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BACKGROUND: Chronic arsenic (As) exposure is a global environmental health issue. Inorganic As (InAs) undergoes methylation to monomethyl (MMAs) and dimethyl-arsenical species (DMAs); full methylation to DMAs facilitates urinary excretion and is associated with reduced risk for As-related health outcomes. Nutritional factors, including folate and creatine, influence one-carbon metabolism, the biochemical pathway that provides methyl groups for As methylation. OBJECTIVE: Our aim was to investigate the effects of supplementation with folic acid (FA), creatine, or the two combined on the concentrations of As metabolites and the primary methylation index (PMI: MMAs/InAs) and secondary methylation index (SMI: DMAs/MMAs) in blood in Bangladeshi adults having a wide range of folate status. METHODS: In a randomized, double-blinded, placebo (PBO)-controlled trial, 622 participants were recruited independent of folate status and assigned to one of five treatment arms: a) PBO (n = 102), b) 400 [micro]g FA/d (400FA; n = 153), c) 800 [micro]g FA/d (800FA; n =151), d) 3 g creatine/d (creatine; n = 101), or e) 3 gcreatine + 400 [micro]g of FA/d (creatine + 400FA; n = 103) for 12 wk. For the following 12 wk, half of the FA participants were randomly switched to the PBO while the other half continued FA supplementation. All participants received As-removal water filters at baseline. Blood As (bAs) metabolites were measured at weeks 0, 1, 12, and 24. RESULTS: At baseline, 80.3% (n = 489) of participants were folate sufficient (>9 nmol/L in plasma). In all groups, bAs metabolite concentrations decreased, likely due to filter use; for example, in the PBO group, blood concentrations of MMAs (bMMAs) (geometric mean [+ or -] geometric standard deviation) decreased from 3.55 [+ or -]1.89 1g/L at baseline to 2.73 [+ or -] 1.74 at week 1. After 1 wk, the mean within- person increase in SMI for the creatine + 400FA group was greater than that of the PBO group (p = 0.05). The mean percentage decrease in bMMAs between baseline and week 12 was greater for all treatment groups compared with the PBO group [400FA: -10.4 (95% CI: -11.9, -8.75), 800FA: -9.54 (95% CI: -11.1, -7.97), creatine: -5.85 (95% CI: -8.59, -3.03), creatine + 400FA: -8.44 (95% CI: -9.95, -6.90), PBO: -2.02 (95% CI: -4.03,0.04)], and the percentage increase in blood DMAs (bDMAs) concentrations for the FA-treated groups significantly exceeded that of PBO [400FA: 12.8 (95% CI: 10.5, 15.2), 800FA: 11.3 (95% CI: 8.95, 13.8), creatine + 400FA: 7.45 (95% CI: 5.23, 9.71), PBO: -0.15 (95% CI: -2.85, 2.63)]. The mean decrease in PMI and increase in SMI in all FA groups significantly exceeded PBO (p < 0.05). Data from week 24 showed evidence of a reversal of treatment effects on As metabolites from week 12 in those who switched from 800FA to PBO, with significant decreases in SMI [-9.0% (95% CI: -3.5, -14.8)] and bDMAs [-5.9% (95% CI: -1.8, -10.2)], whereas PMI and bMMAs concentrations continued to decline [-7.16% (95% CI: -0.48, -14.3) and -3.1% (95% CI: -0.1, -6.2), respectively] for those who remained on 800FA supplementation. CONCLUSIONS: FA supplementation lowered bMMAs and increased bDMAs in a sample of primarily folate-replete adults, whereas creatine supplementation lowered bMMAs. Evidence of the reversal of treatment effects on As metabolites following FA cessation suggests short- term benefits of supplementation and underscores the importance of long-term interventions, such as FA fortification. https://doi.org/10.1289/EHP11270, Introduction Arsenic (As) contamination of groundwater is common in many regions of the world. At least 94 million people worldwide are exposed to concentrations exceeding the World Health Organization (WHO) [...]

BACKGROUND: Global hypomethylation of DNA is thought to constitute an early event in some cancers and occurs in response to arsenic (As) exposure and/or selenium (Se) deficiency in both in [...]

BACKGROUND: Arsenic is a carcinogen to which 35 million people in Bangladesh are chronically exposed. The enzymatic transfer of methyl groups to inorganic As (iAs) generates monomethyl-arsonic (MMA) and dimethylarsinic [...]

BACKGROUND: Approximately 35 million people in Bangladesh are chronically exposed to inorganic arsenic (InAs) in drinking water. Methylation of InAs to monomethylarsonic (MMA) and dimethylarsinic acids (DMA) relies on folate-dependent [...]

Canalization is a fundamental feature of many developmental systems, yet the genetic basis for this property remains elusive. We examine the genetic basis of microenvironmental canalization in the model plant Arabidopsis thaliana, focusing on differential developmental stability between genotypes in one fitness and four quantitative morphological traits. We measured developmental stability in genetically identical replicates of two populations of recombinant inbred (RI) lines and one population of geographically widespread accessions of A. thaliana grown in two different photoperiod-controlled environments. We were able to map quantitative trait loci associated with developmental stability. We also identified a candidate gene, ERECTA, that may contribute to microenvironmental canalization in rosette leaf number under long-day photoperiods, and analysis of mutant lines indicates that the er-105 allele results in increased canalization for this trait. ERECTA, which encodes a signaling protein, appears to act as an ecological amplifier by transducing developmental noise (e.g., microenvironmental variation) into phenotypic differentiation. We also measured genotypic selection on four plant architecture traits and find evidence for selection for both increased and decreased canalization at various traits. developmental noise | developmental stability | ERECTA | phenotypic plasticity | quantitative trait locus mapping

Evolutionary biologists seek to understand the genetic basis for multivariate phenotypic divergence. We constructed an [F.sub.2] mapping population (N = 539) between two distinct populations of Mimulus guttatus. We measured 20 floral, vegetative, and life-history characters on parents and [F.sub.1] and [F.sub.2] hybrids in a common garden experiment. We employed multitrait composite interval mapping to determine the number, effect, and degree of pleiotropy in quantitative trait loci (QTL) affecting divergence in floral, vegetative, and life-history characters. We detected 16 QTL affecting floral traits; 7 affecting vegetative traits; and 5 affecting selected floral, vegetative, and life-history traits. Floral and vegetative traits are clearly polygenic. We detected a few major QTL, with all remaining QTL of small effect. Most detected QTL are pleiotropic, implying that the evolutionary shift between these annual and perennial populations is constrained. We also compared the genetic architecture controlling floral trait divergence both within (our intraspecific study) and between species, on the basis of a previously published analysis of M. guttatus and M. nasutus. Eleven of our 16 floral QTL map to approximately the same location in the interspecific map based on shared, collinear markers, implying that there may be a shared genetic basis for floral divergence within and among species of Mimulus.

We constructed a genetic linkage map between two divergent populations of Mimulus guttatus. We genotyped an [F.sub.2] mapping population (N = 539) at 154 AFLP, microsatellite, and gene-based markers. A framework map was constructed consisting of 112 marker loci on 14 linkage groups with a total map length of 1518 cM Kosambi. Nearly half of all markers (48%) exhibited significant transmission ratio distortion ([alpha] = 0.05). By using a Bayesian multipoint mapping method and visual inspection of significantly distorted markers, we detected 12 transmission ratio distorting loci (TRDL) throughout the genome. The high degree of segregation distortion detected in this intraspecific map indicates substantial genomic divergence that perhaps suggests genomic incompatibilities between these two populations. We compare the pattern of transmission ratio distortion in this map to an interspecific map constructed between M. guttatus and M. nasutus. A similar level of segregation distortion is detected in both maps. Collinear regions between maps are compared to determine if there are shared genetic patterns of non-Mendelian segregation distortion within and among Mimulus species.

BACKGROUND: Exposure to inorganic arsenic is associated with numerous adverse health outcomes, with susceptibility differing by sex. Although evidence from in vitro studies suggests that arsenic alters post-translational histone modifications (PTHMs), evidence in humans is limited. OBJECTIVES: The objectives were to determine: a) if arsenic exposure is associated with global (percent) levels of PTHMs H3K36me2, H3K36me3, and H3K79me2 in a sex-dependent manner, and b) if %PTHMs are stable when arsenic exposure is reduced. METHODS: We examined associations between arsenic, measured in blood and urine, and %PTHMs in peripheral blood mononuclear cells from 317 participants enrolled in the Bangladesh Folic Acid and Creatine Trial (FACT). We also examined the stability of %PTHMs after the use of arsenic-removal water filters (n = 60). RESULTS: Associations between natural log-transformed (ln) urinary arsenic, adjusted for creatinine ([uAs.sub.Cr]), and %H3K36me2 differed significantly between men and women (p = 0.01). ln([uAs.sub.Cr]) was positively associated with %H3K36me2 in men [[beta] = 0.12; 95% confidence interval (CI): 0.01, 0.23, p = 0.03] but was negatively associated with %H3K36me2 in women ([beta] = -0.05; 95% CI: -0.12, 0.02, p = 0.19). The patterns of associations with blood arsenic were similar. On average, water filter use was also associated with reductions in %H3K36me2 (p < 0.01), but this did not differ significantly by sex. Arsenic was not significantly associated with %H3K36me3 or %H3K79me2 in men or women. CONCLUSIONS: Arsenic exposure was associated with %H3K36me2 in a sex-specific manner but was not associated with %H3K36me3 or %H3K79me2. Additional studies are needed to assess changes in %H3K36me2 after arsenic removal. http://dx.doi.org/10.1289/ehp.1510412, Introduction Throughout the world, > 140 million people are exposed to arsenic-contaminated drinking water (Bagchi 2007); in Bangladesh alone, [less than or equal to] 57 million individuals are exposed (Kinniburgh [...]

The most striking feature of the education-reform movement in America today is that it is still with us. During the twentieth century, the country has seen many education-reform efforts come [...]

Public rhetoric on abortion and the journalistic coverage of it has matured in tone and content over the years since women's magazines first broke a long public silence on the issue in the 1940s. Since the 1970s, extremist views on abortion have dominated the press. But new common ground arguments represent an emergence of the feminine ethical response of care and responsibility into the foreground of public discourse where it is tempering the long-dominant language of individual rights with relational concern for others. This article proceeds from a women's voice/experience perspective on feminism and applies a narrative method of rhetorical analysis to the coverage of abortion in American popular media from the 1940s to the 1990s. This analysis is used: (1) to establish that the feminine means of moral reasoning, i.e., the ethic of care (Gilligan, 1982) that is generally relegated to the private sphere, has emerged gradually into the foreground of American public discourse on abortion; (2) to trace a gradual maturation of public discourse on abortion along the path of ethical and epistemological development established by Belenky, Clinchy, Goldberger, and Tarule (1986), and other scholars in the feminist voice tradition; and (3) to compare the recent emergence of common-ground rhetoric on abortion with a similar impulse driving the civic (or public) journalism movement, in terms of the ethical and epistemological orientations they both instantiate.

BACKGROUND: The World Health Organization estimates that >140 million people worldwide are exposed to arsenic (As)--contaminated drinking water. As undergoes biologic methylation, which facilitates renal As elimination. In folate-deficient individuals, this process is augmented by folic acid (FA) supplementation, thereby lowering blood As (bAs). Creatinine concentrations in urine are a robust predictor of As methylation patterns. Although the reasons for this are unclear, creatine synthesis is a major consumer of methyl donors, and this synthesis is down-regulated by dietary/ supplemental creatine. OBJECTIVES: Our aim was to determine whether 400 or 800 µg FA and/or creatine supplementation lowers bAs in an As-exposed Bangladeshi population. METHODS: We conducted a clinical trial in which 622 participants were randomized to receive 400 µg FA, 800 µg FA, 3 g creatine, 3 g creatine+400 µg FA, or placebo daily. All participants received an As-removal filter on enrollment, and were followed for 24 weeks. After the 12th week, half of the two FA groups were switched to placebo to evaluate post-treatment bAs patterns. RESULTS: Linear models with repeated measures indicated that the decline in ln(bAs) from baseline in the 800-µg FA group exceeded that of the placebo group (weeks 1-12: β = -0.09, 95% CI: -0.18, -0.01; weeks 13-24: FA continued: p = -0.12, 95% CI: -0.24, -0.00; FA switched to placebo: β = -0.14, 95% CI: -0.26, -0.02). There was no rebound in bAs related to cessation of FA supplementation. Declines in bAs observed in the remaining treatment arms were not significantly different from those of the placebo group. CONCLUSIONS: In this mixed folate-deficient/replete study population, 12- and 24-week treatment with 800 µg (but not 400 µg) FA lowered bAs to a greater extent than placebo; this was sustained 12 weeks after FA cessation. In future studies, we will evaluate whether FA and/or creatine altered As methylation profiles. Environ Health Perspect 123:1294-1301; http://dx.doi.org/10.1289/ehp.1409396, Introduction Chronic arsenic (As) exposure currently affects well over 140 million people in at least 70 countries worldwide. In Asia, at least 60 million people are at risk of chronic [...]

Background: Intimate partner violence (IPV) and termination of pregnancy (TOP) are global health concerns, but their interaction is undetermined. The aim of this study was to determine whether there is an association between IPV and TOP. Methods and Findings: A systematic review based on a search of Medline, Embase, PsycINFO, and Ovid Maternity and Infant Care from each database's inception to 21 September 2013 for peer-reviewed articles of any design and language found 74 studies regarding women who had undergone TOP and had experienced at least one domain (physical, sexual, or emotional) of IPV. Prevalence of IPV and association between IPV and TOP were meta-analysed. Sample sizes ranged from eight to 33,385 participants. Worldwide, rates of IPV in the preceding year in women undergoing TOP ranged from 2.5% to 30%. Lifetime prevalence by meta-analysis was shown to be 24.9% (95% CI 19.9% to 30.6%);heterogeneity was high ([I.sup.2] > 90%), and variation was not explained by study design, quality, or size, or country gross national income per capita. IPV, including history of rape, sexual assault, contraceptive sabotage, and coerced decision-making, was associated with TOP, and with repeat TOPs. By meta-analysis, partner not knowing about the TOP was shown to be significantly associated with IPV (pooled odds ratio 2.97, 95% CI 2.39 to 3.69). Women in violent relationships were more likely to have concealed the TOP from their partner than those who were not. Demographic factors including age, ethnicity, education, marital status, income, employment, and drug and alcohol use showed no strong or consistent mediating effect. Few long-term outcomes were studied. Women welcomed the opportunity to disclose IPV and be offered help. Limitations include study heterogeneity, potential underreporting of both IPV and TOP in primary data sources, and inherent difficulties in validation. Conclusions: IPV is associated with TOP. Novel public health approaches are required to prevent IPV. TOP services provide an opportune health-based setting to design and test interventions. Please see later in the article for the Editors' Summary., Introduction Intimate partner violence (IPV) has been defined by the World Health Organization (WHO) as 'behaviour within an intimate relationship that causes physical, sexual or psychological harm, including acts of [...]

BACKGROUND: Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a nonlinear relationship between As dose and DNA methylation. OBJECTIVE: The objective of this study was to examine the dose--response relationship between As and global methylation of peripheral blood mononuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water. METHODS: Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [³H]-methyl incorporation assay, which provides disintegration-per-minute (DPM) values that are negatively associated with global DNA methylation. RESULTS: Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-µg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures. CONCLUSIONS: These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate underlying mechanisms and physiologic implications., Introduction An estimated 70 million people in Bangladesh are chronically exposed to arsenic (As)--contaminated drinking water at levels above the World Health Organization (WHO) limit of 10 µg/L (Loewenberg 2007). [...]

BACKGROUND: In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species, thus producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways: a) GSH is synthesized via the transsulfuration pathway, and Cys is the rate-limiting substrate; b) intermediates of the methionine cycle regulate both the transsulfuration pathway and As methylation; c) GSH serves as the electron donor for reduction of arsenate to arsenite; and d) As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys. OBJECTIVES: We tested the hypothesis that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS (i.e., a more oxidized environment). METHODS: For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of five water As concentration categories: < 10 (n = 76), 10-100 (n = 104), 101-200 (n = 86), 201-300 (n = 67), and > 300 µg/L (n = 45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC. RESULTS: An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change, -25.4 µmol/L; 95% CI: -45.3, -5.31) and plasma CySS (mean change, -3.00 µmol/L; 95% CI: -4.61, -1.40). We observed similar associations with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys. CONCLUSIONS: The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other nonprotein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine. http://dx.doi.org/10.1289/ehp.1205727, Introduction Arsenic (As) is a class I human carcinogen that causes several types of cancer (International Agency for Research on Cancer 2004). Chronic As exposure through contaminated drinking water has [...]

A reciprocal transplant experiment is used to examine the presence of divergent natural selection for flowering time and local adaptation between two distinct populations of Mimulus guttatus. Analysis of fitness components indicates that each of these plant populations is locally adapted because of divergent selection suggesting that genetic differentiation in the timing of reproduction may also serve as a partial reproductive isolating barrier to gene flow among populations.

The disciplinary literacy framework, which was introduced in 2002 by the Institute for Learning at the University of Pittsburgh, is grounded in five principles for designing rigorous, inquiry-based instruction that integrates academic content and discipline-appropriate habits of thinking. A discussion on how teachers in the US are using disciplinary literacy principles to help build secondary studentsE academic content knowledge and their reading, writing and thinking skills at the same time.

Suicide notes 'It may be simply that those who write them care more about being remembered.' I know I didn't say much, but I'm in a hurry. 1 There are [...]

Gunshot There seem to be so many movies now, where people get shot in the head. The camera treats them all slightly differently. Tarantino splattered the brains and bits of [...]

Basu et at (2011) reported the associations of both dietary and blood nutrient measures, as well as urinary creatinine (uCr), with arsenic (As) methylation capacity, as assessed by the proportions [...]