11,043 research outputs found
Exploring the Potential of Symmetric Exon Deletion to Treat Non-Ischemic Dilated Cardiomyopathy by Removing Frameshift Mutations in TTN
No full textNon-ischemic dilated cardiomyopathy (DCM) is one of the most frequent pathologies requiring cardiac transplants. Even though the etiology of this disease is complex, frameshift mutations in the giant sarcomeric protein Titin could explain up to 25% of the familial and 18% of the sporadic cases of DCM. Many studies have shown the potential of genome editing using CRISPR/Cas9 to correct truncating mutations in sarcomeric proteins and have established the grounds for myoediting. However, these therapies are still in an immature state, with only few studies showing an efficient treatment of cardiac diseases. This publication hypothesizes that the Titin (TTN)-specific gene structure allows the application of myoediting approaches in a broad range of locations to reframe TTNtvvariants and to treat DCM patients. Additionally, to pave the way for the generation of efficient myoediting approaches for DCM, we screened and selected promising target locations in TTN. We conceptually explored the deletion of symmetric exons as a therapeutic approach to restore TTN’s reading frame in cases of frameshift mutations. We identified a set of 94 potential candidate exons of TTN that we consider particularly suitable for this therapeutic deletion. With this study, we aim to contribute to the development of new therapies to efficiently treat titinopathies and other diseases caused by mutations in genes encoding proteins with modular structures, e.g., Obscurin
SIRT1 Expression and Regulation in the Primate Testis
No full textThe epigenetic mechanisms controlling germ cell development and differentiation are still not well understood. Sirtuin-1 (SIRT1) is a nicotinamide adenosine dinucleotide (NAD)-dependent histone deacetylase and belongs to the sirtuin family of deacetylases. It catalyzes the removal of acetyl groups from a number of protein substrates. Some studies reported a role of SIRT1 in the central and peripheral regulation of reproduction in various non-primate species. However, testicular SIRT1 expression and its possible role in the testis have not been analyzed in primates. Here, we document expression of SIRT1 in testes of different primates and some non-primate species. SIRT1 is expressed mainly in the cells of seminiferous tubules, particularly in germ cells. The majority of SIRT1-positive germ cells were in the meiotic and postmeiotic phase of differentiation. However, SIRT1 expression was also observed in selected premeiotic germ cells, i.e., spermatogonia. SIRT1 co-localized in spermatogonia with irisin, an endocrine factor specifically expressed in primate spermatogonia. In marmoset testicular explant cultures, SIRT1 transcript levels are upregulated by the addition of irisin as compared to untreated controls explants. Rhesus macaques are seasonal breeders with high testicular activity in winter and low testicular activity in summer. Of note, SIRT1 mRNA and SIRT1 protein expression are changed between nonbreeding (low spermatogenesis) and breeding (high spermatogenesis) season. Our data suggest that SIRT1 is a relevant factor for the regulation of spermatogenesis in primates. Further mechanistic studies are required to better understand the role of SIRT1 during spermatogenesis
Martha Enna Rodriguez, piano (Colombia) e Ignacio Pacheco, piano (Cuba)
No full textConcierto celebrado por los pianistas Martha Enna Rodriguez e Ignacio Pacheco en el que se interpretaron obras de Wolfagang Amadeus Mozart, Wiltold Lutoslawski, Mario Gómez-Vignes, Carlos Guastavino, Sergio Vasconcellos, Darius Milhaud
Controlling the Switch from Neurogenesis to Pluripotency during Marmoset Monkey Somatic Cell Reprogramming with Self-Replicating mRNAs and Small Molecules
No full textInduced pluripotent stem cells (iPSCs) hold enormous potential for the development of cell-based therapies; however, the safety and efficacy of potential iPSC-based treatments need to be verified in relevant animal disease models before their application in the clinic. Here, we report the derivation of iPSCs from common marmoset monkeys (Callithrix jacchus) using self-replicating mRNA vectors based on the Venezuelan equine encephalitis virus (VEE-mRNAs). By transfection of marmoset fibroblasts with VEE-mRNAs carrying the human OCT4, KLF4, SOX2, and c-MYC and culture in the presence of small molecule inhibitors CHIR99021 and SB431542, we first established intermediate primary colonies with neural progenitor-like properties. In the second reprogramming step, we converted these colonies into transgene-free pluripotent stem cells by further culturing them with customized marmoset iPSC medium in feeder-free conditions. Our experiments revealed a novel paradigm for flexible reprogramming of somatic cells, where primary colonies obtained by a single VEE-mRNA transfection can be directed either toward the neural lineage or further reprogrammed to pluripotency. These results (1) will further enhance the role of the common marmoset as animal disease model for preclinical testing of iPSC-based therapies and (2) establish an in vitro system to experimentally address developmental signal transduction pathways in primates
Buitres en vivo
No full textRegistro en vivo de la banda Buitres, Teatro de Verano.Dirección y producción: Ignacio Varela, Andrés Rodriguez, Daniela Calcagno, Santiago Turell; sonido: Raúl Locatelli; asistentes: Martín González, Mauro Méndez; cámara y fotografía: Nicolás Lucotti, Fabian Tiscornia, Sebastian Rodriguez, Cecilia Nuñez, Nicolas de Maio, Laura Rocha, Ignacio Sojo. Entrevistados: Buitres, Gustavo Parodi, Gabriel Peluffo, José Rambao,Orlando Fernández, "Cuico" Perazzo. Grabación realizada en el Teatro de Verano
Hijo
No full textDesarmar la casa donde vivió su padre será una ardua tarea.Idea y texto original: Juan Ignacio Fernández; guion: Juan Ignacio Fernández, Matias Paparamborda, Martìn Rivero; dirección: Juan Ignacio Fernández, Matias Paparamborda; fotografía y cámara: Agustin Ferrando; arte: Martín Rivero; producción: Fernanda Rodriguez; sonido: Mauricio Van Der Maesen; continuidad: Marta Ubal; electricos: Guillermo Madeiro, Ignacio Mancebo; elenco: Jorge Temponi, Celeste Villagran
Buitres en vivo: Cambalache
No full textRegistro en vivo de la banda Buitres, Teatro de Verano.Dirección y producción: Ignacio Varela, Andrés Rodriguez, Daniela Calcagno, Santiago Turell; sonido: Raúl Locatelli; asistentes: Martín González, Mauro Méndez; cámara y fotografía: Nicolás Lucotti, Fabian Tiscornia, Sebastian Rodriguez, Cecilia Nuñez, Nicolas de Maio, Laura Rocha, Ignacio Sojo; entrevistados: Gustavo Parodi, Gabriel Peluffo, José Rambao, Orlando Fernández, "Cuico" Perazzo.Dirección: Nicolás de Maio, Ignacio Varela; asistente de dirección: Paulina Portela, Daniela Calcagno; dirección de fotografía: Nicolás Luccotti, Magela Crosignani; cámara: Sebastián Rodríguez, Silvana Bergson; eléctricos: Gonzalo Ribas, Federico Musé, Santiago Turell, Joaquín Spinak, Pablo Schulkin; dirección de arte: Cecilia Nuñez, Soledad Fernandez; asistente: Beatriz Idiarte, Andrés Rodriguez; utileros: Isaac Itman, Florencia Muñoz; sonido: Raúl Locatelli, Ignacio Sojo, Javier Di Lavello, Valentina Álvarez; edición: Ignacio Varela; impresos: Santiago Turell, Joaquin Spinak; producción: Cecilia Benech, Carlos Romay; asistentes Nicolas Etcheverry, Federico Paz
Ignacio F. Gonzalez Polo, Polotitlán en el estado de México
No full textMeyer Jean A. Ignacio F. Gonzalez Polo, Polotitlán en el estado de México. In: Annales. Economies, sociétés, civilisations. 29ᵉ année, N. 1, 1974. p. 260
Ignacio Rodriguez, funcionario público, sentado tras el escritorio de su oficina, retrato.
No full textLic. Ignacio Rodriguez , I.O. v.f. 2711
Ignacio Rodriguez , Enrique Romero Courtade y funcionarios en una oficina de Palacio Nacional; retrato de grupo.
No full textROMERO COURTADE LIC, RODRIGUEZ IGNACIO, I.O. v.f. 2711
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