927 research outputs found

    Analysis of the composition, assembly kinetics and activity of native Apaf-1 apoptosomes

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    The Apaf-1 apoptosome is a multi-subunit caspase-activating scaffold that is assembled in response to diverse forms of cellular stress that culminate in apoptosis. To date, most studies on apoptosome composition and function have used apoptosomes reassembled from recombinant or purified proteins. Thus, the precise composition of native apoptosomes remains unresolved. Here, we have used a one-step immunopurification approach to isolate catalytically active Apaf-1/caspase-9 apoptosomes, and have identified the major constituents of these complexes using mass spectrometry methods. Using this approach, we have also assessed the ability of putative apoptosome regulatory proteins, such as Smac/DIABLO and PHAPI, to regulate the activity of native apoptosomes. We show that Apaf-1, caspase-9, caspase-3 and XIAP are the major constituents of native apoptosomes and that cytochrome c is not stably associated with the active complex. We also demonstrate that the IAP-neutralizing protein Smac/DIABLO and the tumor-suppressor protein PHAPI can enhance the catalytic activity of apoptosome complexes in distinct ways. Surprisingly, PHAPI also enhanced the activity of purified caspase-3, suggesting that it may act as a co-factor for this protease

    Smac/Diablo antagonizes ubiquitin ligase activity of inhibitor of apoptosis proteins

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    Inhibitor of apoptosis proteins (IAPs) can block apoptosis through binding to active caspases and antagonizing their function. IAP function can be neutralized by Smac/Diablo, an IAP-binding protein that is released from mitochondria during apoptosis. In addition to their ability to interact with caspases, certain IAPs also display ubiquitin-protein isopeptide ligase activity because of the presence of a RING domain. However, it is not known whether the ubiquitin-protein isopeptide ligase activities of human IAPs contribute to their apoptosis inhibitory activity or whether this IAP property can be modulated through association with Smac/Diablo. Here we demonstrate that the ubiquitin ligase activities of XIAP, and to a lesser extent c-IAP-1 and c-IAP2, are potently repressed through binding to Smac/Diablo. We also show that mutation of the XIAP RING domain rendered this IAP a less effective inhibitor of apoptosis, suggesting that the ubiquitin ligase activity of XIAP contributes to its anti-apoptotic function. These data suggest that Smac/Diablo potentiates apoptosis by simultaneously antagonizing caspase-IAP interactions and repressing IAP ubiquitin ligase activitie

    Emma Gelders Sterne papers, W.0099

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    Abstract: Contracts and business correspondence related to the publication of books written by Alabama author Emma Gelders Sterne.Scope and Content Note: This collection contains contracts and business correspondence between Alabama author Emma Gelders Sterne and her publishers at Dodd, Mead, and Company. The correspondence and contracts are dated from 1934 to 1953 and mostly include republication agreements between Sterne and the publishers. The collection includes materials related to The Calico Ball, Some Plant Olive Trees, and Drums of Monmouth.Biographical/Historical Note: Emma Gelders Sterne was born on May 13, 1894, in Birmingham, Alabama. She graduated from Smith College in 1916, receiving a BA. After college, Sterne returned to Birmingham, where she was involved in a number of activist efforts, including the suffrage movement.In 1917, she married lawyer Roy M. Sterne; the couple had two daughters, Ann and Barbara. The family moved to New York, where Roy worked for the Liggett Drug Company and Emma became involved in a number of activist groups, including the National Association for the Advancement of Colored People and the American Civil Liberties Union.A prolific children's author, Sterne published a total of forty-four books during a literary career that spanned four decades. Several of her books, including No Surrender, Amarantha Gay, M.D., and The Calico Ball are set in Birmingham; another work, Some Plant Olive Trees, was inspired by the French settlement of Demopolis, Alabama.Sterne spent her final years in California; she died on August 29, 1971, in San Jose.Source: Encyclopedia of Alabam

    Handheld-Impedance-Measurement System with seven-decade capability and potentiostatic function

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    This paper describes design and test of a new impedance-measurement system for nonlinear devices that exhibits a seven-decade range and works down to a frequency of 0.01 Hz. The system is specifically designed for electrochemical measurements, but the proposed architecture can be employed in many other fields where flexible signal generation and analysis are required. The system employs an unconventional signal generator based on two pulsewidth modulation (PWM) oscillators and an autocalibration system that allows uncertainties of less than 3% to be obtained over a range of 1 kΩ to 100 GΩ. A synchronous demodulation processing allows the noise superimposed to the low-amplitude input signals to be made negligibl

    Bicaudal is a conserved substrate for Drosophila and mammalian caspases and is essential for cell survival

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    Members of the caspase family of cysteine proteases coordinate cell death through restricted proteolysis of diverse protein substrates and play a conserved role in apoptosis from nematodes to man. However, while numerous substrates for the mammalian cell death-associated caspases have now been described, few caspase substrates have been identified in other organisms. Here, we have utilized a proteomics-based approach to identify proteins that are cleaved by caspases during apoptosis in Drosophila D-Mel2 cells, a subline of the Schneider S2 cell line. This approach identified multiple novel substrates for the fly caspases and revealed that bicaudal/betaNAC is a conserved substrate for Drosophila and mammalian caspases. RNAi-mediated silencing of bicaudal expression in Drosophila D-Mel2 cells resulted in a block to proliferation, followed by spontaneous apoptosis. Similarly, silencing of expression of the mammalian bicaudal homologue, betaNAC, in HeLa, HEK293T, MCF-7 and MRC5 cells also resulted in spontaneous apoptosis. These data suggest that bicaudal/betaNAC is essential for cell survival and is a conserved target of caspases from flies to man

    Emma ve Sense and sensibility adlı romanlarda okuyucunun Jane Austen tarafından kontrolü

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    This thesis analyses techniques employed by Jane Austen in Emma and Sense & Sensibility to control the readers when they make judgements about characters and events.The thesis will argue that the point of view used in these two novels to present events and characters has great influence upon readers. In addition, the role of skilful use of irony by Austen, and witholding of information by characters and author in keeping readers alert will be analysed.Bu çalışma Emma ve Sense and Sensibility adlı romanlarda, Jane Austen’ın okuyucular karakterler ve olaylar hakkında karar verirken onları kontrol etmek için kullangığı teknikleri incelemektedir.İki romanda da olayları ve karakterleri sunmak için kullanılan bakış açısının okuyucular üzerindeki etkisi incelenecektir.Buna ek olarak, Austen tarafından ustaca kullanılan kinaye sanatının ve karakterler veya yazar tarafından bilginin saklı tutulmasının okuyucuyu dikkatli kılmadaki rolü incelenecektir.M.A. - Master of Art

    Low-cost electrochemical impedance spectroscopy system for corrosion monitoring of metallic antiquities and works of art

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    Electrochemical impedance spectroscopy (EIS) is recognized to be a powerful and noninvasive technique to test the integrity of protective coatings on memorials, but commercial EIS systems are rather costly though versatile devices. This paper describes a low cost and portable EIS system that is based on a compact digital signal processor (DSP) board and embeds the potentiostatic function so that it can be used without requiring an external potentiostat. The software that runs on the DSP is designed to analyze the electrochemical impedance only in a reduced frequency range in order to produce a simple corrosion alert result. The device is equipped with a digital interface and can be connected to a personal computer to carry out a complete frequency analysis and perform a more complex data processing

    Hebrew Divine Names into Latin and Italian, Shiv'ah Shemot and other Samples from Egidio da Viterbo’s Workshop

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    This article deals with evidence, texts, commentaries and notes from Egidio da Viterbo’s collection of Hebrew manuscripts and from his Latin autographic manuscripts that shedding light on Egidio’s devices and perspectives in approaching the Hebrew language and the Hebrew divine names. This evidence is found in translations, marginalia, and book notes which were penned by Egidio himself and by people who assisted him in his reading the Hebrew texts. After providing an insight into Egidio’s premises and aims in the study of Hebrew literature, based on his autographic comments, the first part of the essay focuses on a set of translations from Hebrew into the Italian vernacular prepared by Jewish scribes and scholars for Egidio. The translators’ techniques, methodology, and selection of kabbalistic, aggadic, and midrashic material is examined. Although this translation project is of crucial importance for the transmission of the mystical Jewish literature to the Christian world of the Renaissance, it has received almost no scholarly attention so far. In the second part, this article takes into account a compilation (MS London, British Library, Add. 16390, vols. A–B) that includes, in its first volume, an anonymous glossary entitled Shivʿah Shemot (Seven Names), on the divine names occurring in the Bible, accompanied by masoretic explanation, and in its second volume, excerpts of a Jewish mystical text in vernacular translation entitled Raziel. They are both to be ascribed to Egidio’s workshop and to a collaboration with Elia Levita. The final part of this article concerns two autographic notebooks by Egidio (MSS Paris, Bibliothèque nationale de France, Lat. 596–597), in which our author records and translates Hebrew roots and divine names that he collected during his reading of Hebrew exegetical and mystical works. The combined analysis of these various witnesses opens different viewpoints on the ongoing activities which Egidio promoted, supporting the spread of Hebrew and Jewish studies in Renaissance Rome. Moreover, it enlightens on some of the propaedeutic materials which contributed to Egidio’s key endeavor to attain a mastery of Kabbalah and to shape his own syncretic kabbalistic syste

    Arthur J. Russell Correspondence

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    Entries include brief biographical information corrected in pencil, letters of introduction to Russell and his sister concerning the Maine Author Collection, a handwritten reply from Emma M. Russell, typed correspondence between Dunnack and Russell concerning books that should have been purchased right away at secondhand stores, a Maine Library Bulletin envelope with a small photographic portrait of young Russell and a full-length photograph, a page typed with a misspelling by the Maine State Library presented with a photograph of the home of Russell\u27s birth in Hallowell, Maine, and a lengthy typed biography on Minneapolis Journal stationery
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