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.

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 serine͞threonine protein phosphatase. Overexpression of DIG3 in tobacco BY-2 protoplasts inhibited nuclear import of a ␤-glucuronidase-VirD2 nuclear localization signal fusion protein. Thus, DIG3 may be involved in nuclear import of the VirD2 protein and, consequently, the VirD2͞transferred DNA complex.

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.

Background Myasthenia gravis (MG) is an auto-immune disease, and the mainstay of therapy is immunomodulation. Such patients are at high risk of acquiring any infections. Hence, we sought to determine the impact of the current global pandemic COVID-19 infection in MG patients. Methods For our study, we used Cerner Real-World DataTM that was provided through Cerner’s HealtheDataLab research tool. We ran a database query from January 2019 to July 2020 in our study and identified myasthenia patients with and without COVID-19 infection. To extract these patients’ data, we used ICD 9-CM, ICD-10, and SNOMED-CT codes. We reported the data using means, range, and prevalence rates, and the p-values were calculated using the two-sample t-test and Pearson’s chi-squared test. Results In the COVID-19 data set, a total of twenty-seven myasthenia patients were identified with a positive COVID-19 infection, and four were diagnosed with an exacerbation. The male to female ratio was equal and one unknown gender (3.7%) with a mean (± SD) age of 64.33 ± 18.42 years. This study group was compared with a non-COVID-19 data set in which a total of sixty-four myasthenia patients were identified, and twenty-three had an exacerbation. Among the 13 hospitalized patients in the two groups, the mean length of hospitalization for the myasthenia patients in the COVID-19 data set was 8.28 days (n = 7), and the non-COVID-19 set was 4.33 days (n = 6), and it was statistically significant (p-value= 0.007). Conclusions The mean length of hospital stay is prolonged in myasthenia patients who tested positive for COVID-19.

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.

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Background Adoption and outcomes for conduction system pacing (CSP), which includes His bundle pacing (HBP) or left bundle branch area pacing (LBBAP), in real-world settings are incompletely understood. We sought to describe real-world adoption of CSP lead implantation and subsequent outcomes. Methods We performed an online cross-sectional survey on the implantation and outcomes associated with CSP, between November 15, 2020, and February 15, 2021. We described survey responses and reported HBP and LBBAP outcomes for bradycardia pacing and cardiac resynchronization CRT indications, separately. Results The analysis cohort included 140 institutions, located on 5 continents, who contributed data to the worldwide survey on CSP. Of these, 127 institutions (90.7%) reported experience implanting CSP leads. CSP and overall device implantation volumes were reported by 84 institutions. In 2019, the median proportion of device implants with CSP, HBP, and/or LBBAP leads attempted were 4.4% (interquartile range [IQR], 1.9-12.5%; range, 0.4-100%), 3.3% (IQR, 1.3-7.1%; range, 0.2-87.0%), and 2.5% (IQR, 0.5-24.0%; range, 0.1-55.6%), respectively. For bradycardia pacing indications, HBP leads, as compared to LBBAP leads, had higher reported implant threshold (median [

A young woman with terminal respiratory failure due to idiopathic pulmonary hypertension underwent bilateral lung transplantation. The postoperative course was complicated by herniation of the heart through over the cut pericardial edge on left side leading to left-sided graft infarction requiring pneumonectomy. Unable to wean off mechanical ventilation, patient required lobar transplantation on the left side.