Association between mu opioid receptorgene polymorphisms and alcohol dependence in a Japanese population

Alcohol dependence is an addiction that causes psychological and physical dependence and makes it difficult for those affected to control their intake of alcohol. The μ (mu), δ (delta) and κ (kappa) opioid receptors are thought to be associated with the development of alcohol dependence. Research has shown that μ opioid receptor knockout mice exhibit reduced alcohol consumption and reduced preference for alcohol. In this study, we confirmed whether mu opioid receptor (OPRM1) polymorphisms (IVS2+691C/G, −172G/T and −1748G/A) indeed have an effect on alcohol dependence formation in 64 patients, with 73 healthy people used as a control group. We compared the genotype, allele, carrier (minor allele carriers versus major allele homozygous carriers) and haplotype frequencies between these groups. In addition, the 1510A allele of acetaldehyde dehydrogenase 2 (ALDH2) polymorphism (1510G/A) causes poor metabolism of acetaldehyde, a major metabolite of alcohol. We also focused on ALDH2 1510G/G (ALDH2 *1/*1) carriers in the subjects. Three OPRM1 and one ALDH2 genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. No significant differences were found in the frequency of OPRM1 polymorphisms between those suffering from alcohol dependence and the control group. We concluded that the three OPRM1 polymorphisms (IVS2+691C/G, −172G/T and −1748G/A) were not likely to be risk factors for alcohol dependence in a Japanese population. This report is the first in a Japanese population. Nevertheless, further analysis of the opioid receptor gene in a large sample size is required.アルコール依存症とは，飲酒の自制が困難となる薬物中毒であり，オピオイド受容体との関連が考えられている。μオピオイド受容体欠損マウスは，アルコール自己投与の減少とアルコールに対する嫌悪を示すことが確認されている。本研究では，μオピオイド受容体（OPRM1）遺伝子多型IVS2+691C/G，−172G/Tおよび −1748G/Aがアルコール依存形成に与える影響を調べるため，遺伝子型，アレルおよびマイナーアレル保持者別頻度，ハプロタイプ解析，連鎖不平衡解析を含めた検討を行った。なお，OPRM1遺伝子多型の影響についてより詳細に検討するため，アルコール感受性に関わる2型アルデヒド脱水素酵素遺伝子多型ALDH2 *1/*1を有する対象者に着目した解析も行った。アルコール依存症患者64人，コントロール75人を対象とした。遺伝子多型の解析には，制限酵素断片長多型法（PCR-RFLP）を用いた。解析の結果，患者群および健常者群間における遺伝子型，アレルおよびマイナーアレル保持者別，全てのハプロタイプ頻度において，有意な差異は認められなかった。今回の結果より，着目した3つのOPRM1遺伝子多型がアルコール依存症発症の危険因子となる可能性は低いことが示唆された。今後は，同遺伝子上の他の多型や，他のオピオイド受容体にも着目し，アルコール依存症との関与についてより詳細に検討する必要があると考えられる。journal articl

Improved Constraints on D0-D̅0 Mixing in D0→K+π- Decays from the Belle Detector

journal articl

脊椎運動における瞬間回転軸の評価指標としての有用性

application/pdf三重大学大学院 工学研究科 機械工学専攻 生体システム工学研究室3, 56thesi

西田長寿氏の労作と私の歴史研究(<特集>マスコミ研究30年 : 回顧と展望. II, 歴史)

rights: 日本マス・コミュニケーション学会 rights: 本文データは学協会の許諾に基づきCiNiiから複製したものである relation: IsVersionOf: http://ci.nii.ac.jp/naid/110002772211/textapplication/pdfjournal articl

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Systematic Production of Inactivating and Non-Inactivating Suppressor Mutations at the relA Locus That Compensate the Detrimental Effects of Complete spoT Loss and Affect Glycogen Content in Escherichia coli

In Escherichia coli, ppGpp is a major determinant of growth and glycogen accumulation. Levels of this signaling nucleotide are controlled by the balanced activities of the ppGpp RelA synthetase and the dual-function hydrolase/synthetase SpoT. Here we report the construction of spoT null (ΔspoT) mutants obtained by transducing a ΔspoT allele from ΔrelAΔspoT double mutants into relA+ cells. Iodine staining of randomly selected transductants cultured on a rich complex medium revealed differences in glycogen content among them. Sequence and biochemical analyses of 8 ΔspoT clones displaying glycogen-deficient phenotypes revealed different inactivating mutations in relA and no detectable ppGpp when cells were cultured on a rich complex medium. Remarkably, although the co-existence of ΔspoT with relA proficient alleles has generally been considered synthetically lethal, we found that 11 ΔspoT clones displaying high glycogen phenotypes possessed relA mutant alleles with non-inactivating mutations that encoded stable RelA proteins and ppGpp contents reaching 45-85% of those of wild type cells. None of the ΔspoT clones, however, could grow on M9-glucose minimal medium. Both Sanger sequencing of specific genes and high-throughput genome sequencing of the ΔspoT clones revealed that suppressor mutations were restricted to the relA locus. The overall results (a) defined in around 4 nmoles ppGpp/g dry weight the threshold cellular levels that suffice to trigger net glycogen accumulation, (b) showed that mutations in relA, but not necessarily inactivating mutations, can be selected to compensate total SpoT function(s) loss, and (c) provided useful tools for studies of the in vivo regulation of E. coli RelA ppGpp synthetase.journal articl

Additional file 1: of The inference of gray whale (Eschrichtius robustus) historical population attributes from whole-genome sequences

Table S1. Information on raw reads filtering statistics. Paired-end libraries were sequenced on an Illumina HiSeq 2500. Table S2. Environmental variables used in AQUAMAPS to generate maps of suitable habitat for gray whales during the Holocene. Table S3. The D–test statistic evaluates the number (n) of ABBA and BABA sites (D = (nABBA - nBABA) / (nABBA + nBABA)) and D < 0 means that P1 is more closely related to P3 than to P2, whereas D > 0 indicates that P2 is more closely related to P3 than P1. The significance of the D test was evaluated with a Z-score, where |Z-scores| > 3 was used as the critical value for a significant test. Figure S1. Inferred effective population sizes (Ne) over time. Estimates are averages based on 11 autosomal scaffolds larger than 30 Mb. A substitution rate of a) 10 × 10− 10 bp− 1 year− 1 and b) 1.5 × 10− 10 bp− 1 year− 1 were used. (DOCX 446 kb

Intéractions avec le ribosome et changements conformationnels de la GTPase bactérienne EngA, une cible potentielle pour de nouveaux antibiotiques

The development of new therapeutics against bacterial infections has aroused great interest over the last years in the context of drug resistance. The starting-point in the pursuit of new antibiotics for which bacterial resistance mechanisms do not exist is the identification of novel cellular targets. Genetics studies in the early 2000s have identified engA as a conserved bacterial gene whose product is a GTPase that could represent a potential drug target: it is conserved among bacteria, essential for cell survival, and absent in humans.Since EngA acts as an assembly factor for the bacterial ribosome, one of our aims was to develop an assay to screen inhibitors of the EngA-ribosome interactions. These interactions are modulated by EngA conformational changes that are in turn triggered by the binding of different nucleotides to the catalytic G-domain. As the interplay between all these events in bacteria is still not resolved, we have used a multi-technique approach to explore these questions in order to obtain useful information for the setting up of a robust screening assay.SAXS and limited proteolysis showed a conformational change occurring in solution upon addition of either di- or tri-phosphate nucleotides. While model validation analysis confirmed the GDP-bound conformation, the GTP-bound state does not match any known EngA structure. Binding studies have revealed modulation of interactions by different nucleotide-bound states. Furthermore, response to nucleotides occurs at high concentrations, suggesting that the role of EngA in promoting ribosome assembly could be monitored by the intracellular nucleotide concentration. Efforts on identifying the GTP-bound state 3D structure by crystallography have resulted in EngA structures in different crystal forms. Although all the obtained structures represent the GDP-bound state, packing analysis has revealed conserved crystal contacts that can potentially stabilise this conformation during nucleation. Specific mutations aiming at disrupting these contacts may help to promote crystallisation of alternative conformations. Cryo-EM investigation has been initiated in order to obtain the structure of the B. subtilis EngA:50S complex. So far, an electron density map at 6.4 Å resolution has been obtained and its interpretation is underway.Au cours des dernières années, le développement de nouvelles thérapies contre les infections bactériennes a suscité un grand intérêt face à l’émergence des nombreuses souches résistantes aux antibiotiques. Le point de départ de cette recherche de nouveaux antibiotiques, pour lesquels les bactéries n’ont pas encore acquis de mécanismes de résistance, est l’identification de nouvelles cibles cellulaires. En 2000, des études génétiques ont identifié engA, un gène bactérien dont le produit est une GTPase, comme une cible pharmacologique pertinente: elle est essentielle à la survie cellulaire, conservée au sein des bactéries et absente chez les eucaryotes.Puisque EngA agit comme un facteur d’assemblage pour le ribosome bactérien, un de nos objectifs a été de développer un test de criblage pour identifier des inhibiteurs des interactions EngA-ribosome. Ces interactions sont modulées par des changements conformationnels d'EngA, qui sont eux-mêmes déclenchés par la fixation de différents nucléotides dans le domaine catalytique. Cependant, les liens entre ces différents changements restent encore méconnus. Nous avons utilisé une approche multi-technique pour étudier ces questions et obtenir des informations utiles pour l’optimisation de notre test de criblage.Des analyses de SAXS et protéolyse limitée ont démontré un changement conformationnel en solution après adition de nucléotides di- ou tri-phosphate. La comparaison des données avec des modèles cristallographiques d'EngA a confirmé la conformation de la protéine liée au GDP. Cependant, la conformation de la protéine liée au GTP ne correspond à aucune structure connue. Des essais d’interaction ont démontré que la fixation de différents nucléotides au niveau des domaines catalytiques régule l’interaction d'EngA avec le ribosome. En outre, les effets des nucléotides se produisent en utilisant des fortes concentrations, ce qui suggère que le rôle d'EngA dans la biogenèse du ribosome peut être contrôlé par la concentration intracellulaire de nucléotides. Les travaux visant la détermination de la structure d'EngA dans sa conformation liée au GTP par cristallographie nous ont permis d’obtenir la structure d’EngA dans différentes formes cristallines. Cependant, ces structures représentent la conformation liée au GDP. L’analyse de l’empilement des cristaux a montré des contacts intermoléculaires conservés qui peuvent stabiliser cette conformation pendant la nucléation. Des mutations spécifiques permettant la rupture de ces contacts peuvent éventuellement aider à promouvoir la cristallisation de conformations alternatives. Des analyses de cryo-microscopie électronique ont débuté afin d’obtenir la structure du complexe EngA:50S de chez B. subtilis. Des résultats préliminaires montrent une carte de densité électronique à 6.4 Å de résolution. L’interprétation de ces résultats est en cours

表面の微細形状に注目した皮膚の質感表現の一手法

コンピュータグラフィックスによる皮膚の質感表現は，人体表現のリアリティの実現および手術シミュレーション等への応用といった点から重要であると考えられている．しかしこれまでのところ皮膚の質感を実現する有効な手法は確立されておらず，実写での皮膚画像をテクスチャマッピングするといった簡略的な方法で代用されている．これに対し筆者らは，皮膚の表面形状に注目しその幾何学的特徴である皮野・皮溝及びその集合体についてモデル化およびモデルの実現法について述べた後，皮膚の表示例を表す．モデルの実現に当たっては，表面形状を平面形状と断面形状に分けて考え，平面形状生成には計算幾何学におけるボロノイ分割手法を用い，断面形状生成にはベジェ曲線を用いた．また，各種パラメータを設定することにより，形状をさまざまに変化させることが可能であることも確認した．journal articl

Additional file 3: of New insights into the phylogenetics and population structure of the prairie falcon (Falco mexicanus)

Table S2. Top Pfam domain hits in the F. mexicanus genome and their counts. (PDF 175 kb