Methylation Status of Imprinted Genes and Repetitive Elements in Sperm DNA from Infertile Males

Stochastic, environmentally and/or genetically induced disturbances in the genome-wide epigenetic reprogramming processes during male germ-cell development may contribute to male infertility. To test this hypothesis, we have studied the methylation levels of 2 paternally (H19 and GTL2) and 5 maternally methylated (LIT1, MEST, NESPAS, PEG3, and SNRPN) imprinted genes, as well as of ALU and LINE1 repetitive elements in 141 sperm samples, which were used for assisted reproductive technologies (ART), including 106 couples with strictly male-factor or combined male and female infertility and 28 couples with strictly female-factor infertility. Aberrant methylation imprints showed a significant association with abnormal semen parameters, but did not seem to influence ART outcome. Repeat methylation also differed significantly between sperm samples from infertile and presumably fertile males. However, in contrast to imprinted genes, ALU methylation had a significant impact on pregnancy and live-birth rate in couples with male-factor or combined infertility. ALU methylation was significantly high-er in sperm samples leading to pregnancy and live-birth than in those that did not. Sperm samples leading to abortions showed significantly lower ALU methylation levels than those leading to the birth of a baby. Copyright (C) 2011 S. Karger AG, Base

Electrical field stimulation-induced excitatory responses of pulmonary artery rings from monocrotaline-induced pulmonary hypertensive rats: influence of the endothelium

Background: Nitric oxide-mediated endothelium-dependent relaxation is attenuated in pulmonary artery segments from monocrotaline (MCT)-induced pulmonary hypertensive rats. However, the influence of the endothelium on adrenergic neurotransmission in the rat pulmonary artery has not been investigated. The aim of the present study was to investigate the effect of the endothelium on electrical field stimulation (EFS)-induced excitatory responses of pulmonary artery segments from pulmonary hypertensive rats. Methods: Pulmonary hypertension was induced in rats with a single dose of monocrotaline (60 mg/kg) and 21 days later, arterial rings were set up for isometric tension recording. EFS-induced contractions were recorded in the presence or absence of drugs. Results: Electrical field stimulation (EFS) induced frequency-dependent contractions in artery segments from control rats and these contractions were not affected by removing the endothelium. L-NAME (10-4 M), a nonselective NO synthase inhibitor, but not 7-NI, a selective neuronal NO synthase inhibitor, potentiated EFS-induced contractions. In addition, L-NAME had no effect on EFS-induced contractions in artery segments without the endothelium indicating a role for endotheliumderived NO in modulating adrenergic neurotransmission in the pulmonary artery. EFS also induced frequency-dependent contractions of artery segments from pulmonary hypertensive rats. These contractions, expressed relative to KCl-induced contractions, were greater in artery segments from pulmonary hypertensive rats. L-NAME (10-4 M) potentiated EFS-induced contractions of artery segments from MCT-treated rats and did not discriminate between artery segments from control and MCT-treated rats. L-NAME potentiated noradrenaline-induced contractions in artery segments from both groups indicating that the effect of L-NAME was mediated post-junctionally. Conclusion: Monocrotaline-induced pulmonary hypertension is associated with enhanced contractile response to EFS In addition, the modulatory effect of endothelial nitric oxide is unaltered in artery segments from pulmonary hypertensive rats.Keywords: Monocrotaline, pulmonary artery, pulmonary hypertension, electrical field stimulaion, NO synthas

TREX1 is expressed by microglia in normal human brain and increases in regions affected by ischemia

BACKGROUND: Mutations in the three-prime repair exonuclease 1 (TREX1) gene have been associated with neurological diseases, including Retinal Vasculopathy with Cerebral Leukoencephalopathy (RVCL). However, the endogenous expression of TREX1 in human brain has not been studied. METHODS: We produced a rabbit polyclonal antibody (pAb) to TREX1 to characterize TREX1 by Western blotting (WB) of cell lysates from normal controls and subjects carrying an RVCL frame-shift mutation. Dual staining was performed to determine cell types expressing TREX1 in human brain tissue. TREX1 distribution in human brain was further evaluated by immunohistochemical analyses of formalin-fixed, paraffin-embedded samples from normal controls and patients with RVCL and ischemic stroke. RESULTS: After validating the specificity of our anti-TREX1 rabbit pAb, WB analysis was utilized to detect the endogenous wild-type and frame-shift mutant of TREX1 in cell lysates. Dual staining in human brain tissues from patients with RVCL and normal controls localized TREX1 to a subset of microglia and macrophages. Quantification of immunohistochemical staining of the cerebral cortex revealed that TREX1 CONCLUSIONS: TREX1 is expressed by a subset of microglia in normal human brain, often in close proximity to the microvasculature, and increases in the setting of ischemic lesions. These findings suggest a role for TREX

Homogenization of dislocation dynamics

In this paper we consider the dynamics of dislocations with the same Burgers vector, contained in the same glide plane, and moving in a material with periodic obstacles. We study two cases: i) the particular case of parallel straight dislocations and ii) the general case of curved dislocations. In each case, we perform rigorously the homogenization of the dynamics and predict the corresponding effective macroscopic elasto-visco-plastic flow rule