| 1 | Biochemistry 2004 Oct 43: 12539-48 |
|---|---|
| PMID | 15449943 |
| 标题 | 大肠杆菌Puta脯氨酸脱氢酶结构域的结构与竞争性抑制剂。 |
| 抽象的 | Proline dehydrogenase (PRODH) catalyzes the first step of proline catabolism, the flavin-dependent oxidation of proline to Delta(1)-pyrroline-5-carboxylate. Here we present a structure-based study of the PRODH active site of the multifunctional Escherichia coli proline utilization A (PutA) protein using X-ray crystallography, enzyme kinetic measurements, and site-directed mutagenesis. Structures of the PutA PRODH domain complexed with competitive inhibitors acetate (K(i) = 30 mM), L-lactate (K(i) = 1 mM), and L-tetrahydro-2-furoic acid (L-THFA, K(i) = 0.2 mM) have been determined to high-resolution limits of 2.1-2.0 A. The discovery of acetate as a competitive inhibitor suggests that the carboxyl is the minimum functional group recognized by the active site, and the structures show how the enzyme exploits hydrogen-bonding and nonpolar interactions to optimize affinity for the substrate. The PRODH/L-THFA complex is the first structure of PRODH with a five-membered ring proline analogue bound in the active site and thus provides new insights into substrate recognition and the catalytic mechanism. The ring of L-THFA is nearly parallel to the middle ring of the FAD isoalloxazine, with the inhibitorC5atom 3.3 A from the FAD N5. This geometry suggests direct hydride transfer as a plausible mechanism. Mutation of conserved active site residue Leu432 to Pro caused a 5-fold decrease in k(cat) and a severe loss in thermostability. These changes are consistent with the location of Leu432 in the hydrophobic core near residues that directly contact FAD. Our results suggest that the molecular basis for increased plasma proline levels in精神分裂症subjects carrying the missense mutation L441P is due to decreased stability of human PRODH2. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 2 | 脊髓2007年6月45日：437-43 |
| PMID | 17339888 |
| 标题 | 自杀未遂后的脊髓和相关伤害：精神诊断和长期随访。 |
| 抽象的 | 急性脊髓损伤（ASCI）的回顾性分析。 确定1970年至2000年因自杀企图而导致的ASCI发生率。描述人口统计学，伤害，精神疾病，功能结果和随后死亡的性质。 脊髓损伤状态服务,新多h Wales, Australia. 回顾性记录审查和后续采访。 Of 2752 ASCI admissions, 56 were because of attempted suicide (55 falls, one gun-shot wound). Thirty-six males and 20 females. Median age 30 years (15-74). Most common levels of vertebral injury wereC5和L1。二十三个完全脊髓损伤。32个受伤严重程度> 15。四十人受到了不止一个重大伤害。随着时间的推移，自伤之后，ASCI发生率的发生率显着升高（泊松回归，p = 0.004）。随着时间的推移，医院的受伤现场发生了重大变化（CHI（2）测试，DF = 1，P = 0.0001）。精神诊断是人格障碍27；精神分裂症16; depression 14; chronic alcohol abuse 10; mood disorder 10; chronic substance abuse 10; other four. Follow-up was available in 47 cases (84%) at an average of 8 years. Four subsequent deaths were by suicide. Domiciliary arrangements were: home 28; hospital five; nursing home three; group home/hostel four. Community placement outcomes for survivors were good. Subsequent death by suicide was high. There was a significant rise in cases and a change in injury scene away from hospitals over time. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 3 | Int. Rev. Neurobiol. 2009 -1 89: 67-84 |
| PMID | 19900616 |
| 标题 | DNA甲基化在中枢神经系统和神经精神疾病中的作用。 |
| 抽象的 | DNA methylation is an epigenetic mechanism in which the methyl group is covalently coupled to theC5CpG dinucleoti胞嘧啶残基的位置des. DNA methylation generally leads to gene silencing and is catalyzed by a group of enzymes known as DNA methyltransferases (Dnmt). During development, the epigenome undergoes waves of demethylation and methylation changes. As a result, there are cell type/tissue-specific DNA methylation patterns. Since DNA methylation changes only happen during DNA replication to maintain methylation patterns on hemimethylated DNA or establish new methylation, Dnmt expression generally decreases greatly after cell division. However, significant levels of Dnmts were noticed specifically in postmitotic neurons, suggesting a functional importance of Dnmt in the nervous system. Accumulating evidence showed that DNA methylation correlates with certain neuropsychiatric disorders such as精神分裂症, Rett syndrome, and ICF syndrome. Studies of methyl-CpG-binding proteins, Dnmt inhibitors, and Dnmt knockout mice also explored the key role of DNA methylation in neural development, plasticity, learning, and memory. Though an enzyme exhibiting DNA demethylation capability in vertebrates still remains to be identified, DNA methylation status in the CNS appeared to be reversible at certain genomic loci. This supports a maintenance role of Dnmt to prevent active demethylation in postmitotic neurons. Taken together, DNA methylation provides an epigenetic mechanism of gene regulation in neural development, function, and disorders. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 4 | Niger J Physiol Sci 2012 Jun 27: 19-21 |
| PMID | 23235303 |
| 标题 | 新诊断的尼日利亚精神分裂症患者和抗精神病药疗法的补体因素。 |
| 抽象的 | 补体因素在精神疾病的发病机理中的作用是巨大的，但是有关补体水平和功能的数据精神分裂症稀少和冲突。为了解决这个问题，补体调节剂（C1抑制剂和C3激活剂）和补体因素（C1Q，C3C，C4和C5) were determined in the serum of newly diagnosed drug free精神分裂症患者，精神分裂症使用免疫板的药物和健康受试者的患者。新诊断的C1Q显着降低了精神分裂症病人或精神分裂症与对照组相比，药物治疗患者。新诊断的C3C显着降低了精神分裂症patients compared with controls or精神分裂症药物治疗的患者。两组的C3激活剂，C1抑制剂和C4的水平相似精神分裂症患者与对照组相比。从这项研究可以得出结论，C1Q缺乏精神分裂症患者;并且C3C可能会区分新诊断精神分裂症从精神分裂症药物治疗的患者。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 5 | Niger J Physiol Sci 2012 Jun 27: 19-21 |
| PMID | 23235303 |
| 标题 | 新诊断的尼日利亚精神分裂症患者和抗精神病药疗法的补体因素。 |
| 抽象的 | 补体因素在精神疾病的发病机理中的作用是巨大的，但是有关补体水平和功能的数据精神分裂症稀少和冲突。为了解决这个问题，补体调节剂（C1抑制剂和C3激活剂）和补体因素（C1Q，C3C，C4和C5) were determined in the serum of newly diagnosed drug free精神分裂症患者，精神分裂症使用免疫板的药物和健康受试者的患者。新诊断的C1Q显着降低了精神分裂症病人或精神分裂症与对照组相比，药物治疗患者。新诊断的C3C显着降低了精神分裂症patients compared with controls or精神分裂症药物治疗的患者。两组的C3激活剂，C1抑制剂和C4的水平相似精神分裂症患者与对照组相比。从这项研究可以得出结论，C1Q缺乏精神分裂症患者;并且C3C可能会区分新诊断精神分裂症从精神分裂症药物治疗的患者。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 6 | INT J Psychophyoliol 2013 Jul 89：63-71 |
| PMID | 23707337 |
| 标题 | 在具有听觉幻觉的精神分裂症患者的听觉皮质区域，半球间的脑电图相干性降低。 |
| 抽象的 | Central auditory processing has been reported to be impaired in精神分裂症patients who experience auditory hallucinations, and interhemispheric transfer in auditory circuits may be compromised. In this study, we used EEG spectral coherence to examine interhemispheric connectivity between cortical areas known to be important in the processing of auditory information. Coherence was compared across three subject groups:精神分裂症patients with a recent history of auditory hallucinations (AH),精神分裂症没有经历听觉幻觉（诺阿）和健康对照（HC）的患者。当脑电图连续记录时，受试者听取了纯正的语气和单词刺激。上alpha和上β带相干性是从六对左右脑脑半球同源听觉区域上的电极计算的。在四个电极对上发现了显着的组间差异（C3-C4，C5-C6, Ft7-Ft8 and Cp5-Cp6) in the upper alpha band. Relative to both the HC and nonAH groups, coherence was lower in the AH patients, consistent with the hypothesis that interhemispheric connectivity is reduced in these patients. |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 7 | 精神病学Res 2014年1220：669-78 |
| PMID | 25150922 |
| 标题 | 历史，临床和风险管理量表（HCR-20）对住院攻击的差异预测有效性。 |
| 抽象的 | The Historical, Clinical and Risk Management Scales (HCR-20) may be a better predictor of inpatient aggression for selected demographic and clinical groups but homogeneity of study samples has prevented definitive conclusions. The aim of this study, therefore, was to test the predictive validity of the HCR-20 as a function of gender, diagnosis, age, and ethnicity while controlling for potential covariates. A pseudo-prospective cohort study (n=505) was conducted in a UK secure/forensic mental health setting using routinely collected data. The HCR-20 predicted aggression better for women than men, and for people with精神分裂症and/or personality disorder than for other diagnostic groups. In women, the presence of the risk management items (R5) was important while men?s aggression was best predicted solely by current clinical features from theC5scale. R5 items were better thanC5预测有机和发育诊断患者的侵略性项目。我们的数据提供了有关HCR-20评估者可以根据重要的人口统计和临床特征对住院侵略风险的总体摘要判断提供的其他信息。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |
| 8 | 蛋白质组学临床应用2015年10月9日：907-16 |
| PMID | 25821032 |
| 标题 | Effects of olanzapine on serum protein phosphorylation patterns in patients with schizophrenia. |
| 抽象的 | Previous studies have shown that blood serum phosphoproteins are altered in精神分裂症patients in comparison to controls. However, it is not known whether phosphoproteins are also changed in response to treatment with antipsychotics. 在基线和奥氮平治疗6周后，从患者（n = 23）中采集血液样本。使用固定的金属离子亲和色谱法（IMAC）用于富集血清磷蛋白，并通过表达模式（LC-MS（E））通过无标记的LC-MS分析它们。 我们确定了11种蛋白质，这些蛋白质在整体丰度和45种蛋白质中发生了显着变化，这些蛋白质在抗精神病药物治疗后显示出磷酸化的变化。改变的磷蛋白主要参与急性相反应，脂质和葡萄糖稳态（LXR），视黄酸信号传导（RXR）和补体途径。一些蛋白质显示出明显增加的磷酸化，包括载脂蛋白A-I（3.4倍），α-1-抗抗胆红蛋白（3.1倍）和载脂蛋白B-100（2.2倍）。此外，几种蛋白质显示磷酸化降低（例如补体C4A，胶原蛋白α-1链，补体因子H），或者是phoshphylation升高和降低的混合物（例如，afamin，补体，C5, complement factor B). Finally, 24 of the altered phosphoproteins showed opposite directional changes in a comparison of baseline精神分裂症patients before and after treatment with olanzapine. These included alpha-1B-glycoprotein, apolipoprotein A-IV, vitamin D-binding protein, and prothrombin. 这些数据证明了将来对血清磷蛋白作为生理功能的读数的潜在研究，并且可能具有旨在鉴定生物标志物进行药物反应预测或监测的研究。 |
| SCZ Keywords | 精神分裂症，精神分裂症 |