Pub Date : 2002-08-20DOI: 10.1126/scisignal.1462002tw309
Gene expression varies substantially from one cell to another and depending on the history of the cell, its interactions, the state of its regulatory machinery, and so on. Elowitz et al. (see the Perspective by Fedoroff and Fontana) have focused on the noise in gene expression that is left when all other regulatory influences are equal. To measure this "intrinsic noise," they used strains of Escherichia coli in which two alleles encoding distinguishable green fluorescent proteins were controlled by identical promoters. In these single bacterial cells, genes have essentially the same intracellular environment, so the variation in their expression is a measure of intrinsic noise. Intrinsic noise accounted for a substantial amount of the total variation in gene expression, and amount of noise varied with changes in other factors like transcription rate. M. B. Elowitz, A. J. Levine, E. D. Siggia, P. S. Swain, Stochastic gene expression in a single cell, Science 297, 1183-1186 (2002). [Abstract] [Full Text] N. Fedoroff, W. Fontana, Small numbers of big molecules, Science 297, 1129-1131 (2002). [Summary] [Full Text]
基因表达在不同的细胞之间有很大的差异，这取决于细胞的历史、相互作用、调节机制的状态等等。Elowitz等人(参见Fedoroff和Fontana的观点)关注的是在所有其他调控影响相同的情况下，基因表达中的噪音。为了测量这种“内在噪音”，他们使用了大肠杆菌菌株，其中两个编码可区分的绿色荧光蛋白的等位基因由相同的启动子控制。在这些单一的细菌细胞中，基因的细胞内环境基本相同，因此基因表达的变化是一种内在噪声的度量。内在噪声占基因表达总变异的很大一部分，噪声量随转录率等其他因素的变化而变化。M. B. Elowitz, a . J. Levine, E. D. Siggia, P. S. Swain，单细胞随机基因表达，科学297,1183-1186(2002)。[摘要]N. Fedoroff, W. Fontana，小量大分子，科学，297,1129-1131(2002)。【摘要】【全文】
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Pub Date : 2002-08-13DOI: 10.1126/scisignal.1452002tw301
Phosphoinositide 3-kinase activity regulates many cell processes across many cell types. There are three isoforms of its catalytic subunit p110, but their specificity has not been clear. Okkenhaug et al. generated a mouse that expresses an inactive form of p110 and observed compromised B and T cell immune function. The study reveals a highly selective, nonredundant role for this isoform in lymphocyte antigen receptor signaling, as well as a drug-development target. K. Okkenhaug, A. Bilancio, G. Farjot, H. Priddle, S. Sancho, E. Peskett, W. Pearce, S. E. Meek, A. Salpekar, M. D. Waterfield, A. J. H. Smith, B. Vanhaesebroeck, Impaired B and T cell antigen receptor signaling in p110δ PI 3-kinase mutant mice, Science 297, 1031-1034 (2002). [Abstract] [Full Text]
磷酸肌苷3-激酶活性调节许多细胞类型的许多细胞过程。其催化亚基p110有三种同工异构体，但其特异性尚不清楚。Okkenhaug等人培养了一只表达p110失活形式的小鼠，观察到B细胞和T细胞免疫功能受损。该研究揭示了该异构体在淋巴细胞抗原受体信号传导以及药物开发靶标中的高度选择性，非冗余作用。K. Okkenhaug, A. Bilancio, G. Farjot, H. Priddle, S. Sancho, E. Peskett, W. Pearce, S. E. Meek, A. Salpekar, M. D. Waterfield, A. J. H. Smith, B. Vanhaesebroeck, p110δ PI 3-激酶突变小鼠的B和T细胞抗原受体信号通路受损，科学，297,1031-1034(2002)。【摘要】【全文】
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Pub Date : 2002-08-06DOI: 10.1126/scisignal.1442002tw287
The fungus Neurospora crassa is a light-sensitive organism, but its photoreceptor has remained elusive. The prime candidate, a transcription factor called White Collar-1 (WC-1), is required for all responses to light (see the Perspective by Linden). By eliminating the part of the WC-1 protein that would be expected to bind a chromophore (the LOV, or light, oxygen, and voltage, domain), He et al. show that the LOV domain is required for light responses, but not for the circadian clock function of WC-1. They then identify flavin adenine dinucleotide (FAD) as the chromophore bound to WC-1. Froehlich et al. show that WC-1 acts (as a dimer with WC-2) on two light-responsive elements in the promoter of the clock component frequency (FRQ). By reassembling this system in vitro and inducing FRQ transcription with light, these authors show that WC-1 is the blue light photoreceptor for Neurospora. In their system as well, FAD must be added in order to observe light reception. H. Linden, A white collar protein senses blue light, Science 297, 777-778 (2002). [Summary] [Full Text] He, P. Cheng, Y. Yang, L. Wang, K. H. Gardner, Y. Liu, White Collar-1, a DNA binding transcription factor and a light sensor, Science 297, 840-843 (2002). [Abstract] [Full Text] C. Froehlich, Y. Liu, J. J. Loros, J. C. Dunlap, White Collar-1, a circadian blue light photoreceptor, binding to the frequency promoter, Science 297, 815-819 (2002). [Abstract] [Full Text]
真菌粗神经孢子虫是一种光敏生物，但其光感受器仍然难以捉摸。主要的候选者是一种被称为“白领-1”(WC-1)的转录因子，它是所有对光反应所必需的(见Linden的观点)。通过消除WC-1蛋白中可能与发色团结合的部分(LOV，即光、氧和电压结构域)，He等人表明，LOV结构域是光响应所必需的，而不是WC-1的生物钟功能所必需的。然后他们确定黄素腺嘌呤二核苷酸(FAD)是与WC-1结合的发色团。Froehlich等人表明，WC-1(作为与WC-2的二聚体)作用于时钟分量频率(FRQ)启动子中的两个光响应元件。通过体外重组该系统并用光诱导FRQ转录，这些作者表明WC-1是神经孢子虫的蓝光光感受器。在他们的系统中，为了观察光的接收，必须添加FAD。H. Linden，一种能感知蓝光的白领蛋白，Science, 297, 777-778(2002)。[摘要]何平，程平，杨勇，王丽丽，刘勇，白颈-1，一种DNA结合转录因子和光传感器，科学通报，2002,840-843。[摘要]C. Froehlich, Y. Liu, J. J. Loros, J. C. Dunlap，一种结合频率启动子的昼夜蓝光光感受器White coll -1，科学通报，2002,815-819。【摘要】【全文】
{"title":"Elements of a Fungal Light Receptor","authors":"","doi":"10.1126/scisignal.1442002tw287","DOIUrl":"https://doi.org/10.1126/scisignal.1442002tw287","url":null,"abstract":"The fungus Neurospora crassa is a light-sensitive organism, but its photoreceptor has remained elusive. The prime candidate, a transcription factor called White Collar-1 (WC-1), is required for all responses to light (see the Perspective by Linden). By eliminating the part of the WC-1 protein that would be expected to bind a chromophore (the LOV, or light, oxygen, and voltage, domain), He et al. show that the LOV domain is required for light responses, but not for the circadian clock function of WC-1. They then identify flavin adenine dinucleotide (FAD) as the chromophore bound to WC-1. Froehlich et al. show that WC-1 acts (as a dimer with WC-2) on two light-responsive elements in the promoter of the clock component frequency (FRQ). By reassembling this system in vitro and inducing FRQ transcription with light, these authors show that WC-1 is the blue light photoreceptor for Neurospora. In their system as well, FAD must be added in order to observe light reception. H. Linden, A white collar protein senses blue light, Science 297, 777-778 (2002). [Summary] [Full Text] He, P. Cheng, Y. Yang, L. Wang, K. H. Gardner, Y. Liu, White Collar-1, a DNA binding transcription factor and a light sensor, Science 297, 840-843 (2002). [Abstract] [Full Text] C. Froehlich, Y. Liu, J. J. Loros, J. C. Dunlap, White Collar-1, a circadian blue light photoreceptor, binding to the frequency promoter, Science 297, 815-819 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"37 12 1","pages":"TW287 - tw287"},"PeriodicalIF":0.0,"publicationDate":"2002-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84969742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-06DOI: 10.1126/scisignal.1442002tw291
Sherri Koucky, A. Higgins
How do gene expression patterns change when a cell is perturbed, for example, by exposure to a pathogen or a drug? Although current chip-based methods of transcriptional profiling have provided researchers with a powerful tool for addressing this question, these methods require disruption of cellular architecture, meaning that important information may be lost. By combining elements of fluorescence in situ hybridization (FISH) and microarray technology, Levsky et al. have developed a technique that allows them to visualize the transcription of many genes simultaneously inside a single cell--essentially using the cell nucleus as a "chip." J. M. Levsky, S. M. Shenoy, R. C. Pezo, R. H. Singer, Single-Cell gene expression profiling, Science 297, 836-840 (2002). [Abstract] [Full Text]
当细胞受到干扰，例如暴露于病原体或药物中时，基因表达模式是如何变化的?尽管目前基于芯片的转录谱分析方法为研究人员提供了解决这一问题的有力工具，但这些方法需要破坏细胞结构，这意味着重要信息可能会丢失。通过结合荧光原位杂交(FISH)和微阵列技术，Levsky等人开发了一种技术，使他们能够在单个细胞内同时可视化许多基因的转录-本质上是使用细胞核作为“芯片”。J. M. Levsky, S. M. Shenoy, R. C. Pezo, R. H. Singer，单细胞基因表达谱分析，科学297,836-840(2002)。【摘要】【全文】
{"title":"FISH and Chips","authors":"Sherri Koucky, A. Higgins","doi":"10.1126/scisignal.1442002tw291","DOIUrl":"https://doi.org/10.1126/scisignal.1442002tw291","url":null,"abstract":"How do gene expression patterns change when a cell is perturbed, for example, by exposure to a pathogen or a drug? Although current chip-based methods of transcriptional profiling have provided researchers with a powerful tool for addressing this question, these methods require disruption of cellular architecture, meaning that important information may be lost. By combining elements of fluorescence in situ hybridization (FISH) and microarray technology, Levsky et al. have developed a technique that allows them to visualize the transcription of many genes simultaneously inside a single cell--essentially using the cell nucleus as a \"chip.\" J. M. Levsky, S. M. Shenoy, R. C. Pezo, R. H. Singer, Single-Cell gene expression profiling, Science 297, 836-840 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"15 1","pages":"TW291 - tw291"},"PeriodicalIF":0.0,"publicationDate":"2002-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86617193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-08-06DOI: 10.1126/scisignal.1442002tw290
Herpesviruses replicate in the nucleus of host cells, but the particles formed are too big to pass through nuclear pores. How do they escape? Muranyi et al. (see the Perspective by Sanchez and Spector) found that murine cytomegalovirus subverts the normal activity of a cellular protein to aid its escape. A pair of viral proteins (M50/p35 and M53/p38) form a "docking station" for the viral capsids on the inner nuclear membrane. M50/p35 then recruits cellular protein kinase C to phosphorylate and disassemble the filamentous protein network of the nuclear lamina. W. Muranyi, J. Haas, M. Wagner, G. Krohne, U. H. Koszinowski, Cytomegalovirus recruitment of cellular kinases to dissolve the nuclear lamina, Science 297, 854-857 (2002). [Abstract] [Full Text] V. Sanchez, D. H. Spector, CMV makes a timely exit, Science 297, 778-779 (2002). [Summary] [Full Text]
{"title":"Viral Tricks","authors":"","doi":"10.1126/scisignal.1442002tw290","DOIUrl":"https://doi.org/10.1126/scisignal.1442002tw290","url":null,"abstract":"Herpesviruses replicate in the nucleus of host cells, but the particles formed are too big to pass through nuclear pores. How do they escape? Muranyi et al. (see the Perspective by Sanchez and Spector) found that murine cytomegalovirus subverts the normal activity of a cellular protein to aid its escape. A pair of viral proteins (M50/p35 and M53/p38) form a \"docking station\" for the viral capsids on the inner nuclear membrane. M50/p35 then recruits cellular protein kinase C to phosphorylate and disassemble the filamentous protein network of the nuclear lamina. W. Muranyi, J. Haas, M. Wagner, G. Krohne, U. H. Koszinowski, Cytomegalovirus recruitment of cellular kinases to dissolve the nuclear lamina, Science 297, 854-857 (2002). [Abstract] [Full Text] V. Sanchez, D. H. Spector, CMV makes a timely exit, Science 297, 778-779 (2002). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"32 1","pages":"TW290 - tw290"},"PeriodicalIF":0.0,"publicationDate":"2002-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86173466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-07-23DOI: 10.1126/scisignal.1422002tw268
A large number of B cells inhabit the marginal zones (MZ) of the spleen, where they maintain steady contact with recirculating antigens in the blood. These lymphocytes respond rapidly to bacteria by mobilizing and differentiating into extensive clusters of antibody-producing plasma cells. Lu et al. show that two integrins involved in lymphocyte trafficking across endothelium, LFA-1 and α4β1, appear to be responsible for the migration and localization of MZ B cells. Large-scale egress of B cells from the MZ occurred when interactions of these integrins with their respective ligands were blocked. The retention of lymphocytes within lymphoid niches suggests a wider role for some integrins associated with lymphocyte trafficking. T. T. Lu, J. G. Cyster, Integrin-mediated long-term B cell retention in the splenic marginal zone, Science 297, 409-412 (2002). [Abstract] [Full Text]
{"title":"Staying Put","authors":"","doi":"10.1126/scisignal.1422002tw268","DOIUrl":"https://doi.org/10.1126/scisignal.1422002tw268","url":null,"abstract":"A large number of B cells inhabit the marginal zones (MZ) of the spleen, where they maintain steady contact with recirculating antigens in the blood. These lymphocytes respond rapidly to bacteria by mobilizing and differentiating into extensive clusters of antibody-producing plasma cells. Lu et al. show that two integrins involved in lymphocyte trafficking across endothelium, LFA-1 and α4β1, appear to be responsible for the migration and localization of MZ B cells. Large-scale egress of B cells from the MZ occurred when interactions of these integrins with their respective ligands were blocked. The retention of lymphocytes within lymphoid niches suggests a wider role for some integrins associated with lymphocyte trafficking. T. T. Lu, J. G. Cyster, Integrin-mediated long-term B cell retention in the splenic marginal zone, Science 297, 409-412 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"87 1","pages":"TW268 - TW268"},"PeriodicalIF":0.0,"publicationDate":"2002-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82881097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-07-16DOI: 10.1126/scisignal.1412002tw252
Vernalization, the coordinating of flowering with springtime, allows plants to accelerate flowering once the cold of winter is past. Levy et al. have now identified one of the molecular regulators of the vernalization response in the small flowering plant Arabidopsis. VRN1 is a DNA-binding protein that helps keep a floral repressor molecule out of action and allows flowering to proceed. VRN1 also shows an intriguing propensity to alter flowering time without working through this particular floral repressor, which suggests that floral initiation integrates inputs from multiple pathways. Y. Y. Levy, S. Mesnage, J. S. Mylne, A. R. Gendall, C. Dean, Multiple roles of Arabidopsis VRN1 in vernalization and flowering time control. Science 297, 243-246 (2002). [Abstract] [Full Text]
{"title":"The Bloom in Spring","authors":"","doi":"10.1126/scisignal.1412002tw252","DOIUrl":"https://doi.org/10.1126/scisignal.1412002tw252","url":null,"abstract":"Vernalization, the coordinating of flowering with springtime, allows plants to accelerate flowering once the cold of winter is past. Levy et al. have now identified one of the molecular regulators of the vernalization response in the small flowering plant Arabidopsis. VRN1 is a DNA-binding protein that helps keep a floral repressor molecule out of action and allows flowering to proceed. VRN1 also shows an intriguing propensity to alter flowering time without working through this particular floral repressor, which suggests that floral initiation integrates inputs from multiple pathways. Y. Y. Levy, S. Mesnage, J. S. Mylne, A. R. Gendall, C. Dean, Multiple roles of Arabidopsis VRN1 in vernalization and flowering time control. Science 297, 243-246 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"52 3","pages":"tw252 - tw252"},"PeriodicalIF":0.0,"publicationDate":"2002-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91438376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-07-16DOI: 10.1126/science.297.5579.153k
The fruit fly leg is a complex structure with 10 segments. Studies of Drosophila appendage development have identified several of the components that are needed to establish the dorsal-ventral (DV) and the proximal-distal (PD) axes of the leg. Signaling by wingless (wg) and decapentaplegic (dpp) operate in the developmental program for both of these axes. However, genetics studies by Galindo et al. show that wg and dpp are not sufficient to explain all of the subsequent patterning events in the PD axis. The tarsus segment, an evolutionarily ancient part of the insect leg, is defined by a dpp/wg-independent phase of distalless and dachshund activity combined with a distal gradient of epidermal growth factor receptor-Ras signaling. M. I. Galindo, S. A. Bishop, S. Greig, J. P. Couso, Leg patterning driven by proximal-distal interactions and EGFR signaling. Science 297, 256-259 (2002). [Abstract] [Full Text]
果蝇的腿是一个由10节组成的复杂结构。对果蝇附属物发育的研究已经确定了建立腿的背腹轴(DV)和近端远端轴(PD)所需的几个组成部分。无翼(wg)和失肢(dpp)信号在这两个轴的发展计划中都起作用。然而，Galindo等人的遗传学研究表明，wg和dpp不足以解释PD轴中所有随后的模式事件。跗节是昆虫腿的一个进化上古老的部分，由一个不依赖于dpp/ kg的无肢和腊肠活动阶段，结合远端表皮生长因子受体- ras信号的梯度来定义。M. I. Galindo, S. A. Bishop, S. Greig, J. P. Couso，近端相互作用和EGFR信号驱动的腿部模式。科学297,256-259(2002)。【摘要】【全文】
{"title":"The Legwork of Signaling","authors":"","doi":"10.1126/science.297.5579.153k","DOIUrl":"https://doi.org/10.1126/science.297.5579.153k","url":null,"abstract":"The fruit fly leg is a complex structure with 10 segments. Studies of Drosophila appendage development have identified several of the components that are needed to establish the dorsal-ventral (DV) and the proximal-distal (PD) axes of the leg. Signaling by wingless (wg) and decapentaplegic (dpp) operate in the developmental program for both of these axes. However, genetics studies by Galindo et al. show that wg and dpp are not sufficient to explain all of the subsequent patterning events in the PD axis. The tarsus segment, an evolutionarily ancient part of the insect leg, is defined by a dpp/wg-independent phase of distalless and dachshund activity combined with a distal gradient of epidermal growth factor receptor-Ras signaling. M. I. Galindo, S. A. Bishop, S. Greig, J. P. Couso, Leg patterning driven by proximal-distal interactions and EGFR signaling. Science 297, 256-259 (2002). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"22 1","pages":"tw253 - tw253"},"PeriodicalIF":0.0,"publicationDate":"2002-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73766002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2002-07-09DOI: 10.1126/scisignal.1402002tw243
Among the many new strategies being developed for cancer therapy are drugs that inhibit the function of oncogenes that are involved in tumorigenesis. Such drugs might be toxic if used chronically, yet they might be ineffective in the short-term because of possible reactivation of the oncogene once treatment is stopped. To investigate the latter possibility, Jain et al. (see the Perspective by Weinstein) used a sophisticated mouse genetic model to examine what happens to MYC-induced tumors when the MYC oncogene is briefly inactivated and subsequently reactivated. Surprisingly, they found that transient MYC inactivation leads to permanent loss of the neoplastic phenotype. When MYC was removed, osteogenic sarcoma cells differentiated into bone cells; reexpression of MYC did not restore the cells' tumorigenic potential but rather caused the cells to undergo apoptosis. These results suggest that brief inactivation of an oncogene may permanently change the epigenetic context of a tumor cell so that it cannot revert to its original malignant behavior. M. Jain, C. Arvanitis, K. Chu, W. Dewey, E. Leonhardt, M. Trinh, C. D. Sundberg, J. M. Bishop, D. W. Felsher, Sustained loss of a neoplastic phenotype by brief interaction of MYC. Science 296, 102-104 (2002). [Abstract] [Full Text] I. B. Weinstein, Addiction to oncogenes - the Achilles heal of cancer. Science 297, 63-64 (2002). [Summary] [Full Text]
在许多正在开发的癌症治疗新策略中，抑制参与肿瘤发生的癌基因功能的药物。如果长期使用，这些药物可能是有毒的，但它们可能在短期内无效，因为一旦停止治疗，致癌基因可能会重新激活。为了研究后一种可能性，Jain等人(参见Weinstein的观点)使用了一种复杂的小鼠遗传模型来检查当MYC致癌基因短暂失活并随后重新激活时，MYC诱导的肿瘤会发生什么。令人惊讶的是，他们发现短暂的MYC失活导致肿瘤表型的永久丧失。去除MYC后，成骨肉瘤细胞分化为骨细胞;MYC的重新表达并没有恢复细胞的致瘤潜能，而是导致细胞凋亡。这些结果表明，癌基因的短暂失活可能永久性地改变肿瘤细胞的表观遗传环境，使其不能恢复到原来的恶性行为。M. Jain, C. Arvanitis, K. Chu, W. Dewey, E. Leonhardt, M. Trinh, C. D. Sundberg, J. M. Bishop, D. W. Felsher, MYC短暂相互作用导致肿瘤表型持续丧失。科学296,102-104(2002)。【摘要】【全文】I. B. Weinstein，癌基因成瘾——癌症的阿喀琉斯之疗。科学29,63-64(2002)。【摘要】【全文】
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Pub Date : 2002-07-02DOI: 10.1126/scisignal.1392002tw236
During microbial infection, neutrophils generate microbicidal agents through the release of myeloperoxidase (MPO). Eiserich et al. report that MPO's actions during inflammation extend beyond generating antimicrobial oxidizing species. MPO permeates the mammalian vasculature and alters blood vessel function during acute inflammation by catabolizing nitric oxide (NO). NO is an endothelial-derived blood vessel relaxant that is produced in response to endotoxin. By reducing NO availability, MPO impairs vascular changes produced by infection. This finding may explain the increased susceptibility of humans deficient in MPO to infection. J. P. Eiserich, S. Baldus, M.-L. Brennan, W. Ma, C. Zhang, A. Tousson, L. Castro, A. J. Lusis, W. M. Nauseef, C. R. White, B. A. Freeman, Myeloperoxidase, a leukocyte-derived vascular NO oxidase. Science 296, 2391-2394 (2002). [Abstract] [Full Text]
在微生物感染期间，中性粒细胞通过释放髓过氧化物酶(MPO)产生杀微生物剂。Eiserich等人报道，MPO在炎症中的作用超出了产生抗微生物氧化物质的范围。MPO通过分解一氧化氮(NO)，渗透到哺乳动物的血管中，并在急性炎症期间改变血管功能。一氧化氮是一种内皮来源的血管松弛剂，是对内毒素的反应。通过降低NO的可用性，MPO损害了感染引起的血管变化。这一发现可以解释MPO缺乏的人对感染的易感性增加。J. P.艾塞里奇，S.鲍德斯，M.-L。Brennan, W. Ma, C. Zhang, a . Tousson, L. Castro, a . J. Lusis, W. M. Nauseef, C. R. White, B. a . Freeman，髓过氧化物酶，一种白细胞来源的血管NO氧化酶。科学296,2391-2394(2002)。【摘要】【全文】
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