Risultati per: Atlante globale sull’obesità infantile

Approvazione quasi unanime; il testo ora passa al Senato

Comunicato del 23/05/2023 n°31

Criostimolazione, studio italiano su pazienti

Comunicato del 14/05/2023 n°27

Comunicato del 13/05/2023 n°25

Nei pazienti diabetici peggiora la sopravvivenza. Importanti gli stili di vita

Colao (Endocrinologi),ripensare uso dei farmaci secondo il sesso

Circulation, Ahead of Print. BACKGROUND:During cardiomyocyte maturation, the centrosome, which functions as a microtubule organizing center in cardiomyocytes, undergoes dramatic structural reorganization where its components reorganize from being localized at the centriole to the nuclear envelope. This developmentally programmed process, referred to as centrosome reduction, has been previously associated with cell cycle exit. However, understanding of how this process influences cardiomyocyte cell biology, and whether its disruption results in human cardiac disease, remains unknown. We studied this phenomenon in an infant with a rare case of infantile dilated cardiomyopathy (iDCM) who presented with left ventricular ejection fraction of 18% and disrupted sarcomere and mitochondria structure.METHODS:We performed an analysis beginning with an infant who presented with a rare case of iDCM. We derived induced pluripotent stem cells from the patient to model iDCM in vitro. We performed whole exome sequencing on the patient and his parents for causal gene analysis. CRISPR/Cas9-mediated gene knockout and correction in vitro were used to confirm whole exome sequencing results. Zebrafish andDrosophilamodels were used for in vivo validation of the causal gene. Matrigel mattress technology and single-cell RNA sequencing were used to characterize iDCM cardiomyocytes further.RESULTS:Whole exome sequencing and CRISPR/Cas9 gene knockout/correction identifiedRTTN, the gene encoding the centrosomal protein RTTN (rotatin), as the causal gene underlying the patient’s condition, representing the first time a centrosome defect has been implicated in a nonsyndromic dilated cardiomyopathy. Genetic knockdowns in zebrafish andDrosophilaconfirmed an evolutionarily conserved requirement of RTTN for cardiac structure and function. Single-cell RNA sequencing of iDCM cardiomyocytes showed impaired maturation of iDCM cardiomyocytes, which underlie the observed cardiomyocyte structural and functional deficits. We also observed persistent localization of the centrosome at the centriole, contrasting with expected programmed perinuclear reorganization, which led to subsequent global microtubule network defects. In addition, we identified a small molecule that restored centrosome reorganization and improved the structure and contractility of iDCM cardiomyocytes.CONCLUSIONS:This study is the first to demonstrate a case of human disease caused by a defect in centrosome reduction. We also uncovered a novel role forRTTNin perinatal cardiac development and identified a potential therapeutic strategy for centrosome-related iDCM. Future study aimed at identifying variants in centrosome components may uncover additional contributors to human cardiac disease.

Schillaci, tavolo per introdurre l’ora di prevenzione a scuola

«Tra 2011 e 2021 siamo passati da 155 a 1.824 visite l’anno di Pronto soccorso ad adolescenti che necessitavano il supporto del neuropsichiatra. Un decennio di crescita esponenziale nelle richieste…

Le buone pratiche alimentari e sportive per prevenire danni alla salute, sia fisici che mentali

Impegno di Barilla per migliorare profilo nutrizionale prodotti

Per il 60% causa discriminazioni sul lavoro