E-box元件修饰端粒酶核心启动子序列及体外转录活性分析

人类端粒酶启动子(hTERT启动子)在肿瘤基因治疗中的有效性已经得到了证实. 然而,hTERT启动子有限的肿瘤靶向转录活性困扰着它的临床应用.早期研究已经揭示,核心hTERT启动子上的-34位E-box元件与该启动子的肿瘤靶向转录活性有关.为进一步探索核心hTERT启动子序列3′端富余E-box元件是否能提高启动子的肿瘤靶向转录能力,用化学合成方法在野生型hTERT(WT-hTERT)核心启动子片段(编码蛋白起始子ATG上游-268 bp～-10 bp)的3′端接入3个E-box序列, 构建成修饰型hTERT(Mod-hTERT)启动子. 然后,分别用WT-hTERT和Mod-hTERT启动子去调控增强型绿色荧光蛋白(EGFP)及荧光素酶报告基因在293FT、HepGⅡ、SGC7901、U2OS、以及原代培养人成纤维细胞(PHF)中表达. 结果表明, 在Mod-hTERT启动子的各实验组细胞中,能够在端粒酶阳性的293FT、HepGⅡ及 SGC7901细胞组中观测到EGFP的表达,而在端粒酶阴性的U2OS及PHF细胞组中没有观测到EGFP的表达;在端粒酶阳性的293FT、HepGⅡ和SGC7901细胞株中,Mod-hTERT启动子调控下的荧光素酶活性要高于WT-hTERT启动子组（P＜0.01）; 而在端粒酶阴性的U2OS细胞组中,Mod-hTERT启动子调控下的荧光素酶活性则低于WT-hTERT启动子组（P＜0.01); 在PHF细胞组中,Mod-hTERT启动子组与WT-hTERT启动子组的荧光素酶活性差异不显著(P＞0.05).研究提示,在3′端增加E-box元件可以提高核心hTERT启动子序列的肿瘤靶向转录活性.     

Prognosis in Tetraplegia

A total of 141 cases of traumatic tetraplegia were admitted to the Liverpool Paraplegic Centre between 1947 and 1967. Most of the deaths occurred within three months of injury, and comparison with other centres suggests that the early mortality could be reduced by more use of mechanical respirators.Urological complaints and pressure sores are hazards that can be overcome by careful attention to nursing procedures. Later deaths are more common among patients transferred from the unit to hostels or hospitals than among patients transferred home. Specialist units for these patients improve the quality of their lives as well as their expectation of life. Electronic equipment can also play a large part in helping tetraplegics to play a part in community life.     

The study of animal bones from archaeological sites. By Raymond E. Chaplin. ix + 170 pp., figures,tables, bibliography,index. Seminar press,London. 1971. $5.75 (cloth)

A review of the literature reveals a long history of disagreement on the interpretation of the lower deciduous and permanent dentition of the Indriidae. This disagreement has centered on the existence and/or replacement of a canine as a member of the indriid toothcomb. The presence of a pair of canines in the toothcomb of lemurids and lorisids has rarely been questioned, and there is no evidence to indicate that this interpretation is incorrect. There has, however, been no consistency nor substantiating evidence presented for any interpretation of the indriid toothcomb. By comparing the morphology of the teeth of the lemurid, lorisid, and indriid toothcomb, both deciduous and permanent, comparing the mode of dental development in these three families, identifying the indriid lower deciduous dentition, and by relating the data to an ontogenetic and phylogenetic framework, this study proposes: (1) in all three families, the lateral teeth of the toothcomb are canines, (2) the dental formula for the lower deciduous teeth of indriids is 1.1.4, (3) the dental formula for the lower permanent teeth of indriids is 1.1.2.3, and (4) that decrease in number of incisors during primate evolution was most likely I1 to I2 to I3.     

Brief communication: Minimally invasive bone sampling method for DNA analysis

Obtaining a bone sample for DNA analysis has traditionally been a destructive practice, which has resulted in reluctance on behalf of curators for skeletal collections to allow invasive testing. A novel minimally invasive bone sampling method for DNA analysis is presented here. This method uses a conventional hand drill wherein the bone sample is extracted from the intercondylar fossa of the femur; it does not interfere with any known anthropometric landmarks and only leaves a small hole on the surface of the bone. The temperature of the drill is documented and it was established due to the minor increase in temperature, that this should not affect the molecular integrity of the sample. This method is easily replicated and is suitable for both human and other animal skeletal material and can be applied to rare specimens with little risk. Am J Phys Anthropol, 2009. © 2009 Wiley‐Liss, Inc.     

MicroRNAs in systemic rheumatic diseases

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded RNAs about 21 nucleotides in length. miRNAs have been shown to regulate gene expression and thus influence a wide range of physiological and pathological processes. Moreover, they are detected in a variety of sources, including tissues, serum, and other body fluids, such as saliva. The role of miRNAs is evident in various malignant and nonmalignant diseases, and there is accumulating evidence also for an important role of miRNAs in systemic rheumatic diseases. Abnormal expression of miRNAs has been reported in autoimmune diseases, mainly in systemic lupus erythematosus and rheumatoid arthritis. miRNAs can be aberrantly expressed even in the different stages of disease progression, allowing miRNAs to be important biomarkers, to help understand the pathogenesis of the disease, and to monitor disease activity and effects of treatment. Different groups have demonstrated a link between miRNA expression and disease activity, as in the case of renal flares in lupus patients. Moreover, miRNAs are emerging as potential targets for new therapeutic strategies of autoimmune disorders. Taken together, recent data demonstrate that miRNAs can influence mechanisms involved in the pathogenesis, relapse, and specific organ involvement of autoimmune diseases. The ultimate goal is the identification of a miRNA target or targets that could be manipulated through specific therapies, aiming at activation or inhibition of specific miRNAs responsible for the development of disease.