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

Laboratory Evaluation of Thin Asphalt Concrete Overlays for Pavement Preservation

A significant percentage of the existing lane miles of roadways in the United States, and in particular in Nevada, consists of rural roads. Thus, using a cost-effective pavement surface treatment becomes critical and essential in reducing maintenance and preservation costs on rural and low volume roads. The overall objective of this study was to assess the use of locally available materials in Nevada for the development of a durable fine-graded thin hot-mix asphalt (HMA) overlay mixture for pavement preservation. Accordingly, a comprehensive laboratory evaluation was conducted. The investigation considered establishing two mix designs using typical local materials for the northern and southern part of the state. For each mixture, the determined optimal binder content based on volumetric properties was varied within the allowable tolerances to simulate the potential variation in asphalt binder content during plant production. The performance of the two thin HMA mixtures were then evaluated at the various asphalt binder contents in terms of their resistance to moisture damage, resistance to surface raveling and abrasion, dynamic modulus property, resistance to rutting, and resistance to reflective cracking. Furthermore, the workability of the designed thin HMA overlay mixtures using the locking point concept in addition to the developed interlayer bond strength using the Louisiana Interlayer Shear Strength Tester were evaluated. Overall, both designed fine-graded mixtures showed a very good performance and are expected to perform well when used as a thin HMA overlay in Nevada. In particular, good stability, very good resistance to surface raveling and abrasion, and excellent resistance to reflective cracking were observed for both thin HMA overlay mixtures at all evaluated asphalt binder contents. A cost analysis was also conducted between the thin HMA overlay and a typically used pavement surface treatment. Based on the findings from this study, it was recommended to construct field test sections in various parts of the state to evaluate the field performance of the developed thin HMA overlay mixtures in Nevada

Variability Of The Moisture Sensitivity Of Field HMA Mixes

The objective of this study is to evaluate the variability in moisture sensitivity of lime treated HMA mixes that were sampled during construction from three projects located in the Truckee Meadows region

Use Of Reclaimed Asphalt Pavements (RAP) In Airfields HMA Pavements

This report documents the results and findings of the AAPTP Project No. 05-06: Use of Reclaimed Asphalt Pavements (RAP) in Airfields HMA Pavements. The report includes a review of current technology in RAP pavements and its application in highway and airfield pavements. Additionally, the report includes the current highway specifications on the use of RAP and a mechanistically based method to transfer the RAP technology that has been successfully used on highway pavements into the design and specification systems for RAP on airport pavements. Review of in-service airfield pavements was conducted as part of this study. Furthermore, the report includes an evaluation of the impact of RAP on the performance life of HMA airfield pavements under three actual airport traffic mixes of a large hub, small hub, and general aviation. The Life cycle cost analysis used the characteristics and mechanical properties of HMA mixtures in the LEDFAA1.3 airfield pavement design software to compare the estimated performance life of HMA pavements with and without RAP materials. Finally, sections 401-3.3 and 403-3.3 of FAA’s P-401 and P-403 specifications, respectively, on RAP were reviewed and recommendations were made based on the findings of the research effort conducted in this project

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

Laboratory Evaluation Of HMA Mixes Manufactured With Pg64-28nv And Pg64-28pm Polymer-modified Asphalt Binders

The purpose of this study was to evaluate and compare the mechanical properties of asphalt mixtures manufactured with PG64-28PM to those manufactured with PG64-28NV. Additionally, a mechanistic-empirical analysis was conducted to evaluate the impact of the two polymer-modified HMA mixtures on predicted pavement performance

Pavement Design and Materials Research 2003-2005 Activities

This report documents the workthat has been completed under the NDOT-UNR cooperative agreement for Pavement Design and Materials Research for the 2003-2005 time period