Bcl-xL Deamidation Is a Critical Switch in the Regulation of the Response to DNA Damage

AbstractThe therapeutic value of DNA-damaging antineoplastic agents is dependent upon their ability to induce tumor cell apoptosis while sparing most normal tissues. Here, we show that a component of the apoptotic response to these agents in several different types of tumor cells is the deamidation of two asparagines in the unstructured loop of Bcl-xL, and we demonstrate that deamidation of these asparagines imports susceptibility to apoptosis by disrupting the ability of Bcl-xL to block the proapoptotic activity of BH3 domain-only proteins. Conversely, Bcl-xL deamidation is actively suppressed in fibroblasts, and suppression of deamidation is an essential component of their resistance to DNA damage-induced apoptosis. Our results suggest that the regulation of Bcl-xL deamidation has a critical role in the tumor-specific activity of DNA-damaging antineoplastic agents

Audio-description reloaded : an analysis of visual scenes in 2012 and Hero

This article explores whether the so-called new "cinema of attractions", with its supposed focus on visual effects to the detriment of storytelling, requires a specific approach to audio-description (AD). After some thoughts on film narrative in this type of cinema and the way in which it incorporates special effects, selected scenes with AD from two feature films, 2012 (directed by Emmerich) and Hero (directed by Zhang Yimou), are analysed. 2012 is a disaster movie aiming to thrill the audience with action. Hero is an equally visual movie but its imagery has an aesthetic purpose. The analysis investigates how space, time and action are treated in the films and the ADs, and how the information is presented in terms of focalization, timing and phrasing. The results suggest that effect-driven narratives require carefully timed and phrased ADs that devote much attention to the prosody of the AD script, its interaction with sounds and the use of metapho

‘George Eliot’s French’: transcending the monocultural self in Daniel Deronda

Focusing on an analysis of French lexical items in George Eliot’s Daniel Deronda, this article examines the nature of composite textuality. More precisely, it proposes a way of describing the use of an intercultural idiom in Daniel Deronda as a way of shedding light on the nature of linguistic borrowing in the context of dialogical identity. This will provide the basis for the claim that the characters’ use of mixed utterances generates inferences which make the transcending of the monocultural self possible and create alternatives of being

Oil content of sediments in the sump of a salt dome solution-mined cavern used for crude oil storage. Final report

The studies reported herein were conducted to ascertain if petroleum hydrocarbons are likely to accumulate in the sump sediments of a salt dome solution cavern used for crude oil storage and, if so, which hydrocarbons and in what concentrations. Cavern K 117 at Etzel, West Germany was selected for sampling because considerable data were available pertaining to the cavern and its crude oil inventory as a result of earlier studies. Mineralogical analyses of the sump samples revealed that they predominantly consist of uncemented halite crystals, ranging up to several centimeters in length, with subordinate anhydrite, and traces of gypsum and clay. Some of the mineral particles are colorless and translucent, while others are noticeably contaminated with oil. The samples exuded a distinct petroleum odor. Gas chromatographic analysis of an evolved gas sample showed the presence of the normal-paraffins propane through octane. Gas chromatographic analyses of a solvent extract of the sediment showed hydrocarbon and sulfur-compound distributions typical of crude oil. An infrared spectrum of the extract was also characteristic of a weathered or topped crude oil. The hydrocarbon content of the sediment samples was determined to be 780 ppM on the basis of a tetrachloromethane extract. It is believed that the petroleum present in the sump sediments principally results from cavern workover operations involving the pulling and resetting of the brine tubing string. When the brine string is reset it fills with oil because a packer is not used. To displace this oil, river water is pumped down the tubing at a moderately high rate. During this flushing process, clay particles dispersed in the river water adsorb a film of oil. As the oil-filmed clay particles enter the brine in the cavern they electrolytically flocculate and oil is sedimented to the cavern sump

Untersuchungen zur Funktion von Pex14p im peroxisomalen Matrixproteinimport der Hefe Saccharomyces cerevisiae\textit {Saccharomyces cerevisiae}

Peroxisomen sind ubiquitär in Eukaryonten vorkommende Organellen, deren Matrixproteine posttranslational importiert werden. Die vorliegende Arbeit befasste sich mit der Charakterisierung des peroxisomalen Membranproteins Pex14p aus der Hefe $\textit {Saccharomyces cerevisiae}$. Im Mittelpunkt stand die Kartierung von Bindebereichen für andere Peroxine sowie Analysen zu Auswirkungen von Mutationen in diesen Bindebereichen. Sie zeigten, dass die Pex14p-Termini Bindestellen für die PTS-Rezeptoren darstellen und das PXXP-Motiv von Pex14p an der Pex13p-Bindung beteiligt ist. Der zweite Schwerpunkt beinhaltete die Etablierung einer Methode zur Isolierung von Pex14p enthaltenden Membranproteinkomplexen und die Charakterisierung solcher mittels BN- und SDS-PAGE. So konnten zusammen mit Pex14p die Peroxine Pex5p, Pex10p, Pex12p, Pex13p und Pex17p ko-isoliert werden. Pex14p bildet mit Pex17p einen stabilen 400 kDa großen Subkomplex und zusammen mit Pex17p, Pex13p und Pex5p einen 800 kDa großen Komplex