二苯甲酮衍生物对酪氨酸酶生物活性的影响*

报道了11种二苯甲酮衍生物对酪氨酸酶生物活性的影响。结果显示,7种化合物对酪氨酸酶表现出激活效应,其中4-羟基二苯甲酮与-3羟基二苯甲酮对酪氨酸酶最大激活率分别达到230%和214%。当化合物中羟基被其他官能团,如甲基、甲氧基、氟等取代之后,这类化合物对酪氨酸酶的激活效应会大幅度降低,甚至消失。动力学研究显示,4-羟基二苯甲酮与3-羟基二苯甲酮对酪氨酸酶激活动力学模式均为非竞争性。     

Ultrastructural Studies of Glioma Stem Cells/Progenitor Cells

Although the ultrastructural features of several brain tumor cells have been studied in details, the ultrastructure of glioma stem cells/progenitors cells (GSPC) has rarely been reported. In this paper, the authors describe the ultrastructural features of GSPCs isolated from both a glioma tissue and the human glioma cell SHG-44 cell line. The ultrastructural features of the two kinds of GSPCs were similar, with relatively developed mitochondria, Golgi apparatuses, ribosomes, undeveloped rough endoplasmic reticula, seldom lysosomes and no typical autophagosomes, and high nuclear–cytoplasmic ratio. Their nuclei, frequently containing huge amounts of euchromatin and a small quantity of heterochromatin, were mostly globular; and the majority of the nuclei had only one nucleole. Typical apoptotic cells could hardly be found in tumor spheres, and between adjacent cells there were cell junctions, which probably were incompletely developed desmosomes or intermediate junctions. In conclusion, their ultrastructural features showed that GSPCs were at the primary stage of differentiation, and could even partially reveal the underlying reasons for the malignant proliferation and differential inhibition of GSPCs.     

外周血白细胞端粒长度和线粒体基因拷贝数对急性心肌梗死的诊断预测价值以及相关机制的探讨

目的 探究外周血白细胞端粒长度(LTL)和线粒体基因拷贝数(mtDNA?CN)对急性心肌梗死(AMI)的预测价值,并从端粒酶逆转录酶(TERT)和线粒体氧化损伤的角度探讨其相关机制.方法 选取AMI患者80例,并选同期行冠脉造影检查且结果显示冠脉大致正常者80例作为对照.收集研究对象的临床资料和空腹全血,以qPCR法检测外周血LTL、TERT mRNA、mtDNA?CN和线粒体氧化损伤程度,采用Spearman相关分析评估上述指标间的相关性.采用多因素Logistic回归分析LTL和mtDNA?CN与AMI发生风险的关系,以受试者工作曲线(ROC)评价LTL和mtDNA?CN对AMI诊断的预测价值.结果 AMI组患者外周血LTL、TERT mRNA表达水平和mtDNA?CN均显著低于对照组,线粒体氧化损伤水平显著高于对照组,差异均具有统计学意义(P<0.05).在AMI组和对照组中,LTL分别与TERT mRNA的表达水平和mtDNA?CN呈显著正相关,与线粒体氧化损伤水平呈显著负相关(均P<0.05).在AMI组中,mtDNA?CN与线粒体氧化损伤水平呈显著负相关(P=0.03),但在对照组中两者相关性无统计学意义(P=0.20).Logistic回归分析结果表明,长LTL和高mtDNA?CN是AMI的保护因素;ROC曲线分析结果表明,LTL、mtDNA?CN以及两者联合预测AMI的曲线下面积(AUC)分别为0.748、0.704、0.767.结论 外周血LTL和mtDNA?CN对AMI具有一定的预测诊断价值.AMI患者外周血LTL的缩短可能与TERT mRNA表达的降低有关,外周血白细胞线粒体氧化损伤水平的升高可能是mtDNA?CN降低和LTL缩短的重要原因.     

Mechanism of Pacemaker Activity in Zebrafish DC2/4 Dopaminergic Neurons

Zebrafish models are used increasingly to study the molecular pathogenesis of Parkinson''s disease (PD), owing to the extensive array of techniques available for their experimental manipulation and analysis. The ascending dopaminergic projection from the posterior tuberculum (TPp; diencephalic populations DC2 and DC4) to the subpallium is considered the zebrafish correlate of the mammalian nigrostriatal projection, but little is known about the neurophysiology of zebrafish DC2/4 neurons. This is an important knowledge gap, because autonomous activity in mammalian substantia nigra (SNc) dopaminergic neurons contributes to their vulnerability in PD models. Using a new transgenic zebrafish line to label living dopaminergic neurons, and a novel brain slice preparation, we conducted whole-cell patch clamp recordings of DC2/4 neurons from adult zebrafish of both sexes. Zebrafish DC2/4 neurons share many physiological properties with mammalian dopaminergic neurons, including the cell-autonomous generation of action potentials. However, in contrast to mammalian dopaminergic neurons, the pacemaker driving intrinsic rhythmic activity in zebrafish DC2/4 neurons does not involve calcium conductances, hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, or sodium leak currents. Instead, voltage clamp recordings and computational models show that interactions between three components – a small, predominantly potassium, leak conductance, voltage-gated sodium channels, and voltage-gated potassium channels – are sufficient for pacemaker activity in zebrafish DC2/4 neurons. These results contribute to understanding the comparative physiology of the dopaminergic system and provide a conceptual basis for interpreting data derived from zebrafish PD models. The findings further suggest new experimental opportunities to address the role of dopaminergic pacemaker activity in the pathogenesis of PD.SIGNIFICANCE STATEMENT Posterior tuberculum (TPp) DC2/4 dopaminergic neurons are considered the zebrafish correlate of mammalian substantia nigra (SNc) neurons, whose degeneration causes the motor signs of Parkinson''s disease (PD). Our study shows that DC2/4 and SNc neurons share a number of electrophysiological properties, including depolarized membrane potential, high input resistance, and continual, cell-autonomous pacemaker activity, that strengthen the basis for the increasing use of zebrafish models to study the molecular pathogenesis of PD. The mechanisms driving pacemaker activity differ between DC2/4 and SNc neurons, providing: (1) experimental opportunities to dissociate the contributions of intrinsic activity and underlying pacemaker currents to pathogenesis; and (2) essential information for the design and interpretation of studies using zebrafish PD models.     

Disrupted Intersubject Variability Architecture in Functional Connectomes in Schizophrenia

Schizophrenia (SCZ) is a highly heterogeneous disorder with remarkable intersubject variability in clinical presentations. Previous neuroimaging studies in SCZ have primarily focused on identifying group-averaged differences in the brain connectome between patients and healthy controls (HCs), largely neglecting the intersubject differences among patients. We acquired whole-brain resting-state functional MRI data from 121 SCZ patients and 183 HCs and examined the intersubject variability of the functional connectome (IVFC) in SCZ patients and HCs. Between-group differences were determined using permutation analysis. Then, we evaluated the relationship between IVFC and clinical variables in SCZ. Finally, we used datasets of patients with bipolar disorder (BD) and major depressive disorder (MDD) to assess the specificity of IVFC alteration in SCZ. The whole-brain IVFC pattern in the SCZ group was generally similar to that in HCs. Compared with the HC group, the SCZ group exhibited higher IVFC in the bilateral sensorimotor, visual, auditory, and subcortical regions. Moreover, altered IVFC was negatively correlated with age of onset, illness duration, and Brief Psychiatric Rating Scale scores and positively correlated with clinical heterogeneity. Although the SCZ shared altered IVFC in the visual cortex with BD and MDD, the alterations of IVFC in the sensorimotor, auditory, and subcortical cortices were specific to SCZ. The alterations of whole-brain IVFC in SCZ have potential implications for the understanding of the high clinical heterogeneity of SCZ and the future individualized clinical diagnosis and treatment of this disease.     

Prevalence and genetic diversity of Entamoeba species infecting macaques in southwest China

Many colonies of macaques (Macaca fascicularis and Macaca mulatta) are maintained in China, especially in Guangxi and Guizhou. A total of 803 fresh stool samples infected with Entamoeba were obtained from three big colonies of macaques located in southwest China. The samples were examined for the presence of five Entamoeba species using PCR. Entamoeba nuttalli, Entamoeba dispar, Entamoeba coli, and Entamoeba chattoni infections were detected, but Entamoeba histolytica infection was not. This study is the first to report on the prevalence of E. nuttalli in wild macaques from China. Eighteen E. nuttalli isolates and five E. dispar isolates were obtained by culturing the samples in Tanabe–Chiba medium. The serine-rich protein (SRP), ribosomal RNA (rRNA), hexokinase (HXK), glucose-6-phosphate isomerase (GPI), and phosphoglucomutase (PGM) genes of E. nuttalli isolates were compared with other reported isolates. The results showed clear differences among the Chinese E. nuttalli isolates and other isolates based on the SRP gene sequences. However, HXK, GPI, and PGM genes of these strains were similar to those of other isolates. The rRNA genes of E. coli and E. chattoni were also amplified and analyzed from these samples. The results suggested that host species might be a more important factor than geographic location in amebic genetic diversity.     

A duplex quantitative real-time PCR assay for the detection of Haplosporidium and Perkinsus species in shellfish

A duplex quantitative real-time polymerase chain reaction (dq-PCR) assay was optimized to simultaneously detect Haplosporidium spp. and Perkinsus spp. of shellfish in one reaction. Two sets of specific oligonucleotide primers for Haplosporidium spp. and Perkinsus spp., along with two hydrolysis probes specific for each parasite group, were used in the assay. The dq-PCR results were detected and analyzed using the Light Cycler 2.0 software system. The dq-PCR identified and differentiated the two protozoan parasite groups. The sensitivity of the dq-PCR assay was 200 template copies for both Haplosporidium spp. and Perkinsus spp. No DNA product was amplified when known DNA from Marteilia refringens, Toxoplasma gondii, Bonamia ostreae, Escherichia coli, Cymndinium spp., Mykrocytos mackini, Vibrio parahaemolyticus, and shellfish tissue were used as templates. A total of 840 oyster samples from commercial cultivated shellfish farms from two coastal areas in China were randomly collected and tested by dq-PCR. The detection rate of Haplosporidium spp. was 8.6 % in the Qindao, Shandong coastal area, whereas Perkinsus spp. was 8.3 % coastal oysters cultivated from shellfish farms of Beihai, Guangxi. The dqPCR results suggested that Haplosporidium spp. was prevalent in oysters from Qindao, Shandong, while Perkinsus spp. was prevalent in oysters from the coastal areas of Beihai, Guangxi. This dq-PCR could be used as a diagnostic tool to detect Haplosporidium spp. and Perkinsus spp. in cultivated shellfish.     

自我构念启动效应下大学生自尊与生活满意度的关系

目的:考察不同自我构念启动情境下大学生自尊和生活满意度间的动态关系。方法:选取大学生183名随机分为独立构念启动组(n=58)、互依构念启动组(n=65)和对照组(n=59)。3组阅读不同的启动阅读材料进行构念启动,完成启动任务后立即用自尊量表(SLSC)测评能力自尊和价值自尊,用生活满意度量表(SWLS)测评生活满意度。用多元回归分析并比较能力自尊、互依自尊对生活满意度的预测作用。结果:在独立构念启动组,能力自尊正向预测生活满意度(β=0.48);在互依构念启动组,价值自尊正向预测生活满意度(β=0.35);在对照组,能力自尊和价值自尊对生活满意度的预测作用均无统计学意义(均P>0.05)。结论:大学生在独立和互依构念启动情境下会分别倚重能力自尊、价值自尊来预测生活满意度,提示个体在不同情境下将会以不同的方式评价和体验生活幸福感。