improving lithium‐ion batteries' fast charging/discharging performance and developing free‐standing electrodes in the aspects of flexible/wearable electronic devices. Herein, a simple yet powerful fabricating method for the massive production of mono‐dispersed ultra‐long single‐walled carbon nanotubes (SWCNTs) in N‐methyl‐2‐pyrrolidone solution, benefiting from the electrostatic dipole interaction and steric hindrance of dispersant molecules, is reported. These SWCNTs form a highly efficient conductive network to firmly fix LiFePO4 (LFP) particles in the electrode at low contents of 0.5 wt% as conductive additives. The binder‐free LFP/SWCNT cathode delivers a superior rate capacity of 161.5 mAh g−1 at 0.5 C and 130.2 mAh g−1 at 5 C, with a high‐rate capacity retention of 87.4% after 200 cycles at 2 C. The self‐supporting LFP/SWCNT cathode shows excellent mechanical properties, which can withstand at least 7.2 MPa stress and 5% strain, allowing the fabrication of high mass loading electrodes with thicknesses up to 39.1 mg cm−2. Such self‐supporting electrodes display conductivities up to 1197 S m−1 and low charge‐transfer resistance of 40.53 Ω, allowing fast charge delivery and enabling near‐theoretical specific capacities. A simple yet powerful fabricating method for the massive production of mono‐dispersed ultra‐long single‐walled carbon nanotubes (SWCNTs) in N‐methyl‐2‐pyrrolidone solution, benefiting from the electrostatic dipole interaction and steric hindrance of dispersant molecules, is reported. These SWCNTs form a highly efficient conductive network to firmly fix LiFePO4 particles in the electrode at low contents of 0.5 wt% as conductive additives.
Journal Article
Estimation of plasma levels of bisphenol-A & phthalates in fertile & infertile women by gas chromatography-mass spectrometry
Background & objectives: Bisphenol-A (BPA) and phthalates are utilized widely in consumer products. Due to their ubiquitous presence in the environment, a concern is expressed worldwide about their possible effect on human reproductive health. This study was conducted to compare the internal exposure of BPA and phthalates (using their metabolites as biomarkers) in plasma samples of infertile and fertile women.
Methods: A sensitive gas chromatographic-mass spectrometric (GC-MS) method was developed to simultaneously quantify BPA and four phthalate monoester metabolites [namely mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), mono-2-ethylhexyl phthalate (MEHP) and mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP)] in human plasma. The method was validated using charcoal-stripped human plasma. Activated charcoal was also utilized to reduce contamination from reagents. The method was designed to account for and/or eliminate background contamination from all sources.
Results: The limit of quantification for the method was 5 ng/ml for MMP and MBzP, while 1 ng/ml for BPA, MEHP and MEHHP, respectively. The precision and accuracy were well within the acceptable range. BPA was detectable in 77 per cent of plasma samples of infertile women and 29 per cent of fertile women. All the four phthalate metabolites were detected in plasma samples of both fertile and infertile women.
Interpretation & conclusions: A GC-MS was developed and validated to estimate the BPA and four phthalate monoester metabolites in human plasma. It was utilised to analyse the plasma samples from fertile and infertile women. The infertile women showed significantly higher plasma concentrations of MBzP, BPA and MEHHP as compared to fertile women. The levels of MMP and MEHP were not significantly different between the two groups. Further studies need to be done to confirm these preliminary findings.
Journal Article
Life cycle assessment of most widely adopted solar photovoltaic energy technologies by mid-point and end-point indicators of ReCiPe method
The present article focuses on a cradle-to-grave life cycle assessment (LCA) of the most widely adopted solar photovoltaic power generation technologies, viz., mono-crystalline silicon (mono-Si), multi-crystalline silicon (multi-Si), amorphous silicon (a-Si) and cadmium telluride (CdTe) energy technologies, based on ReCiPe life cycle impact assessment method. LCA is the most powerful environmental impact assessment tool from a product perspective and ReCiPe is one of the most advanced LCA methodologies with the broadest set of mid-point impact categories. More importantly, ReCiPe combines the strengths of both mid-point-based life cycle impact assessment approach of CML-IA, and end-point-based approach of Eco-indicator 99 methods. Accordingly, the LCA results of all four solar PV technologies have been evaluated and compared based on 18 mid-point impact indicators (viz., climate change, ozone depletion, terrestrial acidification, freshwater eutrophication, marine eutrophication, human toxicity, photochemical oxidant formation, particulate matter formation, terrestrial ecotoxicity, freshwater ecotoxicity, marine ecotoxicity, ionising radiation, agricultural land occupation, urban land occupation, natural land transformation, water depletion, metal depletion and fossil depletion), 3 end-point/damage indicators (viz., human health, ecosystems and cost increases in resource extraction) and a unified single score. The overall study has been conducted based on
hierarchist
perspective and according to the relevant ISO standards. Final results show that the CdTe thin-film solar plant carries the least environmental life cycle impact within the four PV technologies, sequentially followed by multi-Si, a-Si and mono-Si technology.
Journal Article