16 research outputs found
Mitochondrial iron and energetic dysfunction distinguish fibroblasts and induced neurons from pantothenate kinase-associated neurodegeneration patients
No full textAbstractPantothenate kinase-associated neurodegeneration is an early onset autosomal recessive movement disorder caused by mutation of the pantothenate kinase-2 gene, which encodes a mitochondrial enzyme involved in coenzyme A synthesis. The disorder is characterised by high iron levels in the brain, although the pathological mechanism leading to this accumulation is unknown. To address this question, we tested primary skin fibroblasts from three patients and three healthy subjects, as well as neurons induced by direct fibroblast reprogramming, for oxidative status, mitochondrial functionality and iron parameters. The patients' fibroblasts showed altered oxidative status, reduced antioxidant defence, and impaired cytosolic and mitochondrial aconitase activities compared to control cells. Mitochondrial iron homeostasis and functionality analysis of patient fibroblasts indicated increased labile iron pool content and reactive oxygen species development, altered mitochondrial shape, decreased membrane potential and reduced ATP levels. Furthermore, analysis of induced neurons, performed at a single cell level, confirmed some of the results obtained in fibroblasts, indicating an altered oxidative status and signs of mitochondrial dysfunction, possibly due to iron mishandling. Thus, for the first time, altered biological processes have been identified in vitro in live diseased neurons. Moreover, the obtained induced neurons can be considered a suitable human neuronal model for the identification of candidate therapeutic compounds for this disease
A longitudinal study on BIO14.6 hamsters with dilated cardiomyopathy: micro-echocardiographic evaluation
No full textAbstract Background In recent years, several new technologies for small-animal imaging have been developed. In particular, the use of ultrasound in animal imaging has focused on the investigation of accessible biological structures such as the heart, of which it provides a morphological and functional assessment. The purpose of this study was to investigate the role of micro-ultrasonography (μ-US) in a longitudinal study on BIO14.6 cardiomyopathic hamsters treated with gene therapy. Methods Thirty hamsters were divided into three groups (n = 10): Group I, untreated BIO 14.6 hamsters; Group II, BIO 14.6 hamsters treated with gene therapy; Group III, untreated wild type (WT) hamsters. All hamsters underwent serial μ-US sessions and were sacrificed at predetermined time points. Results μ-US revealed: in Group I, progressive dilation of the left ventricle with a change in heart morphology from an elliptical to a more spherical shape, altered configuration of the mitral valve and subvalvular apparatus, and severe reduction in ejection fraction; in Group II, mild decrease in contractile function and ejection fraction; in Group III, normal cardiac chamber morphology and function. There was a negative correlation between the percentage of fibrosis observed at histology and the ejection fraction obtained on μ-echocardiography (Spearman r: -0.839; p Conclusions Although histological examination remains indispensable for a conclusive diagnosis, high-frequency μ-echocardiography, thanks to the high spatial and contrast resolution, can be considered sufficient for monitoring therapeutic efficacy and/or the progression of dilated cardiomyopathy, providing an alternative tool for repeatable and noninvasive evaluation.</p
Not informed by author
No full textVerifica o método da Análise Institucional do Discurso (AID) como uma forma de tratamento para crianças com o diagnóstico de transtorno do espectro autista (TEA). Trata-se de uma pesquisa que apresenta a partir da análise do atendimento dessas crianças pela AID, como é conferido a elas um lugar de enunciação na cena discursiva do tratamento clínico, ainda que, em alguns casos, não falem. São apresentadas análises de 6 atendimentos, em situação de acompanhamento escolar ou atendimento clínico em consultório, com foco no resgate dos diferentes caminhos trilhados pelas crianças como efeito de suas terapias, tendo em vista a ideia básica do brincar como discurso e de seu caráter terapêutico. Também, como essa abordagem contribuiu com a redução dos sintomas associados ao TEA, mensurados pela escala diagnóstica Autistic Diagnostic Observation Schedule (ADOS-2). Tais atendimentos receberam supervisão sob orientação da AID, e foram registrados na ocasião em que ocorreram. Foi observado o protagonismo da criança na cena analítica, em sua história como ponto de partida para sua terapia, bem como os efeitos na terapêuticaIt verifies the Institutional Discourse Analysis (IDA) method as a form of treatment for children diagnosed with autism spectrum disorder (ASD). This research presents, based on the analysis of the assistance provided to these children by AID, how they are given a place of enunciation in the discursive scene of clinical treatment, even though, in some cases, they do not speak. Analyzes of 6 appointments are presented, in a situation of school monitoring or clinical assistance in the office, with a focus on recovering the different paths taken by children as an effect of their therapies, bearing in mind the basic idea of playing as discourse and its therapeutic character. Also, how this approach contributed to the reduction of symptoms associated with ASD, measured by the Autistic Diagnostic Observation Schedule (ADOS-2) diagnostic scale. Such assistance received supervision under the guidance of the AID, and were recorded at the time they occurred. The child\'s protagonism in the analytic scene was observed, in its history as a starting point for its therapy, as well as the effects in the therap
Worsening of cardiomyopathy using deflazacort in an animal model rescued by gene therapy.
No full textWe have previously demonstrated that gene therapy can rescue the phenotype and extend lifespan in the delta-sarcoglycan deficient cardiomyopathic hamster. In patients with similar genetic defects, steroids have been largely used to slow down disease progression. Aim of our study was to evaluate the combined effects of steroid treatment and gene therapy on cardiac function. We injected the human delta-sarcoglycan cDNA by adeno-associated virus (AAV) 2/8 by a single intraperitoneal injection into BIO14.6 Syrian hamsters at ten days of age to rescue the phenotype. We then treated the hamsters with deflazacort. Treatment was administered to half of the hamsters that had received the AAV and the other hamsters without AAV, as well as to normal hamsters. Both horizontal and vertical activities were greatly enhanced by deflazacort in all groups. As in previous experiments, the AAV treatment alone was able to preserve the ejection fraction (70±7% EF). However, the EF value declined (52±14%) with a combination of AAV and deflazacort. This was similar with all the other groups of affected animals. We confirm that gene therapy improves cardiac function in the BIO14.6 hamsters. Our results suggest that deflazacort is ineffective and may also have a negative impact on the cardiomyopathy rescue, possibly by boosting motor activity. This is unexpected and may have significance in terms of the lifestyle recommendations for patients
Iluminação e atuação : outros diálogos possíveis
No full textDissertação (Mestrado)—Universidade de Brasília, Instituto de Artes, Departamento de Artes, Programa de Pós- Graduação em Artes Cênicas, Brasília, 2020.A presente pesquisa busca explorar possíveis diálogos entre iluminação e atuação cênica em
uma busca de tornar os processos de criação mais colaborativos e menos hierárquicos. Tendo
a experiência como principal atitude metodológica e apostando em uma epistemologia ecológica,
a pesquisa traça um percurso que se inicia nas experiências vividas pela autora em seus grupos
de teatro (Grupo Tripé e Grupo Liquidificador), e segue para a construção de um modo ecológico
de se relacionar com o mundo, dirigindo-se para uma nova perspectiva de conexão com as luzes
que acompanham o cotidiano da existência humana e estabelecendo um paralelo com os
atuantes e a luz cênica. A partir dessa perspectiva e do conceito de corpo proposto por Espinoza,
propõe-se a compreensão da luz cênica como um corpo – o corpo-luz –, numa tentativa
alternativa de se discutir a iluminação na cena contemporânea. A pesquisa segue, então, para o
relato de uma experiência vivida pela autora através da prática docente em uma disciplina no
curso de graduação em Artes Cênicas da Universidade de Brasília, no primeiro semestre de
2019. Nessa disciplina, buscou-se propor uma prática que pretende complexificar os afetos e as
afetações possíveis entre o corpo-luz e o corpo da atuante, para uma melhor compreensão de
como se pode experienciar uma colaboração mais afetiva e efetiva entre as artistas criadoras de
ambos os campos.The present research seeks to explore possible dialogues between stage lighting and acting, in
a quest to make creative processes more collaborative and less hierarchical. With experience as
the main methodological attitude, and betting on an ecological epistemology, the research traces
a path that begins with the experiences lived by the author in her theatre groups ( Grupo Tripé
and Grupo Liquidificador), and goes on to build an ecological way to relate to the world, seeking
a new perspective of connections between the lights that accompany the daily life of human
existence, creating a parallel with acting and stage lighting. From this perspective, and the
concept of body proposed by Espinoza, is made the proposal of understanding stage lighting as
a body, the body-light, in an alternative attempt to understand the stage lighting in the
contemporary scene. The research then goes on to report an experience lived by the author
through a class in the undergraduate course in Performing Arts at the University of Brasília, in
this class we sought to propose a practice that intends to complex the affects between the body-
light and the acting body, in search of a better understanding of how we can propose a more
affective and effective collaboration between creative artists from both fields.Instituto de Artes (IdA)Programa de Pós-Graduação em Artes Cênica
Combined deficiency of alpha and epsilon sarcoglycan disrupts the cardiac dystrophin complex
No full textUn mercader véneto en la Carrera de Indias: el relato de Alessandro Fontana (1618)
No full textThis article aims, first of all, to publish the manuscript account of a trip made by Alessandro Fontana from Vicenza, between Seville and Mexico in 1618-1619, now at the Biblioteca Marciana of Venice. The research in different archives in Spain and Mexico has allowed us to gather information about the author, placing him within the foreign merchants’ networks that worked in the Carrera de Indias. The archival documents, together with the account, allow us to better know the methods used by foreign merchants to participate in the mentioned Carrera de Indias, as well as the kind of business they carried out. At the same time, this article analyses the circulation of information about the Americas in EuropeEl presente artículo busca, en primer lugar, dar a conocer el relato del viaje de ida y vuelta realizado por el vicentino Alessandro Fontana, entre Sevilla y México en los años 1618-1619. Dicho relato se conserva, manuscrito, en la Biblioteca Marciana de Venecia. Pero además, el trabajo en distintos archivos de España y México nos ha permitido conocer mejor a su autor, situándolo en las redes de mercaderes extranjeros que comerciaban en la Carrera de Indias. La documentación manejada, combinada con el relato, nos permite acercarnos a los métodos usados por los extranjeros para participar en la Carrera de Indias y el tipo de tratos que llevaban a cabo. Así mismo, este artículo analiza la circulación de información sobre América en Europa
Corrigendum: The new Italian registry of infantile thrombosis (RITI): a reflection on its journey, challenges and pitfalls
No full textIn the published article, there was an error in the appendix. An author name was incorrectly written as Foidaelli Thomas. The correct spelling is Foiadelli Thomas. The correct appendix appears below. – Accorsi Patrizia – Aceto Gabriella – Agnoletti Gabriella – Agostini Manuela – Alfarano Angela – Altieri Elena – Amador Carolina – Antonelli Camilla – Arena Vittoria – Asta Francesca – Baggio Laura – Ballardini Elisa – Baracetti Margherita – Baraldi Eugenio – Barberis Laura – Barisone Elena – Basso Anne Letizia – Battajon Nadia – Bersani Iliana – Biddeci Giada – Biffanti Roberta – Bonardi Claudia Maria – Bonaudo Roberto – Boniver Clementina – Boscarol Gianluca – Bottino Roberto – Bravar Giulia – Brizzi Ilaria – Brolatti Noemi – Braguglia Annabella – Guaragni Brunetta – Bugin Samuela – Calvo Pier Luigi – Capasso Antonella – Capodiferro Donatella – Cappelleri Alessia – Cascarano Maria Teresa – Casellato Susanna – Casini Tommaso – Catarzi Serena – Cavaliere Elena – Cavicchiolo Maria Elena – Celestino Silvia – Celle Maria Elena – Centonze Nicola – Cerutti Alessia – Chakrokh Roksana – Offer Chiara – Chiodin Elisabetta – Chirico Gaetano – Chukhlantseva Natalia – Cifarelli Paola – Cinelli Giulia – Coinu Marisa – Colonna Clara – Comito Donatella – Corato Alessandra – Cordelli Duccio Maria – Crichiutti Giovanni – Cursio Ida – Dagri Arianna – De Maria Beatrice – Del Borrello Giovanni – Di Rienzo Francesca – Doglioni Nicoletta – Dolcemascolo Valentina – Dotta Andrea – Drigo Paola – Drimaco Pietro – Ellero Serena – Falcone Alessandra – Fantauzzi Ambra – Farinasso Daniela – Ferilli Michela – Festa Silvia – Fischer Maximilian – Foiadelli Thomas – Fotzi Ilaria – Francavilla Rosa – Freschi Paola – Gaffuri Marcella – Gallo Elena – Gamalero Lisa – Gandioli Claudia – Garuccio Sergio – Gentile Diletta – Ghionzoli Marco – Giliberti Paola – Greco Filippo – Guariento Chiara – Guidotti Isotta – Iodice Alessandro – Janes Augusta – Laghi Elena – Lampugnani Elisabetta – Lassandro Giuseppe – Laverda Anna Maria – Lazzerotti Alessandra – Lo Tartaro Meragliotta Patrizia – Lombardini Martina – Lorenzon Eleonora – Mainini Nicoletta – Massoud Michela – Materia Valeria – Mattera Raffaele – Mauro Isabella – Melani Federico – Meli Mariaclaudia – Messina Giovanni – Monticone Sonia – Moras Marzia – Negro Ilaria – Olzai Giorgio – Pancani Simone – Pandolfi Maria – Passariello Annalisa – Passarini Alice – Passone Eva – Pastorino Myriam – Pegoraro Veronica – Pennoni Serena – Perilongo Giorgio – Pozzessere Anna – Pruna Dario – Pusiol Anna – Putti Maria Caterina – Rabbone Ivana – Radicioni Maurizio – Renna Salvatore – Ricci Maria Luisa – Rimini Alessandro – Rivellini Sara – Rustioni Gianluca – Salvadori Sabrina – Santoiemma Valentina – Santoro Nicola – Schiavulli Michele – Sebellin Sofia – Sesta Michela – Soffiati Massimo – Sorbo Monica – Spanedda Giuseppina – Stangalini Valeria – Stasolla Salvatore – Tanzi Giorgia – Testa Tiziana – Teutonico Federica – Timpani Giuseppina – Toldo Irene – Trapani Sandra – Vaccari Roberto – Vecchi Marilena – Vento Giovanni – Veraldi Daniele – Villa Giovanna – Visintin Gianluca – Zambelloni Cesare – Zellini Francesco – ASST Spedali Civili of Brescia, Brescia – Azienda Ospedaliera Bianchi-Melacrino-Morelli di Reggio Calabria, Reggio Calabria – Azienda Ospedaliera Policlinico Di Bari, Bari – Bambin Gesù Children’s Hospital, Roma – Central Teaching Hospital of Bolzano, Bolzano – Giannina Gaslini Hospital, Genova – Niguarda Hospital, Milano – Ospedale Civile SS. Annunziata, Sassari – San Bortolo Hospital, Vicenza – San Matteo Hospital, Pavia – Santa Chiara Hospital, Trento – ULSS 2 Marca Trevigiana, Treviso – ULSS 8 Berica, Vicenza – University Hospital “Azienda Ospedaliero-Universitaria Meyer”, Firenze – University Hospital Città della Salute e della Scienza, Torino – University Hospital of Modena, Modena – University Hospital of Padova, Padova – University Hospital of Udine, Udine – University Hospital of Verona, Verona – University of Bari, Bari – University of Bologna, Bologna – University of Cagliari, Cagliari – University of Catania, Catania – University of Ferrara, Ferrara – University of Napoli “Federico II”, Napoli – University of Perugia, Perugia The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated
Human L-ferritin deficiency is characterized by idiopathic generalized seizures and atypical restless leg syndrome
No full textThe ubiquitously expressed iron storage protein ferritin plays a central role in maintaining cellular iron homeostasis. Cytosolic ferritins are composed of heavy (H) and light (L) subunits that co-assemble into a hollow spherical shell with an internal cavity where iron is stored. The ferroxidase activity of the ferritin H chain is critical to store iron in its Fe3+ oxidation state, while the L chain shows iron nucleation properties. We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains. Increased iron incorporation into the FtH homopolymer leads to reduced cellular iron availability, diminished levels of cytosolic catalase, SOD1 protein levels, enhanced ROS production and higher levels of oxidized proteins. Importantly, key phenotypic features observed in fibroblasts are also mirrored in reprogrammed neurons from the patient's fibroblasts. Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS
