3,036 research outputs found
Pro-apoptotic role of AMP-activated protein kinase under oxidative conditions linked to bioenergetic impairment: implications for cancer treatment and neurodegeneration
No full textLo squilibrio tra produzione di ROS e loro eliminazione porta a stress ossidativo, una condizione implicata nella patogenesi di molti disordini cellulari come la neurodegenerazione e il cancro.
In questi constesti, condizioni pro-ossidanti attivano molte proteine redox-sensibili coinvolte nella regolazione del programma apoptotico. Tra di questi, p53 e le MAPK sono implicate nella patogenesi dei disordini neurodegenerativi e in molte strategie chemioterapeutiche finalizzate alla eliminazione di cellule cancerose dal pool replicativo. Recentemente AMPK è stata identificata come un componente della cascata di segnalazione capace di percepire stress bioenergetici e ossidativi. Inoltre la sua capacità di indurre apoptosi attivando p53 o taluni membri della famiglia delle MAPK (ad es. p38MAPK), la rende implicata sia nelle malattie neurodegnerative che nel trattamento del cancro. Sulla base di queste conoscenze, questa tesi di dottorato è finalizzata ad elucidare le prpoprietà pro-apoptotiche di AMPK nella linea neuronale SH-SY5Y in risposta a condizioni pro-ossidanti di AMPK associate a stress bioenergetico. La ricerca è stata realizzata usando 3 composti noti influenzare l'omeosatsi redox:Bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N’]copper(II) perchlorate (Cu(isaepy)2), tetrahydrobiopterin (BH4) and sodium nitroprusside (SNP).The imbalance between ROS production and clearance leads to oxidative stress, a condition implicated in the pathogenesis of several cell disorders such as neurodegeneration and cancer. In these settings, pro-oxidant conditions activate many redox-sensitive proteins involved in the regulation of the apoptotic program. Among them, the tumor suppressor p53 and the mitogen-activated protein kinases (MAPK) are implicated both in the pathogenesis of neurodegenerative disorders and in many chemotherapeutic strategies aimed to the elimination of cancer-prone cells from the replicative pool. Recently, AMP-activated protein kinase (AMPK) has been identified as a component of the signaling cascade able to sense bioenergetic and oxidative challenges. Moreover, its capability to trigger apoptosis by activating p53 or some members of the MAPK family (e.g. p38MAPK), makes it a putative player both in neurodegenerative disease and in cancer management.
On the basis of this knowledge, this PhD thesis is aimed to elucidate the pro-apoptotic properties of AMPK in SH-SY5Y neuronal cell line under pro-oxidant conditions associated to bioenergetic impairment. This research has been performed by using three compounds known to affect cellular redox homeostas: Bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N’]copper(II) perchlorate (Cu(isaepy)2), tetrahydrobiopterin (BH4) and sodium nitroprusside (SNP). Our experiments demonstrated that Cu(isaepy)2, by acting as a DLC-like molecule, was able to induce cell death by activating the AMPK/ p38MAPK/p53 signaling axis, in response to a mitochondrial impairment. The cross-talk between these proteins was found to be operative also in SH-SY5Y cell death induced by BH4, an obligatory cofactor for tyrosine hydroxylase in dopamine synthesis, and to be sensitive to the alteration of glycolytic metabolism. Finally the observation that the iron-nytrosil complex SNP was unable to affect cellular energetics, explains on the one hand the uneffectivenes of AMPK in mediating SNP-induced apoptosis and, on the other, suggests a possible role for this energy-responsive kinase in apoptosis engagement only under condition of bioenergetic stress
Pino Pizzigoni’s ‘Minima House’ in Bergamo: from the Architectural Project to Its Safeguarding
No full textThe ‘Casa Minima’ designed by Pino Pizzigoni in Bergamo (1946) is a life-size model of single-family housing. A component of a ‘side-by-side’ system that was planned to generate a popular district, which was ultimately not implemented. To respond to the construction crisis following the Second World War, the architect designed an architecture that was both singular and unique in space and volume. He proposed a new model that encompassed both the housing type and the cost and time savings associated with construction. A minimalist prototype capable of combining modern construction technologies and materials used for the traditional mountain retreats in the Orobic Alps and/or for Mediterranean dwellings in the heart of the Aegean Sea. This paper proposes a new reading of the building through a careful graphical analysis that has highlighted a geometric severity and a rigor of the proportions of each of its parts, even of the furnishings. The review of the archives (architectural drawings, photographs, and documents) was accompanied by a direct observation to uncover the differences between the project idea and the built. An in-depth investigation that underlined the transformations undertaken over the time, not always respectful of the identity of the edifice until the restoration work carried out in the 1990s by the architect’s son, Attilio Pizzigoni, who brought the ‘Casa Minima’ back to its original soul
Rozpor ako východisko, láska ako smer u Simone Weilovej (Contradiction as base, Love as direction in writings of Simone Weil)
No full textArticle is explaining contradiction and love, Simone Weil‘s essential terms of hermeneutics of human Being. It introduces close relation of these terms with her understanding of God as well as with her overall concept of religion. Author also mentions Simone Weil‘s inspirations with philosophical and spiritual concepts of the East
“I beg you to tell me what has become of Djamila”: The Political Mobilization of Simone de Beauvoir’s Readers During the Boupacha Affair
No full textBy Sophia Millman This is a condensed version of a Masters thesis dedicated to the political mobilization of Simone de Beauvoir’s readers. The citations from the letters were translated from French by the author. *** On June 2, 1960, the French government ordered all copies of the daily Algiers edition of Le Monde seized and destroyed to suppress the publication of Simone de Beauvoir’s article “Pour Djamila Boupacha.” Beauvoir, a self-professed “woman of letters”, not “of action[1]”, and one ..
A comparative study of form and theology in the works of Flannery O'Connor and Simone Weil
No full textIn this comparative study of the form and theology of Flannery O'Connor and Simone Weil I interrogate how Weil's philosophical writings and her theology illuminate O'Connor's use of both narrative and non-fictional forms, and her Catholicism. The Introduction analyses how Weil's concept of superposed reading provides a new method of approaching both O'Connor, her writings, and O'Connor
studies, and focuses on how such apparently different women interconnect. Chapter One explores how both Weil and O'Connor attempt to write their theologies on the
souls of their readers yet are each subject to constraints imposed by form. Weil's concept of locating equilibrium between incommensurates is discussed, and her
distinctively philosophical approach to fictions and fictionality is used to investigate O'Connor's notion of prophetic fictions and the writer's role. Chapter Two assesses how both writers revivify Christian paradoxes. Weil's monstrous concept of affiiction, and O'Connor's use of the grotesque genre to jolt secular man into an
awareness of the sacred are scrutinised. Chapter Three studies how both writers consider an encounter between God and man is possible through the action of grace. My Conclusion interrogates how Weil's work can deepen our understanding of O'Connor's writings, and examines how successful O'Connor is at realising a truly
Christian literature. I conclude that despite being a writer of powerful fictions, O'Connor can not be totally successful in her mission as writer-prophet because
ultimately fiction escapes orthodoxy
Microlinices benthovus Simone 2014
No full textbenthovus, Microlinices Simone, 2014 Microlinices benthovus Simone, 2014: 575–578 (figs 6A–J, 7A–H, 11A–C). Gastropoda, Naticidae Paratypes (22 spc): MZSP 105269. Paratypes 1 (15 spc): MZSP 105270. Paratypes 2 (16 spc): MZSP 105271. Paratypes 3 (7 spc): MZSP 105272. Localities: Brazil, Espírito Santo, off Itaúnas, Abrolhos Slope, 18°59' S, 37°50' W, MD55 sta. DC 73, 637 m depth, 27 May 1987; 1) 19°00' S, 37°48' W, MD55 sta. DC72, 950– 1050 m, 27 May 1987; 2) off Regência, 19°40' S, 37°48' W, MD55 sta. CB77, 790– 940 m depth, 27 May 1987; 3) off Itaúnas, Abrolhos Slope, 19°01' S, 37°47' W, MD55 sta. CB79, 1500–1575 m depth, 28 May 1987. Collectors: P. Bouchet, J.H. Leal and B. Métivier. Preservation: Dry. Remarks: Former MNHN, Paris. The catalogue number MZSP 105250 is mentioned twice in Simone’s (2014) paper, among the paratypes of M. ibitingus Simone, 2014 and M. benthovus. This duplicity was a mistake by the author: the latter is an erroneous designation and should be disregarded. The only valid paratype lots for M. benthovus are the ones shown above.Published as part of Cavallari, Daniel C., Dornellas, Ana Paula S. & Simone, Luiz Ricardo L., 2016, Second annotated list of type specimens of molluscs deposited in the Museu de Zoologia da Universidade de São Paulo, Brazil, pp. 1-59 in European Journal of Taxonomy 213 on page 10, DOI: 10.5852/ejt.2016.213, http://zenodo.org/record/384012
Was bringt die Föderalismusreform? Wahrscheinliche Effekte der geänderten Zustimmungspflicht
No full textThe recently enacted reform of German federalism is supposed to make legislation faster, more efficient and better. To what extent are these expectations justified? In order to assess the likely effects of the reform, this study uses a research design that was recently applied by the Research and Reference Services of the German Bundestag (parliament): we estimate the future effects of the reform by analyzing the impact it would have had on the legislation in the 14th and 15th term of the Bundestag if it had already been been in force at that time. In particular we ask: To what extent would the number of laws requiring the consent of the states' chamber, the Bundesrat, have been reduced? Which type of laws would have been affected by this reduction - the more controversial ones, or the less controversial ones? Which policy sectors would have seen the greatest reduction? How much would the reduction have increased the government's capacity to act effectively? Would the legislative process have been accelerated? -- Die verabschiedete Föderalismusreform soll die Gesetzgebung in Deutschland schneller, effizienter und besser machen. Inwiefern sind diese Erwartungen berechtigt? Zur Abschätzung der Reformfolgen auf die Bundesgesetzgebung folgen wir in dem vorliegenden Working Paper einer Vorgehensweise, die der Wissenschaftliche Dienst des Bundestages kürzlich in einer Studie angewandt hat: Die Auswirkungen der Föderalismusreform insbesondere auf die Zustimmungspflicht werden anhand der Gesetzgebung der 14. und 15. Legislaturperiode untersucht. Wir fragen insbesondere: Wie stark hätte sich der Anteil der Zustimmungsgesetze verringert, wenn die neuen Zustimmungsregeln schon in diesen beiden Legislaturperioden gegolten hätten? Wären eher zwischen Regierung strittige oder unstrittige Gesetze von der Zustimmungspflicht befreit worden? Welche Politikbereiche wären betroffen? Wie sehr hätte sich die politische Handlungsfreiheit der Bundesregierung erhöht? Wäre die Gesetzgebung durch die veränderten Zustimmungsregeln beschleunigt worden?
The Tricarboxylic Acid Cycle at the Crossroad Between Cancer and Immunity
No full textSignificance: The tricarboxylic acid (TCA) cycle is a housekeeping metabolic pathway essential for generation of energy and biosynthetic intermediates. Alterations of the TCA cycle play a pivotal role in oncogenesis and inflammation. As such, some metabolic vulnerabilities, imposed by TCA cycle dysfunction in cancer, have been identified. Similarly, the TCA cycle appeared as an actionable pathway in immunopathologies. Recent Advances: Metabolic changes accompanying cell transformation have been usually considered as adaptive mechanisms to malignant transformation. The identification of oncogenic mutations in some TCA cycle enzymes changed this view, indicating altered mitochondrial metabolism as an instrumental mechanism for cancer initiation. Similarly, the observation that TCA cycle-derived metabolites have multiple signaling roles in immune cells supports the idea of this pathway as a metabolic rheostat of immune responses. Critical Issues: This review summarizes the crucial role of the TCA cycle in pathophysiology describing the post-translational and epigenetic impact of oncometabolites accumulation in cancer and immune cells. Future Directions: Additional studies will be necessary to further explore the role of oncometabolites in paracrine signaling and to identify genuine metabolic and nutritional liabilities imposed by TCA cycle dysfunction in cancer, hardly to be escaped by resistance mechanisms
TCA Cycle Defects and Cancer: When Metabolism Tunes Redox State
No full textInborn defects of the tricarboxylic acid (TCA) cycle enzymes have been known for more than twenty years. Until recently, only recessive mutations were described which, although resulted in severe multisystem syndromes, did not predispose to cancer onset. In the last ten years, a causal role in carcinogenesis has been documented for inherited and acquired alterations in three TCA cycle enzymes, succinate dehydrogenase (SDH), fumarate hydratase (FH), and isocitrate dehydrogenase (IDH), pointing towards metabolic alterations as the underlying hallmark of cancer. This paper summarizes the neoplastic alterations of the TCA cycle enzymes focusing on the generation of pseudohypoxic phenotype and the alteration of epigenetic homeostasis as the main tumor-promoting effects of the TCA cycle affecting defects. Moreover, we debate on the ability of these mutations to affect cellular redox state and to promote carcinogenesis by impacting on redox biology
Idea ofiary u Simone Weil
No full textAutorka omawia ofiarę, jaką z samej siebie złożyła Simone Weil. Głównym celem autorki artykułu jest wykazanie, iż idea ofiary była najważniejszą myślą w życiu francuskiej filozof. W artykule ukazano myśl o ofierze w życiu i pismach intelektualistki, jak również analogie, które rzucają nowe światło na ofiarę Weil. Jako klucz do interpretacji i zrozumienia ofiary Weil, autorka analizuje myśl Emmanuela Levinasa oraz Józefa Tischnera.The author interprets the sacrifice that Simone Weil filed with itself. The main point of the present article is the assumption that the sacrifice Simone Weil was the most important idea of her life. A thought about the victim is portraying the article in the life and letters of the intellectual, as well as is portraying analogies which are shedding new light on the Weil victim. As the key to interpretation and understanding the her victim, the author is analysing the thought of Emmanuel Levinas and Jozef Tischner.Udostępnienie publikacji Wydawnictwa Uniwersytetu Łódzkiego finansowane w ramach projektu „Doskonałość naukowa kluczem do doskonałości kształcenia”. Projekt realizowany jest ze środków Europejskiego Funduszu Społecznego w ramach Programu Operacyjnego Wiedza Edukacja Rozwój; nr umowy: POWER.03.05.00-00-Z092/17-00
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