Isolated Cardiac Ryanodine Receptor Function Varies Between Mammals.

Concerted robust opening of cardiac ryanodine receptors' (RyR2) Ca release 1oplasmic reticulum (SR) is fundamental for normal systolic cardiac function. During diastole, infrequent spontaneous RyR2 openings mediate the SR Ca leak that normally constrains SR Ca load. Abnormal large diastolic RyR2-mediated Ca leak events can cause delayed after depolarizations (DADs) and arrhythmias.

Long-Term Alcohol-Activated c-Jun N-terminal Kinase Isoform 2 Preserves Cardiac Function but Drives Ca-Triggered Arrhythmias.

Long-term alcohol consumption leads to cardiac arrhythmias including atrial fibrillation (AF), the most common alcohol-related arrhythmia. While AF significantly increases morbidity and mortality in patients, it takes years for an alcoholic individual undergoing an adaptive status with normal cardiac function to reach alcoholic cardiomyopathy. The underlying mechanism remains unclear to date.

Photochemistry Driven by Excited-State Aromaticity Gain or Antiaromaticity Relief.

Gain of aromaticity or relief of antiaromaticity along a reaction path are important factors to consider in mechanism studies. Analysis of such changes along potential energy surfaces has historically focused on reactions in the electronic ground state (S ), but can also be used for excited states. In the lowest ππ* states, the electron counts for aromaticity and antiaromaticity follow Baird's rule where 4n π-electrons indicate aromaticity and 4n+2 π-electrons antiaromaticity.

Holiday Heart Syndrome, Atrial Fibrillation, and RyR2 Antagonist.

The Holiday Heart Syndrome (HHS) refers to binge alcohol-associated cardiac arrhythmia of which atrial fibrillation (AF) being the most occurred arrhythmia type. Excessive alcohol consumption is a serious public health and economic issue in the US and globally. Despite a tremendous education effort, binge drinking among the population of young and older adults continues to rise.

[Effects of mixing proportions on carbon storage and allocation in mixed plantation of and ].

In this study, four types of mixed and plantations were selected according to the rows-mixing proportions (type Ⅰ: 5:3, type Ⅱ: 6:4, type Ⅲ: 5:5, type Ⅳ: 1:1). The see-mingly unrelated biomass models of and were developed for obtaining biomass values, and the difference and composition of carbon storage in each forest layer and ecosystem were analyzed. The results showed that carbon storage of arbor layer in different stand types was 39.

Carboxin can induce cardiotoxicity in zebrafish embryos.

Carboxin is a heterocyclic systemic fungicide, mainly used to prevent and control grain smut and wheat rust. Although its mammalian toxicity has been reported, its toxicity to acute exposure to aquatic animals is unknown. In our study, we used zebrafish as aquatic organisms to study Carboxin toxicity.

Ero1α-Dependent ERp44 Dissociation From RyR2 Contributes to Cardiac Arrhythmia.

Background: Oxidative stress in cardiac disease promotes proarrhythmic disturbances in Ca homeostasis, impairing luminal Ca regulation of the sarcoplasmic reticulum (SR) Ca release channel, the RyR2 (ryanodine receptor), and increasing channel activity. However, exact mechanisms underlying redox-mediated increase of RyR2 function in cardiac disease remain elusive. We tested whether the oxidoreductase family of proteins that dynamically regulate the oxidative environment within the SR are involved in this process.

Benoxacor caused developmental and cardiac toxicity in zebrafish larvae.

Benoxacor (BN) is a highly effective antidote of dichloroacetamide herbicides generally used to protect crops from herbicidal damage. As a commonly used agrochemical, this herbicide antidote is continuously discharged in watercourses thus causing toxicity to aquatic organisms, and ultimately leading to contamination of the food chain. To date, its potential toxicity to the cardiac development of aquatic organisms has not been evaluated.

Serine-threonine protein phosphatase regulation of Cx43 dephosphorylation in arrhythmogenic disorders.

Regulation of cell-to-cell communication in the heart by the gap junction protein Connexin43 (Cx43) involves modulation of Cx43 phosphorylation state by protein kinases, and dephosphorylation by protein phosphatases. Dephosphorylation of Cx43 has been associated with impaired intercellular coupling and enhanced arrhythmogenesis in various pathologic states. While there has been extensive study of the protein kinases acting on Cx43, there has been limited studies of the protein phosphatases that may underlie Cx43 dephosphorylation.

Molecular remodeling of Cx43, but not structural remodeling, promotes arrhythmias in an arrhythmogenic canine model of nonischemic heart failure.

Background: Both gap junctional remodeling and interstitial fibrosis have been linked to impaired electrical conduction velocity (CV) and fatal ventricular arrhythmias in nonischemic heart failure (HF). However, the arrhythmogenic role of the ventricular gap junctional Cx43 in nonischemic HF remains in debate. Here, we assessed this in a newly developed arrhythmogenic canine model of nonischemic HF.

Alterations of housekeeping proteins in human aged and diseased hearts.

Pathological remodeling includes alterations of ion channel function and calcium homeostasis and ultimately cardiac maladaptive function during the process of disease development. Biochemical assays are important approaches for assessing protein abundance and post-translational modification of ion channels. Several housekeeping proteins are commonly used as internal controls to minimize loading variabilities in immunoblotting protein assays.

Upregulation of transient receptor potential melastatin 4 (TRPM4) in ventricular fibroblasts from heart failure patients.

The transient receptor potential melastatin 4 (TRPM4) is a Ca-activated nonselective monovalent cation channel belonging to the TRP channel superfamily. TRPM4 is widely expressed in various tissues and most abundantly expressed in the heart. TRPM4 plays a critical role in cardiac conduction.

JNK2, a Newly-Identified SERCA2 Enhancer, Augments an Arrhythmic [Ca] Leak-Load Relationship.

Rationale: We recently discovered pivotal contributions of stress kinase JNK2 (c-Jun N-terminal kinase isoform 2) in increased risk of atrial fibrillation through enhanced diastolic sarcoplasmic reticulum (SR) calcium (Ca) leak via RyR2 (ryanodine receptor isoform 2). However, the role of JNK2 in the function of the SERCA2 (SR Ca-ATPase), essential in maintaining SR Ca content cycling during each heartbeat, is completely unknown.

Objective: To test the hypothesis that JNK2 increases SERCA2 activity SR Ca content and exacerbates an arrhythmic SR Ca content leak-load relationship.

Causal roles of stress kinase JNK2 in DNA methylation and binge alcohol withdrawal-evoked behavioral deficits.

Excessive binge alcohol intake is a common drinking pattern in humans, especially during holidays. Cessation of the binge drinking often leads to aberrant withdrawal behaviors, as well as serious heart rhythm abnormalities (clinically diagnosed as Holiday Heart Syndrome (HHS)). In our HHS mouse model with well-characterized binge alcohol withdrawal (BAW)-induced heart phenotypes, BAW leads to anxiety-like behaviors and cognitive impairment.

Ion Channel and Structural Remodeling in Obesity-Mediated Atrial Fibrillation.

Background: Epidemiological studies have established obesity as an independent risk factor for atrial fibrillation (AF), but the underlying pathophysiological mechanisms remain unclear. Reduced cardiac sodium channel expression is a known causal mechanism in AF. We hypothesized that obesity decreases Nav1.

ZO-1 Regulates Intercalated Disc Composition and Atrioventricular Node Conduction.

Rationale: ZO-1 (Zona occludens 1), encoded by the tight junction protein 1 () gene, is a regulator of paracellular permeability in epithelia and endothelia. ZO-1 interacts with the actin cytoskeleton, gap, and adherens junction proteins and localizes to intercalated discs in cardiomyocytes. However, the contribution of ZO-1 to cardiac physiology remains poorly defined.

Metal-Free Synthesis of Benzothiophenes by Twofold C-H Functionalization: Direct Access to Materials-Oriented Heteroaromatics.

Due to their ubiquity in nature and frequent use in organic electronic materials, benzothiophenes are highly sought after. Here we set out an unprecedented procedure for the formation of benzothiophenes by the twofold vicinal C-H functionalization of arenes that does not require metal catalysis. This one-pot annulation proceeds through an interrupted Pummerer reaction/[3,3]-sigmatropic rearrangement/cyclization sequence to deliver various benzothiophene products.

Role of Stress Kinase JNK in Binge Alcohol-Evoked Atrial Arrhythmia.

Background: Excessive binge alcohol drinking has acute cardiac arrhythmogenic effects, including promotion of atrial fibrillation (AF), which underlies "Holiday Heart Syndrome." The mechanism that couples binge alcohol abuse with AF susceptibility remains unclear. We previously reported stress-activated c-Jun N-terminal kinase (JNK) signaling contributes to AF development.

Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKIIδ expression in the aged atrium.

Aims: c-jun N-terminal kinase (JNK) is a critical stress response kinase that activates in a wide range of physiological and pathological cellular processes. We recently discovered a pivotal role of JNK in the development of atrial arrhythmias in the aged heart, while cardiac CaMKIIδ, another pro-arrhythmic molecule, was also known to enhance atrial arrhythmogenicity. Here, we aimed to reveal a regulatory role of the stress kinase JNK2 isoform on CaMKIIδ expression.

Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis.

Rationale: Atrial fibrillation (AF) is the most common arrhythmia, and advanced age is an inevitable and predominant AF risk factor. However, the mechanisms that couple aging and AF propensity remain unclear, making targeted therapeutic interventions unattainable.

Objective: To explore the functional role of an important stress response JNK (c-Jun N-terminal kinase) in sarcoplasmic reticulum Ca handling and consequently Ca-mediated atrial arrhythmias.