Idiopathic Male Infertility Is Strongly Associated with Aberrant Promoter Methylation of Methylenetetrahydrofolate Reductase (MTHFR)

Abnormal germline DNA methylation in males has been proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. Previous studies have been focused on imprinted genes with DNA methylation in poor quality human sperms. However, recent but limited data have revealed that sperm methylation abnormalities may involve large numbers of genes or shown that genes that are not imprinted are also affected.Using the methylation-specific polymerase chain reaction and bisulfite sequencing method, we examined methylation patterns of the promoter of methylenetetrahydrofolate reductase (MTHFR) gene (NG_013351: 1538-1719) in sperm DNA obtained from 94 idiopathic infertile men and 54 normal fertile controls. Subjects with idiopathic infertility were further divided into groups of normozoospermia and oligozoospermia. Overall, 45% (41/94) of idiopathic infertile males had MTHFR hypermethylation (both hemimethylation and full methylation), compared with 15% of fertile controls (P<0.05). Subjects with higher methylation level of MTHFR were more likely to have idiopathic male infertility (P-value for trend  = 0.0007). Comparing the two groups of idiopathic infertile subjects with different sperm concentrations, a higher methylation pattern was found in the group with oligozoospermia.Hypermethylation of the promoter of MTHFR gene in sperms is associated with idiopathic male infertility. The functional relevance of hypermathylation of MTHFR to male fertility warrants further investigation

Large-scale Synthesis of β-SiC Nanochains and Their Raman/Photoluminescence Properties

Although the SiC/SiO2 nanochain heterojunction has been synthesized, the chained homogeneous nanostructure of SiC has not been reported before. Herein, the novel β-SiC nanochains are synthesized assisted by the AAO template. The characterized results demonstrate that the nanostructures are constructed by spheres of 25–30 nm and conjoint wires of 15–20 nm in diameters. Raman and photoluminescence measurements are used to explore the unique optical properties. A speed-alternating vapor–solid (SA-VS) growth mechanism is proposed to interpret the formation of this typical nanochains. The achieved nanochains enrich the species of one-dimensional (1D) nanostructures and may hold great potential applications in nanotechnology

Drugs and herbs given to prevent hepatotoxicity of tuberculosis therapy: systematic review of ingredients and evaluation studies

Background: Drugs to protect the liver are frequently prescribed in some countries as part of treatment for tuberculosis. The biological rationale is not clear, they are expensive and may do harm. We conducted a systematic review to a) describe the ingredients of "liver protection drugs"; and b) compare the evidence base for the policy against international standards. Methods: We searched international medical databases (MEDLINE, EMBASE, LILACS, CINAHL, Cochrane Central Register of Controlled Trials, and the specialised register of the Cochrane Infectious Diseases Group) and Chinese language databases (CNKI, VIP and WanFang) to April 2007. Our inclusion criteria were research papers that reported evaluating any liver protection drug or drugs for preventing liver damage in people taking anti-tuberculosis treatment. Two authors independently categorised and extracted data, and appraised the stated methods of evaluating their effectiveness. Results: Eighty five research articles met our inclusion criteria, carried out in China (77), India (2), Russia (4), Ukraine (2). These articles evaluated 30 distinct types of liver protection compounds categorised as herbal preparations, manufactured herbal products, combinations of vitamins and other non-herbal substances and manufactured pharmaceutical preparations. Critical appraisal of these articles showed that all were small, poorly conducted studies, measuring intermediate outcomes. Four trials that were described as randomised controlled trials were small, had short follow up, and did not meet international standards. Conclusion: There is no reliable evidence to support prescription of drugs or herbs to prevent liver damage in people on tuberculosis treatment

Modular prediction of protein structural classes from sequences of twilight-zone identity with predicting sequences

<p>Abstract</p> <p>Background</p> <p>Knowledge of structural class is used by numerous methods for identification of structural/functional characteristics of proteins and could be used for the detection of remote homologues, particularly for chains that share twilight-zone similarity. In contrast to existing sequence-based structural class predictors, which target four major classes and which are designed for high identity sequences, we predict seven classes from sequences that share twilight-zone identity with the training sequences.</p> <p>Results</p> <p>The proposed MODular Approach to Structural class prediction (MODAS) method is unique as it allows for selection of any subset of the classes. MODAS is also the first to utilize a novel, custom-built feature-based sequence representation that combines evolutionary profiles and predicted secondary structure. The features quantify information relevant to the definition of the classes including conservation of residues and arrangement and number of helix/strand segments. Our comprehensive design considers 8 feature selection methods and 4 classifiers to develop Support Vector Machine-based classifiers that are tailored for each of the seven classes. Tests on 5 twilight-zone and 1 high-similarity benchmark datasets and comparison with over two dozens of modern competing predictors show that MODAS provides the best overall accuracy that ranges between 80% and 96.7% (83.5% for the twilight-zone datasets), depending on the dataset. This translates into 19% and 8% error rate reduction when compared against the best performing competing method on two largest datasets. The proposed predictor provides accurate predictions at 58% accuracy for membrane proteins class, which is not considered by majority of existing methods, in spite that this class accounts for only 2% of the data. Our predictive model is analyzed to demonstrate how and why the input features are associated with the corresponding classes.</p> <p>Conclusions</p> <p>The improved predictions stem from the novel features that express collocation of the secondary structure segments in the protein sequence and that combine evolutionary and secondary structure information. Our work demonstrates that conservation and arrangement of the secondary structure segments predicted along the protein chain can successfully predict structural classes which are defined based on the spatial arrangement of the secondary structures. A web server is available at <url>http://biomine.ece.ualberta.ca/MODAS/</url>.</p

A Multi-Label Predictor for Identifying the Subcellular Locations of Singleplex and Multiplex Eukaryotic Proteins

Subcellular locations of proteins are important functional attributes. An effective and efficient subcellular localization predictor is necessary for rapidly and reliably annotating subcellular locations of proteins. Most of existing subcellular localization methods are only used to deal with single-location proteins. Actually, proteins may simultaneously exist at, or move between, two or more different subcellular locations. To better reflect characteristics of multiplex proteins, it is highly desired to develop new methods for dealing with them. In this paper, a new predictor, called Euk-ECC-mPLoc, by introducing a powerful multi-label learning approach which exploits correlations between subcellular locations and hybridizing gene ontology with dipeptide composition information, has been developed that can be used to deal with systems containing both singleplex and multiplex eukaryotic proteins. It can be utilized to identify eukaryotic proteins among the following 22 locations: (1) acrosome, (2) cell membrane, (3) cell wall, (4) centrosome, (5) chloroplast, (6) cyanelle, (7) cytoplasm, (8) cytoskeleton, (9) endoplasmic reticulum, (10) endosome, (11) extracellular, (12) Golgi apparatus, (13) hydrogenosome, (14) lysosome, (15) melanosome, (16) microsome, (17) mitochondrion, (18) nucleus, (19) peroxisome, (20) spindle pole body, (21) synapse, and (22) vacuole. Experimental results on a stringent benchmark dataset of eukaryotic proteins by jackknife cross validation test show that the average success rate and overall success rate obtained by Euk-ECC-mPLoc were 69.70% and 81.54%, respectively, indicating that our approach is quite promising. Particularly, the success rates achieved by Euk-ECC-mPLoc for small subsets were remarkably improved, indicating that it holds a high potential for simulating the development of the area. As a user-friendly web-server, Euk-ECC-mPLoc is freely accessible to the public at the website http://levis.tongji.edu.cn:8080/bioinfo/Euk-ECC-mPLoc/. We believe that Euk-ECC-mPLoc may become a useful high-throughput tool, or at least play a complementary role to the existing predictors in identifying subcellular locations of eukaryotic proteins

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Influence of InxGa1-xAs (0 <= x <= 0.3) cap layer on structural and optical properties of self-assembled InAs/GaAs quantum dots

Optical and structural properties of self-organized InAs/GaAs quantum dots (QDs) with InxGa1-xAs or GaAs cover layers grown by molecular beam epitaxy (MBE) have been characterized by transmission electron microscopy (TEM), atomic force microscopy (AFM) and photoluminescence (PL) measurements. The TEM and AFM images show that the surface stress of the InAs QDs was suppressed by overgrowth of a InxGa1-xAs covering layer on the top of the QDs and the uniformity of the QDs preserved. PL measurements reveal that red shifts of the PL emission due to the reduction of the surface strain of the InAs islands was observed and the temperature sensitivity of the PL emission energy was suppressed by overgrowth of InxGa1-xAs layers compared to that by overgrowth of GaAs layers

Time-resolved photoluminescence spectra of self-assembled InAs/GaAs quantum dots

Conference Name:3rd Asian Conference on Chemical Vapor Deposition. Conference Address: Taipei, TAIWAN. Time:NOV 12-14, 2004.Two types of InAs self-assembled Quantum dots (QDs) were prepared by Molecular beam epitaxy. Atomic force microscopy (AFM) measurements showed that, compared to QDs grown on GaAs substrate, QDs grown on InGaAs layer has a significantly enhanced density. The short spacing (several nanometer) among QDs stimulates strong coupling and leads to a large red-shift of the 1.3 mu m photoluminescence (PL) peak. We study systematically the dependence of PL lifetime on the QDs size, density and temperature (1). We found that, below 50 K, the PL lifetime is insensitive to temperature, which is interpreted from the localization effects. As T increases, the PL lifetime increases, which can be explained from the competition between the carrier redistribution and thermal emission at higher temperature. The increase of carriers in QDs migrated from barriers and wetting layer (WL), and the redistribution of carriers among QDs enhance the PL lifetime as T increases. The thermal emission and non-radiative recombination have effects to reduce the PL lifetime at higher T. As a result, the radiative recombination lifetime is determined by the wave function overlapping of electrons and holes in QDs, and QDs with different densities have different PL lifetime dependence on the QDs size. (c) 2005 Elsevier B.V. All rights reserved

Modification of emission wavelength of self-assembled In(Ga)As/GaAs quantum dots covered by InxGa1-xAs(0 <= x <= 0.3) layer

Red shifts of emission wavelength of self-organized In(Cla)As/GaAs quantum dots (QDs) covered by 3 nm thick InxGa1-xAs layer with three different In mole fractions (x = 0.1, 0.2 and 0.3, respectively) have been observed. Transmission electron microscopy images demonstrate that the stress along growth direction in the InAs dots was reduced due to introducing the InxGa1-xAs (x = 0.1, 0.2 and 0.3) covering layer instead of GaAs layer. Atomic force microscopy pictures show a smoother surface of InAs islands covered by an In0.2Ga0.8As layer. It is explained by the calculations that the redshifts of the photoluminescence (PL) spectra from the QDs covered by the InxGa1-xAs (x greater than or equal to 0.1) layers were mainly due to the reducing of the strain other than the InAs/GaAs intermixing in the InAs QDs. The temperature dependent PL spectra further confirm that the InGaAs covering layer can effectively suppress the temperature sensitivity of PL emissions. 1.3 mum emission wavelength with a very narrow linewidth of 19.2 mcV at room temperature has been obtained successfully from In,In0.5Ga0.5As/GaAs self-assembled QDs covered by a 3-nm In0.2Ga0.2As strain reducing layer. (C) 2001 Elsevier Science B.V. All rights reserved

Photoluminescence properties of self-organized InGaAs/GaAs quantum dot structures

Optical properties of InGaAs/GaAs self-organized quantum dots (QDs) structures covered by InxGa1-x As capping layers with different In contents chi ranging from 0. 0 (i.e., GaAs) to 0. 3 were investigated systematically by photoluminescence (PL) measurements. Red-shift of the PL peak energies of the InAs QDs covered by InxGa1-xAs layers with narrower linewidth and less shifts of the PL emissions via variations of the measurement temperatures were observed compared with that covered by GaAs layers. Calculation and structural measurements confirm that the red-shift of the PL peaks are mainly due to strain reduction and suppression of the In/Ga intermixing due to the InxGa1-xAs cover layer, leading to better size uniformity and thus narrowing the PL linewidth of the QDs. 1. 3 mum wavelength emission with very narrow linewidth of only 19. 2 meV at room temperature was successfully obtained from the In0.5Ga0.5As/GaAs QDs covered by the In0.2Ga0.8As layer