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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. 相似文献
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Deep Sequencing of HIV-Infected Cells: Insights into Nascent Transcription and Host-Directed Therapy
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William W. Korth 《Journal of Mammalian Evolution》2001,8(4):279-296
The systematics of the beavers (Castoridae) are reviewed and definitions are presented for each subfamilial group. Four subfamilies are recognized: primitive Agnotocastorinae (divided into two tribes, Agnotocastorini and Anchitheriomyini); burrowing beavers, Palaeocastorinae; giant beavers, Castoroidinae (containing two tribes, Castoroidini and Trogontheriini); and the Castorinae. The agnotocastorines are viewed as the ancestral group for all later subfamilies. The Palaeocastorinae is viewed as a side-branch, not ancestral or closely related to any of the later subfamilies. The Castorinae and Castoroidinae may represent a distinct clade united by dental features. 相似文献
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PAF-acether (PAF) is a newly formed mediator not normally present in circulating blood. A compound exhibiting all of its biological characteristics but coeluting with phosphatidylcholine (PC) in high-pressure liquid chromatography (HPLC) was unveiled ('peak X') in normal human plasma. A second HPLC run of peak X HPLC fractions revealed the presence of PAF itself with concomitant disappearance of peak X. Beside PAF, immunoreactive apolipoproteins A-I and E were found in peak X. Also lipoproteins (Ls) purified using either ultracentrifugation or immunoaffinity chromatography yielded peak X and, in a second HPLC run, authentic PAF. L-free plasma was devoid of peak X. Finally, after preincubation with plasma, labeled PAF was found associated with Ls. Thus in human blood preformed PAF is bound in high amounts to Ls, a result of interest given the role of Ls and platelets in vascular diseases and the present knowledge on PAF biosynthesis. 相似文献
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Activation of hypothalamic RIP‐Cre neurons promotes beiging of WAT via sympathetic nervous system 下载免费PDF全文
Baile Wang Ang Li Xiaomu Li Philip WL Ho Donghai Wu Xiaoqi Wang Zhuohao Liu Kelvin KL Wu Sonata SY Yau Aimin Xu Kenneth KY Cheng 《EMBO reports》2018,19(4)
Activation of brown adipose tissue (BAT) and beige fat by cold increases energy expenditure. Although their activation is known to be differentially regulated in part by hypothalamus, the underlying neural pathways and populations remain poorly characterized. Here, we show that activation of rat‐insulin‐promoter‐Cre (RIP‐Cre) neurons in ventromedial hypothalamus (VMH) preferentially promotes recruitment of beige fat via a selective control of sympathetic nervous system (SNS) outflow to subcutaneous white adipose tissue (sWAT), but has no effect on BAT. Genetic ablation of APPL2 in RIP‐Cre neurons diminishes beiging in sWAT without affecting BAT, leading to cold intolerance and obesity in mice. Such defects are reversed by activation of RIP‐Cre neurons, inactivation of VMH AMPK, or treatment with a β3‐adrenergic receptor agonist. Hypothalamic APPL2 enhances neuronal activation in VMH RIP‐Cre neurons and raphe pallidus, thereby eliciting SNS outflow to sWAT and subsequent beiging. These data suggest that beige fat can be selectively activated by VMH RIP‐Cre neurons, in which the APPL2–AMPK signaling axis is crucial for this defending mechanism to cold and obesity. 相似文献
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We have always wanted to save the world from the scourges of virus infection by developing better drugs and vaccines. But fully understanding the intricacies of virus–host interactions, the first step in achieving this goal, requires the ability to view the process on a grand scale. The advent of high-throughput technologies, such as DNA microarrays and mass spectrometry, provided the first opportunities to obtain such a view. Here, we describe our efforts to use these tools to focus on the changes in cellular gene expression and protein abundance that occur in response to virus infection. By examining these changes in a comprehensive manner, we have been able to discover exciting new insights into innate immunity, interferon and cytokine signaling, and the strategies used by viruses to overcome these cellular defenses. Functional genomics may yet save the world from killer viruses. 相似文献
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Claudia Azucena Palafox Sánchez Minoru Satoh Edward KL Chan Wendy C Carcamo José Francisco Muñoz Valle Gerardo Orozco Barocio Edith Oregon Romero Rosa Elena Navarro Hernández Mario Salazar Páramo Antonio Cabral Castañeda Mónica Vázquez del Mercado 《Arthritis research & therapy》2009,11(1):1-12