Variation in Mating Dynamics across Five Species of Leiobunine Harvestmen (Arachnida: Opliones)

The study of mating choices often focuses on correlates of traits to the overall outcome of a mating interaction. However, mating interactions can proceed through a series of stages, with opportunities for assessment at each stage. We compared whether male or female size predicted mating interaction outcome across several stages of mating in five species of North American leiobunine harvestmen (commonly known as daddy longlegs). Leiobunine harvestmen have been previously shown to exhibit incredible morphological diversity consistent with a spectrum of male–female antagonism. Across all of the species, we found a general progression of female size predicting the outcome (success and timing) of early stages of interactions, and male size or male size relative to female size predicting the outcome and timing of later stages of interactions. We also found that size was not a strong predictor of outcome in the two species on the lower end of the antagonism spectrum. The variation in how female and male size predicted outcomes across species and stages of mating suggests that multiple mechanisms may operate to shape mating dynamics within and across species. Given the close relatedness of the species studied, the patterns we uncovered suggest a rapid evolution of the traits and processes predicting the outcome of mating interactions

Epigenetic Regulation of the Nitric Oxide Pathway, 17-α Hydroxyprogesterone Caproate, and Recurrent Preterm Birth

Objective We sought to evaluate nitric oxide pathway placental gene expression and the epigenome (CpG methylation) among women receiving 17-α hydroxyprogesterone caproate (17-OHPC) with and without recurrent preterm birth (PTB). Study Design This was a case-control study. We prospectively recruited women with ≥ 1 prior singleton spontaneous PTB <34 weeks receiving 17-OHPC. DNA and RNA were isolated from placentas. RNA abundance (gene expression) and the methylome were analyzed for 84 genes in nitric oxide pathways. Women with recurrent PTB <34 weeks (cases) were compared with those delivering at term (controls). Statistical analysis included multivariable models with Bonferroni's corrected p -values. Results In this study, 17 women met inclusion criteria; 7 preterm cases (delivered at 22.6 ± 2.9 weeks) and 10 term controls (delivered at 38.5 ± 0.8 weeks). Groups had similar PTB history, race/ethnicity, and socioeconomic risk factors for PTB. Twenty-seven nitric oxide genes displayed differential expression (p < 0.05 and q < 0.10) when comparing placentas from preterm cases and term controls; all were downregulated in preterm cases. Eight hundred sixty corresponding CpG sites were differentially methylated between the preterm cases and term controls (Bonferroni's p -value <0.05). Conclusion CpG methylation and gene expression patterns in nitric oxide pathway genes differ among placentas from recurrent PTB compared with term birth following 17-OHPC exposure

Epigenetic Changes Induced by Air Toxics: Formaldehyde Exposure Alters miRNA Expression Profiles in Human Lung Cells

Bac k g r o u n d: Exposure to formaldehyde, a known air toxic, is associated with cancer and lung disease. Despite the adverse health effects of formaldehyde, the mechanisms underlying formaldehydeinduced disease remain largely unknown. Research has uncovered microRNAs (miRNAs) as key posttranscriptional regulators of gene expression that may influence cellular disease state. Although studies have compared different miRNA expression patterns between diseased and healthy tissue, this is the first study to examine perturbations in global miRNA levels resulting from formaldehyde exposure. Objectives: We investigated whether cellular miRNA expression profiles are modified by formaldehyde exposure to test the hypothesis that formaldehyde exposure disrupts miRNA expression levels within lung cells, representing a novel epigenetic mechanism through which formaldehyde may induce disease. Me t h o d s: Human lung epithelial cells were grown at air–liquid interface and exposed to gaseous formaldehyde at 1 ppm for 4 hr. Small RNAs and protein were collected and analyzed for miRNA expression using microarray analysis and for interleukin (IL-8) protein levels by enzyme-linked immunosorbent assay (ELISA). Res u l t s: Gaseous formaldehyde exposure altered the miRNA expression profiles in human lun

Prenatal exposure to multiple metallic and metalloid trace elements and the risk of bacterial sepsis in extremely low gestational age newborns: A prospective cohort study

Background Prenatal exposures to metallic and metalloid trace elements have been linked to altered immune function in animal studies, but few epidemiologic studies have investigated immunological effects in humans. We evaluated the risk of bacterial sepsis (an extreme immune response to bacterial infection) in relation to prenatal metal/metalloid exposures, individually and jointly, within a US-based cohort of infants born extremely preterm. Methods We analyzed data from 269 participants in the US-based ELGAN cohort, which enrolled infants delivered at <28 weeks' gestation (2002–2004). Concentrations of 8 trace elements—including 4 non-essential and 4 essential—were measured using inductively coupled plasma tandem mass spectrometry in umbilical cord tissue, reflecting in utero fetal exposures. The infants were followed from birth to postnatal day 28 with bacterial blood culture results reported weekly to detect sepsis. Discrete-time hazard and quantile g-computation models were fit to estimate associations for individual trace elements and their mixtures with sepsis incidence. Results Approximately 30% of the extremely preterm infants developed sepsis during the follow-up period (median follow-up: 2 weeks). After adjustment for potential confounders, no trace element was individually associated with sepsis risk. However, there was some evidence of a non-monotonic relationship for cadmium, with hazard ratios (HRs) for the second, third, and fourth (highest) quartiles being 1.13 (95% CI: 0.51–2.54), 1.94 (95% CI: 0.87–4.32), and 1.88 (95% CI: 0.90–3.93), respectively. The HRs for a quartile increase in concentrations of all 8 elements, all 4 non-essential elements, and all 4 essential elements were 0.92 (95% CI: 0.68–1.25), 1.19 (95% CI: 0.92–1.55), and 0.77 (95% CI: 0.57–1.06). Cadmium had the greatest positive contribution whereas arsenic, copper, and selenium had the greatest negative contributions to the mixture associations. Conclusions We found some evidence that greater prenatal exposure to cadmium was associated with an increased the risk of bacterial sepsis in extremely preterm infants. However, this risk was counteracted by a combination of arsenic, copper, and selenium. Future studies are needed to confirm these findings and to evaluate the potential for nutritional interventions to prevent sepsis in high-risk infants

Identifying the transcriptional response of cancer and inflammation-related genes in lung cells in relation to ambient air chemical mixtures in Houston, Texas

Atmospheric pollution represents a complex mixture of air chemicals that continually interact and transform, making it difficult to accurately evaluate associated toxicity responses representative of real-world exposure. This study leveraged data from a previously published article and reevaluated lung cell transcriptional response induced by outdoor atmospheric pollution mixtures using field-based exposure conditions in the industrialized Houston Ship Channel. The tested hypothesis was that individual and co-occurring chemicals in the atmosphere relate to altered expression of critical genes involved in inflammation and cancer-related processes in lung cells. Human lung cells were exposed at an air−liquid interface to ambient air mixtures for 4 h, with experiments replicated across 5 days. Real-time monitoring of primary and secondary gas-phase pollutants, as well as other atmospheric conditions, was simultaneously conducted. Transcriptional analysis of exposed cells identified critical genes showing differential expression associated with both individual and chemical mixtures. The individual pollutant identified with the largest amount of associated transcriptional response was benzene. Tumor necrosis factor (TNF) and interferon regulatory factor 1 (IRFN1) were identified as key upstream transcription factor regulators of the cellular response to benzene. This study is among the first to measure lung cell transcriptional responses in relation to real-world, gas-phase air mixtures

Maternal cadmium, iron and zinc levels, DNA methylation and birth weight

Background Cadmium (Cd) is a ubiquitous and environmentally persistent toxic metal that has been implicated in neurotoxicity, carcinogenesis and obesity and essential metals including zinc (Zn) and iron (Fe) may alter these outcomes. However mechanisms underlying these relationships remain limited. Methods We examined whether maternal Cd levels during early pregnancy were associated with offspring DNA methylation at regulatory sequences of genomically imprinted genes and weight at birth, and whether Fe and Zn altered these associations. Cd, Fe and Zn were measured in maternal blood of 319 women ≤12 weeks gestation. Offspring umbilical cord blood leukocyte DNA methylation at regulatory differentially methylated regions (DMRs) of 8 imprinted genes was measured using bisulfite pyrosequencing. Regression models were used to examine the relationships among Cd, Fe, Zn, and DMR methylation and birth weight. Results Elevated maternal blood Cd levels were associated with lower birth weight (p = 0.03). Higher maternal blood Cd levels were also associated with lower offspring methylation at the PEG3 DMR in females (β = 0.55, se = 0.17, p = 0.05), and at the MEG3 DMR in males (β = 0.72, se = 0.3, p = 0.08), however the latter association was not statistically significant. Associations between Cd and PEG3 and PLAGL1 DNA methylation were stronger in infants born to women with low concentrations of Fe (p < 0.05). Conclusions Our data suggest the association between pre-natal Cd and offspring DNA methylation at regulatory sequences of imprinted genes may be sex- and gene-specific. Essential metals such as Zn may mitigate DNA methylation response to Cd exposure. Larger studies are required

Comparative genomic analyses identify common molecular pathways modulated upon exposure to low doses of arsenic and cadmium

<p>Abstract</p> <p>Background</p> <p>Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored.</p> <p>Results</p> <p>In this study, we examined the effects of <it>in vitro </it>exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis.</p> <p>Conclusions</p> <p>This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.</p

RNA-Sequencing of Umbilical Cord Blood to Investigate Spontaneous Preterm Birth: A Pilot Study

Abstract Objective To analyze the transcriptomic gene expression of umbilical cord blood leukocytes using RNA-sequencing from preterm birth (PTB) and term birth (TB). Study Design Eight women with spontaneous PTB (sPTB) and eight women with unlabored TB were enrolled prospectively. The sPTB and TB cohorts were matched for maternal age, race, mode of delivery, and fetal sex. Cord blood RNA was extracted and a globin depletion protocol was applied, then sequenced on the Illumina HiSeq 4000. Raw read counts were analyzed with DESeq2 to test for gene expression differences between sPTB and TB. Results 148 genes had significant differential expression (q < 0.01). Cell cycle/metabolism gene expression was significantly higher and immune/inflammatory signaling gene expression significantly lower in the sPTB cohort compared with term. In African American (AA) infants, 18 genes specific to cell signaling, neutrophil activity, and major histocompatibility complex type 1 had lower expression in preterm compared with term cohort; the opposite pattern was seen in non-Hispanic Whites (NHWs). Conclusion Compared with term, preterm fetuses have higher cell cycle/metabolism gene expression, suggesting metabolic focus on growth and development. Immune function gene expression in this pilot study is lower in the sPTB group compared with term and differs in AA compared with NHW infants