106 research outputs found

    New imaging techniques project the cellular and molecular alterations underlying bicuspid aortic valve development

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    Bicuspid aortic valve (BAV) disease is the most common congenital cardiac malformation associated with an increased lifetime risk and a high rate of surgically-relevant valve deterioration and aortic dilatation. Genomic data revealed that different genes are associated with BAV. A dominant genetic factor for the recent past was the basis to the recommendation for a more extensive aortic intervention. However very recent evidence that hemodynamic stressors and alterations of wall shear stress play an important role independent from the genetic trait led to more conservative treatment recommendations. Therefore, there is a current need to improve the ability to risk stratify BAV patients in order to obtain an early detection of valvulopathy and aortopathy while also to predict valve dysfunction and/or aortic disease development. Imaging studies based on new cutting-edge technologies, such us 4-dimensional (4D) flow magnetic resonance imaging (MRI), two-dimensional (2D) or three-dimensional (3D) speckle-tracking imaging (STI) and computation fluid dynamics, combined with studies demonstrating new gene mutations, specific signal pathways alterations, hemodynamic influences, circulating biomarkers modifications, endothelial progenitor cell impairment and immune/inflammatory response, all detected BAV valvulopathy progression and aortic wall abnormality. Overall, the main purpose of this review article is to merge the evidences of imaging and basic science studies in a coherent hypothesis that underlies and thus projects the development of both BAV during embryogenesis and BAV-associated aortopathy and its complications in the adult life, with the final goal to identifying aneurysm formation/rupture susceptibility to improve diagnosis and management of patients with BAV-related aortopathy

    Molecular basis of functional myogenic specification of Bona Fide multipotent adult cardiac stem cells

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    Ischemic Heart Disease (IHD) remains the developed world's number one killer. The improved survival from Acute Myocardial Infarction (AMI) and the progressive aging of western population brought to an increased incidence of chronic Heart Failure (HF), which assumed epidemic proportions nowadays. Except for heart transplantation, all treatments for HF should be considered palliative because none of the current therapies can reverse myocardial degeneration responsible for HF syndrome. To stop the HF epidemic will ultimately require protocols to reduce the progressive cardiomyocyte (CM) loss and to foster their regeneration. It is now generally accepted that mammalian CMs renew throughout life. However, this endogenous regenerative reservoir is insufficient to repair the extensive damage produced by AMI/IHD while the source and degree of CM turnover remains strongly disputed. Independent groups have convincingly shown that the adult myocardium harbors bona-fide tissue specific cardiac stem cells (CSCs). Unfortunately, recent reports have challenged the identity and the endogenous myogenic capacity of the c-kit expressing CSCs. This has hampered progress and unless this conflict is settled, clinical tests of repair/regenerative protocols are unlikely to provide convincing answers about their clinical potential. Here we review recent data that have eventually clarified the specific phenotypic identity of true multipotent CSCs. These cells when coaxed by embryonic cardiac morphogens undergo a precisely orchestrated myogenic commitment process robustly generating bona-fide functional cardiomyocytes. These data should set the path for the revival of further investigation untangling the regenerative biology of adult CSCs to harness their potential for HF prevention and treatment

    Alcune osservazioni accanto agli alimenta Italiae

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    After reconstructing the framework of the historical problems evoked by the book of Rossella Laurendi, the author proposes some reflection over the well-known book of evergetism by Paul Veyne concerning economic history,ancient demography and imperial coinag

    Combining cell and gene therapy to advance cardiac regeneration

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    The characterization of multipotent endogenous cardiac stem cells (eCSCs) and the breakthroughs of somatic cell reprogramming to boost cardiomyocyte replacement have fostered the prospect of achieving functional heart repair/regeneration. Areas covered: Allogeneic CSC therapy through its paracrine stimulation of the endogenous resident reparative/regenerative process produces functional meaningful myocardial regeneration in pre-clinical porcine myocardial infarction models and is currently tested in the first-in-man human trial. The in vivo test of somatic reprogramming and cardioregenerative non-coding RNAs revived the interest in gene therapy for myocardial regeneration. The latter, together with the advent of genome editing, has prompted most recent efforts to produce genetically-modified allogeneic CSCs that secrete cardioregenerative factors to optimize effective myocardial repair. Expert opinion: The current war against heart failure epidemics in western countries seeks to find effective treatments to set back the failing hearts prolonging human lifespan. Off-the-shelf allogeneic-genetically-modified CSCs producing regenerative agents are a novel and evolving therapy set to be affordable, safe, effective and available at all times for myocardial regeneration to either prevent or treat heart failure

    The use and abuse of Cre/Lox recombination to identify adult cardiomyocyte renewal rate and origin

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    The adult mammalian heart, including the human, is unable to regenerate segmental losses after myocardial infarction. This evidence has been widely and repeatedly used up-to-today to suggest that the myocardium, contrary to most adult tissues, lacks an endogenous stem cell population or more specifically a bona-fide cardiomyocyte-generating progenitor cell of biological significance. In the last 15 years, however, the field has slowly evolved from the dogma that no new cardiomyocytes were produced from shortly after birth to the present consensus that new cardiomyocytes are formed throughout lifespan. This endogenous regenerative potential increases after various forms of injury. Nevertheless, the degree/significance and more importantly the origin of adult new cardiomyocytes remains strongly disputed. Evidence from independent laboratories has shown that the adult myocardium harbours bona-fide tissue-specific cardiac stem cells (CSCs). Their transplantation and in situ activation have demonstrated the CSCs regenerative potential and have been used to develop regeneration protocols which in pre-clinical tests have shown to be effective in the prevention and treatment of heart failure. Recent reports purportedly tracking the c-kit+CSC's fate using Cre/lox recombination in the mouse have challenged the existence and regenerative potential of the CSCs and have raised scepticism about their role in myocardial homeostasis and regeneration. The validity of these reports, however, is controversial because they failed to show that the experimental approach used is capable to both identify and tract the fate of the CSCs. Despite these serious shortcomings, in contraposition to the CSCs, these publications have proposed the proliferation of existing adult fully-matured cardiomyocytes as the relevant mechanism to explain cardiomyocyte renewal in the adult. This review critically ponders the available evidence showing that the adult mammalian heart possesses a definable myocyte-generating progenitor cell of biological significance. This endogenous regenerative potential is expected to provide the bases for novel approaches of myocardial repair in the near future

    Malevic

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    L'A. espone il percorso dell'artista russo dalla sua formazione simbolista fino alla produzione tarda, insieme ai suoi scritti. Si dà particolare importanza alle relazioni con gli scritti teosofici, la cultura occultista e la meditazione orientale. The Author examines the russian artist from his symbolistic education until the last production, and his writings also. Particularly important are the relationships with theosophical writings, occultist culture and Eastern meditation. Dossier allegato alla rivista "Art e Dossier", maggio 200

    Arte contemporanea: le avanguardie storiche

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    L'A. prende in esame i fauves, il cubismo, l'orfismo, l'espressionismo della "Brücke" e del "Blaue Reiter", il futurismo, il suprematismo, il neoplasticismo e il costruttivismo russo; nonché concezioni architettoniche tra "Art Nouveau" e "Bauhaus". In ogni capitolo si dedica particolare attenzione alle metodologie critiche dall'inizio del secolo ad oggi. The Author examines Fauvism, Cubism, Orfhism, Expressionism of "Die Brücke" and "Der Blaue Reiter", Futurism, Suprematism, Neoplasticism, russian Konstruktivism; and concepts of architecture in the period from "Art Nouveau" to "Bauhaus". In every chapter are particularly focused the critical-methodological approaches from beginning of the XX century up to now

    Severini e Denis

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    L'A. prende in esame i controversi rapporti tra i due artisti, nel primo decennio del secolo e, più tardi, nella produzione di carattere religioso. Severini risulta influenzato da Denis più di quanto sostenga negli scritti teorici. The Author examines the controversial relationships between the two artists, in the first decade of the century and later on, in their religious production. Severini appears influenced by Denis more than he declares in his theoretic writings

    La lingua di Shakespeare e l'ingiuria del tempo: tradurre Troilo e Cressida

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    Il saggio prende in esame la nuova traduzione italiana di Troilo e Cressida (W. Shakespeare) per Feltrinelli, pubblicata dall'autrice stessa, evidenziando le criticità che nascono nella resa contemporanea di un testo 'early modern', adottando una prospettiva di indagine storico-linguistica, e riflettendo su punti di contatto e divergenza tra traduzione per 'la pagina' e per 'la scena'.The essay deals retrospectively with the production of a new translation of Shakespeare's Troilus and Cressida into contemporary Italian (published by the author with Feltrinelli in 2015). Literary translation problems and open questions about the differences between translation 'for the page' and 'for the stage' are explored within a historical-linguistic perspective

    Archiviare il contemporaneo. Lo Spazio di Via Lazzaro Palazzi come paradigma

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    The archive is an inclusive and never static memory device. Thus, it is necessary to take care of it, carefully considering the specificity of collectibles, reviewing and updating continuously the criteria and methods of selection, cataloging and conservation. Only through this assumption of responsibility, which also involves raising awareness of public attention, the archive redefines itself in the present, and in anticipation of the future, as a place of (mnestic, political, social, cultural) possibility. This article presents how the project of the enhancement of the Archive of the artist-run space Lo Spazio di Via Lazzaro Palazzi (Milan, 1989-1992) at the Museo del Novecento di Milano was created collectively -- as a collaboration between the artists, the museum and the scientific coordinators of the project (among which the author) -- with this awareness. The wish is that the constitution, donation and enhancement of this specific Archive will represent a paradigm for the preservation, accessibility and (public) knowledge of contemporary artist archives
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