Science's STKEPub Date : 2003-07-22DOI: 10.1126/scisignal.1922003tw286
{"title":"Boning Up on Hox Genes","authors":"","doi":"10.1126/scisignal.1922003tw286","DOIUrl":"https://doi.org/10.1126/scisignal.1922003tw286","url":null,"abstract":"In vertebrate development, the Hox genes, which establish patterns and encode positional information, are found in groups of paralogs. Mutations in individual mouse Hox genes can perturb skeletal elements, but the variable expressivities and penetrance observed with mutations in paralogous Hox genes make it hard to distinguish whether these genes cause patterning at the global or local level. Wellik et al. now report targeted disruptions of all of the alleles of the Hox10 or Hox11 paralogous family to show that Hox genes act in globally patterning of the lumbosacral region of the axial skeleton and are integral in patterning principal elements of the limbs. D. M. Wellik, M. R. Capecchi, Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton. Science 301, 363-367 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"136 1","pages":"TW286 - tw286"},"PeriodicalIF":0.0,"publicationDate":"2003-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72689034","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}
Science's STKEPub Date : 2003-07-15DOI: 10.1126/scisignal.1912003tw279
{"title":"A Double Dose of Trp Regulation","authors":"","doi":"10.1126/scisignal.1912003tw279","DOIUrl":"https://doi.org/10.1126/scisignal.1912003tw279","url":null,"abstract":"Amino acid synthesis is tightly controlled in bacteria by a system in which the amino acids themselves, as well as their corresponding transfer RNAs (tRNAs), regulate production. For example, in Bacillus subtilis, the mechanism for regulating tryptophan (Trp) synthesis involves an antiterminator protein called TRAP, which is activated by Trp. However, TRAP activity is antagonized by a protein called anti-TRAP (AT), where the synthesis of AT is induced by uncharged tRNATrp. Chen and Yanofsky now show another level of regulation for the Trp operon in which uncharged tRNATrp also regulates the translation of AT through tandem Trp codons in a leader peptide coding sequence. This mechanism is somewhat reminiscent of the classical Trp attenuation system in Escherchia coli; however, the leader peptide in B. subtilis exerts its effect at the level of translation instead of transcription termination, as seen in E. coli. The authors term the B. subtilis system \"regulatory sophistication\" because it shows both transcriptional and translational regulation of AT in response to tRNATrp. G. Chen, C. Yanofsky, Tandem transcription and translation regulatory sensing of uncharged tryptophan tRNA. Science 301, 211-213 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"51 1","pages":"TW279 - tw279"},"PeriodicalIF":0.0,"publicationDate":"2003-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73275272","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}
Science's STKEPub Date : 2003-07-01DOI: 10.1126/scisignal.1892003tw252
{"title":"How to Concentrate Sodium Channels","authors":"","doi":"10.1126/scisignal.1892003tw252","DOIUrl":"https://doi.org/10.1126/scisignal.1892003tw252","url":null,"abstract":"Neurons target and concentrate voltage-dependent sodium channels in microdomains of the axonal membrane. These sodium channels are clustered at the axonal initial segment, where action potentials are generated, and in the nodes of Ranvier of myelinated axons. How are these components selectively sorted to these domains? Garrido et al. show that a 27-amino acid motif contained in one of the intracellular linkers of the pore-forming subunit can target and concentrate the sodium channel within the initial segment of the axon. This peptide motif was sufficient to direct and to concentrate different proteins to the initial segment. In addition, the overexpression of a cytosolic chimeric protein containing the motif disorganized endogenous sodium channels. J. J. Garrido, P. Giraud, E. Carlier, F. Fernandes, A. Moussif, M.-P. Fache, D. Debanne, B. Dargent, A targeting motif involved in sodium channel clustering at the axonal initial segment. Science 300, 2091-2094 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"2 1","pages":"TW252 - tw252"},"PeriodicalIF":0.0,"publicationDate":"2003-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75902627","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}
Science's STKEPub Date : 2003-06-03DOI: 10.1126/scisignal.1852003tw211
{"title":"The Wild Side of Adaptive Mutation","authors":"","doi":"10.1126/scisignal.1852003tw211","DOIUrl":"https://doi.org/10.1126/scisignal.1852003tw211","url":null,"abstract":"The evidence for adaptive mutation in response to environmental stress has been obtained from laboratory strains of organisms that tend to be more homologous than the wild type. Bjedov et al. (see the Perspective by Rosenberg and Hastings) collected about 800 natural isolates of the bacterium Escherichia coli and found that the majority display stress-inducible (or stationary-phase) elevation of mutation in response to growth-limiting conditions. Their analysis shows that carbon starvation is the physiologically relevant trigger and that removing oxygen largely eliminated enhanced mutation in aging colonies. Genetic analysis of a single natural isolate revealed the roles of the carbon-sensing genetic regulators, the stationary-phase and stress-response regulon, the RecA protein, high-fidelity DNA polymerase II, and compromised mismatch repair. Computer simulations showed that the remarkably high frequency of aging colony mutators in natural isolates could be accounted for by the indirect selective advantage of increased genetic variability. I. Bjedov, O. Tenaillon, B. Gérard, V. Souza, E. Denamur, M. Radman, F. Taddei, I. Matic. Stress-induced mutagenesis in bacteria. Science 300, 1404-1409 (2003). [Abstract] [Full Text] S. M. Rosenberg, P. J. Hastings, Modulating mutation rates in the wild. Science 300, 1382-1383 (2003). [Summary] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"37 1","pages":"TW211 - tw211"},"PeriodicalIF":0.0,"publicationDate":"2003-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90656948","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}
Science's STKEPub Date : 2003-06-03DOI: 10.1126/scisignal.1852003tw212
{"title":"Phospholipid Signaling in Plant Development","authors":"","doi":"10.1126/scisignal.1852003tw212","DOIUrl":"https://doi.org/10.1126/scisignal.1852003tw212","url":null,"abstract":"Cellular morphogenesis is particularly important in plant development, because these cells do not migrate but remain where they are formed. The highly patterned formation of root hairs from some (but not all) epidermal cells of the growing root in Arabidopsis offers an opportunity to study tissue patterning as well as cellular morphogenesis. Ohashi et al. searched for the genes downstream of the group of transcription factors that regulate whether a root hair develops. Beginning with GLABRA2, the furthest downstream of the transcription factors, the authors identified a phospholipase D gene as its direct target. Experimental alterations of the phospholipase D gene expression indicate that phospholipid signaling contributes to cellular morphogenic choices. Y. Ohashi, A. Oka, R. Rodrigues-Pousada, M. Possenti, I. Ruberti, G. Morelli, T. Aoyama, Modulation of phospholipid signaling by GLABRA2 in root-hair pattern formation. Science 300, 1427-1430 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"191 1","pages":"TW212 - tw212"},"PeriodicalIF":0.0,"publicationDate":"2003-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75019654","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}
Science's STKEPub Date : 2003-05-27DOI: 10.1126/scisignal.1842003tw203
Jonathan Rigelsford
{"title":"Hot Sites","authors":"Jonathan Rigelsford","doi":"10.1126/scisignal.1842003tw203","DOIUrl":"https://doi.org/10.1126/scisignal.1842003tw203","url":null,"abstract":"Capsaicin, a natural compound in chili peppers that produces a burning sensation in the mouth, acts through a pain receptor in the mammalian peripheral nervous system, the TRPV1 ion channel. Neurons expressing TRPV1 also perceive pain associated with stimuli such as high temperature and acidity. TRPV1 is activated by the hydrolysis of a membrane phospholipid called phosphatidylinositol 4,5-bisphosphate (PIP2). Prescott and Julius have identified a direct binding site on TRPV1 for PIP2 and show that the strength of this interaction determines the activation threshold of the channel. E. D. Prescott, D. Julius, A modular PIP2 binding site as a determinant of capsaicin receptor sensitivity. Science 300, 1284-1288 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"10 1","pages":"tw203 - tw203"},"PeriodicalIF":0.0,"publicationDate":"2003-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91364191","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}
Science's STKEPub Date : 2003-05-27DOI: 10.1126/scisignal.1842003tw205
{"title":"Infectious Synapse","authors":"","doi":"10.1126/scisignal.1842003tw205","DOIUrl":"https://doi.org/10.1126/scisignal.1842003tw205","url":null,"abstract":"Dendritic cells (DCs) may play a role in host-pathogen interactions. For example, certain proteins expressed on DCs, such as DC-SIGN, can stimulate the efficiency of infection of target cells by the human immunodeficiency virus (HIV). McDonald et al. visualized individual particles of HIV in living cells and found that DC-associated HIV was recruited to the site of contact with target cells such as T cells. Simultaneously, the HIV receptor and coreceptor were recruited to the contact site. This recruitment effectively concentrates HIV, its receptor, and its coreceptor and presumably facilitates infection. D. McDonald, L. Wu, S. M. Bohks, V. N. KewalRamani, D. Unutmaz, T. J. Hope, Recruitment of HIV and its receptors to dendritic cell-T cell junctions. Science 300, 1295-1297 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"64 1","pages":"tw205 - tw205"},"PeriodicalIF":0.0,"publicationDate":"2003-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91002367","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}
Science's STKEPub Date : 2003-05-20DOI: 10.1126/scisignal.1832003tw198
{"title":"Making and Breaking an Antiviral Response","authors":"","doi":"10.1126/scisignal.1832003tw198","DOIUrl":"https://doi.org/10.1126/scisignal.1832003tw198","url":null,"abstract":"Viral infection activates type I interferon genes. This process requires the cooperative activation of several transcription factors, including interferon regulatory factor (IRF)-3 and IFR-7. Signals such as double-stranded RNA lead to the phosphorylation of IRF-3 and IRF-7 by a yet-uncharacterized virus-activated kinase (VAK). Sharma et al. now show that the component of VAK responsible for IRF-3 and IRF-7 phosphorylation is IKKε-TBK-1, an IKK-related kinase complex. Foy et al. observed that the hepatitis C virus (HCV) serine protease (NS3/4A) blocks IFR-3 phosphorylation. Thus, HCV has evolved a mechanism of obstructing the cellular interferon response, potentially through the proteolytic cleavage of this IKKε-TBK-1 complex. S. Sharma, B. R. tenOever, N. Grandvaux, G.-P. Zhou, R. Lin, J. Hiscott, Triggering the interferon antiviral response through an IKK-related pathway. Science 300 1148-1151 (2003). [Abstract] [Full Text] E. Foy, K. Li, C. Wang, R. Sumpter Jr., M. Ikeda, S. M. Lemon, M. Gale Jr., Regulation of interferon regulatory factor-3 by the hepatitis C virus serine protease. Science 300, 1145-1148 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"43 1","pages":"TW198 - tw198"},"PeriodicalIF":0.0,"publicationDate":"2003-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78548731","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}
Science's STKEPub Date : 2003-05-06DOI: 10.1126/scisignal.1812003tw182
{"title":"More Responsive to Stimuli When Inhibited","authors":"","doi":"10.1126/scisignal.1812003tw182","DOIUrl":"https://doi.org/10.1126/scisignal.1812003tw182","url":null,"abstract":"The decline of cortical functions with age occurs not only in humans but also in monkeys. Degradation of intracortical inhibition may underlie these declines. Leventhal et al. tested this hypothesis by applying either γ-amino-butyric acid (GABA) or GABA receptor agonists directly on neurons in the primary visual cortex of old macaque monkeys. This treatment improved orientation and direction selectivity to visual stimuli in neurons of aged monkeys, but not in young ones. A. G. Leventhal, Y. Wang, M. Pu, Y. Zhou, Y. Ma, GABA and its agonists improved visual cortical function in senescent monkeys. Science 300, 812-815 (2003). [Abstract] [Full Text]","PeriodicalId":21619,"journal":{"name":"Science's STKE","volume":"4 1","pages":"TW182 - tw182"},"PeriodicalIF":0.0,"publicationDate":"2003-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81353934","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}
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