Meta-analysis of gross insertions causing human genetic disease: novel mutational mechanisms and the role of replication slippage

Although gross insertions (>20 bp) comprise <1% of disease-causing mutations, they nevertheless represent an important category of pathological lesion. In an attempt to study these insertions in a systematic way, 158 gross insertions ranging in size between 21 bp and approximately 10 kb were identified using the Human Gene Mutation Database (www.hgmd.org). A careful meta-analytical study revealed extensive diversity in terms of the nature of the inserted DNA sequence and has provided new insights into the underlying mutational mechanisms. Some 70% of gross insertions were found to represent sequence duplications of different types (tandem, partial tandem, or complex). Although most of the tandem duplications were explicable by simple replication slippage, the three complex duplications appear to result from multiple slippage events. Some 11% of gross insertions were attributable to nonpolyglutamine repeat expansions (including octapeptide repeat expansions in the prion protein gene [PRNP] and polyalanine tract expansions) and evidence is presented to support the contention that these mutations are also caused by replication slippage rather than by unequal crossing over. Some 17% of gross insertions, all >or=276 bp in length, were found to be due to LINE-1 (L1) retrotransposition involving different types of element (L1 trans-driven Alu, L1 direct, and L1 trans-driven SVA). A second example of pathological mitochondrial-nuclear sequence transfer was identified in the USH1C gene but appears to arise via a novel mechanism, trans-replication slippage. Finally, evidence for another novel mechanism of human genetic disease, involving the possible capture of DNA oligonucleotides, is presented in the context of a 26-bp insertion into the ERCC6 gene.     

尼古丁依赖的功能影像学研究进展

在过去10年中,随着功能脑影像学技术在物质滥用领域的发展,越来越多的研究者运用这些技术以探讨尼古丁成瘾的神经生物学机制。本文主要总结了尼古丁急、慢性暴露下对脑功能影响的神经脑影像学研究进展,证实了尼古丁依赖与中脑边缘犒赏系统、调节注意、记忆、运动以及联想相关脑环路之间的相关性。这些研究发现将为揭示尼古丁依赖的神经生物学机制提供更多的证据支持,进一步促进今后戒烟治疗的发展。     

物质成瘾Stroop效应研究进展

物质成瘾Stroop任务是考察物质成瘾者对成瘾相关刺激产生注意偏向的一种研究范式。研究者们采用多种实验任务和研究方法,对物质成瘾Stroop干扰产生的心理机制进行了考察,并提出了几种理论解释,但目前这些理论解释之间还存在一定的分歧。最后,本文提出了未来研究的一些建议。     

原发性肝癌患者抑郁症状与不成熟防御机制的关系

目的：了解原发性肝癌（PLC）患者的抑郁症状和不成熟防御机制（IDM）的水平，探讨PLC患者的抑郁症状与IDM的关系。方法：采用流调用抑郁自评量表（CES－D）和防御式方式问卷（DSQ）对PLC患者和健康组各100例进行调查。结果：1）PLC患者中49％可能或肯定有抑郁症状，其中23％肯定有抑郁症状，其发生率高于健康组；2）PLC组的CES－D总分高于健康组；3）PLC组比健康组采用较多分裂和潜意显现机制，采用较少抱怨机制；4）肯定有抑郁症状者比无抑郁症状者采用较多IDM；5）两组CES－D总分与IDM均分呈显著正相关，Pearson r为0.473-0.776，其中PLC组为0．473。结论：抑郁症状是PLC患者常见的负性情绪，医护人员应引起重视，并指导患者采用成熟的防御机制代替不成熟防御机制，预防并减轻患者的抑郁症状，以提高患者的生活质量。     

电磁脉冲辐射对猕猴凝血机制影响研究

目的:探讨电磁脉冲对猕猴凝血机制影响。方法:经高场强电磁脉冲源以6×104V/m全身辐照5只猕猴,于照前及照后1、3、7、14、28及90d下肢前静脉采血,采用AYW-8001型血凝仪检测电磁脉冲对动物血浆中TT、PT、APTT及FIB的影响。结果:动物血浆中TT于伤后1d及14～28d延长,APTT于伤后1d延长,FIB含量于伤后14d减少,PT在照射前后无明显变化。结论:电磁脉冲照射可对实验猕猴凝血机制产生影响,可通过TT、APTT延长和FIB含量减少而使机体凝血机制发生障碍。     

躯体形式障碍的治疗分析

目的探讨躯体形式障碍的治疗方法。方法用钟友彬的认识领悟疗法对躯体形式障碍3案例治疗通程予以报告和分析。结果认识领悟疗法对躯体形式障碍有一定的临床治疗效果。结论认识领悟疗法治疗躯体形式障碍是有效的和可行的。     

TP73-AS1在肿瘤中的表达及调控作用

<正>随着高通量测序技术的发展,成千上万种长链非编码RNA(long non-coding RNA,lncRNA)进入人们的视野。lncRNA是一类长度超过200个核苷酸并缺少开放阅读框的不具备蛋白质编码功能的RNA~([1-2])。研究发现lncRNA参与诸多生物学进程的关键步骤,包括染色质重塑、基因转录、转录后调节和蛋白质翻译等~([3-5])。LncRNA机制的不断被阐明,也为肿瘤的研究提供了新的可能。LncRNA在多种肿瘤的增殖、迁移侵袭和抗凋亡     

Pemphigus vulgaris: the role of IL-1 and IL-1 receptor antagonist in pathogenesis and effects of intravenous immunoglobulin on their production

Intravenous immunoglobulin (IVIG) is increasingly being used for the treatment of autoimmune diseases. In the present report, the role of IVIG on in vivo and in vitro production of IL-1 and IL-1 receptor antagonist (Ra) was studied in patients with pemphigus vulgaris (PV). Serum samples from 20 untreated patients with active PV prior to initiation of systemic therapy, 20 patients receiving IVIG treatment, 20 patients in clinical remission after conventional therapy, and 20 normal human controls were studied to determine the serum levels of IL-1alpha, IL-1beta, and IL-1Ra. The in vitro production of these cytokines was measured in the culture supernatant of peripheral blood mononuclear cells (PBMC) from 10 PV patients immediately before and after IVIG therapy and from age and sex-matched 10 healthy donors simultaneously. Elevated levels of IL-1alpha and IL-1beta were detected (i) in the serum of untreated PV patients with active disease prior to systemic therapy and (ii) before IVIG infusions in patients receiving IVIG therapy. These increased levels are statistically significant when compared to the levels in healthy controls (P < 0.01). A marked reduction of IL-1alpha and IL-1beta was detected (i) in the serum of patients in prolonged clinical remission and (ii) immediately after IVIG infusion in those patients on IVIG therapy. Increased level of IL-1Ra was detected in PV patients in prolonged clinical remission and after IVIG infusion in those receiving IVIG therapy. These differences were statistically significant when compared to the levels in normal controls and to the levels in the sera of patients with active disease (P < 0.01) or just before the beginning of IVIG infusion (P < 0.01). Similar differences in the levels of IL-1alpha, IL-1beta, and IL-1Ra were found in the culture supernatant of PBMC isolated from the PV patients pre and post IVIG therapy. These observations suggests that, compared to normal controls, patients with active PV have reversed levels of IL-1alpha, IL-1beta, and IL-1Ra. IVIG therapy may down-regulate production of IL-1alpha and IL-1beta and enhance production of IL-1Ra, in vivo and in vitro. This might be one of the important mechanisms by which IVIG produces its early therapeutic effects in pemphigus vulgaris.     

首诊强迫症患者的临床特点与心理防御机制研究

目的：探讨首次诊断为强迫症（OCD）患者的临床特点及其与心理防御机制的关系。方法：42例强迫症患者用耶鲁-布朗强迫评定量表（Y—BOCS）、汉米顿焦虑量表（HAMA）、汉米顿抑郁量表（HAMD）、防御方式问卷（DSQ）和艾森克人格问卷（EPQ）进行评定并与42例正常对照者比较。结果：强迫症患者以强迫观念或强迫行为为主要表现的和混合状态的各占近一半，强迫检查和强迫联想出现的频率较高，约5／6的患者有两种以上的症状，混合型的患者病程长且症状较重：强迫症患者与对照组相比更多地使用被动攻击、潜意识显现、分裂、幻想、退缩等不成熟防御机制和中间型防御机制．而较少使用升华等成熟防御机制：强迫症患者EPQ中的神经质标准分（N）显著高于对照组，而内-外向标准分（E）则低于对照组。三种不同类型的强迫症患者之间的心理防御机制以及EPQ问卷各因子的标准分的差异无显著性、结论：三组首诊的OCD患者具有不同的临床特征；不同类型的OCD均较多的使用不成熟和中间的防御机制且多具有内向、神经质的个性。     

鞭毛抗原与细菌的群集运动

群集运动是指在培养基表面某些运动细菌依赖鞭毛的群体迁移行为,涉及繁殖体细胞分化成群集细胞,发生形态、代谢以及蛋白表达等显著变化。菌细胞密度、表面接触和生理学信号均可成为群集运动的刺激因素。群集运动的关键是鞭毛的生物合成,flhDC鞭毛操纵子是支配分化和迁移的细菌调控网络的焦点。