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• Prenatal exposure to metals is associated with DNA methylation of repair-genes. • The interaction of potentially toxic and essential elements modified DNA methylation. • PARP1 and OGG1 DNA methylation modulated their mRNA expression. • The role of the interactions of metals on gene regulation needs to be understood. The developmental period in utero is a critical window for environmental exposure. Epigenetic fetal programming via DNA methylation is a pathway through which metal exposure influences the risk of developing diseases later in life. Genetic damage repair can be modified by alterations in DNA methylation, which, in turn, may modulate gene expression due to metal exposure. We investigated the impact of prenatal metal exposure on global and gene-specific DNA methylation and mRNA expression in 181 umbilical cord blood samples from newborns in Mexico City. Global (LINE1) and promoter methylation of DNA-repair (OGG1 and PARP1) and antioxidant (Nrf2) genes was evaluated by pyrosequencing. Prenatal metal exposure (As, Cu, Hg, Mn, Mo, Pb, Se, and Zn) was determined by ICP-MS analysis of maternal urine samples. Multiple regression analyses revealed that DNA methylation of LINE1, Nrf2 , OGG1 , and PARP1 was associated with potentially toxic (As, Hg, Mn, Mo, and Pb) and essential (Cu, Se, and Zn) elements, and with their interactions. We also evaluated the association between gene expression (mRNA levels quantified by p-PCR) and DNA methylation. An increase in OGG1 methylation at all sites and at CpG2, CpG3, and CpG4 sites was associated with reduced mRNA levels; likewise, methylation at the CpG5, CpG8, and CpG11 sites of PARP1 was associated with reduced mRNA expression. In contrast, methylation at the PARP1 CpG7 site was positively associated with its mRNA levels. No associations between Nrf2 expression and CpG site methylation were observed. Our data suggest that DNA methylation can be influenced by prenatal metal exposure, which may contribute to alterations in the expression of repair genes, and therefore, result in a lower capacity for DNA damage repair in newborns. [ABSTRACT FROM AUTHOR]

Abstract: Xylan was isolated from birch wood chips by using pressurized hot water extraction (PHWE). The extracted xylan was chemically modified yielding three different xylan derivatives (XDs): xylan sulfate (XS), carboxymethyl xylan (CMX) and xylan-4-[N,N,N-trimethylammonium]butyrate chloride (XTMAB). The structure and molecular weight of XDs was determined by using NMR spectroscopy and size exclusion chromatography (SEC). The potential utilization of xylan polyelectrolytes for modifying fibre surfaces was assessed by sorption experiments using bleached pine Kraft pulp as substrate. Polyelectrolyte titration method was chosen for estimating the amount of sorbed XDs onto the fibres. The cationic xylan derivative XTMAB had a strong interaction with fibres while the anionic derivatives did not show any sorption. X-ray photoelectron spectroscopy (XPS) and time of flight secondary ion mass spectrometry (ToF-SIMS) were selected as advanced surface analyses for studying the amount of surface anionic groups and the surface distribution of the XTMAB. XPS and polyelectrolyte titration results suggested that the XTMAB is sorbed onto the fibre surfaces. ToF-SIMS imaging showed that XTMAB was evenly distributed on fibre surfaces. [Copyright &y& Elsevier]

Childhood trauma is intimately related with suicidal behaviour. Patients who have suffered childhood trauma develop impaired Reflective Functioning (RF), which refers to the capacity to understand ourselves and others in terms of intentional mental states. An improvement in RF has been associated with a reduction in suicidal attempts, but the mediating role of RF between childhood trauma and suicidal behaviour has not been addressed so far. We aim to examine the potential mediating effect of RF among childhood trauma and suicide attempts. We included 748 patients who had attempted suicide at least once. They were asked to complete the Reflective Functioning Questionnaire (RFQ-8), the Columbia-Suicide Severity Rating scale (CSSRS), and the Childhood Trauma Questionnaire-Short Form (CTQ-SF). We conducted linear regressions by simple mediating model to examine the role of RF in the indirect association between childhood trauma and the number of suicide attempts. Our results show significant indirect effects through hypo and hypermentalizing between Emotional Abuse (EA) and Sexual Abuse (SA) in childhood and the number of suicide attempts in lifetime. These results indicate that ineffective RF significantly mediates the association between childhood trauma and suicidality. This is the first study supporting the mediational role of RF in the relationship between EA and SA , and the number of suicide attempt in lifetime. These findings have important implications for reducing suicide rates and preventing future re-attempts. Further studies analysing this mediating role and focusing efforts on increasing RF-based interventions are required. [ABSTRACT FROM AUTHOR]

BACKGROUND: Alport syndrome (AS) is a genetically heterogeneous hereditary renal disease. X-Linked AS (XLAS) is responsible for 80% to 85% of familial cases and is caused by mutations in the COL4A5 collagen gene. To date, indirect molecular diagnosis for XLAS is not well defined, and mutation screening of the COL4A5 gene is time consuming and complicated because of its large size and high allelic heterogeneity. Our aim is to facilitate XLAS genetic testing. METHODS: For linkage analysis, we tested the applicability of 4 microsatellite markers defining a 1.2-megabase region flanking the COL4A5 gene. For mutation screening of the COL4A5 gene, we describe a new strategy based on direct sequencing of hair root COL4A5 messenger RNA (mRNA). RESULTS: Three microsatellite markers proved accurate (DXS1120, DXS6802, and DXS1210) and 1 was discarded (DXS6797) because it was difficult to interpret. The mutation screening method provides results in 4 days, and when applied to 29 patients suspected of having XLAS, it identified mutations in 76% (22 of 29 patients). This study correlates COL4A5 mutations with effects at the mRNA level and suggests that mutations affecting mRNA splicing of the COL4A5 gene (41%; 9 of 22 patients) are more common than previously described. Many splicing mutations did not alter the canonical 5' and 3' splice sites. CONCLUSIONS: A more reliable linkage analysis and a simple, fast, and efficient mutation screening are now available for the genetic testing of patients with XLAS.Copyright © 2007 by National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that is metabolized to mono(2-ethylhexyl) phthalate (MEHP). Inhalation is an important exposure route for both phthalates, and their effects on lungs include inflammation, alteration of postnatal maturation (alveolarization), enlarged airspaces and cell differentiation changes, suggesting that alveolar epithelial cells-2 (AEC) are targets of phthalates. This study evaluated the cell progression, epithelial and mesenchymal markers, including surfactant secretion in A549 cells (AEC) that were exposed to DEHP (1–100 μM) or MEHP (1–50 μM) for 24–72 h. The results showed an increased cell proliferation at all concentrations of each phthalate at 24 and 48 h. Cell migration showed a concentration-dependent increase at 24 and 48 h of exposure to either phthalate and enlarged structures were seen. Decreased levels of both surfactants (SP-B/SP-C) were observed after the exposure to either phthalate at 48 h, and of SP-C positive cells exposed to MEHP, suggesting a loss of the epithelial phenotype. While a decrease in the epithelial marker E-cadherin and an increase in the mesenchymal marker fibronectin were observed following exposure to either phthalate. Our results showed that DEHP and MEHP altered the structure and migration of A549 cells and promoted the loss of the epithelial phenotype. [ABSTRACT FROM AUTHOR]

Abstract: Lead (Pb) alters sperm chromatin condensation (CC) and the mechanisms are investigated. During spermatogenesis, protamines replace histones and disulfide bonds formation during epididymal maturation condense the chromatin. We evaluated sperm Pb uptake in testis and epididymis and the effects on CC in mice (0.06% Pb2+/16 weeks/drinking water). Spermatozoa from caput epididymis (CP) and cauda epididymis–vas deferens (CE–VD) were obtained and CC was measured by SCSA. Lead levels in spermatozoa from CP were lower than those from CE–VD, and correlated with a decreased CC, while Pb in CE–VD spermatozoa correlated with an increased CC. Lead accumulation into the nucleus was observed and Pb binding to nuclear sulfhydryl groups decreased chromatin decondensation in vitro. Our results suggest that spermatozoa take up Pb during testicular development and epididymal transport and alter CC, depending of the timing of Pb incorporation into the sperm nucleus, which finally may interfere with the chromatin decondensation process after fertilization. [Copyright &y& Elsevier]