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  • 1
    Publikationsdatum: 2011-06-15
    Beschreibung: Author(s): Alexandre M. Souza, Gonzalo A. Álvarez, and Dieter Suter Dynamical decoupling (DD) is a popular technique for protecting qubits from the environment. However, unless special care is taken, experimental errors in the control pulses used in this technique can destroy the quantum information instead of preserving it. Here, we investigate techniques for makin... [Phys. Rev. Lett. 106, 240501] Published Tue Jun 14, 2011
    Schlagwort(e): General Physics: Statistical and Quantum Mechanics, Quantum Information, etc.
    Print ISSN: 0031-9007
    Digitale ISSN: 1079-7114
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 2
    Publikationsdatum: 2014-10-04
    Beschreibung: Author(s): Tiago B. Batalhão, Alexandre M. Souza, Laura Mazzola, Ruben Auccaise, Roberto S. Sarthour, Ivan S. Oliveira, John Goold, Gabriele De Chiara, Mauro Paternostro, and Roberto M. Serra A liquid-state nuclear magnetic resonance platform allows control and quantification of the non-equilibrium spin dynamics of a closed quantum system. [Phys. Rev. Lett. 113, 140601] Published Fri Oct 03, 2014
    Schlagwort(e): General Physics: Statistical and Quantum Mechanics, Quantum Information, etc.
    Print ISSN: 0031-9007
    Digitale ISSN: 1079-7114
    Thema: Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 3
    Publikationsdatum: 2011-10-01
    Beschreibung: Author(s): R. Auccaise, L. C. Céleri, D. O. Soares-Pinto, E. R. deAzevedo, J. Maziero, A. M. Souza, T. J. Bonagamba, R. S. Sarthour, I. S. Oliveira, and R. M. Serra [Phys. Rev. Lett. 107, 140403] Published Fri Sep 30, 2011
    Schlagwort(e): General Physics: Statistical and Quantum Mechanics, Quantum Information, etc.
    Print ISSN: 0031-9007
    Digitale ISSN: 1079-7114
    Thema: Physik
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  • 4
    Publikationsdatum: 2008-03-26
    Beschreibung: Tribolium castaneum is a member of the most species-rich eukaryotic order, a powerful model organism for the study of generalized insect development, and an important pest of stored agricultural products. We describe its genome sequence here. This omnivorous beetle has evolved the ability to interact with a diverse chemical environment, as shown by large expansions in odorant and gustatory receptors, as well as P450 and other detoxification enzymes. Development in Tribolium is more representative of other insects than is Drosophila, a fact reflected in gene content and function. For example, Tribolium has retained more ancestral genes involved in cell-cell communication than Drosophila, some being expressed in the growth zone crucial for axial elongation in short-germ development. Systemic RNA interference in T. castaneum functions differently from that in Caenorhabditis elegans, but nevertheless offers similar power for the elucidation of gene function and identification of targets for selective insect control.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Tribolium Genome Sequencing Consortium -- Richards, Stephen -- Gibbs, Richard A -- Weinstock, George M -- Brown, Susan J -- Denell, Robin -- Beeman, Richard W -- Gibbs, Richard -- Bucher, Gregor -- Friedrich, Markus -- Grimmelikhuijzen, Cornelis J P -- Klingler, Martin -- Lorenzen, Marce -- Roth, Siegfried -- Schroder, Reinhard -- Tautz, Diethard -- Zdobnov, Evgeny M -- Muzny, Donna -- Attaway, Tony -- Bell, Stephanie -- Buhay, Christian J -- Chandrabose, Mimi N -- Chavez, Dean -- Clerk-Blankenburg, Kerstin P -- Cree, Andrew -- Dao, Marvin -- Davis, Clay -- Chacko, Joseph -- Dinh, Huyen -- Dugan-Rocha, Shannon -- Fowler, Gerald -- Garner, Toni T -- Garnes, Jeffrey -- Gnirke, Andreas -- Hawes, Alica -- Hernandez, Judith -- Hines, Sandra -- Holder, Michael -- Hume, Jennifer -- Jhangiani, Shalini N -- Joshi, Vandita -- Khan, Ziad Mohid -- Jackson, LaRonda -- Kovar, Christie -- Kowis, Andrea -- Lee, Sandra -- Lewis, Lora R -- Margolis, Jon -- Morgan, Margaret -- Nazareth, Lynne V -- Nguyen, Ngoc -- Okwuonu, Geoffrey -- Parker, David -- Ruiz, San-Juana -- Santibanez, Jireh -- Savard, Joel -- Scherer, Steven E -- Schneider, Brian -- Sodergren, Erica -- Vattahil, Selina -- Villasana, Donna -- White, Courtney S -- Wright, Rita -- Park, Yoonseong -- Lord, Jeff -- Oppert, Brenda -- Brown, Susan -- Wang, Liangjiang -- Weinstock, George -- Liu, Yue -- Worley, Kim -- Elsik, Christine G -- Reese, Justin T -- Elhaik, Eran -- Landan, Giddy -- Graur, Dan -- Arensburger, Peter -- Atkinson, Peter -- Beidler, Jim -- Demuth, Jeffery P -- Drury, Douglas W -- Du, Yu-Zhou -- Fujiwara, Haruhiko -- Maselli, Vincenza -- Osanai, Mizuko -- Robertson, Hugh M -- Tu, Zhijian -- Wang, Jian-jun -- Wang, Suzhi -- Song, Henry -- Zhang, Lan -- Werner, Doreen -- Stanke, Mario -- Morgenstern, Burkhard -- Solovyev, Victor -- Kosarev, Peter -- Brown, Garth -- Chen, Hsiu-Chuan -- Ermolaeva, Olga -- Hlavina, Wratko -- Kapustin, Yuri -- Kiryutin, Boris -- Kitts, Paul -- Maglott, Donna -- Pruitt, Kim -- Sapojnikov, Victor -- Souvorov, Alexandre -- Mackey, Aaron J -- Waterhouse, Robert M -- Wyder, Stefan -- Kriventseva, Evgenia V -- Kadowaki, Tatsuhiko -- Bork, Peer -- Aranda, Manuel -- Bao, Riyue -- Beermann, Anke -- Berns, Nicola -- Bolognesi, Renata -- Bonneton, Francois -- Bopp, Daniel -- Butts, Thomas -- Chaumot, Arnaud -- Denell, Robin E -- Ferrier, David E K -- Gordon, Cassondra M -- Jindra, Marek -- Lan, Que -- Lattorff, H Michael G -- Laudet, Vincent -- von Levetsow, Cornelia -- Liu, Zhenyi -- Lutz, Rebekka -- Lynch, Jeremy A -- da Fonseca, Rodrigo Nunes -- Posnien, Nico -- Reuter, Rolf -- Schinko, Johannes B -- Schmitt, Christian -- Schoppmeier, Michael -- Shippy, Teresa D -- Simonnet, Franck -- Marques-Souza, Henrique -- Tomoyasu, Yoshinori -- Trauner, Jochen -- Van der Zee, Maurijn -- Vervoort, Michel -- Wittkopp, Nadine -- Wimmer, Ernst A -- Yang, Xiaoyun -- Jones, Andrew K -- Sattelle, David B -- Ebert, Paul R -- Nelson, David -- Scott, Jeffrey G -- Muthukrishnan, Subbaratnam -- Kramer, Karl J -- Arakane, Yasuyuki -- Zhu, Qingsong -- Hogenkamp, David -- Dixit, Radhika -- Jiang, Haobo -- Zou, Zhen -- Marshall, Jeremy -- Elpidina, Elena -- Vinokurov, Konstantin -- Oppert, Cris -- Evans, Jay -- Lu, Zhiqiang -- Zhao, Picheng -- Sumathipala, Niranji -- Altincicek, Boran -- Vilcinskas, Andreas -- Williams, Michael -- Hultmark, Dan -- Hetru, Charles -- Hauser, Frank -- Cazzamali, Giuseppe -- Williamson, Michael -- Li, Bin -- Tanaka, Yoshiaki -- Predel, Reinhard -- Neupert, Susanne -- Schachtner, Joachim -- Verleyen, Peter -- Raible, Florian -- Walden, Kimberly K O -- Angeli, Sergio -- Foret, Sylvain -- Schuetz, Stefan -- Maleszka, Ryszard -- Miller, Sherry C -- Grossmann, Daniela -- BBS/B/12067/Biotechnology and Biological Sciences Research Council/United Kingdom -- BBS/B/12067/2/Biotechnology and Biological Sciences Research Council/United Kingdom -- R01 GM058634/GM/NIGMS NIH HHS/ -- R01 HD029594/HD/NICHD NIH HHS/ -- R01 HD029594-16/HD/NICHD NIH HHS/ -- U54 HG003273/HG/NHGRI NIH HHS/ -- Intramural NIH HHS/ -- England -- Nature. 2008 Apr 24;452(7190):949-55. doi: 10.1038/nature06784. Epub 2008 Mar 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Human Genome Sequencing Center, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA. stephenr@bcm.edu〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18362917" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Base Composition ; Body Patterning/genetics ; Cytochrome P-450 Enzyme System/genetics ; DNA Transposable Elements/genetics ; Genes, Insect/*genetics ; Genome, Insect/*genetics ; Growth and Development/genetics ; Humans ; Insecticides/pharmacology ; Neurotransmitter Agents/genetics ; Oogenesis/genetics ; Phylogeny ; Proteome/genetics ; RNA Interference ; Receptors, G-Protein-Coupled/genetics ; Receptors, Odorant/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Taste/genetics ; Telomere/genetics ; Tribolium/classification/embryology/*genetics/physiology ; Vision, Ocular/genetics
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 5
    Publikationsdatum: 2009-04-28
    Beschreibung: Dengue fever is the most frequent arthropod-borne viral disease of humans, with almost half of the world's population at risk of infection. The high prevalence, lack of an effective vaccine, and absence of specific treatment conspire to make dengue fever a global public health threat. Given their compact genomes, dengue viruses (DENV-1-4) and other flaviviruses probably require an extensive number of host factors; however, only a limited number of human, and an even smaller number of insect host factors, have been identified. Here we identify insect host factors required for DENV-2 propagation, by carrying out a genome-wide RNA interference screen in Drosophila melanogaster cells using a well-established 22,632 double-stranded RNA library. This screen identified 116 candidate dengue virus host factors (DVHFs). Although some were previously associated with flaviviruses (for example, V-ATPases and alpha-glucosidases), most of the DVHFs were newly implicated in dengue virus propagation. The dipteran DVHFs had 82 readily recognizable human homologues and, using a targeted short-interfering-RNA screen, we showed that 42 of these are human DVHFs. This indicates notable conservation of required factors between dipteran and human hosts. This work suggests new approaches to control infection in the insect vector and the mammalian host.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462662/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462662/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Sessions, October M -- Barrows, Nicholas J -- Souza-Neto, Jayme A -- Robinson, Timothy J -- Hershey, Christine L -- Rodgers, Mary A -- Ramirez, Jose L -- Dimopoulos, George -- Yang, Priscilla L -- Pearson, James L -- Garcia-Blanco, Mariano A -- 1R01AI061576-01/AI/NIAID NIH HHS/ -- 1R01AI076442/AI/NIAID NIH HHS/ -- 1SA0RR024572-1/RR/NCRR NIH HHS/ -- 5P30-CA14236/CA/NCI NIH HHS/ -- 5U54-AI057157-05S/AI/NIAID NIH HHS/ -- R01 AI076442/AI/NIAID NIH HHS/ -- R01 AI078997/AI/NIAID NIH HHS/ -- R01 AI078997-01A1/AI/NIAID NIH HHS/ -- R01 AI078997-02/AI/NIAID NIH HHS/ -- R01 GM067761/GM/NIGMS NIH HHS/ -- R21 AI090188/AI/NIAID NIH HHS/ -- R21 AI090188-01/AI/NIAID NIH HHS/ -- R21 NS063845/NS/NINDS NIH HHS/ -- R21-AI64925/AI/NIAID NIH HHS/ -- T32 AI007417/AI/NIAID NIH HHS/ -- U54 AI057157/AI/NIAID NIH HHS/ -- U54 AI057159/AI/NIAID NIH HHS/ -- England -- Nature. 2009 Apr 23;458(7241):1047-50. doi: 10.1038/nature07967.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19396146" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Aedes/genetics/virology ; Animals ; Cell Line ; Conserved Sequence/*genetics/physiology ; Dengue Virus/*physiology ; Drosophila melanogaster/*genetics/physiology/*virology ; Gene Knockdown Techniques ; Genome, Insect/genetics ; Host-Pathogen Interactions/*genetics ; Humans ; Insect Vectors/*genetics/*physiology ; RNA Interference ; RNA, Double-Stranded/genetics/metabolism ; Virus Replication
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 6
    Publikationsdatum: 2011-05-14
    Beschreibung: Malaria parasite transmission depends on the successful transition of Plasmodium through discrete developmental stages in the lumen of the mosquito midgut. Like the human intestinal tract, the mosquito midgut contains a diverse microbial flora, which may compromise the ability of Plasmodium to establish infection. We have identified an Enterobacter bacterium isolated from wild mosquito populations in Zambia that renders the mosquito resistant to infection with the human malaria parasite Plasmodium falciparum by interfering with parasite development before invasion of the midgut epithelium. Phenotypic analyses showed that the anti-Plasmodium mechanism requires small populations of replicating bacteria and is mediated through a mosquito-independent interaction with the malaria parasite. We show that this anti-Plasmodium effect is largely caused by bacterial generation of reactive oxygen species.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154605/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154605/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Cirimotich, Chris M -- Dong, Yuemei -- Clayton, April M -- Sandiford, Simone L -- Souza-Neto, Jayme A -- Mulenga, Musapa -- Dimopoulos, George -- R01 AI061576/AI/NIAID NIH HHS/ -- R01AI061576/AI/NIAID NIH HHS/ -- T32 AI007417/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2011 May 13;332(6031):855-8. doi: 10.1126/science.1201618.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉W. Harry Feinstone Department of Molecular Microbiology and Immunology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD 21205-2179, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21566196" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Anopheles gambiae/immunology/*microbiology/*parasitology ; Digestive System/microbiology/parasitology ; Enterobacter/growth & development/isolation & purification/*physiology ; Host-Parasite Interactions ; Immunity, Innate ; Insect Vectors/immunology/microbiology/parasitology ; Plasmodium berghei/growth & development ; Plasmodium falciparum/*growth & development/pathogenicity ; Reactive Oxygen Species/*metabolism ; Zambia
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 7
    Publikationsdatum: 2003-05-31
    Beschreibung: The evolutionary significance of stress-induced mutagenesis was evaluated by studying mutagenesis in aging colonies (MAC) of Escherichia coli natural isolates. A large fraction of isolates exhibited a strong MAC, and the high MAC variability reflected the diversity of selective pressures in ecological niches. MAC depends on starvation, oxygen, and RpoS and adenosine 3',5'-monophosphate regulons; thus it may be a by-product of genetic strategies for improving survival under stress. MAC could also be selected through beneficial mutations that it generates, as shown by computer modeling and the patterns of stress-inducible and constitutive mutagenesis. We suggest that irrespective of the causes of their emergence, stress-induced mutations participate in adaptive evolution.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Bjedov, Ivana -- Tenaillon, Olivier -- Gerard, Benedicte -- Souza, Valeria -- Denamur, Erick -- Radman, Miroslav -- Taddei, Francois -- Matic, Ivan -- New York, N.Y. -- Science. 2003 May 30;300(5624):1404-9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉INSERM U571, Faculte de Medecine Necker-Enfants Malades, Universite ParisV, 156 rue Vaugirard, 75730 ParisCedex 15, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/12775833" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Adaptation, Physiological ; Air Microbiology ; Alleles ; Animals ; Bacterial Proteins/genetics/metabolism ; *Biological Evolution ; Computer Simulation ; DNA Repair ; DNA-Directed RNA Polymerases/genetics ; Escherichia coli/classification/*genetics/growth & development/*physiology ; Escherichia coli Infections/microbiology ; Escherichia coli Proteins/genetics/metabolism ; Feces/microbiology ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Geologic Sediments ; Humans ; Lac Operon ; Models, Biological ; *Mutagenesis ; Oxidative Stress ; Oxygen/metabolism ; Phenotype ; Phylogeny ; Rec A Recombinases/metabolism ; Regulon ; SOS Response (Genetics) ; Selection, Genetic ; Sigma Factor/genetics/metabolism ; Water Microbiology
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
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  • 8
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    Nature Publishing Group (NPG)
    Publikationsdatum: 2013-06-15
    Beschreibung: 〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Novaes, Roberto Leonan Morim -- Felix, Saulo -- Souza, Renan de Franca -- England -- Nature. 2013 Jun 13;498(7453):170. doi: 10.1038/498170a.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23765481" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Agriculture/*statistics & numerical data ; Animals ; Animals, Wild ; Biodiversity ; Brazil ; Disasters/economics/*prevention & control ; Droughts/economics/*statistics & numerical data ; Ecology/*methods ; Trees/physiology ; Water Supply/statistics & numerical data
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 9
    Publikationsdatum: 2013-09-06
    Beschreibung: Ubiquitin-mediated targeting of intracellular bacteria to the autophagy pathway is a key innate defence mechanism against invading microbes, including the important human pathogen Mycobacterium tuberculosis. However, the ubiquitin ligases responsible for catalysing ubiquitin chains that surround intracellular bacteria are poorly understood. The parkin protein is a ubiquitin ligase with a well-established role in mitophagy, and mutations in the parkin gene (PARK2) lead to increased susceptibility to Parkinson's disease. Surprisingly, genetic polymorphisms in the PARK2 regulatory region are also associated with increased susceptibility to intracellular bacterial pathogens in humans, including Mycobacterium leprae and Salmonella enterica serovar Typhi, but the function of parkin in immunity has remained unexplored. Here we show that parkin has a role in ubiquitin-mediated autophagy of M. tuberculosis. Both parkin-deficient mice and flies are sensitive to various intracellular bacterial infections, indicating parkin has a conserved role in metazoan innate defence. Moreover, our work reveals an unexpected functional link between mitophagy and infectious disease.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886920/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3886920/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Manzanillo, Paolo S -- Ayres, Janelle S -- Watson, Robert O -- Collins, Angela C -- Souza, Gianne -- Rae, Chris S -- Schneider, David S -- Nakamura, Ken -- Shiloh, Michael U -- Cox, Jeffery S -- P01 AI063302/AI/NIAID NIH HHS/ -- P30NS069496/NS/NINDS NIH HHS/ -- R01 AI081727/AI/NIAID NIH HHS/ -- R01 AI099439/AI/NIAID NIH HHS/ -- T32 AI060537/AI/NIAID NIH HHS/ -- England -- Nature. 2013 Sep 26;501(7468):512-6. doi: 10.1038/nature12566. Epub 2013 Sep 4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Microbiology and Immunology Program in Microbial Pathogenesis and Host Defense, University of California, San Francisco, San Francisco, California 94158, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24005326" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Autophagy/immunology ; Bone Marrow Cells/microbiology ; Drosophila melanogaster/genetics/*immunology/metabolism/*microbiology ; Female ; Immunity, Innate/*immunology ; Lysine/metabolism ; Macrophages/microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/metabolism/pathology ; Mitochondrial Degradation ; Models, Immunological ; Mycobacterium marinum/*immunology ; Mycobacterium tuberculosis/growth & development/*immunology/metabolism ; Polyubiquitin/chemistry/metabolism ; Salmonella typhimurium/*immunology ; Symbiosis/immunology ; Tuberculosis/enzymology/immunology/microbiology/pathology ; Ubiquitin/analysis/chemistry/metabolism ; Ubiquitin-Protein Ligases/chemistry/deficiency/*immunology/metabolism
    Print ISSN: 0028-0836
    Digitale ISSN: 1476-4687
    Thema: Biologie , Chemie und Pharmazie , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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  • 10
    Publikationsdatum: 2015-05-23
    Beschreibung: The development of effective pharmacological inhibitors of multidomain scaffold proteins, notably transcription factors, is a particularly challenging problem. In part, this is because many small-molecule antagonists disrupt the activity of only one domain in the target protein. We devised a chemical strategy that promotes ligand-dependent target protein degradation using as an example the transcriptional coactivator BRD4, a protein critical for cancer cell growth and survival. We appended a competitive antagonist of BET bromodomains to a phthalimide moiety to hijack the cereblon E3 ubiquitin ligase complex. The resultant compound, dBET1, induced highly selective cereblon-dependent BET protein degradation in vitro and in vivo and delayed leukemia progression in mice. A second series of probes resulted in selective degradation of the cytosolic protein FKBP12. This chemical strategy for controlling target protein stability may have implications for therapeutically targeting previously intractable proteins.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Winter, Georg E -- Buckley, Dennis L -- Paulk, Joshiawa -- Roberts, Justin M -- Souza, Amanda -- Dhe-Paganon, Sirano -- Bradner, James E -- P01 CA066996/CA/NCI NIH HHS/ -- P01-CA066996/CA/NCI NIH HHS/ -- R01-CA176745/CA/NCI NIH HHS/ -- New York, N.Y. -- Science. 2015 Jun 19;348(6241):1376-81. doi: 10.1126/science.aab1433. Epub 2015 May 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. james_bradner@dfci.harvard.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25999370" target="_blank"〉PubMed〈/a〉
    Schlagwort(e): Animals ; Azepines/chemistry/*pharmacology/therapeutic use ; Cell Line, Tumor ; Crystallography, X-Ray ; Disease Models, Animal ; *Drug Design ; Leukemia, Promyelocytic, Acute/drug therapy ; Ligands ; Mice ; Molecular Targeted Therapy ; Nuclear Proteins/antagonists & inhibitors/chemistry/*metabolism ; Peptide Hydrolases/*metabolism ; Phthalimides/*chemistry ; Protein Stability/drug effects ; Protein Structure, Tertiary ; Proteolysis/*drug effects ; Tacrolimus Binding Protein 1A/metabolism ; Thalidomide/*analogs & derivatives/chemistry/pharmacology/therapeutic use ; Transcription Factors/antagonists & inhibitors/chemistry/*metabolism ; Ubiquitin-Protein Ligases/metabolism
    Print ISSN: 0036-8075
    Digitale ISSN: 1095-9203
    Thema: Biologie , Chemie und Pharmazie , Informatik , Medizin , Allgemeine Naturwissenschaft , Physik
    Standort Signatur Erwartet Verfügbarkeit
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