肿瘤坏死因子家族新成员——TRAIL

肿瘤坏死因子相关的凋亡诱导配体(TRAIL)或称凋亡素2配体(Apo2 ligand, Apo-2L), 是TNF家族的新成员.它是从表达序列标签库(expressed sequenced tag, EST)中寻找TNF的同源分子时发现的.TRAIL是一种分子质量为32.5 ku的Ⅱ型跨膜糖蛋白, 活性形式呈同源三聚体.TRAIL和可溶性的TRAIL强烈诱导肿瘤细胞株凋亡.新近发现的TRAIL受体DR4和DR5及TRID说明了TRAIL与TNF和Fas/Apo-1配体的作用途径是不同的.随着对TRAIL的受体及作用机理研究的深入, TRAIL很可能成为新一代抗肿瘤制剂.     

核仁骨架(核仁基质)的结构与成分——肌动蛋白与fibrillarin是核仁骨架的主要成分

将分离纯化的HeLa细胞核仁经非离子去垢剂、核酸酶、低盐及高盐选择性抽提结合DGD包埋去包埋技术 ,在电镜下显示了HeLa细胞的核仁骨架呈精细网络结构 .BHK -2 1细胞及小鼠肝细胞的核仁骨架与HeLa细胞的核仁骨架结构相类似 .对HeLa细胞的核仁骨架的蛋白成分进行了分析 .结果表明核仁骨架蛋白组成与核基质及染色体骨架有明显差异 .HeLa细胞核仁骨架的蛋白成分主要包括分子量为48,43,36及 33ku左右的 6～ 7种多肽 .证明分子量为 43ku的肌动蛋白与 36ku的fibrillarin是构成核仁骨架的两种主要蛋白成分     

杜氏盐藻(Dunalielle salina)盐适应相关蛋白

观察不同盐浓度培养液中生长的杜氏盐藻可溶性蛋白SDS-PAG图谱,发现高盐与低盐相比,其51kD和63kD蛋白含量高,而23kD的蛋白含量则低。高渗骤变后,51kD蛋白的含量减少,而23kD蛋白的含量增加两倍或两倍以上,骤变23h后含量增加已非常明显;低渗骤变后24h,51kD和23kD蛋白的含量变化不明显。另外,有一分子量约为26kD的蛋白在高盐下易降解。分析了这些蛋白与社氏盐藻渗透调节的可能关系。     

中国人肤纹研究：Ⅲ.中国52个民族的肤纹聚类

中国有56个民族,肤纹学研究中的最后一个民族——门巴族——的肤纹研究至今刚刚完成。根据52个民族的122个群体指掌纹的11个参数:TFRC、a-bRC、A、L~u、L~r、W、T、Ⅱ、Ⅲ、Ⅳ、H做聚类分析,在系统树上可以见到南方群、混合群、北方群。混合群包括了各自南、北方民族的聚类群,聚类群与其地理位置有平行关系,南北间以长江或北纬30°～33°度为界带。     

羟基化修饰对大鼠胶原热稳定性的影响研究

采用差示扫描量热仪(DSC)研究羟脯氨酸(Hyp)含量对胶原热稳定性的影响。以不同周龄BN大鼠皮肤为原料制备了胶原,分析制备胶原中Hyp的含量;采用DSC测定不同Hyp含量胶原的临界变性温度及焓变;采用圆二色光谱(CD)检测提取胶原的二级结构。结果表明,提取胶原在41.3℃发生三螺旋解聚,CD光谱分析结果表明,当样品经临界变性温度处理后,部分三螺旋结构转化为无规则线圈结构。胶原变性过程中所需热量与羟脯氨酸含量呈正相关,实验建立了胶原热变性过程中焓变与Hyp含量的关系。该研究表明胶原中脯氨酸羟基化修饰是影响胶原热稳定性的关键因素。     

不同治疗方案对原发免疫性血小板减少症患者外周血调节T细胞水平变化的影响及其意义分析(英文)

目的:探讨原发免疫性血小板减少症(immune thrombocytopenia,ITP)患者治疗前后外周血调节性T细胞(regulatory T cell,Treg)水平变化及其在ITP发病中的作用。方法:选取2010年6月至2013年7月间276例新诊断ITP患者,男114例、女162例,中位年龄40(18-70)岁。按治疗方案随机分为地塞米松组(90例):地塞米松40 mg/d第1~4天口服;泼尼松组(98例):泼尼松1.5 mg·kg-1·d-1口服;2泼尼松组(98例):泼尼松1.5 mg·kg-1·d-1口服;地塞米松+小剂量利妥昔单抗组(88例):地塞米松40 mg/d第1-4天口服,利妥昔单抗100 mg第7、14、21、28天静脉滴注。各组患者于治疗前、治疗后14 d和28 d分别采取外周静脉血,采用流式细胞术检测CD4+CD25+CD127-细胞水平。以60名健康体检者为正常对照组。结果:治疗后第28天,地塞米松组、泼尼松组、地塞米松+小剂量利妥昔单抗组的总有效率分别66.7%、69.4%、79.5%,差异无统计学意义;随访12个月,泼尼松组(37.8%)和地塞米松组(22.7%)之间差异无统计学意义,而与地塞米松+小剂量利妥昔单抗组持续有效率(66.7%),差异有统计学意义(P0.05)。所有ITP患者治疗前外周血CD4+CD25+CD127-细胞表达水平低于健康对照组[(1.66±0.69)%对(4.01±0.38)%,P0.05];地塞米松组、泼尼松组患者治疗后14d CD4+CD25high CD127low细胞水平均高于治疗前[(3.46±0.76)%对(1.68±0.72)%、(3.22±0.77)%对(1.69±0.74)%,P值均0.05];地塞米松+小剂量利妥昔单抗组治疗后14、28d CD4+CD25+CD127-细胞水平[(4.27±1.08)%、(4.43±0.62)%]均高于治疗前[(1.67±0.67)%],差异有统计学意义(P值均0.05);治疗后28 d,泼尼松组、地塞米松组患者CD4+CD25+CD127-细胞水平[(2.68±0.63)%、(2.58±0.66)%]与治疗前比较差异无统计学意义。结论:地塞米松联合小剂量利妥昔单抗在长期疗效及提升T细胞数量方面显著优于地塞米松和泼尼松,值得临床推广。     

Neuropsychological Investigation in Chinese Patients with Progressive Muscular Atrophy

Background

Progressive muscular atrophy (PMA) is a rare type of degenerative motor neuron disease (MND) of which the onset happens in adult period. Despite its well-defined clinical characteristics, its neuropsychological profile has remained poorly understood, considering the consensus of cognitive and behavioral impairment reached in amyotrophic lateral sclerosis (ALS).

Methods

We conducted a cross-sectional evaluation of Chinese PMA patients with a series of comprehensive batteries emphasizing the executive and attention function, and covering other domains of memory, language, visuospatial function, calculation and behavior as well. Their performances were compared with those of age- and education-matched ALS and healthy controls (HC).

Results

21 patients newly diagnosed with PMA were consecutively enrolled into our ALS and other MND registry platform, accounting for 14.7% of all the incident MND cases registered during the same period. 20 patients who completed the neuropsychological batteries were included into analysis. Compared with HC, PMA performed significantly worse in maintenance function of attention, while they exhibited quantitative similarity to ALS in all behavioral inventories and neuropsychological tests except the time for Stroop interference effect.

Conclusion

PMA could display mild cognitive dysfunction in the same frontal-mediated territory of ALS but in a lesser degree, whereas they did not differ from ALS behaviorally.     

Large Cohort Screening of G6PD Deficiency and the Mutational Spectrum in the Dongguan District in Southern China

Background

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzymatic disorder of the erythrocytes that affects 400 million people worldwide. We developed a PCR-reverse dot blot (RDB) assay to screen twenty genotypes of seventeen Chinese G6PD mutations and investigate the spectrum of G6PD deficiency mutations in Dongguan District, Guangdong Province, in southern China.

Method

The PCR-RDB assay consists of multiplex PCR amplification of seven fragments in the G6PD target sequence of wild-type and mutant genomic DNA samples followed by hybridization to a test strip containing allele-specific oligonucleotide probes. A total of 16,464 individuals were analyzed by a combination of phenotypic screening and genotypic detection using the PCR-RDB assay and DNA sequence analysis.

Results

The PCR-RDB assay had a detection rate of 98.1%, which was validated by direct sequencing in a blind study with 100% concordance. The G6PD deficiency incidence rate in Dongguan District is 4.08%. Thirty-two genotypes from 469 individuals were found. The two most common variants were c.1376G>T and c.1388G>A, followed by c.95A>G, c.871G>A, c.392G>T, and c.1024 C>T. In addition, two rare mutations (c.703C>A and c.406C>T) were detected by DNA sequencing analysis. In our study, 65 cases harbored the C1311T/IVS polymorphism and 67 cases were homozygote.

Conclusion

The PCR-RDB assay we established is a reliable and effective method for screening G6PD mutations in the Chinese population. Data on the spectrum of mutations in the Dongguan District is beneficial to the clinical diagnosis and prevention of G6PD deficiency.     

Energy Landscape Reveals That the Budding Yeast Cell Cycle Is a Robust and Adaptive Multi-stage Process

Quantitatively understanding the robustness, adaptivity and efficiency of cell cycle dynamics under the influence of noise is a fundamental but difficult question to answer for most eukaryotic organisms. Using a simplified budding yeast cell cycle model perturbed by intrinsic noise, we systematically explore these issues from an energy landscape point of view by constructing an energy landscape for the considered system based on large deviation theory. Analysis shows that the cell cycle trajectory is sharply confined by the ambient energy barrier, and the landscape along this trajectory exhibits a generally flat shape. We explain the evolution of the system on this flat path by incorporating its non-gradient nature. Furthermore, we illustrate how this global landscape changes in response to external signals, observing a nice transformation of the landscapes as the excitable system approaches a limit cycle system when nutrients are sufficient, as well as the formation of additional energy wells when the DNA replication checkpoint is activated. By taking into account the finite volume effect, we find additional pits along the flat cycle path in the landscape associated with the checkpoint mechanism of the cell cycle. The difference between the landscapes induced by intrinsic and extrinsic noise is also discussed. In our opinion, this meticulous structure of the energy landscape for our simplified model is of general interest to other cell cycle dynamics, and the proposed methods can be applied to study similar biological systems.