Psoralen attenuates bleomycin‐induced pulmonary fibrosis in mice through inhibiting myofibroblast activation and collagen deposition

Idiopathic pulmonary fibrosis (IPF) is a progressive disease characterized by excessive deposition of extracellular matrix (ECM) and chronic inflammation with limited therapeutic options. Psoralen, a major active component extracted from Psoralea corylifolia L. seed, has several biological effects. However, the role of psoralen in IPF is still unclear. Here, we hypothesized that psoralen played an essential role in IPF in the inhibition of fibroblast proliferation and inflammatory response. A murine model of IPF was established by injecting bleomycin (BLM) intratracheally, and psoralen was administered for 14 days from the 7^th to 21^st day after BLM injection. Our results demonstrated that psoralen treatment reduced body weight loss and improved the survival rate of mice with IPF. Histological and immunofluorescent examination showed that psoralen alleviated BLM‐induced lung parenchymal inflammatory and fibrotic alteration. Furthermore, psoralen inhibited proliferation and collagen synthesis of mouse fibroblasts and partially reversed BLM‐induced expression of α‐smooth muscle actin at both the tissue and cell level. Moreover, psoralen decreased the expression of transforming growth factor‐β1, interleukin‐1β, and tumor necrosis factor‐α in the lungs of BLM‐stimulated mice. Our results reveale for the first time that psoralen exerts therapeutic effects against IPF in a BLM‐induced murine model.     

Low penetrance of Leber's hereditary optic neuropathy in ten Han Chinese families carrying the ND6 T11484C mutation

Background

Leber’s hereditary optic neuropathy (LHON) is a maternally inherited disorder. The purpose of this investigation is to understand the role of mitochondrial haplotypes in the development of LHON associated with ND6 T14484C mutation in Chinese families.

Methods

One hundred fourteen subjects from ten Han Chinese families with LHON were studied by the clinical and genetic evaluation as well as molecular and biochemical analyses of mitochondrial DNA (mtDNA).

Results

Clinical evaluation revealed that ten families exhibited extremely low penetrance of visual impairment, with an average of 10%. In particular, ten (8 males/2 females) of 114 matrilineal relatives in these families exhibited the variable severity and age-at-onset in visual dysfunction. The average age-of-onset of vision loss was 19 years old. Molecular analysis of mitochondrial DNA (mtDNA) identified the homoplasmic T14484C mutation and distinct sets of variants, belonging to the Asian haplogroups B5b, D4, D4g1b, G3a2, R11, R11a and Z3, respectively. However, there was the absence of secondary LHON-associated mtDNA mutations in these ten Chinese families.

Conclusion

The low penetrance of vision loss in these Chinese pedigrees strongly indicated that the T14484C mutation was itself insufficient to produce a clinical phenotype. The absence of secondary LHON mtDNA mutations suggests that these mtDNA haplogroup-specific variants may not play an important role in the phenotypic expression of the T14484C mutation in those Chinese families with low penentrace of vision loss. However, nuclear modifier genes and environmental factors appear to be modifier factors for the phenotypic manifestation of the T14484C mutation in these Chinese families.     

Kaposi's Sarcoma-Associated Herpesvirus ORF45 Interacts with Kinesin-2 Transporting Viral Capsid-Tegument Complexes along Microtubules

Open reading frame (ORF) 45 of Kaposi''s sarcoma-associated herpesvirus (KSHV) is a tegument protein. A genetic analysis with a null mutant suggested a possible role for this protein in the events leading to viral egress. In this study, ORF45 was found to interact with KIF3A, a kinesin-2 motor protein that transports cargoes along microtubules to cell periphery in a yeast two-hybrid screen. The association was confirmed by both co-immunoprecipitation and immunoflorescence approaches in primary effusion lymphoma cells following virus reactivation. ORF45 principally mediated the docking of entire viral capsid-tegument complexes onto the cargo-binding domain of KIF3A. Microtubules served as the major highways for transportation of these complexes as evidenced by drastically reduced viral titers upon treatment of cells with a microtubule depolymerizer, nocodazole. Confocal microscopic images further revealed close association of viral particles with microtubules. Inhibition of KIF3A–ORF45 interaction either by the use of a headless dominant negative (DN) mutant of KIF3A or through shRNA-mediated silencing of endogenous KIF3A expression noticeably decreased KSHV egress reflecting as appreciable reductions in the release of extracellular virions. Both these approaches, however, failed to impact HSV-1 egress, demonstrating the specificity of KIF3A in KSHV transportation. This study thus reports on transportation of KSHV viral complexes on microtubules by KIF3A, a kinesin motor thus far not implicated in virus transportation. All these findings shed light on the understudied but significant events in the KSHV life cycle, delineating a crucial role of a KSHV tegument protein in cellular transport of viral particles.     

人α1/158Ⅴ型(α1c型)干扰素基因在大肠杆菌中的表达及其产物的初步纯化

采用DNA聚合酶链反应(PCR)技术,将本实验室从中国人胎肝细胞染色体DNA中发现和分离的IFN-α1/158V基因的原始克隆,改造成适于进行非融合蛋白原核表达的结构形式,并在大肠杆菌中获得高效表达。测得重组IFN-α1/158V的抗病毒活性为1.9×10~7单位/升菌液。随后又采用以单克隆抗体亲和层析为主的纯化流程对表达产物进行初步纯化,获得了在SDS-聚丙烯酰胺凝胶电泳上呈现单一条带的纯化产物。     

湖北郧西范家坪早石炭世四射珊瑚

本文描述了贵阳西北郊探矿厂对面山坡上发现的早二叠世晚期茅口组双切尾虫亚科三叶虫的1新属——棘菲利普虫属(Acanthophillipsia),计4新种:Acanthophillipsia guiyangensis, A. abrota, A. abnormis和A.granurosa,丰富了我国二叠纪三叶虫动物群的资料,对研究二叠纪三叶虫的分类、演化和古生物地理分区都具有一定的意义。     

SCOPmap: Automated assignment of protein structures to evolutionary superfamilies

Background  

Inference of remote homology between proteins is very challenging and remains a prerogative of an expert. Thus a significant drawback to the use of evolutionary-based protein structure classifications is the difficulty in assigning new proteins to unique positions in the classification scheme with automatic methods. To address this issue, we have developed an algorithm to map protein domains to an existing structural classification scheme and have applied it to the SCOP database.     

磷脂DMPC Langmuir－Blodgett膜晶格结构的原子力显微镜研究

用原子力显微镜（ＡＦＭ）研究了磷脂ＤＭＰＣ三层Ｌａｎｇｍｕｉｒ－Ｂｌｏｄｇｅｔｔ（ＬＢ）膜的分子排列结构,结果表明：在磷脂ＬＢ膜的两相（液体压缩相Ｌｉｑｕｉｄ－ｃｏｎｄｅｎｓｅｄｐｈａｓｅ和液体扩张相Ｌｉｑｕｉｄ－ｅｘｐａｎｄｅｄｐｈａｓｅ）共存时,液体压缩相中的磷脂分子排列紧密,取向一致,分子间作用力较大,因而能够得到分子图像。而液体扩张相中的磷脂分子排列松散,取向混乱。分子间的作用力较弱,难于得到分子图像。在液体压缩相中磷脂分子以单斜晶格结构排列,分子间隔为０．７２ｎｍ．分子高度为２．１ｎｍ。这一结果和ＤＭＰＣ的单晶结构进行了比较。     

Measles outbreak in 31 schools: risk factors for vaccine failure and evaluation of a selective revaccination strategy.

OBJECTIVE: To examine the risk factors for measles vaccine failure and to evaluate the effectiveness of a selective revaccination strategy during a measles outbreak. DESIGN: Matched case-control study. SETTING: Thirty-one schools in Mississauga, Ont. SUBJECTS: Eighty-seven previously vaccinated school-aged children with measles that met the Advisory Committee on Epidemiology''s clinical case definition for measles. Two previously vaccinated control subjects were randomly selected for each case subject from the same homeroom class. INTERVENTIONS: All susceptible contacts were vaccinated, and contacts who had been vaccinated before Jan. 1, 1980, were revaccinated. When two or more cases occurred in a school all children vaccinated before 1980 were revaccinated. MAIN OUTCOME MEASURES: Risk of measles associated with age at vaccination, time since vaccination, vaccination before 1980 and revaccination. RESULTS: Subjects vaccinated before 12 months of age were at greater risk of measles than those vaccinated later (adjusted odds ratio [OR] 7.7, 95% confidence interval [CI] 1.6 to 38.3; p = 0.01). Those vaccinated between 12 and 14 months of age were at no greater risk than those vaccinated at 15 months or over. Subjects vaccinated before 1980 were at greater risk than those vaccinated after 1980 (adjusted OR 14.5, 95% CI 1.5 to 135.6). Time since vaccination was not a risk factor. Revaccination was effective in reducing the risk of measles in both subjects vaccinated before 1980 and those vaccinated after 1980 (adjusted OR reduced to 0.6 [95% CI 0.1 to 5.3] and 0.3 [95% CI 0.13 to 2.6] respectively). However, only 18 cases were estimated to have been prevented by this strategy. CONCLUSIONS: Adherence to routine measles vaccination for all eligible children is important in ensuring appropriate coverage with a single dose. The selective revaccination strategy''s high labour intensiveness and low measles prevention rate during the outbreak bring into question the effectiveness of such a strategy.     

新疆准噶尔盆地玛湖凹陷玛页1井宾夕法尼亚亚系至乌拉尔统风城组孢粉地层学研究

提要准噶尔盆地西北缘玛湖凹陷风城组主要形成于碱湖环境,含有优质生烃母岩。对玛页1井风城组岩心样品的孢粉分析建立了Protohaploxypinus perfectus–Lunatisporites tersus (PT)孢粉组合。该组合包括20属29种孢粉化石。PT组合以双气囊具肋花粉占主导,蕨类孢子含量很低为特征;孢粉母体植物类群以裸子植物门种子蕨盾籽目为主,其次为松柏纲松柏目。该组合与准噶尔盆地南缘塔什库拉组上部至乌拉泊组的Crustaesporites–Protohaploxypinus–Hamiapollenites孢粉组合可以对比,均以双气囊具肋花粉为主要特征,又同时出现重要的属种Gardenasporites bilabiatus,Triangulisaccites boleensis和Hamiapollenites saccatus。孢粉地层学和同位素年代学资料表明,玛页1井风城组PT组合的时代很可能属于石炭纪宾夕法尼亚亚纪卡西莫夫期至二叠纪乌拉尔世阿瑟尔期,玛湖凹陷区整个风城组沉积时代晚于宾夕法尼亚亚纪巴什基尔期,其上部可能包含部分乌拉尔世阿瑟尔期沉积。风城组黑色页岩中...