C atecholaminergic polymorphic ventricular tachycardia (CPVT) is a life-threatening familial disorder characterized by adrenergically mediated arrhythmias in a structurally normal heart that may lead to sudden death.1 Two genetic forms of CPVT have been identified: the autosomal-dominant variant caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) gene 2 and the autosomal-recessive variantBackground-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 CASQ2 R33Q/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. caused by mutations in the cardiac calsequestrin 2 (CASQ2) gene. 3 Additionally, 4 other genes have been associated with a clinical spectrum of manifestations consistent with the diagnosis of CPVT or with its phenocopies. [4][5][6] Interestingly, RyR2 and CASQ2 mutations induce diastolic Ca 2+ release from the sarcoplasmic reticulum (SR), leading to the development of delayed afterdepolarizations (DADs) and triggered activity (TA), which may precipitate life-threatening arrhythmias.7-10 This arrhythmogenic mechanism has been confirmed in patients during monophasic action potential recordings that documented the presence of adrenergically mediated DADs and TA in patients with CPVT. 11CPVT, unless promptly diagnosed and treated, may be lethal, as documented by the fact that up to 30% of untreated individuals die suddenly before the ...

The authors studied grooming and yawning caused by mild stress in laboratory Sprague-Dawley rats (Rattus norvegicus). Two groups received 3 and 6 sequences of 5 foot shocks at random intervals (RI) and fixed intervals (FI), respectively. A 3rd group was not shocked (NS). The groups were exposed for 60 min twice. Grooming did not differ among groups, but yawning diminished with RI. Yawning increased and grooming decreased with the 2nd exposure, except in RI in which grooming increased. In NS and FI, grooming prevailed during the first 20 and 30 min, respectively, whereas yawning dominated the remainder of the time. In RI, grooming occurred more than yawning. An upward shift on this scale causes grooming to substitute yawning, whereas a downward shift causes the reverse effect.

Most vertebrates yawn in situations ranging from relaxation to tension, but only humans and other primate species that show mental state attribution skills have been convincingly shown to display yawn contagion. Whether complex forms of empathy are necessary for yawn contagion to occur is still unclear. As empathy is a phylogenetically continuous trait, simple forms of empathy, such as emotional contagion, might be sufficient for non-primate species to show contagious yawning. In this study, we exposed pairs of male rats, which were selected for high yawning, with each other through a perforated wall and found that olfactory cues stimulated yawning, whereas visual cues inhibited it. Unexpectedly, cage-mate rats failed to show yawn contagion, although they did show correlated emotional reactivity. In contrast, stranger rats showed auditory contagious yawning and greater rates of smell-facilitated auditory contagious yawning, although they did not show correlated emotional reactivity. Strikingly, they did not show contagious yawning to rats from a low-yawning strain. These findings indicate that contagious yawning may be a widespread trait amongst vertebrates and that mechanisms other than empathy may be involved. We suggest that a communicatory function of yawning may be the mechanism responsible for yawn contagion in rats, as contagiousness was strain-specific and increased with olfactory cues, which are involved in mutual recognition.

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Male secondary sexual traits may increase the risk of predation because mating signals make them conspicuous to predators and hamper evasive manoeuvres. Males of Xenotoca variata, a viviparous freshwater fish, show on their flanks bright and colourful spots (speckles), the number of which varies geographically. In this study, the association of this variation with the presence of the piscivorous snake Thamnophis melanogaster, which co-occurs with X . variata, was investigated. A test was also done to establish whether the snake distinguishes between male fish with contrasting numbers of speckles and if the perception of speckles is influenced by water turbidity. The amount of speckling and the prevalence of snakes in key localities was assessed by using one-way mirrors, and the effect of speckles on the predatory responsiveness of snakes was evaluated by presenting them with pairs of male fish in clear and in turbid water. In localities where snakes were infrequent there was a tendency for male fish to have many speckles. The snakes preferentially approached the males with more speckles than the males with fewer speckles. The direction of the preference did not change with the conditions of the water, but the magnitude was stronger in clear water than in turbid water. The snakes also approached first the males with more speckles. These findings indicate that predation risk by T. melanogaster may select against speckles and produce population differentiation.