Single delivery of an adeno-associated viral construct to transfer the CASQ2 gene to knock-in mice affected by catecholaminergic polymorphic ventricular tachycardia is able to cure the disease from birth to advanced age

Background. Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is therefore a need to explore the curative potential of gene therapy for this disease. We investigated the efficacy and durability of viral gene transfer of the calsequestrin 2 (CASQ2) wild-type gene in a catecholaminergic polymorphic ventricular tachycardia knock-in mouse model carrying the CASQ2R33Q/R33Q (R33Q) mutation. Methods and Results. We engineered an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of CASQ2wild-type (AAV9-CASQ2) plus the green fluorescent protein (GFP) gene to infect newborn R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to investigate the ability of the infection to prevent the disease and adult R33Q mice studied after 2 months to assess whether the AAV9-CASQ2 delivery could revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In both protocols, we observed the restoration of physiological expression and interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological and ultrastructural abnormalities in calcium release units present in R33Q mice; and the lack of life-threatening arrhythmias. Conclusions. Our data demonstrate that viral gene transfer of wild-type CASQ2 into the heart of R33Q mice prevents and reverts severe manifestations of catecholaminergic polymorphic ventricular tachycardia and that this curative effect lasts for 1 year after a single injection of the vector, thus posing the rationale for the design of a clinical trial.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Single delivery of an adeno-associated viral construct to transfer the CASQ2 gene to knock-in mice affected by catecholaminergic polymorphic ventricular tachycardia is able to cure the disease from birth to advanced age

Background. Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is therefore a need to explore the curative potential of gene therapy for this disease. We investigated the efficacy and durability of viral gene transfer of the calsequestrin 2 (CASQ2) wild-type gene in a catecholaminergic polymorphic ventricular tachycardia knock-in mouse model carrying the CASQ2R33Q/R33Q (R33Q) mutation. Methods and Results. We engineered an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of CASQ2wild-type (AAV9-CASQ2) plus the green fluorescent protein (GFP) gene to infect newborn R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to investigate the ability of the infection to prevent the disease and adult R33Q mice studied after 2 months to assess whether the AAV9-CASQ2 delivery could revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In both protocols, we observed the restoration of physiological expression and interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological and ultrastructural abnormalities in calcium release units present in R33Q mice; and the lack of life-threatening arrhythmias. Conclusions. Our data demonstrate that viral gene transfer of wild-type CASQ2 into the heart of R33Q mice prevents and reverts severe manifestations of catecholaminergic polymorphic ventricular tachycardia and that this curative effect lasts for 1 year after a single injection of the vector, thus posing the rationale for the design of a clinical trial.Facultad de Ciencias MédicasCentro de Investigaciones Cardiovasculare

Visual Detection of Speckles in the Fish <i>Xenotoca variata</i> by the Predatory Snake <i>Thamnophis melanogaster</i> in Water of Different Turbidity

<div><p>Semi-aquatic snakes integrate visual and chemical stimuli, and prey detection and capture success are therefore linked to the display of visual predatory behavior. The snake <i>Thamnophis melanogaster</i> responds preferentially to individuals of the fish <i>Xenotoca variata</i> with a greater number of bright, colorful spots (lateral speckles) compared with those with a smaller number; however, water turbidity can reduce underwater visibility and effect the vulnerability of fish. In this study, we tested whether the presence of iridescent speckles on the flanks of male <i>X</i>. <i>variata</i> interacted with water turbidity to modify the predatory behavior displayed by the snake <i>T</i>. <i>melanogaster</i>. We predicted that in an experimental laboratory test, the snakes would increase the frequency of their predatory behavior to the extent that the water turbidity decreases. The snakes were tested at six different levels of water turbidity, in combination with three categories of male fish (with few, a median number of, or many speckles). The results showed that in a pool with high or zero turbidity, the number of speckles is not a determining factor in the deployment of the predatory behavior of the snake <i>T</i>. <i>melanogaster</i> toward <i>X</i>. <i>variata</i>. Our findings suggest that snakes can view the fish at intermediate percentages of turbidity, but the number of speckles in male <i>X</i>. <i>variata</i> is irrelevant as an interspecific visual signal in environments with insufficient luminosity. The successful capture of aquatic prey is influenced by integration between chemical and visual signals, according to environmental factors that may influence the recognition of individual traits.</p></div

Plot showing average position (centroid) of predatory behavior of 18 treatments displayed by snake <i>T</i>. <i>melanogaster</i>, depending of three categories (few, median, many) of number of lateral iridescent specks, on the male fish <i>X</i>. <i>variata</i> and five categories of water turbidity (100, 80, 60, 40, 20 and 0%).

<p>The first two roots of LDFA account the 88.2% variability. The position of centroids on the first root were positively associated to variations to visual fixation (a) and orientations of snakes (b), while on the second root centroid position were positively associated to orientation and slow crawling. Plot show contours of visual fixation and orientation displayed of snakes when snakes were exposed to a gradient of turbidity and number of speckles.</p

Use of Hydrogels to Regulate Orthodontic Tooth Movement in Animal Models: A Systematic Review

The objective of this article is to conduct a systematic review of the literature to contrast the existing evidence regarding the use of hydrogels during and after experimental orthodontic treatment in animals. An extensive search was performed through the electronic databases, Medline, Web of Science and Scopus, from December 2020 to April 2021 for in vivo animal studies. A total of 282 studies were reviewed. Eight studies were included for final revision; four studies were conducted in rats, two in rabbits, one study in mice and one study in guinea pigs. The quality assessment of the eight included studies was performed according to the ARRIVE guidelines and the risk of bias was assessed using the Center for Systematic Review of Laboratory Animal Experimentation tool; in four of the eight articles evaluated, a high risk-of-bias rating was obtained in 40% of the criteria evaluated. In the studies reviewed, the hydrogel acted as a carrier, and inhibition (post-treatment retention) or acceleration of orthodontic tooth movement was assessed according to the active substance used in each of the articles. The uses of hydrogels for transporting active substances to regulate the rate of orthodontic tooth movement remains debatable. Future studies are suggested to evaluate the feasibility of hydrogel as a transport method in humans

Single delivery of an Adeno-Associated viral Construct to Transfer the CASQ2 Gene to Knock-In Mice Affected by Catecholaminergic Polymorphic Ventricular Tachycardia Is Able to Cure the Disease From Birth to Advanced Age

Background — Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmogenic disorder characterized by sudden cardiac death in children. Drug therapy is still insufficient to provide full protection against cardiac arrest, and the use of implantable defibrillators in the pediatric population is limited by side effects. There is therefore a need to explore the curative potential of gene therapy for this disease. We investigated the efficacy and durability of viral gene transfer of the calsequestrin 2 (CASQ2) wild-type gene in a catecholaminergic polymorphic ventricular tachycardia knock-in mouse model carrying the CASQ2R33Q/R33Q (R33Q) mutation. Methods and Results — We engineered an adeno-associated viral vector serotype 9 (AAV9) containing cDNA of CASQ2 wild-type (AAV9-CASQ2) plus the green fluorescent protein (GFP) gene to infect newborn R33Q mice studied by in vivo and in vitro protocols at 6, 9, and 12 months to investigate the ability of the infection to prevent the disease and adult R33Q mice studied after 2 months to assess whether the AAV9-CASQ2 delivery could revert the catecholaminergic polymorphic ventricular tachycardia phenotype. In both protocols, we observed the restoration of physiological expression and interaction of CASQ2, junctin, and triadin; the rescue of electrophysiological and ultrastructural abnormalities in calcium release units present in R33Q mice; and the lack of life-threatening arrhythmias. Conclusions — Our data demonstrate that viral gene transfer of wild-type CASQ2 into the heart of R33Q mice prevents and reverts severe manifestations of catecholaminergic polymorphic ventricular tachycardia and that this curative effect lasts for 1 year after a single injection of the vector, thus posing the rationale for the design of a clinical trial.Fil: Denegri, Marco. Fondazione Salvatore Maugeri; ItaliaFil: Bongianino, Rossana. Fondazione Salvatore Maugeri; ItaliaFil: Lodola, Francesco. Fondazione Salvatore Maugeri; ItaliaFil: Boncompagni, Simona. University G. d’Annunzio; ItaliaFil: de Giusti, Verónica Celeste. Fondazione Salvatore Maugeri; Italia. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Centro Cientifico Tecnológico la Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Médicas; ArgentinaFil: Avelino Cruz, José E.. Fondazione Salvatore Maugeri; Italia. Benemerita Universidad Autonoma de Puebla; MéxicoFil: Liu, Nian. Capital Medical University; ChinaFil: Persampieri, Simone. Fondazione Salvatore Maugeri; ItaliaFil: Curcio, Antonio. Fondazione Salvatore Maugeri; Italia. University of Magna Graecia; ItaliaFil: Esposito, Francesca. Fondazione Salvatore Maugeri; Italia. Università Degli Studi Di Napoli Federico Ii; ItaliaFil: Pietrangelo, Laura. University G. d’Annunzio; ItaliaFil: Marty, Isabelle. Grenoble Institut des Neurosciences; Francia. Universite Joseph Fourier; FranciaFil: Villani, Laura. Fondazione Salvatore Maugeri; ItaliaFil: Moyaho, Alejandro. Benemerita Universidad Autonoma de Puebla; MéxicoFil: Baiardi, Paola. Fondazione Salvatore Maugeri; ItaliaFil: Auricchio, Alberto. Telethon Institute of Genetics and Medicine; Italia. Università Degli Studi Di Napoli Federico Ii; ItaliaFil: Protasi, Feliciano. University G. d’Annunzio; ItaliaFil: Napolitano, Carlo. Fondazione Salvatore Maugeri; ItaliaFil: Priori, Silvia G.. Fondazione Salvatore Maugeri; Italia. University of Pavia; Itali

Ciencia Odontológica

Es para los integrantes de la Red de Investigación en Estomatología (RIE) una enorme alegría presentar el primero de una serie de 5 libros sobre casos clínicos, revisiones de la literatura e investigaciones. La RIE está integrada por cuerpos académicos de la Universidad Autónoma del Estado de Hidalgo, Universidad Autónoma del Estado de México, Universidad Autónoma de Campeche y Universidad de Guadalajara