凋亡蛋白抑制剂(inhibitor of apoptosis proteins,IAPs)编码一组结构相关的蛋白,该家族成员不仅可以抑制细胞凋亡, 而且参与多种似无关联的生物学功能,如调节细胞周期和细胞分裂等.迄今为止,在人体新发现的IAPs家族有8个成员,分别是HIA...凋亡蛋白抑制剂(inhibitor of apoptosis proteins,IAPs)编码一组结构相关的蛋白,该家族成员不仅可以抑制细胞凋亡, 而且参与多种似无关联的生物学功能,如调节细胞周期和细胞分裂等.迄今为止,在人体新发现的IAPs家族有8个成员,分别是HIAP-1、HIAP-2、XIAP、ML-IAP、Survivin 和ILP-2/Ts-IAP、NAIP、BRUCE/apollon等.本文对现有的IAPs家族成员的结构特征和功能作一总结,尤其对Survivin的分子构成、功能、作用机制、组织分布、表达特点、生物学特性以及与肿瘤治疗相关的研究进展方面进行重点综述.展开更多
The inflammasome is an emerging new pathway in innate immune defense against microbial infection or endogenous danger signals.The inflammasome stimulates activation of inflammatory caspases,mainly caspase-1.Caspase-1 ...The inflammasome is an emerging new pathway in innate immune defense against microbial infection or endogenous danger signals.The inflammasome stimulates activation of inflammatory caspases,mainly caspase-1.Caspase-1 activation is responsible for processing and secretion of IL-1βand IL-18 as well as for inducing macrophage pyroptotic death.Assembly of the large cytoplasmic inflammasome complex is thought to be mediated by members of NOD-like receptor(NLR)family.While functions of most of the NLR proteins remain to be defined,several NLR proteins including NLRC4 have been shown to assemble distinct inflammasome complexes.These inflammasome pathways,particularly the NLRC4 inflammasome,play a critical role in sensing and restricting diverse types of bacterial infections.Here we review recent advances in defining the exact bacterial ligands and the ligand-binding receptors involved in NLRC4 inflammasome activation.Implications of the discovery of the NAIP family of inflammasome receptors for bacterial flagellin and type III secretion apparatus on future inflammasome and bacterial infection studies are also discussed.展开更多
Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Thr...Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: SMA1, SMA2, and SMA3. The survival of motor neuron (SMN) gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein (NAlP) gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed to detect the deletion of both exon 7 and exon 8 of SMN1 and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMA1 patients and 76% (13/17) of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMNI exon 7 along with 24% (4/17) of SMA2 patients. Eleven out of 32 (34%) SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NA1P deletion. The findings of homozygous deletions ofexon 7 and/or exon 8 ofSMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion ofSMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NAIP gene may be a modifying factor for disease severity of SMAI. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.展开更多
2001年,哥伦比亚大学的国家艺术媒体研究项目(National Arts Journalism Program,简称NAJP)针对40位美国的建筑评论家进行了一次问卷调查,调查结果比较清晰地反映了美国建筑评论界的一些现实状况。本文重点介绍分析了美国建筑评论家如...2001年,哥伦比亚大学的国家艺术媒体研究项目(National Arts Journalism Program,简称NAJP)针对40位美国的建筑评论家进行了一次问卷调查,调查结果比较清晰地反映了美国建筑评论界的一些现实状况。本文重点介绍分析了美国建筑评论家如何看待建筑评论的作用和意义,建筑评论在美国大众媒体上受到的重视程度以及美国建筑评论家的特点这三方面的内容,以期对中国建筑评论的发展有所启迪。展开更多
基金by the National Basic Research Program of China(973 Program)(Grant Nos.2010CB835400 and 2012CB518700)Howard Hughes Medical Institute,USA.
文摘The inflammasome is an emerging new pathway in innate immune defense against microbial infection or endogenous danger signals.The inflammasome stimulates activation of inflammatory caspases,mainly caspase-1.Caspase-1 activation is responsible for processing and secretion of IL-1βand IL-18 as well as for inducing macrophage pyroptotic death.Assembly of the large cytoplasmic inflammasome complex is thought to be mediated by members of NOD-like receptor(NLR)family.While functions of most of the NLR proteins remain to be defined,several NLR proteins including NLRC4 have been shown to assemble distinct inflammasome complexes.These inflammasome pathways,particularly the NLRC4 inflammasome,play a critical role in sensing and restricting diverse types of bacterial infections.Here we review recent advances in defining the exact bacterial ligands and the ligand-binding receptors involved in NLRC4 inflammasome activation.Implications of the discovery of the NAIP family of inflammasome receptors for bacterial flagellin and type III secretion apparatus on future inflammasome and bacterial infection studies are also discussed.
基金Project supported by the National Natural Science Foundation of China (No. J0710043)the Natural Science Foundation of Zheji-ang Province (No. 2007C33049), China
文摘Spinal muscular atrophy (SMA) is a disorder characterized by degeneration of lower motor neurons and occasionally bulbar motor neurons leading to progressive limb and trunk paralysis as well as muscular atrophy. Three types of SMA are recognized depending on the age of onset, the maximum muscular activity achieved, and survivorship: SMA1, SMA2, and SMA3. The survival of motor neuron (SMN) gene has been identified as an SMA determining gene, whereas the neuronal apoptosis inhibitory protein (NAlP) gene is considered to be a modifying factor of the severity of SMA. The main objective of this study was to analyze the deletion of SMN1 and NAIP genes in southern Chinese children with SMA. Here, polymerase chain reaction (PCR) combined with restriction fragment length polymorphism (RFLP) was performed to detect the deletion of both exon 7 and exon 8 of SMN1 and exon 5 of NAIP in 62 southern Chinese children with strongly suspected clinical symptoms of SMA. All the 32 SMA1 patients and 76% (13/17) of SMA2 patients showed homozygous deletions for exon 7 and exon 8, and all the 13 SMA3 patients showed single deletion of SMNI exon 7 along with 24% (4/17) of SMA2 patients. Eleven out of 32 (34%) SMA1 patients showed NAIP deletion, and none of SMA2 and SMA3 patients was found to have NA1P deletion. The findings of homozygous deletions ofexon 7 and/or exon 8 ofSMN1 gene confirmed the diagnosis of SMA, and suggested that the deletion ofSMN1 exon 7 is a major cause of SMA in southern Chinese children, and that the NAIP gene may be a modifying factor for disease severity of SMAI. The molecular diagnosis system based on PCR-RFLP analysis can conveniently be applied in the clinical testing, genetic counseling, prenatal diagnosis and preimplantation genetic diagnosis of SMA.
文摘2001年,哥伦比亚大学的国家艺术媒体研究项目(National Arts Journalism Program,简称NAJP)针对40位美国的建筑评论家进行了一次问卷调查,调查结果比较清晰地反映了美国建筑评论界的一些现实状况。本文重点介绍分析了美国建筑评论家如何看待建筑评论的作用和意义,建筑评论在美国大众媒体上受到的重视程度以及美国建筑评论家的特点这三方面的内容,以期对中国建筑评论的发展有所启迪。