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1.
Tissue-specific and reversible RNA interference in transgenic mice 总被引:11,自引:0,他引:11
Dickins RA McJunkin K Hernando E Premsrirut PK Krizhanovsky V Burgess DJ Kim SY Cordon-Cardo C Zender L Hannon GJ Lowe SW 《Nature genetics》2007,39(7):914-921
Genetically engineered mice provide powerful tools for understanding mammalian gene function. These models traditionally rely on gene overexpression from transgenes or targeted, irreversible gene mutation. By adapting the tetracycline (tet)-responsive system previously used for gene overexpression, we have developed a simple transgenic system to reversibly control endogenous gene expression using RNA interference (RNAi) in mice. Transgenic mice harboring a tet-responsive RNA polymerase II promoter driving a microRNA-based short hairpin RNA targeting the tumor suppressor Trp53 reversibly express short hairpin RNA when crossed with existing mouse strains expressing general or tissue-specific 'tet-on' or 'tet-off' transactivators. Reversible Trp53 knockdown can be achieved in several tissues, and restoring Trp53 expression in lymphomas whose development is promoted by Trp53 knockdown leads to tumor regression. By leaving the target gene unaltered, this approach permits tissue-specific, reversible regulation of endogenous gene expression in vivo, with potential broad application in basic biology and drug target validation. 相似文献
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Sobacchi C Frattini A Guerrini MM Abinun M Pangrazio A Susani L Bredius R Mancini G Cant A Bishop N Grabowski P Del Fattore A Messina C Errigo G Coxon FP Scott DI Teti A Rogers MJ Vezzoni P Villa A Helfrich MH 《Nature genetics》2007,39(8):960-962
Autosomal recessive osteopetrosis is usually associated with normal or elevated numbers of nonfunctional osteoclasts. Here we report mutations in the gene encoding RANKL (receptor activator of nuclear factor-KB ligand) in six individuals with autosomal recessive osteopetrosis whose bone biopsy specimens lacked osteoclasts. These individuals did not show any obvious defects in immunological parameters and could not be cured by hematopoietic stem cell transplantation; however, exogenous RANKL induced formation of functional osteoclasts from their monocytes, suggesting that they could, theoretically, benefit from exogenous RANKL administration. 相似文献
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High-frequency generalised transduction by bacteriophage T4 总被引:30,自引:0,他引:30
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Summary The crucial functional groups of phorbol-12-myristate-13-acetate (PMA) are superimposable with those of the glucocorticoid cortisol in a unique manner which suggests a mechanism for PMA activity, i.e. the alkylation of a cortisol receptor. 相似文献
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Wilson J. E. M. Costa Axel M. Katz José Leonardo O. Mattos Pedro F. Amorim Beatrizz O. Mesquita Paulo J. Vilardo 《Journal of Natural History》2019,53(47-48):2905-2928
ABSTRACT This study is primarily directed to the most poorly known species of the genus Trichomycterus, comprising five nominal species (T. florensis, T. immaculatus, T. nigricans, T. paquequerensis and T. santaeritae) endemic to south-eastern Brazil. One of them, T. nigricans, is the type species of the genus, involved in taxonomic problems for over 150 years. A detailed historical review, accompanied by examination of type specimens and recent collections, revealed that the correct type locality of T. nigricans is in the vicinity of Rio de Janeiro, not Santa Catarina as commonly appears in the literature; specimens previously misidentified as T. nigricans from Santa Catarina belong to a possibly undescribed species of the genus Cambeva; T. paquequerensis is a synonym of T. immaculatus, and T. florensis is a synonym of T. santaeritae; and the hypothesis that T. santaeritae is closely related to the Amazon Sarcoglanidinae is refuted. The three valid species are redescribed. These species are members of a clade also including T. caipora that is highly supported by molecular data, diagnosed by a pronounced posterior maxillary process and caudal fin emarginate at least in larger specimens. A subclade comprising T. caipora, T. nigricans and T. santaeritae is diagnosed by a long maxilla and a bifid anterior extremity of hypobranchial 3. 相似文献
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Douglas A. Wilson Victoria Raish Alison Carr-Chellman 《Systemic Practice and Action Research》2017,30(3):277-293
The paper explores cinematic films as a pedagogical tool to promote critical thinking and student discussions in a doctoral-level learning, design, and technology seminar course at a major U.S. research university. These discussions focused on systemic change and systemic thinking concepts. The authors offer evidence from the literature that supports films’ power as a visual metaphor and neurocognitive stimulator to promote development of new perspectives in graduate students on case studies through articulation, reflection, and explanation of their thought processes on change and diffusion of innovation. There are theoretical, political, social, and technological issues that create tensions during any systemic change effort. The goal of using film in this seminar is to equip students with the requisite skills, theoretical frameworks, and interpersonal experiences needed to address these issues within organizations and communities. The change expected from systemic thinking is for students to think more deeply about the interconnectedness of systems and the importance of bottom-up change efforts that consider the perspective of all stakeholders. 相似文献
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This article by Curtis Wilson is an account of the origin of Hansen’s powerful systematic method for finding contributions of higher order perturbations in celestial mechanics. Hansen’s method was developed in the course of improving on Laplace’s treatment of the mutual perturbations of Jupiter and Saturn. This method, an entirely new way of doing celestial mechanics when it first appeared, later made possible the successful treatment of the complicated motions of our moon (see Wilson 2010). In this paper Wilson gives a brief historical introduction followed by an account of relevant technical details of the Laplacian background, an account illustrating technical details in Hansen’s initial development in his Disquisitions of 1829, and a treatment illustrating details contributing to the achievement of Hansen’s more refined development in his Untersuchung of 1831. These details include conditional equations Hansen provides for checking the accuracy of calculations. Wilson also includes a detailed assessment showing the extraordinary improvement in empirical accuracy of Hansen’s treatment over the best earlier treatment of the Jupiter-Saturn interactions. 相似文献