Biallelic variants in PPP1R13L cause paediatric dilated cardiomyopathy.

Childhood dilated cardiomyopathy (DCM) is a leading cause of heart failure requiring cardiac transplantation and approximately 5% of cases result in sudden death. Knowledge of the underlying genetic cause can aid prognostication and clinical management and enables accurate recurrence risk counselling for the family. Here we used genomic sequencing to identify the causative genetic variant(s) in families with children affected by severe DCM.

Polymorphism of gene in three sheep breeds grown in the steppe zone of the Russian Federation.

Objective: This study aims to investigate the callipyge gene () polymorphism in sheep of Edilbay, Volgograd, and Kalmyk breeds.

Materials And Methods: The analysis was performed by the polymerase chain reaction-restriction fragment length polymorphisms method. The objects of the study were Edilbay fat-tailed sheep ( = 500) at the breeding plant Volgograd-Edilbay (Volgograd region), Volgograd fine-wool sheep ( = 500) at the breeding plant Romashkovskiy (Volgograd region), and Kalmyk fat-tailed sheep ( = 500) at the breeding plant Kirovsky (the Republic of Kalmykia, Yashkul rayon).

Prevention of connexin-43 remodeling protects against Duchenne muscular dystrophy cardiomyopathy.

Aberrant expression of the cardiac gap junction protein connexin-43 (Cx43) has been suggested as playing a role in the development of cardiac disease in the mdx mouse model of Duchenne muscular dystrophy (DMD); however, a mechanistic understanding of this association is lacking. Here, we identified a reduction of phosphorylation of Cx43 serines S325/S328/S330 in human and mouse DMD hearts. We hypothesized that hypophosphorylation of Cx43 serine-triplet triggers pathological Cx43 redistribution to the lateral sides of cardiomyocytes (remodeling).

S-nitrosylation of connexin43 hemichannels elicits cardiac stress-induced arrhythmias in Duchenne muscular dystrophy mice.

Patients with Duchenne muscular dystrophy (DMD) commonly present with severe ventricular arrhythmias that contribute to heart failure. Arrhythmias and lethality are also consistently observed in adult Dmdmdx mice, a mouse model of DMD, after acute β-adrenergic stimulation. These pathological features were previously linked to aberrant expression and remodeling of the cardiac gap junction protein connexin43 (Cx43).

Sensitizes TRPM8 to Inhibition by PI(4,5)P Depletion upon Receptor Activation.

The cold- and menthol-sensitive transient receptor potential melastatin 8 (TRPM8) channel is important for both physiological temperature detection and cold allodynia. Activation of G-protein-coupled receptors (GPCRs) by proinflammatory mediators inhibits these channels. It was proposed that this inhibition proceeds via direct binding of to the channel.

Normalization of connexin 43 protein levels prevents cellular and functional signs of dystrophic cardiomyopathy in mice.

Duchenne muscular dystrophy (DMD) associated cardiomyopathy remains incurable. Connexin 43 (Cx43) is upregulated and remodeled in the hearts of mdx mice, a mouse model of DMD. Hearts from Wild Type, mdx, and mdx:Cx43(+/-) mice were studied before (4-6 months) and after (10-15 months) the onset of cardiomyopathy to assess the impact of decreasing Cx43 levels on cardiac pathology in dystrophic mice.

Deficit in PINK1/PARKIN-mediated mitochondrial autophagy at late stages of dystrophic cardiomyopathy.

Aims: Duchenne muscular dystrophy (DMD) is an inherited devastating muscle disease with severe and often lethal cardiac complications. Emerging evidence suggests that the evolution of the pathology in DMD is accompanied by the accumulation of mitochondria with defective structure and function. Here, we investigate whether defects in the housekeeping autophagic pathway contribute to mitochondrial and metabolic dysfunctions in dystrophic cardiomyopathy.

Small Fractions of Muscular Dystrophy Embryonic Stem Cells Yield Severe Cardiac and Skeletal Muscle Defects in Adult Mouse Chimeras.

Duchenne muscular dystrophy (DMD) is characterized by the loss of the protein dystrophin, leading to muscle fragility, progressive weakening, and susceptibility to mechanical stress. Although dystrophin-negative mdx mouse models have classically been used to study DMD, phenotypes appear mild compared to patients. As a result, characterization of muscle pathology, especially in the heart, has proven difficult.

[Maternal effect obscures adaptation to adverse environments and hinders divergence in Drosophila melanogaster].

Adaptation to contrasting environments can facilitate ecological divergence and sympatric speciation. Factors that influence the probability and tempo of these processes are poorly known. We performed an evolutionary experiment on Drosophila melanogaster in order to attain better understanding of adaptation dynamics and to model the initial steps of sympatric speciation.

Pivotal role of miR-448 in the development of ROS-induced cardiomyopathy.

Aims: Nicotinamide adenine dinucleotide oxidases (NOXs) are important contributors to cellular oxidative stress in the cardiovascular system. The NOX2 isoform is upregulated in numerous disorders, including dystrophic cardiomyopathy, where it drives the progression of the disease. However, mechanisms underlying NOX2 overexpression are still unknown.

Mitochondrial dysfunctions during progression of dystrophic cardiomyopathy.

Duchenne muscular dystrophy (DMD) is a progressive muscle disease with severe cardiac complications. It is believed that cellular oxidative stress and augmented Ca(2+) signaling drives the development of cardiac pathology. Some mitochondrial and metabolic dysfunctions have also been reported.

Oxidative stress and ca(2+) release events in mouse cardiomyocytes.

Cellular oxidative stress, associated with a variety of common cardiac diseases, is well recognized to affect the function of several key proteins involved in Ca(2+) signaling and excitation-contraction coupling, which are known to be exquisitely sensitive to reactive oxygen species. These include the Ca(2+) release channels of the sarcoplasmic reticulum (ryanodine receptors or RyR2s) and the Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Oxidation of RyR2s was found to increase the open probability of the channel, whereas CaMKII can be activated independent of Ca(2+) through oxidation.

The significance of increased levels of end nitric oxide metabolites in blood serum of children with celiac disease.

Objectives: The aim of the study was to determine serum nitric oxide (NO) metabolites and correlate them to gluten-free diet (GFD) compliance, the parameters of morphological and functional condition of the small intestine in patients with celiac disease (CD) in a long-term follow-up.

Patients And Methods: The study included 35 children (age median 8.0 years) with previously diagnosed CD, among them 15 - on a strict GFD and 20 - on a semistrict GFD.

Duodenal mucosa in children with coeliac disease in catamnesis and varying compliance with the gluten-free diet.

Objectives: the aim of the study was to identify the characteristic morphometric data changes in the small intestine mucosa in response to varied compliance with gluten-free diet in children with coeliac disease.

Methods: 71 children (47 girls and 24 boys) aged 2.5 to 16.

[Features of mucosal lesions of stomach and duodenum in children with chronic gastroduodenitis with different microflora content].

Objective: Our aim was to reveale the features of histological mucosa with different composition of the microflora of stomach and duodenum in children with chronic gastroduodenitis.

Methods: The study included 122 children with chronic gastroduodenitis from 5 to 17 years old. All patients underwent endoscopy with histology of biopsy specimens of gastric and duodenal mucosa in 94 patients and in 48 patients among them with morphometry of biological material.

Ganglionated plexus ablation vs linear ablation in patients undergoing pulmonary vein isolation for persistent/long-standing persistent atrial fibrillation: a randomized comparison.

Background: The optimal ablation technique for persistent and long-standing persistent atrial fibrillation (AF) is unclear. Both linear lesion (LL) and ganglionated plexus (GP) ablation have been used in addition to pulmonary vein isolation (PVI), but no direct comparison of the 2 methods exists.

Objective: The aim of this study is to assess the comparative safety and efficacy of 2 different ablation strategies-PVI+LL vs PVI+GP ablation -in patients with persistent or long-standing persistent AF.

[Changes of epidermal growth factor level in blood serum, saliva and gastric juice in children with duodenal ulcer].

Aim: The aim of our study is to investigate EGF content in biological mediums in children with duodenum ulcer depending on phase of the disease and different variants of its course.

Materials And Methods: The present study was performed in Federal State Establishment "Nizhniy Novgorod Research Institute of Children Gastroenterology", Nizhniy Novgorod, Russia. 92 children, between the ages of 8 to 17, with duodenum ulcer were under observation.

Hierarchical accumulation of RyR post-translational modifications drives disease progression in dystrophic cardiomyopathy.

Aims: Duchenne muscular dystrophy (DMD) is a muscle disease with serious cardiac complications. Changes in Ca(2+) homeostasis and oxidative stress were recently associated with cardiac deterioration, but the cellular pathophysiological mechanisms remain elusive. We investigated whether the activity of ryanodine receptor (RyR) Ca(2+) release channels is affected, whether changes in function are cause or consequence and which post-translational modifications drive disease progression.

Cardiac phenotype of Duchenne Muscular Dystrophy: insights from cellular studies.

Dilated cardiomyopathy is a serious and almost inevitable complication of Duchenne Muscular Dystrophy, a devastating and fatal disease of skeletal muscle resulting from the lack of functional dystrophin, a protein linking the cytoskeleton to the extracellular matrix. Ultimately, it leads to congestive heart failure and arrhythmias resulting from both cardiac muscle fibrosis and impaired function of the remaining cardiomyocytes. Here we summarize findings obtained in several laboratories, focusing on cellular mechanisms that result in degradation of cardiac functions in dystrophy.

Type 1 inositol (1,4,5)-trisphosphate receptor activates ryanodine receptor 1 to mediate calcium spark signaling in adult mammalian skeletal muscle.

Functional coupling between inositol (1,4,5)-trisphosphate receptor (IP(3)R) and ryanodine receptor (RyR) represents a critical component of intracellular Ca(2+) signaling in many excitable cells; however, the role of this mechanism in skeletal muscle remains elusive. In skeletal muscle, RyR-mediated Ca(2+) sparks are suppressed in resting conditions, whereas application of transient osmotic stress can trigger activation of Ca(2+) sparks that are restricted to the periphery of the fiber. Here we show that onset of these spatially confined Ca(2+) sparks involves interaction between activation of IP(3)R and RyR near the sarcolemmal membrane.

Posttranslational modifications of cardiac ryanodine receptors: Ca(2+) signaling and EC-coupling.

In cardiac muscle, a number of posttranslational protein modifications can alter the function of the Ca(2+) release channel of the sarcoplasmic reticulum (SR), also known as the ryanodine receptor (RyR). During every heartbeat RyRs are activated by the Ca(2+)-induced Ca(2+) release mechanism and contribute a large fraction of the Ca(2+) required for contraction. Some of the posttranslational modifications of the RyR are known to affect its gating and Ca(2+) sensitivity.

A randomized comparison of pulmonary vein isolation with versus without concomitant renal artery denervation in patients with refractory symptomatic atrial fibrillation and resistant hypertension.

Objectives: The aim of this prospective randomized study was to assess the impact of renal artery denervation in patients with a history of refractory atrial fibrillation (AF) and drug-resistant hypertension who were referred for pulmonary vein isolation (PVI).

Background: Hypertension is the most common cardiovascular condition responsible for the development and maintenance of AF. Treating drug-resistant hypertension with renal denervation has been reported to control blood pressure, but any effect on AF is unknown.