来自瑞典Karolinska研究所和芬兰赫尔辛基大学的科学家们证实了一些调控基因表达的“开关”在癌症的形成中起重大作用。在发表于《科学》(Science)杂志上的这项研究中,他们研究了一个基因区域,该区域包含了某个与结直肠癌和前列腺癌风险增高相关的特异单核苷酸变异,发现移除这一区域可显著抵制肿瘤形成。 来自瑞典Karolinska研究所和芬兰赫尔辛基大学的科学家们证实了一些调控基因表达的“开关”在癌症的形成中起重大作用。在发表于《科学》(Science)杂志上的这项研究中,他们研究了一个基因区域,该区域包含了某个与结直肠癌和前列腺癌风险增高相关的特异单核苷酸变异,发现移除这一区域可显著抵制肿瘤形成。 全基因组关联研究揭示了与包括心脏病、糖尿病和不同类型癌症在内的200多种疾病相关的基因组区域。揭示的这些人类遗传变异吸引了科技和大众媒体的广泛关注。然而对于这些遗传区域的作用机制却尚不完全清楚。有一种已引起大量兴趣的观点提出了一种可能性,即定位远离基因的风险多态有可能是作为基因调控元件或是调控基因表达的“开关”来发挥作用。 当前的研究在小鼠中展开,科学家们对某个与结直肠癌和前列腺癌形成风险增高相关区域中的一个特殊单核苷酸变异进行了分析,一直以来并不清楚其作用机制。这一变异将癌症风险提高了20%,其非常的常见,因此相比其他当前已知的遗传变异或突变它导致了更多的遗传性癌症。 科学家们将包含这一风险变异的基因区域从小鼠基因组中移除,发现小鼠健康,但附近一个称作MYC的癌基因表达则显示小幅度下降。在激活人类中可引起结直肠癌的某个致癌信号后,研究人员测试了这些小鼠形成肿瘤的能力,他们证实显著抵制了肿瘤形成。因此这一移除的基因区域似乎充当了一个重要的基因开关促进了癌症,没有它则更少形成肿瘤。生物通 根据科学家们所说,这些结果表明尽管使得人类个体彼此各异的基因变异通常对于疾病形成具有微小的影响,它们定位的基因开关有可能发挥了重大的作用。 “我们的研究也阐明不同的基因开关驱动了正常细胞和癌细胞的生长,表明开展进一步的研究寻找途径控制这样的疾病特异性开关的活性有可能促成新的高度特异性的治疗干预方法,”该研究的领导者Jussi Taipale教授说。生物通 (生物通:何嫱) Publication: "Mice Lacking a Myc Enhancer Element that Includes Human SNP rs6983267 Are Resistant to Intestinal Tumors", Sur, I., Hallikas, O., Vhrautio, A., Yan, J., Turunen, M., Enge, M., Taipale, M., Karhu, A., Aaltonen, L. A., and Taipale, J., Science, in press, online 1 November 2012.
From IEEE Spectrum: http://spectrum.ieee.org/semiconductors/materials/graphene-the-ultimate-switch/0 石墨烯可以代替晶体管开关,因为它可以像镜子控制光束一样控制电子 llustration: Bryan Christie Design 对于晶体管来讲,从外面看其工作原理比较简单和直接,电子的运动受到栅极电压的控制。而在晶体管内部,以原子层级来看,电子的运动却非常混乱,电子不断地与大量的缺陷和振动的部位相撞,影响电子的迁移速率。 而在石墨烯内部运动的电子却具有不同的特性,由于量子力学的奇异特性,电子在通过仅有原子厚度的石墨烯薄层时不会发生那么多的碰撞,因此电子的运动轨迹为与光子可比拟的直线,产生类光的特性。可以想象,电子的运动速率将会大大增加,并且在进入另一种介质时会产生反射和折射的现象。 CMOS集成电路的进程已经要走到头了,美国已经开展了大量的研究来对CMOS的替代技术进行验证,例如 Nanoelectronics Research Initiative 计划。大概有6、7种替代技术正在研究,原文作者对石墨烯的替代技术抱有很大希望。 在石墨烯内,电子运行的速率为光速的1/300,大概是Si CMOS内部的10倍,显然可以制造出更快速的器件。采用石墨烯的技术甚至可以对器件逻辑进行真正意义上的重配置,将一个与门变成或门等等,这是普通技术无法实现的梦。 石墨烯内部的电子能级中,禁带与导带刚好重叠,这不同于金属和半导体的特性,电子从禁带跃迁到导带几乎不需要能量。电子一开始运动似乎就无法再停下来了。光子没有质量但是有动量,电子的质量也可以忽略,所以在石墨烯内,电子业可以轻易达到很快的速度。 虽然石墨烯已经被用来制造了高速的晶体管,用于射频放大,现在已达到280 GHz的工作速率( up to frequencies of 280 gigahertz .),预期将在2013年达到500 GHz的速率。但是用于石墨烯晶体管较差的开关性能,用来实现二进制逻辑还是十分困难。 如何实现开关晶体管,原文作者采用了类似光的控制思路,在石墨烯内部形成反射面的方法来达到开关的目的。 那么如何在石墨烯内部实现反射呢?这需要先介绍石墨烯的一个重要特性,这需要在石墨烯中产生不同性质的介质,例如p型和n型材料 首先,如何将石墨烯变成p型或n型的材料?在基底上面生长一层金属或者过掺杂,然后再将表面氧化,再将石墨烯铺在该氧化层上,石墨烯的边缘再加上电极。生长的那一层金属就成为了栅极,如果栅极加正电压,就会吸引电子从电极转移到石墨烯上面,而使石墨烯变成n型材料,反之则会使石墨烯变成p型材料。 其次,如果将p型石墨烯和n型石墨烯放在一起,在交界面处就会产生奇特的性质,电子从一侧电极出发,遇到p-n交界面时,就会产生反射。如果交界面与入射电子呈45°角,则反射后电子会改变方向。另外,电子穿越p-n交界面时会产生折射,并且其折射率为负数,这是很奇异的特性,原来只能通过人造材料来模拟负折射率的特性,而石墨烯的负折射率却是天然形成的。 因此,控制栅极加电压的正负,可以改变交界面的特性,成为p-n,p-p,n-n或n-p。而同型材料,例如p-p则不会使电子产生反射,而可以畅通无阻。通过该特性,结合栅极控制特性,可以形成二进制逻辑,或者其他诸如门电路或者多路分配器等复杂逻辑。采用类似光的控制特性,与Si器件相比,在相同体积和功耗的限制下,可以实现更复杂的功能和更快的运算速度,达到石墨烯材料优异的特性。 Photos: Ji Ung Lee, et al. Gate test: Laboratory experiments have shown that graphene's resistance to the flow of current varies, depending on how it is angled when placed atop a pair of gates. The results suggest that the fraction of electrons that pass through the gate interface changes with the angle, just like light. Click on the image to enlarge. 简单的二进制逻辑实现:如下图所示,一个方形的石墨烯材料,底部叠加的是两个分开的栅极,分别受不同的电压控制,从而形成n-p或n-n的交界面,控制电子通过或不通过,形成导通或截止的特性。其导通和截止的电流可以相差1000-100000倍,这与CMOS开关的性能相当,比普通石墨烯晶体管性能好1000倍,却比CMOS开关快57%。 Illustration: Bryan Christie Design Refractive Logic: One way to make a simple binary graphene device is to divide a square gate beneath a graphene sheet into two triangles. Electrons are reflected if the gates have opposite voltage and pass through the device if the voltages are the same. 多路分配器结构: Illustration: Bryan Christie Design Multiple modes: A more complex gate scheme, containing three buried gates beneath a graphene sheet and three electrodes on top for input and output, can be used to support multiple logic functions. 聚焦和负折射率特性 Illustration: Bryan Christie Design Focusing effect: Electrons moving in graphene can be focused and defocused at the interface between gates with opposite voltages. 类似于光纤的电子传输波导,电子在里面遇到石墨烯界面产生类似全反射的现象,在夹层中受引导传递。 Illustration: Bryan Christie Design Total reflection: Electrons moving in graphene can be made to bounce back and forth in the electronic equivalent of an optical fiber, which can be built with fields generated by top and bottom gates. 要达到上述石墨烯的特殊性质,需要解决的是石墨烯制造的纯度。现在也取得了较大的进展,例如将SiC加热增发,仅留下C,就形成了石墨烯。或者通过化学气相沉积的方法制得更加纯净的石墨烯。IBM用该技术制造了第一个基于石墨烯的射频器件和放大器,晶圆大小达到了200mm。 first graphene-based RF devices and amplifier circuits built on a 200-millimeter wafer 。
最近,在Journal of Materials Chemistry杂志上接收了一篇文章,很高兴,和大家一起共享。 http://www.rsc.org/Publishing/Journals/JM/article.asp?doi=b917739f 在本文中,以透明柔性十钨酸铕/琼脂糖薄膜为研究对象,构建了一个便携式的酸碱气体响应性发光开关。 Title: Chemically Responsive Luminescent Switching in Transparent Flexible Self-supporting 9 -Agarose Nanocomposite Thin Films Abstract: Europium-containing polyoxometalates (Eu-POMs) is widely used for fabrication of the hybrid inorganic-organic luminescent materials. A few efforts have been devoted to develop active Eu-POM-based luminescent sensors and switches. In this study, highly transparent flexible self-supporting decatungsteuropate(EuW 10 )-agarose thin films were successfully fabricated by a facile hydrogel casting technique. It was identified that strong interaction between agarose and EuW 10 by hydrogen bonds at the hydroxyl sites and densely-packed 3D network structure of agarose in the gel state account for the homogenous distribution of EuW 10 , and good mechanical properties of the nanocomposite films. More importantly, the obtained thin films displayed strong red emission of Eu(III) ion, and the luminescence of these thin films was sensitive to the acid and base gases. When the thin films were exposed to HCl gas, their luminescence was sharply decreased, while the luminescence was recovered upon subsequent exposing the films to NH 3 gas. Such process could be repeated many times and a portable switch based on these thin films was proposed.
http://www.sciencenet.cn/htmlnews/2009/9/223364.shtm 《自然免疫学》:研究发现人体存在抗癌基因开关 癌症每年造成全球数百万人死亡,是最主要的致死原因之一。不少人因此谈癌色变。 英国科学家研究发现,人体中存在一个抗癌基因开关。通过控制这个基因,人体血液中可以产生抵御并杀死癌细胞的免疫细胞。这一发现为癌症治疗开辟了一条新路。 天生杀手 人体内有一种叫做天然杀伤细胞(又称NK细胞)的免疫细胞。它是血液白细胞的一种,也是所有免疫细胞中的快速反应部队。当人体遭受病毒或细菌感染,或出现肿瘤时,这种细胞会迅速组织防御,杀死被感染和癌变细胞。 虽然天然杀伤细胞作用很大,但科学家对它的了解却不如对免疫T细胞和B细胞那样深入。 英国《每日邮报》9月14日援引伦敦帝国理工学院研究员休布雷迪博士的话说:天然杀伤细胞就像灰姑娘一样神秘。我们对它了解不多。 每个人体内都存在这种天然杀伤细胞,但它们数量有限,约占全部白细胞数的五分之一。研究人员说,如果能增加人体内天然杀伤细胞数量,它们就能对癌细胞发起反击。 基因开关 研究人员曾尝试抽出志愿者体内天然杀伤细胞,然后注入癌症患者体内,期望借此杀死癌细胞。但由于来自他人的天然杀伤细胞与患者身体常出现不匹配现象,因此无法每次起效。 一个关键基因的发现,使癌症患者自身产生大量天然杀伤细胞成为可能。 布雷迪和他的研究小组发现,一个名为E4bp4的基因可以控制血液干细胞转化为天然杀伤细胞。 在实验中,布雷迪利用基因工程培育出一只体内不含E4bp4基因的小白鼠。与普通小白鼠相比,这只小白鼠血液中只缺少天然杀伤细胞,其他成分完全相同。这说明E4bp4基因对天然杀伤细胞的产生起关键作用。 这一研究成果刊登在13日出版的英国《自然免疫学》杂志上。 治疗新路 研究人员正在研制一种新药,通过增加患者体内天然杀伤细胞数量来抗击癌症。预期这种新药将对乳腺癌、肠癌、肺癌和白血病产生明显疗效。 布雷迪说,天然杀伤细胞是一种重要的免疫细胞,但也可能出现机能失常而引发糖尿病和多发性硬化症等疾病。 随着控制天然杀伤细胞的基因开关的发现以及不含这一基因的小白鼠诞生,我们可以进一步研究天然杀伤细胞与一系列疾病之间的关系,他说。 英国癌症研究会新闻官员约瑟芬克里多说:人体免疫系统是抵御疾病的有力武器。这一新发现揭示了这种武器的工作原理,为未来癌症治疗开辟了新路。 http://www.nature.com/ni/journal/vaop/ncurrent/abs/ni.1787.html Nature Immunology Published online: 13 September 2009 | :10.1038/ni.1787 :10.1038/ni.1787 The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development Duncan M Gascoyne 1 , Elaine Long 1 , Henrique Veiga-Fernandes 2 , 6 , Jasper de Boer 1 , Owen Williams 1 , Benedict Seddon 3 , Mark Coles 4 , Dimitris Kioussis 2 Hugh J M Brady 1 , 5 Abstract Natural killer (NK) cells are a subset of lymphocytes crucial for innate immunity and modification of adaptive immune responses. In contrast to commitment to the T cell or B cell lineage, little is known about NK cell lineage commitment. Here we show that the basic leucine zipper (bZIP) transcription factor E4BP4 (also called NFIL3) is essential for generation of the NK cell lineage. E4BP4-deficient mice ( Nfil3 -/ ; called ' E4bp4 -/ ' here) had B cells, T cells and NKT cells but specifically lack NK cells and showed severely impaired NK cellmediated cytotoxicity. Overexpression of E4bp4 was sufficient to increase NK cell production from hematopoietic progenitor cells. E4BP4 acted in a cell-intrinsic manner 'downstream' of the interleukin 15 receptor (IL-15R) and through the transcription factor Id2. E4bp4 -/- mice may provide a model for definitive analysis of the contribution of NK cells to immune responses and pathologies. Molecular Haematology and Cancer Biology Unit, University College London Institute of Child Health and Great Ormond Street Hospital for Children, London, UK. Division of Molecular Immunology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK. Division of Immune Cell Biology, Medical Research Council National Institute for Medical Research, Mill Hill, London, UK. Centre for Immunology and Infection, Department of Biology and Hull York Medical School, University of York, UK. Immunology and Infection Section, Division of Cell and Molecular Biology, Sir Alexander Fleming Building, Imperial College, London, UK. Present address: Immunobiology Unit, Instituto de Medicina Molecular, Faculdade de Medicina de Lisboa, Lisboa, Portugal. Correspondence to: Hugh J M Brady 1 , 5 e-mail: h.brady@imperial.ac.uk . 信息分析平台: http://www.gopubmed.org/web/gopubmed/1?WEB01dvvul63ftcj4I1aI2I00d000j10040001rl 检索策略:E4bp4 and cancer 相关文献计量分析结果: Top Years Publications 2008 3 2004 2 2006 1 2001 1 1998 1 1995 1 1992 1 Top Countries Publications USA 4 Japan 3 United Kingdom 2 Italy 1 Top Cities Publications London 2 Bari 1 Fukuoka 1 Tsukuba 1 Lawrence 1 Tokyo 1 New York 1 Philadelphia 1 Top Journals Publications Mol Cell Biol 2 Clin Cancer Res 1 Gastroenterology 1 Neurosci Res 1 Biochem Bioph Res Co 1 J Virol 1 Brit J Haematol 1 Oncogene 1 J Biol Chem 1 1 2 3 Top Authors Publications Dammacco F 1 Silvestris F 1 Cafforio P 1 De Matteo M 1 Calvani N 1 Frassanito M 1 Ohdo S 1 Murakami Y 1 Higashi Y 1 Matsunaga N 1 Koyanagi S 1 Ishida N 1 Kotaka M 1 Onishi Y 1 Ohno T 1 Akaike T 1 Medh R 1 Priceman S 1 Kirzner J 1 Nary L 1 1 2 3 1 2 3 ... 16 Top Terms Publications e4bp4 10 Genes 8 Basic-Leucine Zipper Transcription Factors 8 Transcription Factors 7 transcription repressor activity 6 positive regulation of transcription 6 Proteins 6 Humans 6 Trans-Activation (Genetics) 5 Binding Sites 4 Luciferases 4 luciferase 4 Animals 4 Plasmids 4 Base Sequence 4 DNA-Binding Proteins 4 G-Box Binding Factors 4 RNA, Messenger 3 hlf 3 Leucine Zippers 3 1 2 3 ... 16 相关研究报道: Negative regulation of the osteoblast function in multiple myeloma through the repressor gene E4BP4 activated by malignant plasma cells. PMID: 18829486 Related Articles Authors: Silvestris, F , Cafforio, P , De Matteo, M , Calvani, N , Frassanito, M A , Dammacco, F Journal: Clin Cancer Res , Vol. 14 (19): 6081-91 , 2008 Abstract: PURPOSE: To explore the pathogenetic mechanisms that suppress the osteoblast function in multiple myeloma because osteogenesis results in defective new bone formation and repair. EXPERIMENTAL DESIGN: Microarray gene analysis revealed the overexpression of E4BP4 , a transcriptional repressor gene, in normal osteoblasts cocultured with myeloma cells that were releasing the parathyroid hormone-related protein ( PTHrP ). Thus, the effect of E4BP4 was assessed in PTHrP -stimulated osteoblasts by measuring the RNA levels of both Runx2 and Osterix as major osteoblast transcriptional activators. Because E4BP4 is a negative regulator of the cyclooxygenase-2 ( COX-2 ) pathway that drives the expression of both Runx2 and Osterix, these factors were investigated after prostaglandin E(2) treatment to overcome the COX-2 defect as well as in E4BP4 -silenced osteoblasts. Finally, E4BP4 , PTHrP , Osterix, and osteocalcin levels were measured in vivo in patients with bone disease together with the E4BP4 protein in bone biopsies. RESULTS: E4BP4 was specifically induced by PTHrP and inhibited both Runx2 and Osterix, whereas E4BP4 -silenced osteoblasts expressed functional levels of both factors. The prostaglandin E(2) treatment of E4BP4 -up-regulated osteoblasts promptly restored Runx2 and Osterix activities, suggesting that integrity of COX-2 pathway is essential for their transcription. Down-regulation of Osterix by E4BP4 was confirmed in vivo by its inverse levels in osteoblasts from myeloma patients with increased serum PTHrP , whose bone biopsies expressed the E4BP4 protein. CONCLUSIONS: Our data support the role of E4BP4 as osteoblast transcriptional repressor in inhibiting both Runx2 and Osterix in myeloma bone disease and correlate its effect with the increased PTHrP activity. Affiliation: Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Piazza Giulio Cesare 11, Bari , Italy . f.silvestris@dimo.uniba.it Pubmed MeSH: Adult , Basic-Leucine Zipper Transcription Factors , Core Binding Factor Alpha 1 Subunit , Dinoprostone , Gene Expression Regulation, Neoplastic , Gene Silencing , Humans , Oligonucleotide Array Sequence Analysis , Transcription Factors Wikipedia: Biopsies , Biopsy , Blood serum , Bone Disease , Bone diseases , Cistron , Client , Cyclooxygenase 2 , Down-regulation , Downregulation , Gene , Gene Expression , Gene activation , Gene expression regulation , Genetic material , Microarray analysis , Multiple Myeloma , Osteoblast , Osteocalcin , Osteogenesis , PTGS2 , PTHrP , Parathyroid hormone-related peptide , Parathyroid hormone-related protein , Patient , Plasma cell , Prostaglandins , Prostanoids , Proteins , RNA , Receptor down-regulation , RiboNucleic Acid , Serum , Transactivation Title: Circadian clock-controlled intestinal expression of the multidrug-resistance gene mdr1a in mice. PMID: 18773899 Related Articles Authors: Murakami, Y , Higashi, Y , Matsunaga, N , Koyanagi, S , Ohdo, S Journal: Gastroenterology , Vol. 135 (5): 1636-1644.e3 , 2008 Abstract: BACKGROUND AIMS: P-glycoprotein, the product of the multidrug resistance (mdr) gene, functions as a xenobiotic transporter contributing to the intestinal barrier. Although intestinal expression of the mdr1a gene and its efflux pump function has been shown to exhibit 24-hour variation, the mechanism of the variations remains poorly understood. Here, we demonstrated that the molecular components of the circadian clock act as regulators to control 24-hour variation in the expression of the mdr1a gene. METHODS: Luciferase reporter assay and gel mobility shift assay were used to study the mechanism of transcriptional regulation of the mdr1a gene by clock gene products. The messenger RNA levels and protein abundances in colon 26 cells and mouse intestine were measured by quantitative real-time polymerase chain reaction and Western blotting, respectively. RESULTS: Hepatic leukemia factor ( HLF ) and E4 promoter binding protein-4 ( E4BP4 ) regulated transcription of the mdr1a gene by competing with each other for the same DNA binding site. Molecular and biochemical analyses of HLF - and E4BP4 -down-regulated colon 26 cells and the intestinal tract of Clock mutant mice suggested that these 2 proteins consisted of a reciprocating mechanism in which HLF activated the transcription of the mdr1a gene, whereas E4BP4 periodically suppressed transcription at the time of day when E4BP4 was abundant. CONCLUSIONS: The intestinal expression of the mdr1a gene is influenced by the circadian organization of molecular clockwork. Our present findings provide a link between the circadian timekeeping system and xenobiotic detoxification. Affiliation: Pharmaceutics, Division of Clinical Pharmacy, Department of Medico-Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka , Japan . Pubmed MeSH: Adenocarcinoma , Animals , Basic-Leucine Zipper Transcription Factors , Chromatin Immunoprecipitation , Circadian Rhythm , Colonic Neoplasms , Disease Models, Animal , Gene Expression Regulation, Neoplastic , Intestinal Mucosa , Leucine Zippers , Mice, Mutant Strains , RNA, Neoplasm Wikipedia: Active site , B-DNA , Binding site , Blotting, western , Cistron , DNA , Deoxyribonucleic Acid , Electrophoretic mobility shift assay , Gel retardation assay , Gene , Genetic material , Hepatitis , House Mouse , House mice , Intestine , Inverse PCR , Inverse polymerase chain reaction , Laboratory mice , Laboratory mouse , Leukemia , Luciferase , Messenger RNA , Mice , Mouse , Multi-drug resistance , Multidrug resistance , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Nested PCR , Nested polymerase chain reaction , P-glycoprotein , PCR , Poly(A) tail , Polymerase Chain Reaction , Proteins , RNA , RiboNucleic Acid , Western Blot , Western blotting , Xenobiotics Title: Identification of negative transcriptional factor E4BP4 -binding site in the mouse circadian-regulated gene Mdr2 . PMID: 18242748 Related Articles Authors: Kotaka, M , Onishi, Y , Ohno, T , Akaike, T , Ishida, N Journal: Neurosci Res , Vol. 60 (3): 307-13 , 2008 Abstract: The hepatic transporter Mdr2 is an ATP-binding cassette transporter which excretes phosphatidylcholine into the bile. We showed that the level of Mdr2 mRNA oscillated in circadian fashion in mouse liver whereas such oscillation was dampened in the liver of Clock mutants. To examine transcriptional regulation of the Mdr2 gene we performed luciferase reporter assays using plasmid constructs containing the 5'-flanking region of the Mdr2 gene. Reporter assays using deletion constructs demonstrated that E4BP4 represses the transcriptional activity of the promoter including the D1 and D2 sites within four putative E4BP4 -binding sites. Chromatin immunoprecipitation and gel shift assays showed that E4BP4 binds to the D2 site, but not to the D1 site. These data suggested that E4BP4 is a negative transcription factor for circadian Mdr2 mRNA expression. Affiliation: Clock Cell Biology Research Group, Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba 305-8566, Japan . Pubmed MeSH: Animals , Basic-Leucine Zipper Transcription Factors , Carcinoma, Hepatocellular , Cell Line, Tumor , Circadian Rhythm , Humans , Liver , Liver Neoplasms , Mice, Inbred C57BL , Mice, Inbred ICR , Mice, Mutant Strains , P-Glycoproteins , Trans-Activators Wikipedia: ABC transporter , ATP-Binding Cassette Transporter , ATP binding cassette transporters , Atp-binding cassette transporters , Bile , Chromatin , Chromatin immunoprecipitation , Cistron , Co-immunoprecipitation , Episome , Gene , Genetic material , Hepatitis , House Mouse , House mice , Immunoprecipitation , Laboratory mice , Laboratory mouse , Luciferase , Messenger RNA , Mice , Mouse , Mus , Mus domesticus , Mus musculus , Mus musculus domesticus , Phosphatidylcholine , Plasmid , Poly(A) tail , Transactivation , Transcription factor Title: Calcium-dependent upregulation of E4BP4 expression correlates with glucocorticoid-evoked apoptosis of human leukemic CEM cells. PMID: 16630563 Related Articles Authors: Priceman, S J , Kirzner, J D , Nary, L J , Morris, D , Shankar, D B , Sakamoto, K M , Medh, R D Journal: Biochem Biophys Res Commun , Vol. 344 (2): 491-9 , 2006 Abstract: Glucocorticoid (GC)-evoked apoptosis of T-lymphoid cells is preceded by increases in the intracellular Ca2+ concentration ( i), which may contribute to apoptosis. This report demonstrates that GC-mediated upregulation of the bZIP transcriptional repressor gene, E4BP4 , is dependent on i levels, and correlates with GC-evoked apoptosis of GC-sensitive CEM -C7-14 cells. Calcium chelators EGTA and BAPTA reduced i levels and protected CEM -C7-14 cells from Dex -evoked E4BP4 upregulation as well as apoptosis. In the GC-resistant sister clone, CEM -C1-15, Dex treatment did not induce i levels, E4BP4 expression or apoptosis, however, the calcium ionophore A23187 restored Dex-evoked E4BP4 upregulation and apoptosis. CEM -C7-14 cells were more sensitive to GC-independent increases in i levels by thapsigargin, and a corresponding increase in E4BP4 expression and cell death, compared to CEM-C1-15 cells, suggesting a direct correlation between i levels, E4BP4 expression, and apoptosis. Affiliation: Department of Biology, California State University at Northridge, Northridge, CA 91330-8303, USA . Pubmed MeSH: Basic-Leucine Zipper Transcription Factors , Cell Line, Tumor , Dose-Response Relationship, Drug , Humans , Leukemia, Lymphoid , Statistics as Topic Wikipedia: A23187 , Antibiotic A23187 , Apoptosis , Calcimycin , Calcium , Calcium metabolism , Cell death , Chelating agents , Cistron , EGTA , Gene , Genetic material , Glucocorticoids , Ionophores , Thapsigargin , Up-regulation , Upregulation Title: Identification and characterization of cis-acting elements residing in the walleye dermal sarcoma virus promoter. PMID: 15220434 Related Articles Authors: Hronek, B W , Meagher, A , Rovnak, J , Quackenbush, S L Journal: J Virol , Vol. 78 (14): 7590-601 , 2004 Abstract: Walleye dermal sarcoma virus ( WDSV ) is a complex retrovirus found associated with tumors that appear and regress on a seasonal basis. There are quantitative and qualitative differences in the amount of virus expression between developing and regressing tumors. To understand the role of host cell factors in WDSV expression, DNase I footprint analysis, electrophoretic mobility shift assays (EMSA), and reporter gene assays were employed. DNase I footprint analysis of the U3 region of the WDSV long terminal repeat with nuclear extract prepared from a walleye cell line revealed protection of an Oct1 , AP1 , Whn , and two E4BP4 sites. Additionally, three regions that contained no putative transcription factor binding sites were protected. EMSA confirmed the specific binding of the protected sites and revealed three additional sites, NF1 , AP3 , and LVa, not protected in DNase I footprint analysis. Site-directed mutagenesis of the individual sites, in the context of a luciferase reporter plasmid, revealed that the NF1 , Oct1 , AP1 , E4BP4 #2, AP3 , and LVa sites contributed to transcription activation driven by the WDSV U3 region. Mutation of Novel#2 resulted in an increase in luciferase activity, suggesting the Novel#2 site may function to bind a negative regulator of transcription. Anti- Jun and anti- Fos antiserum specifically inhibited protein-DNA complex formation, indicating the presence of c- Jun and c- Fos in the walleye cell nuclear extracts and their participation in binding to the AP1 site. Interestingly, degenerative 15-bp repeats found in the U3 region are differentially protected in DNase I footprint analysis by the walleye cell line nuclear extract and regressing-tumor nuclear extract. EMSA utilizing the 15-bp repeat probe revealed that there are similarities of binding with W12 cell and developing-tumor nuclear extracts and that the binding differs from that observed with regressing-tumor nuclear extract. Affiliation: Department of Molecular Biosciences, University of Kansas, Lawrence , KS 66045, USA . Pubmed MeSH: Animals , Base Sequence , DNA Footprinting , Electrophoresis , Fish Diseases , Gene Deletion , Gene Expression Regulation, Viral , Mutagenesis, Site-Directed , Perciformes , Retroviridae Infections , Tumor Virus Infections Wikipedia: Active site , Animal virus , Benign neoplasm , Binding site , Cancer , Cell line , Cistron , DNAase , DNAse , DNase I , Deoxyribonuclease I , Deoxyribonucleases , Electrophoretic mobility shift assay , Episome , Epithelioid Sarcoma , Epsilonretrovirus , Gel retardation assay , Gene , Genetic material , Host factor , Long terminal repeat , Luciferase , Mutation , Neoplasm , Oncovirus , Plasmid , Reporter gene , Retroviridae , Retrovirus , Sarcoma , Soft Tissue Sarcoma , Spindle cell sarcoma , Terminal repeat , Transactivation , Transcription factor , Tumor , Virus Title: E4BP4 expression is regulated by the t(17;19)-associated oncoprotein E2A - HLF in pro-B cells. PMID: 15147370 Related Articles Authors: Yeung, J , O'Sullivan, E , Hubank, M , Brady, H J Journal: Br J Haematol , Vol. 125 (5): 560-7 , 2004 Abstract: The E4BP4 basic leucine zipper ( bZIP ) transcription factor is regulated by interleukin-3 ( IL-3 ) in pro-B cells and has been reported to promote survival of the murine IL-3 -dependent pro-B cell lines, FL5.12 and Baf-3. The E2A - HLF oncoprotein arises from a t(17;19) translocation in childhood pro-B cell acute lymphoblastic leukaemia and acts as an anti-apoptotic factor in FL5.12 and Baf -3 cells. To assess the functions of E2A - HLF and E4BP4 in cell survival, a tetracycline-inducible system was established in Baf-3 cells to express E4BP4 or E2A - HLF . Upon IL-3 withdrawal, expression of E2A - HLF conferred resistance to apoptosis whereas overexpression of E4BP4 did not. E4BP4 and E2A - HLF both recognized the same DNA sequence in reporter gene assays, but had opposite effects on transcription. E2A - HLF acts as a transcriptional activator and E4BP4 as a transcriptional repressor. Furthermore, E4BP4 is a downstream transcriptional target of E2A - HLF . Our data suggests that the overexpression of E4BP4 is unable to block apoptosis induced by IL-3 withdrawal and that the expression of E2A - HLF does not replace the function of E4BP4 in mediating survival. Affiliation: Molecular Haematology and Cancer Biology Unit, Institute of Child Health, University College London, London , UK . Pubmed MeSH: Blotting, Northern , Blotting, Western , Cell Line, Tumor , Child , Chromosomes, Human, Pair 17 , Chromosomes, Human, Pair 19 , DNA-Binding Proteins , Doxycycline , G-Box Binding Factors , Gene Expression , Humans , Oncogene Proteins, Fusion , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Translocation, Genetic Wikipedia: Apoptosis , B-DNA , Base sequence , Basic-leucine zipper transcription factors , Cell line , Cistron , DNA , DNA sequence , Deoxyribonucleic Acid , Gene , Genetic material , IL-3 , Interleukin-3 , Interleukin 3 , L-Leucine , Leucine , Leucine Zipper , Leucine zippers , Nucleotide sequence , Oncogene protein , Reporter gene , Transactivation , Transcription factor Title: Growth-suppressive effects of BPOZ and EGR2 , two genes involved in the PTEN signaling pathway. PMID: 11494141 Related Articles Authors: Unoki, M , Nakamura, Y K Journal: Oncogene , Vol. 20 (33): 4457-65 , 2001 Abstract: Defects in PTEN , a tumor suppressor, have been found in cancers arising in a variety of human tissues. To elucidate the tumor-suppressive function of this gene, we have been analysing expression profiles of cancer cells after introduction of exogenous PTEN . Those experiments identified 99 candidate genes that were transcriptionally transactivated. Among them, we report here the further analyses of eight genes, EGR2/ Krox-20 , BPOZ , APS, HCLS1 / HS1 , DUSP1 / MKP1 , NDRG1 / Drg1 / RTP , NFIL3 / E4BP4 , and a novel gene ( PINK1 , PTEN -induced putative kinase). Expression of six of them ( PINK1 , EGR2 , HCLS1 , DUSP1 , BPOZ, and NFIL3) was decreased in ovarian tumors compared with corresponding normal tissues. Colony-formation assays using plasmid clones designed to express each gene indicated that EGR2 and BPOZ were able to suppress growth of cancer cells significantly; in particular, cancer -cell lines stably expressing BPOZ grew more slowly than control cells containing mock vector. Flow cytometry suggested that over-expression of BPOZ inhibited progression of the cell cycle at the G(1)/S transition. Anti-sense oligonucleotides for BPOZ or EGR2 effectively inhibited their expression, and cell growth was accelerated. Therefore both genes appear to be novel candidates as mediators of the PTEN growth-suppressive signaling pathway. Affiliation: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo , 4-6-1 Shirokanedai, Minato-ku, Tokyo , 108-8639, Japan . Pubmed MeSH: Adaptor Proteins, Vesicular Transport , Adult , Amino Acid Sequence , Ankyrin Repeat , Basic-Leucine Zipper Transcription Factors , Blood Proteins , Cell Cycle Proteins , Cell Division , DNA-Binding Proteins , Dual Specificity Phosphatase 1 , Early Growth Response Protein 2 , Expressed Sequence Tags , G-Box Binding Factors , Gene Expression Profiling , Genes, Tumor Suppressor , Humans , Immediate-Early Proteins , Intracellular Signaling Peptides and Proteins , Neoplasm Proteins , Nerve Tissue Proteins , Oligodeoxyribonucleotides, Antisense , Ovarian Neoplasms , PTEN Phosphohydrolase , Phosphoprotein Phosphatases , Phosphoric Monoester Hydrolases , Protein Kinases , Protein Phosphatase 1 , Protein Structure, Tertiary , Protein Tyrosine Phosphatases , Proteins , RNA Splicing , Recombinant Fusion Proteins , Repressor Proteins , Sequence Alignment , Signal Transduction , Subcellular Fractions , Transcription Factors , Trans-Activation (Genetics) , Transfection , Tumor Cells, Cultured , Tumor Stem Cell Assay , Tumor Suppressor Proteins Wikipedia: Acceleration , Benign neoplasm , Cancer , Cell Cycle , Cell Division Cycle , Cistron , Episome , Flow cytometry , Gene , Genetic material , Kinase , Neoplasm , Oligonucleotides , Oligonucleotides, antisense , Phosphotransferases , Plasmid , Tissue , Trans-acting factor , Trans-activator , Transactivator , Tumor Title: Keratinocyte growth factor down-regulates expression of the sucrase-isomaltase gene in Caco-2 intestinal epithelial cells. PMID: 9837912 Related Articles Authors: Zhou, J , Wu, K , Fernandes, C L , Cheng, A L , Finch, P W Journal: J Biol Chem , Vol. 273 (50): 33367-73 , 1998 Abstract: The molecular mechanisms that regulate the proliferation and differentiation of intestinal mucosal epithelial cells are not well understood. Keratinocyte growth factor ( KGF ) is an epithelial cell-specific growth factor that may be involved in the maintenance of mucosal epithelial populations and in mediating epithelial repair after injury. The sucrase-isomaltase (SI) gene, which encodes an enterocyte brush border disaccharidase, has served as a model for study of intestinal-specific gene expression and differentiation. KGF down-regulated SI mRNA and protein expression in Caco-2 intestinal epithelial cells but not the expression of other brush border enzymes. The down-regulation was dose- and time-dependent and specifically blocked by anti- KGF antibodies. Transfection experiments using SI promoter constructs demonstrated that KGF decreased SI gene transcription. In contrast, the stability of SI mRNA was not affected by incubation of Caco-2 cells with KGF . Electrophoretic mobility shift analysis demonstrated that binding of nuclear proteins to the SI footprint (SIF) 3 and SIF4 regulatory elements within the SI promoter region was increased in Caco-2 cells that had been incubated with KGF . In transfection experiments using a construct in which tandem copies of the SIF4-binding site were inserted upstream of the SV40 promoter and luciferase gene, incubation with KGF resulted in a significant decrease in luciferase activity. However, transfection with a similar construct containing tandem copies of SIF3 had no significant effect on SV40 promoter activity following KGF treatment. SIF4 may bind E4BP4 , a previously identified transcriptional repressor protein. This factor may in part mediate the decrease in SI transcription by KGF in Caco-2 cells. Affiliation: Derald H. Ruttenberg Cancer Center, Mount Sinai School of Medicine, New York , New York 10029, USA . Pubmed MeSH: Cell Differentiation , Fibroblast Growth Factor 10 , Fibroblast Growth Factors , Growth Substances , Humans , Intestinal Mucosa , Protein Binding , Receptor, Fibroblast Growth Factor, Type 2 , Receptors, Fibroblast Growth Factor , Receptors, Growth Factor , Sucrase-Isomaltase Complex Wikipedia: Antibodies , Brush border , Cistron , Disaccharidases , Down-regulation , Downregulation , Enterocyte , Enzymes , Epithelial cell , Gene , Gene Expression , Genetic material , Growth factors , Incubator , Injuries , Injury , Intercellular signaling peptides and proteins , Intestine , Keratinocyte , Keratinocyte Growth Factor , Luciferase , Maintenance , Messenger RNA , Microvilli , Microvillus , Mucositis , Nuclear protein , Palifermin , Poly(A) tail , Proteins , Receptor down-regulation , Transfection , Trauma , Wound , Wounds and injuries Title: DNA-binding specificity of the PAR basic leucine zipper protein VBP partially overlaps those of the C/EBP and CREB / ATF families and is influenced by domains that flank the core basic region. PMID: 7891686 Related Articles Authors: Haas, N B , Cantwell, C A , Johnson, P F , Burch, J B Journal: Mol Cell Biol , Vol. 15 (4): 1923-32 , 1995 Abstract: The PAR subfamily of basic leucine zipper (bZIP) factors comprises three proteins ( VBP / TEF , DBP , and HLF ) that have conserved basic regions flanked by proline- and acidic-amino-acid-rich (PAR) domains and functionally compatible leucine zipper dimerization domains. We show that VBP preferentially binds to sequences that consist of abutted GTAAY half-sites (which we refer to as PAR sites) as well as to sequences that contain either a C/ EBP half-site (GCAAT) or a CREB / ATF half-site (GTCAT) in place of one of the PAR half-sites. Since the sequences that we describe as PAR sites and PAR- CREB / ATF chimeric sites, respectively, were both previously described as high-affinity binding sites for the E4BP4 transcriptional repressor, we infer that these sequences may be targets for positive and negative regulation. Similarly, since the sequences that we describe as PAR-C / EBP and PAR- CREB / ATF chimeric sites are known to be high-affinity binding sites for C/EBP and CREB / ATF factors, respectively, we infer that these sites may each be targets for multiple subfamilies of bZIP factors. To gain insights regarding the molecular basis for the binding-site specificity of PAR factors, we also carried out an extensive mutational analysis of VBP . By substituting five amino acid residues that differ between the Drosophila giant bZIP factor and the vertebrate PAR bZIP factors, we show that the fork region, which bridges the basic and leucine zipper domains, contributes to half-site sequence specificity. In addition, we report that at least two domains amino terminal to the core basic region are required for VBP to bind to the full spectrum of PAR target sites. Thus, whereas direct base contacts may be restricted to basic-region residues (as indicated by GCN4 -DNA crystal structures), several other domains also influence the DNA-binding specificity of PAR bZIP proteins. Affiliation: Fox Chase Cancer Center, Philadelphia , Pennsylvania 19111. Pubmed MeSH: Activating Transcription Factor 2 , Avian Proteins , Base Sequence , CCAAT-Enhancer-Binding Proteins , Carrier Proteins , Cyclic AMP Response Element-Binding Protein , DNA Mutational Analysis , DNA-Binding Proteins , G-Box Binding Factors , Models, Molecular , Nuclear Proteins , Protein Binding , Structure-Activity Relationship , Transcription Factors Wikipedia: Active site , Amino Acids , Basic-leucine zipper transcription factors , Binding site , Chimerism , Dimerization , Drosophila , L-Leucine , L-Proline , Leucine , Leucine Zipper , Leucine zippers , Microchimerism , Mutation , ProLine , Proteins , Vertebrate Title: Transcriptional repression by a novel member of the bZIP family of transcription factors. PMID: 1620116 Related Articles Authors: Cowell, I G , Skinner, A , Hurst, H C Journal: Mol Cell Biol , Vol. 12 (7): 3070-7 , 1992 Abstract: We describe here a novel member of the bZIP family of DNA-binding proteins, designated E4BP4 , that displays an unusual DNA-binding specificity which overlaps that of the activating transcription factor family of factors. When expressed in a transient transfection assay with a suitable reporter plasmid, E4BP4 strongly repressed transcription in a DNA-binding-site-dependent manner. Examination of a series of deletion mutants revealed that sequences responsible for the repressing potential of E4BP4 lie within the carboxyl-terminal region of the protein. No similarity was found between this region and the repressing domains of other known eukaryotic transcriptional repressors. Affiliation: Gene Transcription Laboratory, Imperial Cancer Research Fund, Hammersmith Hospital, London , England . Pubmed MeSH: Amino Acid Sequence , Animals , Base Sequence , Basic-Leucine Zipper Transcription Factors , Binding Sites , DNA Mutational Analysis , G-Box Binding Factors , Multigene Family , Placenta , Plant Proteins , Protein Conformation , Repressor Proteins , Sequence Homology, Nucleic Acid , Transcription, Genetic Wikipedia: DNA binding protein , Dna-binding proteins , Episome , Plasmid , Proteins , Transcription factor , Transfection 原始研究论文: E4bp4 and cancer 知识发现平台: http://arrowsmith.psych.uic.edu/cgi-bin/arrowsmith_uic/edit_b.cgi?refresh=TID=24532 检索策略:E4bp4 and cancer Start A-Literature C-Literature B-list Filter Literature A-query: E4bp4 C-query: cancer The B-list contains title words and phrases (terms) that appeared in both the A and the C literature. 10 articles appeared in both literatures and were not included in the process of computing the B-list but can be viewed here . The results of this search are saved under id # 24532 and can be accessed from the start page after you leave this session. There are 359 terms on the current B-list (92 are predicted to be relevant), which is shown ranked according to predicted relevance. The list can be further trimmed down using the filters listed in the left margin. To assess whether there appears to be a biologically significant relationship between the AB and BC literatures for specific B-terms, please select one or more B-terms and then click the button to view the corresponding AB and BC literatures. Use Ctrl to select multiple B-terms. Rank Prob B-term 10.99mapk 20.99bcl xl 30.99yy1 40.99hepatitis b virus 50.99expression analysis 60.99kinase signaling 70.99genome wide 80.99gene promoter 90.98circadian gene 100.98transcriptional repression 110.98bcl 120.98hepg2 cell 130.98topoisomerase 140.98clock gene 150.98nuclear receptor 160.98expression profile 170.97transcription factor 180.97body mass index 190.97topoisomerase i 200.97transcriptional repressor 210.96transcriptional 220.96bzip 230.96calcineurin 240.96regulate transcription 250.96nuclear factor 260.95gata 270.95molecular cloning 280.94cyp3a4 290.93gata-1 300.92genome wide expression 310.92cdna 320.92hepatitis b 330.92controlled tumor protein 340.91translationally controlled tumor 350.91factor expression 360.90protein kinase signaling 370.89igh 380.89pai-1 390.88protein protein interaction 400.87hepg2 410.87nf 420.86body mass 430.86enhancer 440.85repression 450.85zebrafish 460.85repressor 470.85signal pathway 480.85adenovirus 490.84protein kinase 500.84na h exchanger 510.84circadian clock 520.84activated t cell 530.83casein kinase 540.83promoter 550.82xl 560.81gene regulation 570.80activated t 580.79calcineurin nuclear factor 590.77clock 600.77transcription 610.77ras 620.76expression gene 630.75nih3t3 cell 640.75hematopoietic cell 650.74ba f3 660.72analysis reveal 670.72gata factor 680.71gene expression 690.70calmodulin 700.69hematopoietic 710.69t cell 720.68rev 730.68na h 740.67cell survival 750.66endothelin 760.62activation nuclear factor 770.61interleukin 780.61genome 790.60potential transcriptional 800.59novel mechanism 810.56down regulate 820.56prion 830.53domain 840.52expression analysis reveal 850.51molecular cloning characterization 860.50mass index 870.50dependent protein kinase 880.49b virus enhancer 890.49cloning characterization 900.49interleukin-4 910.48receptor rev 920.45growth survival 930.45expression cell 940.42protein protein 950.41family member 960.41b cell 970.41osteoblast 980.40regulator 990.39cell specific 1000.38uterine 1010.38kinase 1020.37b lymphocyte 1030.37parathyroid 1040.36nuclear factor activated 1050.35dependent protein 1060.34activator 1070.34protein interaction 1080.30phosphorylation 1090.30nih3t3 1100.29expression cell survival 1110.27mrna 1120.27protein gene 1130.27expression calcineurin 1140.26reperfusion 1150.24pivotal 1160.23expressed gene 1170.23pivotal role 1180.22melatonin 1190.21pineal gland 1200.21expression adenovirus 1210.20parathyroid hormone 1220.20survival murine 1230.19protein gene expression 1240.19pineal 1250.19mediated phosphorylation 1260.19control circadian clock 1270.18expression topoisomerase 1280.18survival 1290.17pro 1300.17exhibit 1310.16exchanger 1320.16nuclear 1330.15bile acid 1340.15gene 1350.15|--gene a 1360.15cloning 1370.15factor activated t 1380.13age body mass 1390.12translationally 1400.12activation nuclear 1410.11tumor protein 1420.11cell line 1430.11regulatory 1440.10expression 1450.10calcium dependent activation 1460.10controlled 1470.10virus gene 1480.09gene regulation glucocorticoid 1490.09characterization human 1500.09molecular 1510.09mrna encoding 1520.09adipose tissue 1530.08wide 1540.08period2 1550.08cluster 1560.08cell identified 1570.07circadian 1580.07glucocorticoid 1590.07ischemia reperfusion 1600.06embryonic 1610.06hepatitis 1620.06adrenal gland 1630.06gene expression mouse 1640.06adipose 1650.06novel 1660.06na 1670.05bile 1680.05regulatory protein 1690.05b cell specific 1700.05hepatic 1710.05identification 1720.05activation 1730.05expressed 1740.05hormone induced 1750.04growth 1760.04regulation 1770.04hydroxylase 1780.04rat heart 1790.04mass 1800.04potential 1810.04negative transcription 1820.04core 1830.04negative 1840.03von willebrand 1850.03signal 1860.03phosphorylated 1870.03key 1880.03tumor 1890.03index 1900.03mouse liver 1910.03liver 1920.03protein 1930.03molecular mechanism 1940.03phase 1950.03signaling 1960.03f3 1970.02mouse brain 1980.02murine 1990.02line 2000.02specific 2010.02adrenal 2020.02minimal 2030.02receptor 2040.02regulated 2050.02rhythm 2060.02multiple 2070.02messenger 2080.02cholesterol 2090.02lymphocyte 2100.023-mediated 2110.02diet 2120.02key enzyme 2130.01cis 2140.01element 2150.01expression mouse 2160.01autonomous 2170.01member 2180.01regulate 2190.01binding protein 2200.01early 2210.01related 2220.01motif 2230.01embryo 2240.01mammalian 2250.01cell 2260.01|--cell calcium 2270.01drive 2280.01reveal 2290.01dependent 2300.01protein human 2310.01binding site 2320.01ontogeny 2330.01response 2340.01family 2350.01high 2360.01adenosine 2370.01tissue 2380.01intrinsic 2390.00antagonistic 2400.00human 2410.00heart 2420.00dependent activation 2430.00molecular basis 2440.00analysis 2450.00encoding 2460.00promote 2470.00alter gene expression 2480.00chicken 2490.00down 2500.00cyclic 2510.00activated 2520.00role 2530.00viability 2540.00regulating 2550.00identified 2560.00distinct 2570.00par 2580.00induce 2590.00von 2600.00survival gene 2610.00gene mouse 2620.00ovine 2630.00rhythmic 2640.00phase delay 2650.00delta 2660.00gland 2670.00enhance 2680.00regulate survival 2690.007alpha 2700.00mouse 2710.00binding 2720.00essential 2730.00responsiveness 2740.00cyclic adenosine 5'-monophosphate 2750.00ischemia 2760.00hormone 2770.00acid synthesis 2780.00virus 2790.00mice 2800.00gamma 2810.00mammal 2820.00biosynthesis 2830.00induction 2840.00site 2850.00pathway 2860.00control 2870.00calcium 2880.00subcutaneous 2890.00mediated 2900.00acid expression 2910.00light 2920.00development 2930.00factor regulated 2940.00brain 2950.00implantation 2960.00multiple mechanism 2970.00level 2980.00synthesis 2990.00specific regulation 3000.00hormone induce 3010.00basis 3020.00early development 3030.00mechanism regulating 3040.00tissue correlation 3050.00daily 3060.00age 3070.00peripheral 3080.00absence 3090.00period 3100.00interaction 3110.00deficiency 3120.00adjacent 3130.00enzyme 3140.00difference 3150.00mechanism 3160.00treated 3170.00inducibility 3180.00factor 3190.00rat 3200.00light induced 3210.00two distinct 3220.00serum 3230.00attenuation 3240.00controlled gene 3250.00characterization peripheral 3260.00induced 3270.00acid 3280.00associated 3290.00body 3300.00alter 3310.00profile 3320.00representational 3330.00correlation 3340.00underlying 3350.00two 3360.00function 3370.00activator human 3380.005'-monophosphate 3390.00system level 3400.00suggest a 3410.00negative control 3420.00associated induction 3430.00delay 3440.00correlation age 3450.00system 3460.00characterization 3470.00amplitude 3480.00rapid 3490.00controlling 3500.00definition 3510.00retained 3520.00suggest 3530.00shocked 3540.00oscillation 3550.00interval 3560.00circuit 3570.00factor role 3580.00function early 3590.00following Restrict by semantic categories? 发现新的知识单元和研究主题,可以作为科研选题的重要参考。 job id # 24532 started Tue Sep 15 03:36:31 2009 Max_citations: 50000 Stoplist: /var/www/html/arrowsmith_uic/data/stopwords_pubmed Ngram_max: 3 24532 Search ARROWSMITH A A_query_raw: E4bp4 Tue Sep 15 03:36:44 2009 A query = E4bp4 started Tue Sep 15 03:36:45 2009 A query resulted in 54 titles 24532 Search ARROWSMITH C C_query_raw: cancer Tue Sep 15 03:36:59 2009 C: cancer 2301845 A: pubmed_query_A 54 AC: ( E4bp4 ) AND ( cancer ) 10 C query = cancer started Tue Sep 15 03:36:59 2009 C query resulted in 50000 titles A AND C query resulted in 10 titles 359 B-terms ready on Tue Sep 15 03:38:08 2009 Viewed B-terms Tue Sep 15 03:40:37 2009 hepatitis b virus Viewed B-terms Tue Sep 15 03:41:15 2009 mapk B-list on Tue Sep 15 03:41:52 2009 1 mapk 2 bcl xl 3 yy1 4 hepatitis b virus 5 expression analysis 6 kinase signaling 7 genome wide 8 gene promoter 9 circadian gene 10 transcriptional repression 11 bcl 12 hepg2 cell 13 topoisomerase 14 clock gene 15 nuclear receptor 16 expression profile 17 transcription factor 18 body mass index 与(E4bp4、 cancer)的研究报道见后,科研人员可能从中获得科研信息、得到启发,进行选题研究。 19 topoisomerase i 20 transcriptional repressor 21 transcriptional 22 bzip 23 calcineurin 24 regulate transcription 25 nuclear factor 26 gata 27 molecular cloning 28 cyp3a4 29 gata-1 30 genome wide expression 31 cdna 32 hepatitis b 33 controlled tumor protein 34 translationally controlled tumor 35 factor expression 36 protein kinase signaling 37 igh 38 pai-1 39 protein protein interaction 40 hepg2 41 nf 42 body mass 43 enhancer 44 repression 45 zebrafish 46 repressor 47 signal pathway 48 adenovirus 49 protein kinase 50 na h exchanger 51 circadian clock 52 activated t cell 53 casein kinase 54 promoter 55 xl 56 gene regulation 57 activated t 58 calcineurin nuclear factor 59 clock 60 transcription 61 ras 62 expression gene 63 nih3t3 cell 64 hematopoietic cell 65 ba f3 66 analysis reveal 67 gata factor 68 gene expression 69 calmodulin 70 hematopoietic 71 t cell 72 rev 73 na h 74 cell survival 75 endothelin 76 activation nuclear factor 77 interleukin 78 genome 79 potential transcriptional 80 novel mechanism 81 down regulate 82 prion 83 domain 84 expression analysis reveal 85 molecular cloning characterization 86 mass index 87 dependent protein kinase 88 b virus enhancer 89 cloning characterization 90 interleukin-4 91 receptor rev 92 growth survival 93 expression cell 94 protein protein 95 family member 96 b cell 97 osteoblast 98 regulator 99 cell specific 100 uterine 101 kinase 102 b lymphocyte 103 parathyroid 104 nuclear factor activated 105 dependent protein 106 activator 107 protein interaction 108 phosphorylation 109 nih3t3 110 expression cell survival 111 mrna 112 protein gene 113 expression calcineurin 114 reperfusion 115 pivotal 116 expressed gene 117 pivotal role 118 melatonin 119 pineal gland 120 expression adenovirus 121 parathyroid hormone 122 survival murine 123 protein gene expression 124 pineal 125 mediated phosphorylation 126 control circadian clock 127 expression topoisomerase 128 survival 129 pro 130 exhibit 131 exchanger 132 nuclear 133 bile acid 134 gene 135 gene a 136 cloning 137 factor activated t 138 age body mass 139 translationally 140 activation nuclear 141 tumor protein 142 cell line 143 regulatory 144 expression 145 calcium dependent activation 146 controlled 147 virus gene 148 gene regulation glucocorticoid 149 characterization human 150 molecular 151 mrna encoding 152 adipose tissue 153 wide 154 period2 155 cluster 156 cell identified 157 circadian 158 glucocorticoid 159 ischemia reperfusion 160 embryonic 161 hepatitis 162 adrenal gland 163 gene expression mouse 164 adipose 165 novel 166 na 167 bile 168 regulatory protein 169 b cell specific 170 hepatic 171 identification 172 activation 173 expressed 174 hormone induced 175 growth 176 regulation 177 hydroxylase 178 rat heart 179 mass 180 potential 181 negative transcription 182 core 183 negative 184 von willebrand 185 signal 186 phosphorylated 187 key 188 tumor 189 index 190 mouse liver 191 liver 192 protein 193 molecular mechanism 194 phase 195 signaling 196 f3 197 mouse brain 198 murine 199 line 200 specific 201 adrenal 202 minimal 203 receptor 204 regulated 205 rhythm 206 multiple 207 messenger 208 cholesterol 209 lymphocyte 210 3-mediated 211 diet 212 key enzyme 213 cis 214 element 215 expression mouse 216 autonomous 217 member 218 regulate 219 binding protein 220 early 221 related 222 motif 223 embryo 224 mammalian 225 cell 226 cell calcium 227 drive 228 reveal 229 dependent 230 protein human 231 binding site 232 ontogeny 233 response 234 family 235 high 236 adenosine 237 tissue 238 intrinsic 239 antagonistic 240 human 241 heart 242 dependent activation 243 molecular basis 244 analysis 245 encoding 246 promote 247 alter gene expression 248 chicken 249 down 250 cyclic 251 activated 252 role 253 viability 254 regulating 255 identified 256 distinct 257 par 258 induce 259 von 260 survival gene 261 gene mouse 262 ovine 263 rhythmic 264 phase delay 265 delta 266 gland 267 enhance 268 regulate survival 269 7alpha 270 mouse 271 binding 272 essential 273 responsiveness 274 cyclic adenosine 5'-monophosphate 275 ischemia 276 hormone 277 acid synthesis 278 virus 279 mice 280 gamma 281 mammal 282 biosynthesis 283 induction 284 site 285 pathway 286 control 287 calcium 288 subcutaneous 289 mediated 290 acid expression 291 light 292 development 293 factor regulated 294 brain 295 implantation 296 multiple mechanism 297 level 298 synthesis 299 specific regulation 300 hormone induce 301 basis 302 early development 303 mechanism regulating 304 tissue correlation 305 daily 306 age 307 peripheral 308 absence 309 period 310 interaction 311 deficiency 312 adjacent 313 enzyme 314 difference 315 mechanism 316 treated 317 inducibility 318 factor 319 rat 320 light induced 321 two distinct 322 serum 323 attenuation 324 controlled gene 325 characterization peripheral 326 induced 327 acid 328 associated 329 body 330 alter 331 profile 332 representational 333 correlation 334 underlying 335 two 336 function 337 activator human 338 5'-monophosphate 339 system level 340 suggest a 341 negative control 342 associated induction 343 delay 344 correlation age 345 system 346 characterization 347 amplitude 348 rapid 349 controlling 350 definition 351 retained 352 suggest 353 shocked 354 oscillation 355 interval 356 circuit 357 factor role 358 function early 359 following Start A-Literature C-Literature B-list Filter Literature AB literature B-term BC literature E4bp4 body mass index cancer 1: Expression profile of mRNAs encoding core circadian regulatory proteins in human subcutaneous adipose tissue: correlation with age and body mass index .2009 Add to clipboard 1: Impact of body mass index on clinical and cost outcomes after radical cystectomy.2009 Add to clipboard 2: Body mass index as a prognostic marker for biochemical recurrence in Dutch men treated with radical prostatectomy.2009 Add to clipboard 3: The effect of preoperative weight loss and body mass index on postoperative outcome in patients with esophagogastric carcinoma.2009 Add to clipboard 4: Increase in body mass index category since age 20 years and all-cause mortality: a prospective cohort study (the Ohsaki Study).2009 Add to clipboard 5: Impact of body mass index on colorectal cancer treatment and outcomes: need for prospective and comprehensive data.2009 Add to clipboard 6: Effect of body mass index on short-term outcomes after colectomy for cancer .2009 Add to clipboard 7: 2009 Add to clipboard 8: Effect of population trends in body mass index on prostate cancer incidence and mortality in the United States.2009 Add to clipboard 9: Perceived barriers to physical activity according to stage of change and body mass index in the west virginia wisewoman population.2009 Add to clipboard 10: Ovarian stimulation in polycystic ovary syndrome patients: the role of body mass index .2009 Add to clipboard 11: Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies.2009 Add to clipboard 12: Triple-negative breast cancer s are increased in black women regardless of age or body mass index .2009 Add to clipboard 13: Body Mass Index and Barrett's Oesophagus in Women.2009 Add to clipboard 14: Body mass index predicts insulin resistance in survivors of pediatric acute lymphoblastic leukemia.2009 Add to clipboard 15: Diabetes prevalence and body mass index differ by ethnicity: the Multiethnic Cohort.2009 Add to clipboard 16: The impact of a high body mass index on laparoscopy assisted gastrectomy for gastric cancer .2009 Add to clipboard 17: Correlation of body mass index and menopausal status with the intra-tumoral estrogen system in invasive breast cancer .2009 Add to clipboard 18: Self-perception and Body Image Associations with Body Mass Index among 8-10-year-old African American Girls.2009 Add to clipboard 19: Body mass index before and after breast cancer diagnosis: associations with all-cause, breast cancer , and cardiovascular disease mortality.2009 Add to clipboard 20: Association of diabetes and body mass index with levels of prostate-specific antigen: implications for correction of prostate-specific antigen cutoff values?2009 Add to clipboard 21: Effect of body mass index on the outcome of patients with rectal cancer receiving curative anterior resection: disparity between the upper and lower rectum.2009 Add to clipboard 22: The association between body mass index and Barrett's esophagus: a systematic review.2009 Add to clipboard 23: Role of educational level in the relationship between Body Mass Index (BMI) and health-related quality of life (HRQL) among rural Spanish women.2009 Add to clipboard 24: Body mass index in the evaluation of thyroid cancer risk.2009 Add to clipboard 25: Effect of body mass index and waist circumference on prostate specific antigen and prostate volume in a generally healthy Korean population.2009 Add to clipboard 26: Abdominal obesity and physical inactivity are associated with erectile dysfunction independent of body mass index .2009 Add to clipboard 27: Body mass index , height, and risk of lymphatic malignancies: a prospective cohort study.2009 Add to clipboard 28: Body mass index and breast cancer survival in relation to the introduction of mammographic screening.2009 Add to clipboard 29: Polycystic ovary syndrome, body mass index and outcomes of assisted reproductive technologies.2009 Add to clipboard 30: A cohort study of p27 localization in colon cancer , body mass index , and patient survival.2009 Add to clipboard 31: Influence of body mass index on operability, morbidity and disease outcome following radical cystectomy.2009 Add to clipboard 32: Temporal association of changes in fasting blood glucose and body mass index with diagnosis of pancreatic cancer .2009 Add to clipboard 33: A cohort study of STMN1 expression in colorectal cancer : body mass index and prognosis.2009 Add to clipboard 34: Body mass index is not a prognostic marker for prostate-specific antigen failure and survival in Dutch men treated with brachytherapy.2009 Add to clipboard 35: The role of pretreatment percutaneous endoscopic gastrostomy in facilitating therapy of head and neck cancer and optimizing the body mass index of the obese patient.2009 Add to clipboard 36: Body mass index and prostate specific antigen as predictors of adverse pathology and biochemical recurrence after prostatectomy.2009 Add to clipboard 37: A quantitative analysis of body mass index and colorectal cancer : findings from 56 observational studies.2009 Add to clipboard 38: Trends in esophageal cancer and body mass index by race and gender in the state of Michigan.2009 Add to clipboard 39: Body mass index and risk, age of onset, and survival in patients with pancreatic cancer .2009 Add to clipboard 40: Physical activity attenuates the body mass index -increasing influence of genetic variation in the FTO gene.2009 Add to clipboard 41: Body mass index and mortality from lung cancer in smokers and nonsmokers: a nationally representative prospective study of 220,000 men in China.2009 Add to clipboard 42: Liver transplantation at the extremes of the body mass index .2009 Add to clipboard 43: Incident Cancer Burden Attributable to Excess Body Mass Index in 30 European countries.2009 Add to clipboard 44: Body mass index , waist circumference and waist:hip ratio as predictors of cardiovascular risk-a review of the literature.2009 Add to clipboard 45: The dependency of vitamin D status on body mass index , gender, age and season.2009 Add to clipboard 46: Different Markers of Alcohol Consumption, Smoking and Body Mass Index in Relation to Risk of Pancreatic Cancer . A Prospective Cohort Study within the Malmo Preventive Project.2009 Add to clipboard 47: p21 expression in colon cancer and modifying effects of patient age and body mass index on prognosis.2009 Add to clipboard 48: 2009 Add to clipboard 49: The effect of body mass index on overall and disease-free survival in node-positive breast cancer patients treated with docetaxel and doxorubicin-containing adjuvant chemotherapy: the experience of the BIG 02-98 trial.2009 Add to clipboard