Repetitive element hypomethylation in blood leukocyte DNA and cancer incidence, prevalence, and mortality in elderly individuals : the Normative Aging Study

BACKGROUND: Global genomic hypomethylation is a common epigenetic event in cancer that mostly results from hypomethylation of repetitive DNA elements. Case-control studies have associated blood leukocyte DNA hypomethylation with several cancers. Because samples in case-control studies are collected after disease development, whether DNA hypomethylation is causal or just associated with cancer development is still unclear. METHODS: In 722 elderly subjects from the Normative Aging Study cohort, we examined whether DNA methylation in repetitive elements (Alu, LINE-1) was associated with cancer incidence (30 new cases, median follow-up: 89 months), prevalence (205 baseline cases), and mortality (28 deaths, median follow-up: 85 months). DNA methylation was measured by bisulfite pyrosequencing. RESULTS: Individuals with low LINE-1 methylation (<median) had a 3.0-fold (95%CI 1.3-6.9) increased incidence of all cancers combined. LINE-1 and Alu methylation were not significantly associated with cancer prevalence at baseline (all cancers combined). However, individuals with low LINE-1 methylation (<median) had a 3.2-fold (95% CI 1.4-7.5) higher prevalence of lung cancer. Individuals with low LINE-1 or Alu methylation (<median) had increased cancer mortality (HR = 3.2, 95%CI 1.3-7.9 for LINE-1; HR = 2.5, 95%CI 1.1-5.8 for Alu). CONCLUSION: These findings suggest that individuals with lower repetitive element methylation are at high risk of developing and dying from cancer

Arsenic exposure and DNA methylation among elderly men

BACKGROUND: Arsenic exposure has been linked to epigenetic modifications such as DNA methylation in in-vitro and animal studies. This association has also been explored in highly exposed human populations, but studies among populations environmentally exposed to low arsenic levels are lacking. METHODS: We evaluated the association between exposure to arsenic, measured in toenails, and blood DNA methylation in Alu and Long Interspersed Nucleotide Element-1 (LINE-1) repetitive elements in elderly men environmentally exposed to low levels of arsenic. We also explored potential effect modification by plasma folate, cobalamin (vitamin B12), and pyridoxine (vitamin B6). The study population was 581 participants from the Normative Aging Study in Boston, of whom 434, 140, and 7 had 1, 2, and 3 visits, respectively, between 1999-2002 and 2006-2007. We used mixed-effects models and included interaction terms to assess potential effect modification by nutritional factors. RESULTS: There was a trend of increasing Alu and decreasing LINE-1 DNA methylation as arsenic exposure increased. In subjects with plasma folate below the median (<14.1 ng/mL), arsenic was positively associated with Alu DNA methylation (\u3b2 = 0.08 [95% confidence interval = 0.03 to 0.13] for one interquartile range [0.06 \u3bcg/g] increase in arsenic), whereas a negative association was observed in subjects with plasma folate above the median (\u3b2 = -0.08 [-0.17 to 0.01]). CONCLUSIONS: We found an association between arsenic exposure and DNA methylation in Alu repetitive elements that varied by folate level. This suggests a potential role for nutritional factors in arsenic toxicity

Prenatal arsenic exposure and DNA methylation in maternal and umbilical cord blood leukocytes

Background: Arsenic is an epigenetic toxicant and could influence fetal developmental programming.Objectives: We evaluated the association between arsenic exposure and DNA methylation in maternal and umbilical cord leukocytes.Methods: Drinking-water and urine samples were collected when women were at 64 28 weeks gestation; the samples were analyzed for arsenic using inductively coupled plasma mass spectrometry. DNA methylation at CpG sites in p16 (n = 7) and p53 (n = 4), and in LINE-1 and Alu repetitive elements (3 CpG sites in each), was quantified using pyrosequencing in 113 pairs of maternal and umbilical blood samples. We used general linear models to evaluate the relationship between DNA methylation and tertiles of arsenic exposure.Results: Mean (\ub1 SD) drinking-water arsenic concentration was 14.8 \ub1 36.2 \u3bcg/L (range: < 1-230 \u3bcg/L). Methylation in LINE-1 increased by 1.36% [95% confidence interval (CI): 0.52, 2.21%] and 1.08% (95% CI: 0.07, 2.10%) in umbilical cord and maternal leukocytes, respectively, in association with the highest versus lowest tertile of total urinary arsenic per gram creatinine. Arsenic exposure was also associated with higher methylation of some of the tested CpG sites in the promoter region of p16 in umbilical cord and maternal leukocytes. No associations were observed for Alu or p53 methylation.Conclusions: Exposure to higher levels of arsenic was positively associated with DNA methylation in LINE-1 repeated elements, and to a lesser degree at CpG sites within the promoter region of the tumor suppressor gene p16. Associations were observed in both maternal and fetal leukocytes. Future research is needed to confirm these results and determine if these small increases in methylation are associated with any health effect

A self-interaction corrected pseudopotential scheme for magnetic and strongly-correlated systems

Local-spin-density functional calculations may be affected by severe errors when applied to the study of magnetic and strongly-correlated materials. Some of these faults can be traced back to the presence of the spurious self-interaction in the density functional. Since the application of a fully self-consistent self-interaction correction is highly demanding even for moderately large systems, we pursue a strategy of approximating the self-interaction corrected potential with a non-local, pseudopotential-like projector, first generated within the isolated atom and then updated during the self-consistent cycle in the crystal. This scheme, whose implementation is totally uncomplicated and particularly suited for the pseudopotental formalism, dramatically improves the LSDA results for a variety of compounds with a minimal increase of computing cost.Comment: 18 pages, 14 figure

Metabolic Outcomes in Southern Italian Preadolescents Residing Near an Industrial Complex: The Role of Residential Location and Socioeconomic Status

Evidence suggests that environmental exposures and socioeconomic factors may interact to produce metabolic changes in children. We assessed the influence of residential location and socioeconomic status (SES) on pediatric body mass index (BMI) Z-score and fasting blood glucose (FBG) concentration. Participants included 214 children aged 6-11 years who live near a large industrial complex in Taranto, Italy. Participants were grouped into residential zones based on the distance between their home address and the complex periphery (Zone 1: 0.000-4.999 km, Zone 2: 5.000-9.999 km, Zone 3: 10.000-15.000 km). BMI Z-scores were calculated via World Health Organization (WHO) pediatric reference curves. FBG was obtained via venous blood sampling. Closer residential location to the industrial complex on the order of 5.000 km was significantly associated with worsened metabolic outcomes, particularly in female children. Zone 1 participants had higher BMI-adjusted FBG than Zone 2 and 3 participants (p &lt; 0.05 versus Zone 2; p &lt; 0.01 versus Zone 3). SES did not significantly influence BMI-adjusted FBG. Moreover, BMI Z-scores indicated high rates of overweight (22.0%) and obesity (22.9%) in the cohort. BMI Z-score was not significantly associated with SES or residential zone but was negatively associated with maternal education level (p &lt; 0.05). These results offer new evidence that residing near industrial activity may predict adverse effects on child metabolic health

Use of secondary forests by understory birds in a fragmented landscape in central Amazonia

Rates of deforestation in the Brazilian Amazon have increased since 1991 and forecasts are not optimistic about the slowing of this process. Some authors believe that the Amazon may be experiencing a massive process of species extinction. However, the deforestation is accompanied by the expansion of secondary forests that are established in the abandoned areas. The trend is an increase in secondary forests cover, resulting in a mosaic of primary forest (FP) and fragments separated by an array of secondary forests (FS). In this scenario, the prediction of a massive extinction could be wrong if many species could survive in the secondary forests. To assess the importance of FS for the understory birds we sampled areas in regeneration and a continuous forest of a fragmented landscape. We conducted mist netting (24 nets/day) for six consecutive days/month, for 8 months (May-November) in 2009. Some forest species as do not seem to be adapted to the secondary forest environment and their occurrences are restricted to continuous forest environments. But most focal species showed no significant difference in apparent survival rates between the enviroments, suggesting that these species inhabit the secondary forest and the primary forest similarly. Because most of the matrix in fragmented landscapes are composed by secondary forests, such results highlights the conservation value that these habitats present in the long term. Thus, FS should be regarded as dynamic matrix that not only allows the movement of individuals but also function as habitat for many species typical of FP.Na Amazônia, as taxas de desmatamento crescem desde 1991 e as previsões não são otimistas quanto à desaceleração desse processo. A devastação da floresta é acompanhada de uma expansão de florestas secundárias (FS) que se estabelecem nas áreas abandonadas. A tendência é um aumento de florestas secundárias, resultando num mosaico de floresta contínua e fragmentos separados por uma matriz de FS. Nesse cenário, autores acreditam que a Amazônia pode passar por um processo massivo de extinção de espécies. Por outro lado, a previsão de um processo massivo de extinção pode ser equivocada, pois muitas espécies florestais poderiam sobreviver nas florestas secundárias. Para avaliar o valor das florestas secundárias para espécies florestais amostramos por oito meses com redes de neblina uma capoeira (FS) em regeneração e uma floresta primária (FP) de uma paisagem fragmentada. Algumas espécies não foram capturadas na capoeira e aparentemente evitam esse tipo de hábitat. No entanto, a maioria das espécies do grupo focal não apresentou diferença na sobrevivência aparente entre os ambientes, o que nos indica que estão habitando a capoeira e a floresta primária da mesma forma. Na realidade amazônica, onde grande parte da matriz é composta por floresta secundária, a matriz tem valor para conservação e deve ser analisada como um elemento dinâmico que não apenas permite a movimentação de indivíduos, mas também serve de hábitat para muitas espécies de floresta primária. Mas ressaltamos que é fundamental a preservação de áreas de floresta primária que servirão de fonte às florestas secundárias adjacentes

Health Care Utilization During the COVID-19 Pandemic Among Individuals Born Preterm

Importance: Limited data exist on pediatric health care utilization during the COVID-19 pandemic among children and young adults born preterm. Objective: To investigate differences in health care use related to COVID-19 concerns during the pandemic among children and young adults born preterm vs those born at term. Design, Setting, and Participants: In this cohort study, questionnaires regarding COVID-19 and health care utilization were completed by 1691 mother-offspring pairs from 42 pediatric cohorts in the National Institutes of Health Environmental Influences on Child Health Outcomes Program. Children and young adults (ages 1-18 years) in these analyses were born between 2003 and 2021. Data were recorded by the August 31, 2021, data-lock date and were analyzed between October 2021 and October 2022. Exposures: Premature birth (<37 weeks' gestation). Main Outcomes and Measures: The main outcome was health care utilization related to COVID-19 concerns (hospitalization, in-person clinic or emergency department visit, phone or telehealth evaluations). Individuals born preterm vs term (≥37 weeks' gestation) and differences among preterm subgroups of individuals (<28 weeks', 28-36 weeks' vs ≥37 weeks' gestation) were assessed. Generalized estimating equations assessed population odds for health care used and related symptoms, controlling for maternal age, education, and psychiatric disorder; offspring history of bronchopulmonary dysplasia (BPD) or asthma; and timing and age at COVID-19 questionnaire completion. Results: Data from 1691 children and young adults were analyzed; among 270 individuals born preterm, the mean (SD) age at survey completion was 8.8 (4.4) years, 151 (55.9%) were male, and 193 (71.5%) had a history of BPD or asthma diagnosis. Among 1421 comparison individuals with term birth, the mean (SD) age at survey completion was 8.4 (2.4) years, 749 (52.7%) were male, and 233 (16.4%) had a history of BPD or asthma. Preterm subgroups included 159 individuals (58.5%) born at less than 28 weeks' gestation. In adjusted analyses, individuals born preterm had a significantly higher odds of health care utilization related to COVID-19 concerns (adjusted odds ratio [aOR], 1.70; 95% CI, 1.21-2.38) compared with term-born individuals; similar differences were also seen for the subgroup of individuals born at less than 28 weeks' gestation (aOR, 2.15; 95% CI, 1.40-3.29). Maternal history of a psychiatric disorder was a significant covariate associated with health care utilization for all individuals (aOR, 1.44; 95% CI, 1.17-1.78). Conclusions and Relevance: These findings suggest that during the COVID-19 pandemic, children and young adults born preterm were more likely to have used health care related to COVID-19 concerns compared with their term-born peers, independent of a history of BPD or asthma. Further exploration of factors associated with COVID-19-related health care use may facilitate refinement of care models

On the origin and evolution of the material in 67P/Churyumov-Gerasimenko

International audiencePrimitive objects like comets hold important information on the material that formed our solar system. Several comets have been visited by spacecraft and many more have been observed through Earth- and space-based telescopes. Still our understanding remains limited. Molecular abundances in comets have been shown to be similar to interstellar ices and thus indicate that common processes and conditions were involved in their formation. The samples returned by the Stardust mission to comet Wild 2 showed that the bulk refractory material was processed by high temperatures in the vicinity of the early sun. The recent Rosetta mission acquired a wealth of new data on the composition of comet 67P/Churyumov-Gerasimenko (hereafter 67P/C-G) and complemented earlier observations of other comets. The isotopic, elemental, and molecular abundances of the volatile, semi-volatile, and refractory phases brought many new insights into the origin and processing of the incorporated material. The emerging picture after Rosetta is that at least part of the volatile material was formed before the solar system and that cometary nuclei agglomerated over a wide range of heliocentric distances, different from where they are found today. Deviations from bulk solar system abundances indicate that the material was not fully homogenized at the location of comet formation, despite the radial mixing implied by the Stardust results. Post-formation evolution of the material might play an important role, which further complicates the picture. This paper discusses these major findings of the Rosetta mission with respect to the origin of the material and puts them in the context of what we know from other comets and solar system objects