A5007280724- Cardiac Arrest and Resuscitation
- DNA Repair Mechanisms
- Cardiovascular Effects of Exercise
- ECG Monitoring and Analysis
- Cardiac electrophysiology and arrhythmias
- Carcinogens and Genotoxicity Assessment
- Cancer-related Molecular Pathways
- Cardiac pacing and defibrillation studies
- Trauma and Emergency Care Studies
- Cardiomyopathy and Myosin Studies
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- Drug Transport and Resistance Mechanisms
- RNA Research and Splicing
- Heart Failure Treatment and Management
- Cholesterol and Lipid Metabolism
- CRISPR and Genetic Engineering
- Cardiovascular Function and Risk Factors
- Cardiovascular Health and Risk Factors
- COVID-19 and healthcare impacts
- Emergency and Acute Care Studies
- Blood Pressure and Hypertension Studies
- Effects of Radiation Exposure
- Cardiovascular and Diving-Related Complications
- Cardiovascular Issues in Pregnancy
Cedars-Sinai Smidt Heart Institute
2020-2024
Cedars-Sinai Medical Center
2021-2024
Sinai Health System
2020-2023
Oregon Health & Science University
2022
University of California, Los Angeles
1998-2020
Howard Hughes Medical Institute
1998
University of Utah
1998
Conventional ECG-based algorithms could contribute to sudden cardiac death (SCD) risk stratification but demonstrate moderate predictive capabilities. Deep learning (DL) models use the entire digital signal and potentially improve power. We aimed train validate a 12 lead DL algorithm for SCD assessment.
The murine Abcg1 gene is reported to consist of 15 exons that encode a single mRNA (herein referred as Abcg1-a) and protein. We now demonstrate (i) the contains two additional coding downstream exon 1, (ii) transcription involves use multiple promoters, (iii) RNA undergoes alternative splicing reactions. As result, three mRNAs are expressed putative protein isoforms differ at their amino terminus. ABCG1 transcripts induced in vivo tissues response liver X receptor ligand T0901317....
Abstract MicroRNA (miRNA) expression is tightly regulated by several mechanisms, including transcription and cleavage of the miRNA precursor RNAs, to generate a mature miRNA, which thought be directly correlated with activity. MiR-34 tumour-suppressor important in cell survival, that transcriptionally upregulated p53 response DNA damage. Here, we show for first time there pool miR-34 cells lacks 5′-phosphate inactive. Following exposure DNA-damaging stimulus, inactive rapidly activated...
Electrocardiogram (ECG) abnormalities have been evaluated as static risk markers for sudden cardiac death (SCD), but the potential importance of dynamic ECG remodelling has not investigated. In this study, nature and prevalence were studied among individuals who eventually suffered SCD.
The functional consequences of missense variants are often difficult to predict. This becomes especially relevant when DNA sequence changes used determine a diagnosis or prognosis. To analyze the 12 in patients with mild forms ataxia-telangiectasia (A-T), we employed site-directed mutagenesis mutated (ATM) cDNA followed by stable transfections into single A-T cell line isolate effects each allele on cellular phenotype. After induction transfected cells CdCl2, monitored for successful ATM...
Introduction: At least 50% of individuals who suffer sudden cardiac arrest (SCA) experience warning symptoms before their SCA. We have previously reported chest pain and dyspnea as the most common potentially predictive symptoms. Combining with clinical features could improve sensitivity specificity for prediction imminent SCA (ISCA). Hypothesis: A combination profiles can predict ISCA. Methods: From two community-based studies in Oregon California, we conducted a case-control study. Cases...
ATM plays a critical role in cellular responses to DNA double-strand breaks (DSBs). We describe new ATM–mediated DSB–induced damage response pathway involving microRNA (miRNA): irradiation (IR)-induced DSBs activate ATM, which leads the downregulation of miR-335, miRNA that targets CtIP, is an important trigger end resection homologous recombination repair (HRR). demonstrate CREB responsible for large portion miR-335 expression by binding promoter region miR-335. greatly reduced after IR,...
<h3>Importance</h3> Sudden cardiac arrest (SCA) is a major public health problem. Owing to lack of population-based studies in multiracial/multiethnic communities, little information available regarding race/ethnicity-specific epidemiologic factors SCA. <h3>Objective</h3> To evaluate the association race/ethnicity with burden, outcomes, and clinical profile individuals experiencing <h3>Design, Setting, Participants</h3> A 5-year prospective, cohort study out-of-hospital SCA was conducted...
A recent challenge for investigators studying the progressive neurological disease ataxia-telangiectasia (A-T) is to identify mutations whose effects might be alleviated by mutation-targeted therapies. We studied ATM in eight families of Japanese A-T patients (JPAT) and were able all 16 mutations. The probands compound heterozygotes seven families, one (JPAT2) was homozygous a frameshift mutation. All mutations—four frameshift, two nonsense, four large genomic deletions, six affecting...
The ability to use a vital cell marker study mouse embryogenesis will open new avenues of experimental research. Recently, the transgenic mice, containing multiple copies jellyfish gene encoding green fluorescent protein (GFP), has begun realize this potential. Here, we show that signals produced by single-copy, targeted GFP in-frame fusions with two different murine Hox genes, Hoxa1 and Hoxc13, are readily detectable using confocal microscopy. Since is expressed early Hoxc13 late in...
Background Out-of-hospital sudden cardiac arrest (SCA) is a leading cause of mortality, making prevention SCA public health priority. No studies have evaluated predictors risk among Hispanic or Latino individuals in the United States. Methods and Results In this case-control study, adult cases ages 18-85 (n=1,468) were ascertained ongoing Ventura
Sudden cardiac arrest is a global public health problem with mortality rate of more than 90%. Prearrest warning symptoms could be harnessed using digital technology to potentially improve survival outcomes. We aimed estimate the strength association between and imminent sudden arrest.We conducted case-control study individuals participants without who had similar identified from two US community-based studies patients in California state, USA (discovery population; Ventura Prediction Death...
Ataxia Telangiectasia (A-T) and with Ocular Apraxia Type 1 (AOA1) are devastating neurological disorders caused by null mutations in the genome stability genes, A-T mutated ( ATM ) Aprataxin APTX ), respectively. Our mechanistic understanding therapeutic repertoire for treating these severely lacking, large part due to failure of prior animal models similar recapitulate characteristic loss motor coordination (i.e., ataxia) associated cerebellar defects. By increasing genotoxic stress through...
The study of rare human syndromes characterized by radiosensitivity has been instrumental in identifying novel proteins and pathways involved DNA damage responses to ionizing radiation. In the present study, a mutation mitochondrial poly-A-polymerase (MTPAP), not previously recognized for its role response, was identified exome sequencing subsequently associated with cellular radiosensitivity. Cell lines derived from two patients homozygous MTPAP missense were radiosensitive, this could be...
Abstract We studied 10 Mennonite patients who carry the c.6200C>A missense mutation (p.A2067D) in ATM gene, all of whom exhibited a phenotypic variant ataxia‐telangiectasia (A‐T) that is characterized by early‐onset dystonia and late‐onset mild ataxia, as previously described. This report provides pathogenetic evidence for this on cellular functions. Several have developed cancer subsequently experienced life‐threatening adverse reactions to radiation (radiotoxicity) and/or chemotherapy....
In an effort to explore the possible causes of human radiosensitivity and identify more rapid assays for cellular radiosensitivity, we interrogated a set that evaluate functions involved in recognition repair DNA double-strand breaks: (1) neutral comet assay, (2) radiation-induced γ-H2AX focus formation, (3) temporal kinetics structural maintenance chromosomes 1 phosphorylation, (4) intra-S-phase checkpoint integrity, (5) mitochondrial respiration. We characterized unique panel 19...