Vitamin A deficiency and male-specific effects on heart function in mice.

Hepatic stores of Vitamin A (retinol) are mobilized and metabolized in the heart following myocardial infarction. The physiological consequences of this mobilization are poorly understood. Here we used dietary depletion in a lecithin retinol acyltransferase mutant mouse line to induce Vitamin A deficiency and investigate the effects on cardiac function and recovery from myocardial infarction.

Global screening of base excision repair in nucleosome core particles.

DNA damage is a fundamental molecular cause of genomic instability. Base excision repair (BER) is one line of defense to minimize the potential mutagenicity and/or toxicity derived from damaged nucleobase lesions. However, BER in the context of chromatin, in which eukaryotic genomic DNA is compacted through a hierarchy of DNA-histone protein interactions, is not fully understood.

ALK1 Signaling in Human Cardiac Progenitor Cells Promotes a Pro-angiogenic Secretome.

Pro-angiogenic paracrine/autocrine signaling impacts myocardial repair in cell-based therapies. Activin A receptor-like type 1 (, ALK1) signaling plays a pivotal role in cardiovascular development and maintenance, but its importance in human-derived therapeutic cardiac cells is not well understood. Here, we isolated a subpopulation of human highly proliferative cells (hHiPCs) from adult epicardial tissue and found that they express ALK1, a high affinity receptor for bone morphogenetic protein-9 (BMP9), which signals via SMAD1/5 to regulate paracrine/autocrine signaling and angiogenesis.

Collapsed State Mediates the Low Fidelity of the DNA Polymerase β I260 Mutant.

DNA polymerase β (Pol β) fills single nucleotide gaps during base excision repair. Deficiencies in Pol β can lead to increased mutagenesis and genomic instability in the cell, resulting in cancer. Our laboratory has previously shown that the I260 M somatic mutation of Pol β, which was first identified in prostate cancer, has reduced nucleotide discrimination in a sequence context-dependent manner.

Directed Evolution of Acoustic Reporter Genes Using High-Throughput Acoustic Screening.

A major challenge in the fields of biological imaging and synthetic biology is noninvasively visualizing the functions of natural and engineered cells inside opaque samples such as living animals. One promising technology that addresses this limitation is ultrasound (US), with its penetration depth of several cm and spatial resolution on the order of 100 μm. Within the past decade, reporter genes for US have been introduced and engineered to link cellular functions to US signals heterologous expression in commensal bacteria and mammalian cells.

Laser Tracker and Terrestrial Laser Scanner Range Error Evaluation by Stitching.

Laser trackers (LTs) are dimensional measurement instruments commonly employed in the manufacture and assembly of large structures. Terrestrial laser scanners (TLSs) are a related class of dimensional measurement instruments more commonly employed in surveying, reverse engineering, and forensics. Commercially available LTs typically have measurement ranges of up to 80 m.

Recurrent joint infection caused by a multidrug-resistant capnophilic ST131 O25H4 strain.

We report a case of a native knee septic arthritis and subsequent osteomyelitis due to a CO-dependent (capnophilic) multidrug-resistant ST131 O25:H4 strain. Capnophilic phenotype made microbiology investigation challenging; susceptibility testing could not be performed and the organism did not grow in the urine culture using standard method. The combination of unique virotype and capnophilia may have contributed to the aggressiveness of this organism and the initial unsuccessful carbapenem course, leading to recurrent infection.

Directed Evolution of Acoustic Reporter Genes Using High-Throughput Acoustic Screening.

A major challenge in the fields of biological imaging and synthetic biology is noninvasively visualizing the functions of natural and engineered cells inside opaque samples such as living animals. One promising technology that addresses this limitation is ultrasound (US), with its penetration depth of several cm and spatial resolution on the order of 100 µm. Within the past decade, reporter genes for US have been introduced and engineered to link cellular functions to US signals via heterologous expression in commensal bacteria and mammalian cells.

Delayed CCL23 response is associated with poor outcomes after cardiac arrest.

Chemokines, a family of chemotactic cytokines, mediate leukocyte migration to and entrance into inflamed tissue, contributing to the intensity of local inflammation. We performed an analysis of chemokine and immune cell responses to cardiac arrest (CA). Forty-two patients resuscitated from cardiac arrest were analyzed, and twenty-two patients who underwent coronary artery bypass grafting (CABG) surgery were enrolled.

Earthquake-enhanced dissolved carbon cycles in ultra-deep ocean sediments.

Hadal trenches are unique geological and ecological systems located along subduction zones. Earthquake-triggered turbidites act as efficient transport pathways of organic carbon (OC), yet remineralization and transformation of OC in these systems are not comprehensively understood. Here we measure concentrations and stable- and radiocarbon isotope signatures of dissolved organic and inorganic carbon (DOC, DIC) in the subsurface sediment interstitial water along the Japan Trench axis collected during the IODP Expedition 386.

Decreased circulating CD73 and adenosine deaminase are associated with disease severity in hospitalized patients with COVID-19.

Objective: SARS-CoV-2 infection has been shown to result in increased circulating levels of adenosine triphosphate and adenosine diphosphate and decreased levels of adenosine, which has important anti-inflammatory activity. The goal of this pilot project was to assess the levels of soluble CD73 and soluble Adenosine Deaminase (ADA) in hospitalized patients with COVID-19 and determine if levels of these molecules are associated with disease severity.

Methods: Plasma from 28 PCR-confirmed hospitalized COVID-19 patients who had varied disease severity based on WHO classification (6 mild/moderate, 10 severe, 12 critical) had concentrations of both soluble CD73 and ADA determined by ELISA.

DNA Polymerase β in the Context of Cancer.

DNA polymerase beta (Pol β) is a 39 kD vertebrate polymerase that lacks proofreading ability, yet still maintains a moderate fidelity of DNA synthesis. Pol β is a key enzyme that functions in the base excision repair and non-homologous end joining pathways of DNA repair. Mechanisms of fidelity for Pol β are still being elucidated but are likely to involve dynamic conformational motions of the enzyme upon its binding to DNA and deoxynucleoside triphosphates.

Genomically mined acoustic reporter genes for real-time in vivo monitoring of tumors and tumor-homing bacteria.

Ultrasound allows imaging at a much greater depth than optical methods, but existing genetically encoded acoustic reporters for in vivo cellular imaging have been limited by poor sensitivity, specificity and in vivo expression. Here we describe two acoustic reporter genes (ARGs)-one for use in bacteria and one for use in mammalian cells-identified through a phylogenetic screen of candidate gas vesicle gene clusters from diverse bacteria and archaea that provide stronger ultrasound contrast, produce non-linear signals distinguishable from background tissue and have stable long-term expression. Compared to their first-generation counterparts, these improved bacterial and mammalian ARGs produce 9-fold and 38-fold stronger non-linear contrast, respectively.

Cytosolic and mitochondrial tRNA synthetase inhibitors increase lifespan in a /-dependent manner.

Deletion of genes encoding ribosomal proteins extends lifespan in yeast. This increases translation of the functionally conserved transcription factor Gcn4, and lifespan extension in these mutants is dependent. Gcn4 is also translationally upregulated by uncharged tRNAs, as are its and mammalian functional orthologs.

Community consultation for Exception from Informed consent (EFIC) before and during the COVID-19 pandemic.

Aim: Describe community consultation and surrogate consent rates for two Exception From Informed Consent (EFIC) trials for out-of-hospital cardiac arrest (OOHCA) - before and during the COVID-19 pandemic.

Methods: The PEARL study (2016-2018) randomized OOHCA patients without ST-elevation to early cardiac catheterization or not. Community consultation included flyers, radio announcements, newspaper advertisements, mailings, and in-person surveys at basketball games and ED waiting rooms.

Cardiovascular disease associated with methamphetamine use: a review.

Methamphetamine abuse is a global epidemic associated with a wide-ranging array of adverse effects on the cardiovascular system including dilated cardiomyopathy, malignant and benign arrhythmias, coronary vasospasm, and atherosclerotic coronary artery disease. While the acute behavioral manifestations of amphetamine abuse are the most easily clinically identified, cardiovascular toxicity is common in this patient population and should be considered in this setting due to its high morbidity and mortality. The specific mechanisms for amphetamine cardiotoxicity have not been fully established, but new research implicates activation of several cellular targets including Sigma-1 receptors and trace amine-associated receptor 1 (TAAR1) leading to a myriad of negative downstream effects including increased reactive oxygenating species (ROS), mitochondrial dysfunction, and modulations of intracellular calcium.

Effect of Electronic and Mail Outreach From Primary Care Physicians for COVID-19 Vaccination of Black and Latino Older Adults: A Randomized Clinical Trial.

Importance: COVID-19 morbidity is highest in Black and Latino older adults. These racial and ethnic groups initially had lower vaccination uptake than others, and rates in Black adults continue to lag.

Objectives: To evaluate the effect of outreach via electronic secure messages and mailings from primary care physicians (PCPs) on COVID-19 vaccination uptake among Black and Latino older adults and to compare the effects of culturally tailored and standard PCP messages.

Heart to Heart Discussions: Characterizing Goals of Care Conversations for Advanced Heart Failure Patients Initiating Palliative Inotropes.

Background: Guidelines recommend goals of care conversations (GOCC) and specialty palliative care at the time of initiation of palliative inotropes for patients with advanced heart failure. The extent to which GOCC are occurring, the content of the GOCC, and the frequency of palliative care involvement is unknown.

Methods And Results: We conducted a retrospective chart review of all patients discharged from a tertiary medical center between October 2015 and April 2020 initiated on continuous palliative inotropes.

Neuregulin (NRG-1β) Is Pro-Myogenic and Anti-Cachectic in Respiratory Muscles of Post-Myocardial Infarcted Swine.

Neuregulin-1β (NRG-1β) is a growth and differentiation factor with pleiotropic systemic effects. Because NRG-1β has therapeutic potential for heart failure and has known growth effects in skeletal muscle, we hypothesized that it might affect heart failure-associated cachexia, a severe co-morbidity characterized by a loss of muscle mass. We therefore assessed NRG-1β's effect on intercostal skeletal muscle gene expression in a swine model of heart failure using recombinant glial growth factor 2 (USAN-cimaglermin alfa), a version of NRG-1β that has been tested in humans with systolic heart failure.

Decreased expression of ErbB2 on left ventricular epicardial cells in patients with diabetes mellitus.

We investigated the cell surface expression of ErbB receptors on left ventricular (LV) epicardial endothelial cells and CD105 cells obtained from cardiac biopsies of patients undergoing coronary artery bypass grafting surgery (CABG). Endothelial cells and CD105 non-endothelial cells were freshly isolated from LV epicardial biopsies obtained from 15 subjects with diabetes mellitus (DM) and 8 controls. The expression of ErbB receptors was examined using flow cytometry.