8,219 research outputs found
Pancreatic beta-cells: From generation to regeneration.
No full textThe pancreas is composed of two main compartments consisting of endocrine and exocrine tissues. The majority of the organ is exocrine and responsible for the synthesis of digestive enzymes and for their transport via an intricate ductal system into the duodenum. The endocrine tissue represents less than 2% of the organ and is organized into functional units called islets of Langerhans, comprising alpha-, beta-, delta-, epsilon- and PP-cells, producing the hormones glucagon, insulin, somatostatin, ghrelin and pancreatic polypeptide (PP), respectively. Insulin-producing beta-cells play a central role in the control of the glucose homeostasis. Accordingly, absolute or relative deficiency in beta-cells may ultimately lead to type 1 and/or type 2 diabetes, respectively. One major goal of diabetes research is therefore to understand the molecular mechanisms controlling the development of beta-cells during pancreas morphogenesis, but also those underlying the regeneration of adult injured pancreas, and assess their significance for future cell-based therapy. In this review, we will therefore present new insights into beta-cell development with focus on beta-cell regeneration
A genetic mouse model for progressive ablation and regeneration of insulin producing beta-cells
No full text<div><p>The putative induction of adult β-cell regeneration represents a promising approach for the treatment of type 1 diabetes. Toward this ultimate goal, it is essential to develop an inducible model mimicking the long-lasting disease progression. In the current study, we have established a novel β-cell ablation mouse model, in which the β-cell mass progressively declines, as seen in type 1 diabetes. The model is based on the β-cell specific genetic ablation of the transcription initiation factor 1A, TIF-IA, essential for RNA Polymerase I activity (TIF-IA<sup>Δ/Δ</sup>). Using this approach, we induced a slow apoptotic response that eventually leads to a protracted β-cell death. In this model, we observed β-cell regeneration that resulted in a complete recovery of the β-cell mass and normoglycemia. In addition, we showed that adaptive proliferation of remaining β-cells is the prominent mechanism acting to compensate for the massive β-cell loss in young but also aged mice. Interestingly, at any age, we also detected β-like cells expressing the glucagon hormone, suggesting a transition between α- and β-cell identities or <i>vice versa</i>. Taken together, the TIF-IA<sup>Δ/Δ</sup> mouse model can be used to investigate the potential therapeutic approaches for type 1 diabetes targeting β-cell regeneration.</p></div
Art, Biography, Sexuality: Patrick Procktor and Keith Vaughan
No full textThis critical review forms a reflection on the research published within the following publications:
Patrick Procktor: Art and Life (Unicorn Press, 2010)
Keith Vaughan: The Mature Oils 1946-1977, (Sansom & Co., 2012)
The research is on two artists, Patrick Procktor (1936-2003), and Keith Vaughan (1912-1977). The monograph on Procktor – previously one of the least documented of the generation of artists who came to prominence in London in the Sixties – positions him in a history of art from which he had been notably absent. The research on Vaughan asserts a new reading of his work, one that is both deeper and more nuanced in its analysis of the ways in which personal experience and sexuality are encoded autobiographically within his work. Crucially, in both artists biography and work are symbiotically linked; the research therefore examines the links between life and art.
Revisionary in intent, the work examines trajectories of experience of gay British (or rather, English) artists in the twentieth century, artists who sought to express themselves and forge careers within the constraints of a heteronormative society, albeit one in which attitudes to sexuality were undergoing change. As gay men, both were constrained by the social mores of their times, and each used painting as a means to affirm personal and sexual identities. A key research interest is in the ways in which sexuality and persona are reflected in critical responses to the artist’s work: in Vaughan, Procktor and other gay male artists of the period. The writing on both Procktor and Vaughan examines the relationship between their personal and professional/artistic lives, framed within a broader socio-political and art historical context. It asserts the place of biography as a means to understand and form new readings of the work. The work adds substantially to the literature and wider discourse on post-war British painting and social history
Forcing alpha-cell-mediated beta-cell regeneration
No full textLe diabète de type 1 (DT1) résulte de la destruction des cellules β productrices d’insuline par le système immunitaire. Cette condition représente un enjeu de santé publique majeur car, malgré les thérapies actuelles, les patients atteints développent trop souvent des complications cardio-vasculaires. Des thérapies alternatives se doivent donc d’être mises au point. Ainsi, diverses approches visent à reprogrammer/différencier (in vitro ou in vivo) différents types cellulaires pancréatiques afin de générer des cellules β (productrices d’insuline) fonctionnelles. Dans ce but, notre laboratoire a notamment montré que les cellules α (productrices de glucagon) embryonnaires peuvent être régénérées et converties en cellules β fonctionnelles par l’expression ectopique du seul gène Pax4 (un gène normalement impliqué dans la spécification embryonnaire du lignage β - (Collombat and Mansouri, 2009)). Dans la première partie de ce travail, nous démontrons que les cellules α à l’âge adulte (Al-Hasani et al., 2013) retiennent leur capacité de régénération et de conversion en cellules β, celles-ci étant fonctionnelles et capable de remplacer plusieurs fois l’ensemble des cellules β du pancréas. Cependant, cette approche transgénique serait difficile à mettre en œuvre chez l’homme. De nombreux cribles furent donc initiées dans le but de trouver des petites molécules/composés chimiques mimant les effets de Pax4. Un composé potentiel, GABA, fut ainsi identifié et caractérisé.Type 1 diabetes (T1D) results from the destruction of insulin-producing β-cells by the immune system. This condition is a major public health issue because, despite current therapies, patients often develop cardiovascular complications. Therefore alternative therapies need to be developed. Thus, various approaches are designed to reprogram / differentiate (in vitro or in vivo) different pancreatic cell types to generate functional (insulin-producing) β-cells. To this end, our laboratory has shown that especially the embryonic α-cells (producing glucagon) can be regenerated and converted into functional β-cells by the ectopic expression of the Pax4 gene (usually a gene involved in the specification of embryonic lineage β - (Collombat and Mansouri, 2009)). In the first part of this work, we show that α-cells in adulthood (Al-Hasani et al., 2013) retain their capacity for regeneration and conversion into β-cells, the latter being functional and able to replace repeatedly all the β-cells of the pancreas. However, this transgenic approach would be difficult to implement in humans. Many screens were therefore initiated in order to find small molecules / chemical compounds that mimic the effects of Pax4. A potential compound, GABA, was identified and characterized. Our results demonstrate that treatment of WT mice with GABA results in a significant increase in the number and size of the islets (caused by insulin+ cell hyperplasia). By using lineage tracing tools, our results indicate that these "β-like" neo-generated cells are coming from glucagon+ cells
Patrick Chamoiseau Recovering Memory
No full textThis timely new book skillfully examines the work of the award-winning writer Patrick Chamoiseau. Considered by many as one of the most innovative writers to hit the French literary scene in over 40 years, Chamoiseau made his name with his book Texaco (published in 1992 and winner of the highest literary prize in France, the Prix Goncourt). His books have gone on to sell millions and his work has been translated by a number of academic presses. McCusker sets the author in context, providing a valuable contribution to 'memory studies' by looking at literary representation of memory in Martinique, a society founded on slavery but now politically assimilated to the metropolitan centre, France.Title Page -- Contents -- Introduction -- 1: Beginnings: The Enigma of Origin -- 2: 'Une tracée de survie': Autobiographical Memory -- 3: Memory Re-collected: Witnesses and Words -- 4: Memory Materialized: Traces of the Past -- 5: Flesh Made Word: Traumatic Memory in Biblique des derniers gestes -- Afterword -- Notes -- Bibliography -- IndexThis timely new book skillfully examines the work of the award-winning writer Patrick Chamoiseau. Considered by many as one of the most innovative writers to hit the French literary scene in over 40 years, Chamoiseau made his name with his book Texaco (published in 1992 and winner of the highest literary prize in France, the Prix Goncourt). His books have gone on to sell millions and his work has been translated by a number of academic presses. McCusker sets the author in context, providing a valuable contribution to 'memory studies' by looking at literary representation of memory in Martinique, a society founded on slavery but now politically assimilated to the metropolitan centre, France.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
Replication Data for: Endogenous Price Commitment, Sticky and Leadership Pricing: Evidence from the Italian Petrol Market
No full textThe do-file contains the code to replicate "Endogenous Price Commitment, Sticky and Leadership Pricing: Evidence from the Italian Petrol Market", published in the International Journal of Industrial Organization, vol. 40(C), pages 32-48, by Patrick Andreoli-Versbach and Jens-Uwe Franck.
Contact author is Patrick Andreoli-Versbach. E-Mail: [email protected]
Replication Data for: Endogenous Price Commitment, Sticky and Leadership Pricing: Evidence from the Italian Petrol Market
No full textThe do-file contains the code to replicate "Endogenous Price Commitment, Sticky and Leadership Pricing: Evidence from the Italian Petrol Market", published in the International Journal of Industrial Organization, vol. 40(C), pages 32-48, by Patrick Andreoli-Versbach and Jens-Uwe Franck.
Contact author is Patrick Andreoli-Versbach. E-Mail: [email protected]
The investigation in "Dora Bruder" of Patrick Modiano
No full textreservedIl presente lavoro si propone di affrontare il tema dell’indagine, dell’inchiesta investigativa nel romanzo “Dora Bruder” dello scrittore francese Patrick Modiano, pubblicato nel 1997. Si tratta del più noto successo editoriale dell’autore, il quale, in una narrazione al contempo biografica ed autobiografica, si mette sulle tracce di Dora Bruder, una giovane ragazza ebrea scomparsa nel 1941, di cui si sono perse definitivamente le tracce. La presente tesi si compone di tre capitoli. Nel primo, si analizzeranno i motivi che spingono l’autore ad occuparsi della vicenda della giovane ragazza scomparsa proprio durante la seconda guerra mondiale. Successivamente, nel secondo capitolo, si passerà ad affrontare come l’autore compie la propria indagine per comprendere che cosa le sia accaduto, diventando una sorta di investigatore su un vecchio caso di scomparsa. Ed infine, nell’ultimo capitolo, si analizzerà quale sarà l’esito della sua indagine.This work proposes to deal with the subject of investigation in the novel "Dora Bruder" by French writer Patrick Modiano, published in 1997. It’s the most known publishing success of the author, which, in a narrative in the meantime biographical and autobiographical, goes on the trail of Dora Bruder, a young Jewish girl disappeared in 1941, of whom all traces have been definitively lost. This thesis is composed by three chapters. In the first, we will analyse the reasons why the author deal with the story of the young girl vanished during the Second World War. Then, in the second chapter, we will approach how the author does his own investigation to understand what happened to her, becoming sort of a detective on an old case of disappearence. Finally, in the last chapter, we focus on which it’ll be the outcome of his investigation
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