968 research outputs found
The Nuclear Export Signal within the E4orf6 Protein of Adenovirus Type 5 Supports Virus Replication and Cytoplasmic Accumulation of Viral mRNA
ABSTRACT During the late phase of adenovirus infection, viral mRNA is efficiently transported from the nucleus to the cytoplasm while most cellular mRNA species are retained in the nucleus. Two viral proteins, E1B-55 kDa and E4orf6, are both necessary for these effects. The E4orf6 protein of adenovirus type 5 binds and relocalizes E1B-55 kDa, and the complex of the two proteins was previously shown to shuttle continuously between the nucleus and cytoplasm. Nucleocytoplasmic transport of the complex is achieved by a nuclear export signal (NES) within E4orf6. Mutation of this signal sequence severely reduces the ability of the E1B-55 kDa–E4orf6 complex to leave the nucleus. Here, we examined the role of functional domains within E4orf6 during virus infection. E4orf6 or mutants derived from it were transiently expressed, followed by infection with recombinant adenovirus lacking the E4 region and determination of virus yield. An arginine-rich putative alpha helix near the carboxy terminus of E4orf6 contributes to E1B-55 kDa binding and relocalization as well as to the synthesis of viral DNA, mRNA, and proteins. Further mutational analysis revealed that mutation of the NES within E4orf6 considerably reduces its ability to support virus production. The same effect was observed when nuclear export was blocked with a competitor. Further, a functional NES within E4orf6 contributed to the efficiency of late virus protein synthesis and viral DNA replication, as well as total and cytoplasmic accumulation of viral late mRNA. Our data support the view that NES-mediated nucleocytoplasmic shuttling strongly enhances most, if not all, intracellular activities of E4orf6 during the late phase of adenovirus infection.ABSTRACT During the late phase of adenovirus infection, viral mRNA is efficiently transported from the nucleus to the cytoplasm while most cellular mRNA species are retained in the nucleus. Two viral proteins, E1B-55 kDa and E4orf6, are both necessary for these effects. The E4orf6 protein of adenovirus type 5 binds and relocalizes E1B-55 kDa, and the complex of the two proteins was previously shown to shuttle continuously between the nucleus and cytoplasm. Nucleocytoplasmic transport of the complex is achieved by a nuclear export signal (NES) within E4orf6. Mutation of this signal sequence severely reduces the ability of the E1B-55 kDa–E4orf6 complex to leave the nucleus. Here, we examined the role of functional domains within E4orf6 during virus infection. E4orf6 or mutants derived from it were transiently expressed, followed by infection with recombinant adenovirus lacking the E4 region and determination of virus yield. An arginine-rich putative alpha helix near the carboxy terminus of E4orf6 contributes to E1B-55 kDa binding and relocalization as well as to the synthesis of viral DNA, mRNA, and proteins. Further mutational analysis revealed that mutation of the NES within E4orf6 considerably reduces its ability to support virus production. The same effect was observed when nuclear export was blocked with a competitor. Further, a functional NES within E4orf6 contributed to the efficiency of late virus protein synthesis and viral DNA replication, as well as total and cytoplasmic accumulation of viral late mRNA. Our data support the view that NES-mediated nucleocytoplasmic shuttling strongly enhances most, if not all, intracellular activities of E4orf6 during the late phase of adenovirus infection
Rezension zu: Weigel, Petra: Ordensreform und Konziliarismus. Der Franziskanerprovinzial Matthias Döring (1427-1461) (Jenaer Beiträge zur Geschichte 7), Frankfurt/Main u. a. 2005
Riedel P. Rezension zu: Weigel, Petra: Ordensreform und Konziliarismus. Der Franziskanerprovinzial Matthias Döring (1427-1461) (Jenaer Beiträge zur Geschichte 7), Frankfurt/Main u. a. 2005. Wissenschaft und Weisheit. Franziskanische Studien zu Theologie, Philosophie und Geschichte. 2008;71.2:298-302
Weigel
Lutheran pastor and author of writings of a critical, theoretical, theological, and devotional character. The son of commoner parents, Weigel depended upon princely patronage to attend an elite Latin school and subsequently studied theology at the Universities of Leipzig and Wittenberg, possibly also teaching briefly at the latter
Investigation and modeling of magnetization transfer effects in two-dimensional multislice turbo spin echo sequences with low constant or variable flip angles at 3 T
Magnetization transfer effects represent a major source of contrast in multislice turbo spin echo sequences (TSE)/fast spin echo sequences. Generally, low refocusing flip angles have become common in such MRI sequences, especially to mitigate specific absorption rate problems. Since the strength of magnetization transfer effects is related to the radiofrequency power and therefore specific absorption rate applied, magnetization transfer induced signal attenuations are investigated for a variety of TSE sequences with low constant and variable flip angles. Noticeable differences between the sequences have been observed. In particular, fewer signal attenuations are observed for TSE with low flip angles such as hyperecho-TSE and smooth transitions between pseudo steady states-TSE, leading to contrast that is less dependent on the number of slices. It is shown that the strength of the magnetization transfer-induced signal attenuations can be understood and described by a physical framework, which is based on the mean square flip angle of a given TSE sequence. Magn Reson Med 63:230-234, 2010. (C) 2009 Wiley-Liss, Inc
Le monde dans une noix c'est à dire un abrégé de l'histoire universelle chronologique... representez par tables et par figures... traduit de l'allemand en françois... par Matthias Cramer,...
Titre original : Die Welt in einer Nus
Courage to Be Catholic: Crisis, Reform, and the Future of the Church
with George Weigel, author of a biography on Pope John Paul II, entitled Witness to HopeMcGuinn Hall 12
Moral Good, the Beatific Vision, and God’s Kingdom Writings by Germain Grisez and Peter Ryan, S.J.. Edited by Peter J. Weigel
For close to half a century, the work of Germain Grisez has been highly influential, and his writings continue to receive considerable attention from philosophers and theologians of diverse viewpoints. His co-author for this work is the professor and noted moral theologian Fr. Peter Ryan, S.J., currently the executive director of the Secretariat of Doctrine and Canonical Affairs of the United States Conference of Catholic Bishops (USCCB). These two eminent scholars explore fundamental questions about Christian eschatology, moral theory, the purpose of human life, and the promise of human fulfilment. The authors examine Christian teaching on the final destiny of persons, investigating the meaning of God's kingdom, the hope of the beatific vision, and the centrality of moral goodness and divine grace in one's final end. This work is an ideal source for students, scholars, ministers and lay persons interested in basic questions of Christian theology, the philosophy of religion, ethical theory, and Catholic doctrin
Inactivation of p53 but Not p73 by Adenovirus Type 5 E1B 55-Kilodalton and E4 34-Kilodalton Oncoproteins
ABSTRACT The adenovirus E1B 55-kDa and E4 34-kDa oncoproteins bind and inactivate the p53 tumor suppressor gene product, resulting in cell transformation. A recently discovered cellular protein, p73, shows extensive similarities to p53 in structure and function. Here we show that the simultaneous transient expression of E1B 55-kDa and E4 34-kDa proteins is sufficient to drastically shorten the intracellular half-life of p53, leading to strongly reduced steady-state p53 levels. Concomitantly, the E1B 55-kDa and E4 34-kDa proteins act synergistically to inactivate the transcriptional activity of p53. Mutational analysis suggests that physical interactions between the E1B 55-kDa protein and p53 and between the E1B 55-kDa and E4 34-kDa proteins are both required for p53 degradation. In contrast, the ability of p53 to interact with the cellular mdm2 oncoprotein or with its cognate DNA element appears to be dispensable for its destabilization by adenovirus gene products. The adenovirus E1B 55-kDa protein did not detectably interact with p73 and failed to inhibit p73-mediated transcription; also, the E1B 55-kDa and E4 34-kDa proteins did not promote p73 degradation. When five amino acids near the amino termini were exchanged at corresponding positions between p53 and p73, this rendered p53 resistant and p73 susceptible to complex formation and inactivation by the E1B 55-kDa protein. Our results suggest that while p53 inactivation is a central step in virus-induced tumor development, efficient transformation can occur without targeting p73.ABSTRACT The adenovirus E1B 55-kDa and E4 34-kDa oncoproteins bind and inactivate the p53 tumor suppressor gene product, resulting in cell transformation. A recently discovered cellular protein, p73, shows extensive similarities to p53 in structure and function. Here we show that the simultaneous transient expression of E1B 55-kDa and E4 34-kDa proteins is sufficient to drastically shorten the intracellular half-life of p53, leading to strongly reduced steady-state p53 levels. Concomitantly, the E1B 55-kDa and E4 34-kDa proteins act synergistically to inactivate the transcriptional activity of p53. Mutational analysis suggests that physical interactions between the E1B 55-kDa protein and p53 and between the E1B 55-kDa and E4 34-kDa proteins are both required for p53 degradation. In contrast, the ability of p53 to interact with the cellular mdm2 oncoprotein or with its cognate DNA element appears to be dispensable for its destabilization by adenovirus gene products. The adenovirus E1B 55-kDa protein did not detectably interact with p73 and failed to inhibit p73-mediated transcription; also, the E1B 55-kDa and E4 34-kDa proteins did not promote p73 degradation. When five amino acids near the amino termini were exchanged at corresponding positions between p53 and p73, this rendered p53 resistant and p73 susceptible to complex formation and inactivation by the E1B 55-kDa protein. Our results suggest that while p53 inactivation is a central step in virus-induced tumor development, efficient transformation can occur without targeting p73
Destra e sinistra nello spazio iconico tra iconografia cristiana e antropologia
Proceeding from the statement that «reading» images is not at all analogous to any culturally codified lecture of written texts, Sigrid Weigel develops a crucial critic of the anthropological paradigm linked to the left-right problem in the visual arts. Focusing on various examples of painted and sculpted Annunciations, the author argues how the decline of the traditional orientation, based on the figure of God in central position, leads to a growing importance of the spectator gaze and to a new relation between iconic narration and symbolic meaning
- …
