Mohammed Palimpsests : Nascent Islam in the Late Twentieth Century Novel

[À l'origine dans / Was originally part of : Thèses et mémoires - FAS - Département de littérature comparée]Le sujet de cette étude est Mohammed et sa montée fulgurante depuis ses humbles origines jusqu’à ce qu’il devienne Prophète de l’Islam, celui dont la vie et les dires forment le grand récit des Musulmans. Cette thèse s’intitule “Les Palimpsestes de Mohammed: l’Islam naissant dans le roman de la fin du XXe siècle” et a pour corpus The Satanic Verses [Les versets sataniques] (1988) de Salman Rushdie, Loin de Médine (1991) d’Assia Djebar et L’Homme du Livre (1995) de Driss Chraïbi. Ils partagent tous le genre romanesque, le cadre temporel relativement restreint, la question de la récriture —au moins partielle— de la biographie de Mohammed, ainsi que l’appartenance religieuse des auteurs. Malgré ces similitudes, une certaine division institutionnelle les a jusqu’ici cloisonnés dans différents départements universitaires. Je suis persuadé qu’une étude comparative de ces trois romans marquants servira de maïeutique à un dialogue qui n’attendait qu’à voir le jour. Je crois également que seule une analyse comparative permettra une appréciation plus ambitieuse et nuancée des questionnements qu’ils soulèvent. Le premier chapitre examine les complexes relations intertextuelles que chaque roman entretien avec les textes souches de l’Islam, dont le plus important est le Coran. Il propose l’intertextualité non seulement comme manière de ressourcer des écrits, mais aussi comme poiésis. Le deuxième chapitre traite de l’histoire, en se penchant sur le rapport entre la fiction et l’histoire, sur l’historiographie, de même que sur certaines notions de la conscience historique. Il considère diverses notions du temps (le progrès, la stasis, le retour à la source) et le savoir historique. Parmi les théoriciens dont les écrits sont discutés, on compte de Certeau, Kracauer, Laroui et White. Le troisième chapitre s’articule autour du genre sexuel. Alors que chacun des trois auteurs féminise en quelque sorte l’histoire de l’Islam des premiers temps dans le but de rendre leurs récits plus inclusifs, ils s’intéressent tout autant à la masculinité qu’au rapport entre les des deux genres. Je traite de notions comme l’échec noble (Spivak) attribué à Rushdie, ainsi que la critique multiple ou la foi interrogative chez Djebar et le spiritualisme féminin chez Chraïbi. Dans ce chapitre particulièrement interdisciplinaire, des approches anthropologiques et psychanalytiques viennent nourrir la réflexion. J’avance que l’Islam constitue une notion clé pour la compréhension de ces romans. Non seulement narrent-ils les débuts de l’Islam, mais ils ouvrent l’Islam à de nouvelles interprétations, particulièrement pour les musulmans qui partagent la situation en diaspora des auteurs.This study has as its subject Mohammed the Prophet, the fascinating rise of a humble man whose life and teachings have formed the grand narrative for Muslims the world over. It is entitled “Mohammed Palimpsests: Nascent Islam in the Late Twentieth Century Novel” and is based on a corpus comprised of Salman Rushdie’s The Satanic Verses (1988), Assia Djebar’s Loin de Médine (1991), and Driss Chraïbi’s L’Homme du Livre (1995). What they all share includes the genre novel, the brief time span in which the novels were published, the extent to which they rewrite the biography of Mohammed, and the at least nominal Muslim identity of their authors. Despite these similarities, institutional divisions have led to these seminal texts being discussed separately. Yet convinced that this is very much a dialogue that was waiting to happen, I bring these three novels into comparative focus in the desire for a more complete and varied understanding of the issues they bring to light. Chapter one looks at the complex intertextual relations that each novel maintains with a number of Islamic source texts, most notable of which is the Quran. It argues that intertextuality is not simply resourcing, but also creation and demonstrates the wealth of intertextual strategies used by these authors in their re-writings of Mohammed’s life. Chapter two is concerned with history. It examines the relation between fiction and history, historiography and notions of historical consciousness. In so doing, it considers various concepts of time (progress, stasis, return to the source) and historical knowledge. Theorists discussed include de Certeau, Kracauer, Laroui, and White. Chapter three examines gender. While all three authors clearly feminize the history of early Islam, making their accounts inclusive, they are equally concerned with masculinity. I therefore address the success of each of these efforts, from the purported “noble failure” (Spivak) of Rushdie, to Djebar’s notion of interrogative faith and multiple critique, and feminine spiritualism, which is given expression in Djebar and Chraïbi’s work. In this most interdisciplinary chapter, anthropological and psychoanalytical perspectives are used. I argue that Islam is very central to The Satanic Verses, Loin de Médine, and L’Homme du Livre. These novels not only narrate early Islam, they ultimately are engaged in opening it up to new interpretations, particularly for French and English-speaking Muslims who share their authors’ diasporic situation

3-Fluoro-4-hydroxyprolines:Synthesis, conformational analysis and stereoselective recognition by the VHL E3 ubiquitin ligase for targeted protein degradation

Hydroxylation and fluorination of proline alters the pyrrolidine ring pucker and the trans:cis amide bond ratio in a stereochemistry-dependent fashion, affecting molecular recognition of proline-containing molecules by biological systems. While hydroxyprolines and fluoroprolines are common motifs in medicinal and biological chemistry, the synthesis and molecular properties of prolines containing both modifications, i.e., fluoro-hydroxyprolines, have not been described. Here we present a practical and facile synthesis of all four diastereoisomers of 3-fluoro-4-hydroxyprolines (F-Hyps), starting from readily available 4-oxo-l-proline derivatives. Small-molecule X-ray crystallography, NMR spectroscopy, and quantum mechanical calculations are consistent with fluorination at C³ having negligible effects on the hydrogen bond donor capacity of the C⁴ hydroxyl, but inverting the natural preference of Hyp from C⁴-exo to C⁴-endo pucker. In spite of this, F-Hyps still bind to the von Hippel–Lindau (VHL) E3 ligase, which naturally recognizes C⁴-exo Hyp in a stereoselective fashion. Co-crystal structures and electrostatic potential calculations support and rationalize the observed preferential recognition for (3<i>R</i>,4<i>S</i>)-F-Hyp over the corresponding (3<i>S</i>,4<i>S</i>) epimer by VHL. We show that (3<i>R</i>,4<i>S</i>)-F-Hyp provides bioisosteric Hyp substitution in both hypoxia-inducible factor 1 alpha (HIF-1α) substrate peptides and peptidomimetic ligands that form part of PROTAC (proteolysis targeting chimera) conjugates for targeted protein degradation. Despite a weakened affinity, Hyp substitution with (3<i>S</i>,4<i>S</i>)-F-Hyp within the PROTAC MZ1 led to Brd4-selective cellular degradation at concentrations >100-fold lower than the binary <i>K</i>_d for VHL. We anticipate that the disclosed chemistry of 3-fluoro-4-hydroxyprolines and their application as VHL ligands for targeted protein degradation will be of wide interest to medicinal organic chemists, chemical biologists, and drug discoverers alike

Chemical genetics approaches for selective intervention in epigenetics

Chemical genetics is the use of biologically active small molecules (chemical probes) to investigate the functions of gene products, through the modulation of protein activity. Recent years have seen significant progress in the application of chemical genetics to study epigenetics, following the development of new chemical probes, a growing appreciation of the role of epigenetics in disease and a recognition of the need and utility of high-quality, cell-active chemical probes. In this review, we single out the bromodomain reader domains as a prime example of both the success, and challenges facing chemical genetics. The difficulty in generating single-target selectivity has long been a thorn in the side of chemical genetics, however, recent developments in advanced forms of chemical genetics promise to bypass this, and other, limitations. The ‘bump-and-hole’ approach has now been used to probe — for the first time — the BET bromodomain subfamily with single-target selectivity and may be applicable to other epigenetic domains. Meanwhile, PROTAC compounds have been shown to be significantly more efficacious than standard domain inhibitors, and have the potential to enhance target selectivity

Reading Room Electives: Say Goodbye to the “Radi-Holiday”

Reading room electives are among the most challenging curricula to develop for medical student educators. Students tend to have few responsibilities and poorly defined learning objectives. The authors review the components of a successful reading room elective. The important components include a thorough orientation, written goals and expectations, attendance and feedback systems, objective mid-elective and end-of-elective evaluations, and an end-of-elective debriefing session. Many educational activities, tools, and assessments are available and should be considered to supplement the curriculum. Radiology electives must break free of the "radi-holiday" stereotype and adopt increased responsibilities and expectations, similar to rigorous clinical subinternships

Synthesis and biological investigation of (+)-JD1, an organometallic BET bromodomain inhibitor

(+)-JD1, a rationally designed ferrocene analogue of the BET bromodomain (BRD) probe molecule (+)-JQ1, has been synthesized and evaluated in biophysical, cell-based assays as well as in pharmacokinetic studies. It displays nanomolar activity against BRD isoforms, and its cocrystal structure was determined in complex with the first bromodomain of BRD4 and compared with that of (+)-JQ1, a known BRD4 small-molecule probe. At 1 μM concentration, (+)-JD1 was able to inhibit c-Myc, a key driver in cancer and an indirect target of BRD4

The Digital Fish Library: Using MRI to Digitize, Database, and Document the Morphological Diversity of Fish

Museum fish collections possess a wealth of anatomical and morphological data that are essential for documenting and understanding biodiversity. Obtaining access to specimens for research, however, is not always practical and frequently conflicts with the need to maintain the physical integrity of specimens and the collection as a whole. Non-invasive three-dimensional (3D) digital imaging therefore serves a critical role in facilitating the digitization of these specimens for anatomical and morphological analysis as well as facilitating an efficient method for online storage and sharing of this imaging data. Here we describe the development of the Digital Fish Library (DFL, http://www.digitalfishlibrary.org), an online digital archive of high-resolution, high-contrast, magnetic resonance imaging (MRI) scans of the soft tissue anatomy of an array of fishes preserved in the Marine Vertebrate Collection of Scripps Institution of Oceanography. We have imaged and uploaded MRI data for over 300 marine and freshwater species, developed a data archival and retrieval system with a web-based image analysis and visualization tool, and integrated these into the public DFL website to disseminate data and associated metadata freely over the web. We show that MRI is a rapid and powerful method for accurately depicting the in-situ soft-tissue anatomy of preserved fishes in sufficient detail for large-scale comparative digital morphology. However these 3D volumetric data require a sophisticated computational and archival infrastructure in order to be broadly accessible to researchers and educators

Identifying knowledge gaps in seagrass research and management: An Australian perspective

Seagrass species form important marine and estuarine habitats providing valuable ecosystem services and functions. Coastal zones that are increasingly impacted by anthropogenic development have experienced substantial declines in seagrass abundance around the world. Australia, which has some of the world's largest seagrass meadows and is home to over half of the known species, is not immune to these losses. In 1999 a review of seagrass ecosystems knowledge was conducted in Australia and strategic research priorities were developed to provide research direction for future studies and management. Subsequent rapid evolution of seagrass research and scientific methods has led to more than 70% of peer reviewed seagrass literature being produced since that time. A workshop was held as part of the Australian Marine Sciences Association conference in July 2015 in Geelong, Victoria, to update and redefine strategic priorities in seagrass research. Participants identified 40 research questions from 10 research fields (taxonomy and systematics, physiology, population biology, sediment biogeochemistry and microbiology, ecosystem function, faunal habitats, threats, rehabilitation and restoration, mapping and monitoring, management tools) as priorities for future research on Australian seagrasses. Progress in research will rely on advances in areas such as remote sensing, genomic tools, microsensors, computer modeling, and statistical analyses. A more interdisciplinary approach will be needed to facilitate greater understanding of the complex interactions among seagrasses and their environment

Innovation, conservation, and repurposing of gene function in root cell type development

Plant species have evolved myriads of solutions, including complex cell type development and regulation, to adapt to dynamic environments. To understand this cellular diversity, we profiled tomato root cell type translatomes. Using xylem differentiation in tomato, examples of functional innovation, repurposing, and conservation of transcription factors are described, relative to the model plant Arabidopsis. Repurposing and innovation of genes are further observed within an exodermis regulatory network and illustrate its function. Comparative translatome analyses of rice, tomato, and Arabidopsis cell populations suggest increased expression conservation of root meristems compared with other homologous populations. In addition, the functions of constitutively expressed genes are more conserved than those of cell type/tissue-enriched genes. These observations suggest that higher order properties of cell type and pan-cell type regulation are evolutionarily conserved between plants and animals