Differential Wnt-mediated programming and arrhythmogenesis in right versus left ventricles.

Several inherited arrhythmias, including Brugada syndrome and arrhythmogenic cardiomyopathy, primarily affect the right ventricle and can lead to sudden cardiac death. Among many differences, right and left ventricular cardiomyocytes derive from distinct progenitors, prompting us to investigate how embryonic programming may contribute to chamber-specific conduction and arrhythmia susceptibility. Here, we show that developmental perturbation of Wnt signaling leads to chamber-specific transcriptional regulation of genes important in cardiac conduction that persists into adulthood. Transcriptional profiling of right versus left ventricles in mice deficient in Wnt transcriptional activity reveals global chamber differences, including genes regulating cardiac electrophysiology such as Gja1 and Scn5a. In addition, the transcriptional repressor Hey2, a gene associated with Brugada syndrome, is a direct target of Wnt signaling in the right ventricle only. These transcriptional changes lead to perturbed right ventricular cardiac conduction and cellular excitability. Ex vivo and in vivo stimulation of the right ventricle is sufficient to induce ventricular tachycardia in Wnt transcriptionally inactive hearts, while left ventricular stimulation has no effect. These data show that embryonic perturbation of Wnt signaling in cardiomyocytes leads to right ventricular arrhythmia susceptibility in the adult heart through chamber-specific regulation of genes regulating cellular electrophysiology.

COVID-19 pandemic and inflammatory bowel disease from patients' perspective: A survey from COVID epicenter in India.

BACKGROUND AND AIM: The COVID pandemic and countrywide lockdown has had significant impact on patients with inflammatory bowel disease (IBD), with delay in diagnosis, difficulty in access to healthcare and unavailability of drugs. We conducted a telephonic survey to assess this impact. METHODS: Out of 350, 302 participated in the survey. Demographic data, disease severity at the time of survey, extent of disease, details of therapy, and adherence were noted. A validated questionnaire addressing information source, perception of COVID-19 situation, contact with healthcare, and adherence to standard precautions was administered telephonically. RESULTS: Out of 350 contacted patients, 302 (86.28%) patients participated in the survey. Median age of cohort was 39 years. Ulcerative colitis (UC) constituted 79%, 16% Crohn's disease (CD), and 5% IBD-unclassified. At the time of survey, 86.98% patients with UC were in clinical remission and 75.75% of CD patients were generally well. A total of 115 (38%) cases were nonadherent to therapy due to unavailability of medicines (66.38%), financial constraints (25.21%) and inability to reach healthcare facility (3.6%). Disease flare was seen in 14.2% and correlated well with nonadherence. Existing drug therapy was switched to alternative drug in 70 (23.17%) cases due to unavailability (74%). Social media (52.3%) and television (40.4%) were the common sources of information about the pandemic. Telemedicine platforms (WhatsApp and telephone) were used by 180 (59.6%) patients for consultation with good acceptance (81.6%). 87 (28.8%) patients failed to contact healthcare. Apprehension regarding severe COVID infection was noted in 80% while 29% thought that IBD therapy could increase infection risk. Adherence to wearing mask, hand washing, and social distancing was 100%. CONCLUSION: Pandemic resulted in disruption of healthcare visits and medication supply. Majority were concerned about increased risk of COVID-19 infection and adhered to standard precautions. Mobile phone-based formats for patient care may be an alternative due to patient acceptance and convenience.

Malignant Ventricular Tachycardia, Ventricular Wall Ablation, and Orthotopic Heart Transplantation.

Described herein are three patients with refractory ventricular tachycardia and one or more unsuccessful ablation procedures finally leading to orthotropic heart transplantation (OHT). The latter procedure allowed examination of the ventricular ablation sites, an unusual opportunity reported previously in few patients (all case reports). The acute ablation lesions are unique, with necrosis of the myocardial fibers adjacent to the endocardium and encircled by layers of extravasated erythrocytes in the deeper myocardial wall. All 3 patients returned to normal activities following the OHT.

The ketogenic diet and the QT interval.

Long QT syndrome is a disorder of ventricular myocardial repolarization associated with an increased risk of life-threatening cardiac arrhythmias and sudden cardiac death. This report highlights a case of QT prolongation with torsades de pointes in a patient with baseline congenital long QT syndrome, believed to be precipitated by metabolic changes associated with the "ketogenic diet."

Expression of plant protein phosphatase 2C interferes with nuclear import of the Agrobacterium T-complex protein VirD2.

Agrobacterium tumefaciens transfers DNA to plant cells as a single-stranded DNA molecule (the T-strand) covalently linked to VirD2 protein. VirD2 contains nuclear localization signal sequences that presumably help direct the T-strand to the plant nucleus. We identified a tomato cDNA clone, DIG3, that encodes a protein that interacts with the C-terminal region of VirD2. DIG3 encodes an enzymatically active type 2C serine/threonine protein phosphatase. Overexpression of DIG3 in tobacco BY-2 protoplasts inhibited nuclear import of a beta-glucuronidase-VirD2 nuclear localization signal fusion protein. Thus, DIG3 may be involved in nuclear import of the VirD2 protein and, consequently, the VirD2/transferred DNA complex.

Identification of Arabidopsis rat mutants.

Limited knowledge currently exists regarding the roles of plant genes and proteins in the Agrobacterium tumefaciens-mediated transformation process. To understand the host contribution to transformation, we carried out root-based transformation assays to identify Arabidopsis mutants that are resistant to Agrobacterium transformation (rat mutants). To date, we have identified 126 rat mutants by screening libraries of T-DNA insertion mutants and by using various "reverse genetic" approaches. These mutants disrupt expression of genes of numerous categories, including chromatin structural and remodeling genes, and genes encoding proteins implicated in nuclear targeting, cell wall structure and metabolism, cytoskeleton structure and function, and signal transduction. Here, we present an update on the identification and characterization of these rat mutants.