Journal ArticleAm J Transplant · November 13, 2025
Implantation of cultured allogeneic thymus tissue (CTTI) into athymic human recipients generates functional recipient-derived naïve T cells that are tolerant to the donor. Currently, CTTI is always performed with 12 to 21 days of thymus procurement to avoi ...
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Journal ArticleNat Cardiovasc Res · November 2025
Heart disease, a leading cause of mortality worldwide, is in urgent need of improved therapies. Fibrosis, an accumulation of collagen-rich extracellular matrix in response to injury, is a hallmark of heart disease, but clinical agents that can interfere wi ...
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Journal ArticleNat Commun · July 25, 2025
It is well established tumour cells secrete signalling factors affecting distant normal tissues. What remains unresolved is whether these factors initiate a signalling cascade rendering terminally differentiated cardiomyocytes susceptible to apoptosis, a f ...
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Journal ArticleJ Vis Exp · June 6, 2025
The number of advanced heart failure patients who can receive a heart transplant is limited by a shortage of suitable organ donors. In efforts to expand the donor pool, alternative donation and procurement methods have been developed, including heart trans ...
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Journal ArticleJ Heart Lung Transplant · April 2025
Heart transplantation remains a critical therapy for patients with end-stage heart failure, offering incremental survival and improved quality of life. One of the key components behind the success of heart transplantation is the condition and preservation ...
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ConferenceFrontiers in Cardiovascular Medicine · January 1, 2025
Ex vivo machine perfusion has been growing in utility for preserving donor organs prior to transplantation. This modality has tremendous potential for bioengineering and conditioning organs prior to transplantation using small molecule or advanced therapeu ...
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Journal ArticleHypertension · January 2025
BACKGROUND: Ang-II (angiotensin II) impairs the function of the antihypertensive enzyme ACE2 (angiotensin-converting enzyme 2) by promoting its internalization, ubiquitination, and degradation, thus contributing to hypertension. However, few ACE2 ubiquitin ...
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Journal ArticleTranspl Int · 2025
Normothermic ex-vivo organ perfusion (EVP) systems not only provide a physiological environment that preserves donor organ function outside the body but may also serve as platforms for ex-vivo organ modification via gene therapy. In this study, we demonstr ...
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Journal ArticlePLoS One · 2025
Acute rejection, one of the most devastating complications that can occur following organ transplantation, is caused by antigenic differences between the organ donor and the recipient. Following cardiac transplantation, an estimated 12% of patients will ex ...
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Journal ArticleCirc Res · July 5, 2024
BACKGROUND: The tumor suppressor and proapoptotic transcription factor P53 is induced (and activated) in several forms of heart failure, including cardiotoxicity and dilated cardiomyopathy; however, the precise mechanism that coordinates its induction with ...
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Journal ArticleImmunohorizons · July 1, 2024
The critical importance of the thymus for generating new naive T cells that protect against novel infections and are tolerant to self-antigens has led to a recent revival of interest in monitoring thymic function in species other than humans and mice. Nonh ...
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Journal ArticlemedRxiv · May 25, 2024
BACKGROUND: Angiotensin (Ang)-II impairs the function of the antihypertensive enzyme ACE2 by promoting its internalization, ubiquitination and degradation thus contributing to hypertension. However, few ACE2 ubiquitination partners have been identified and ...
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ConferenceJ Heart Lung Transplant · May 2024
BACKGROUND: Cardiac metabolism is altered in heart failure and ischemia-reperfusion injury states. We hypothesized that metabolomic profiling during ex situ normothermic perfusion before heart transplantation (HT) would lend insight into myocardial substra ...
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Journal ArticleJACC Basic Transl Sci · May 2024
The adult mammalian heart harbors minute levels of cycling cardiomyocytes (CMs). Large numbers of images are needed to accurately quantify cycling events using microscopy-based methods. CardioCount is a new deep learning-based pipeline to rigorously score ...
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Journal ArticleHum Gene Ther · April 2024
Ex vivo machine perfusion (EVMP) is rapidly growing in utility during solid organ transplantation. This form of organ preservation is transforming how organs are allocated and expanding the definition of what is considered a suitable organ for transplantat ...
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Journal ArticleCells · March 4, 2024
Cardiomyocytes rely on proper mitochondrial homeostasis to maintain contractility and achieve optimal cardiac performance. Mitochondrial homeostasis is controlled by mitochondrial fission, fusion, and mitochondrial autophagy (mitophagy). Mitophagy plays a ...
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Journal ArticleFront Physiol · 2024
Introduction: It may take decades to develop cardiovascular dysfunction following exposure to high doses of ionizing radiation from medical therapy or from nuclear accidents. Since astronauts may be exposed continually to a complex space radiation environm ...
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Journal ArticlePLoS One · 2024
Preclinical disease models are important for the advancement of therapeutics towards human clinical trials. One of the difficult tasks of developing a well-characterized model is having a reliable modality with which to trend the progression of disease. Ac ...
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Chapter · January 1, 2024
The use of ex vivo machine perfusion for organ preservation has significantly improved solid organ transplantation outcomes. This modality of organ preservation has increased the donor pool and extended criteria for donor organs that would have previously ...
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Journal ArticleNat Commun · December 11, 2023
The serine/threonine kinase, PINK1, and the E3 ubiquitin ligase, Parkin, are known to facilitate LC3-dependent autophagosomal encasement and lysosomal clearance of dysfunctional mitochondria, and defects in this process contribute to a variety of cardiomet ...
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Journal ArticleCardiovasc Res · September 5, 2023
AIMS: Angiotensin-converting enzyme 2 (ACE2) is a critical component of the compensatory renin-angiotensin system that is down-regulated during the development of hypertension, possibly via ubiquitination. However, little is known about the mechanisms invo ...
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Journal ArticleDevelopment · August 15, 2023
Developmentally programmed polyploidy (whole-genome duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, in both Drosophila larvae and human organ donors, we reveal distinct polyploidy level ...
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Journal ArticleJ Cardiovasc Transl Res · June 2023
The porcine intra-abdominal heterotopic heart transplantation model allows for the assessment of immunologic effects on cardiac transplantation without relying on the allograft to maintain hemodynamic support for the animal. Historically, allograft functio ...
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Journal ArticleHum Gene Ther · April 2023
Transplantation, the gold standard intervention for organ failure, is a clinical field that is ripe for applications of gene therapy. One of the major challenges in applying gene therapy to this field is the need for a method that achieves consistent and r ...
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Journal ArticlebioRxiv · February 11, 2023
Developmentally programmed polyploidy (whole-genome-duplication) of cardiomyocytes is common across evolution. Functions of such polyploidy are essentially unknown. Here, we reveal roles for precise polyploidy levels in cardiac tissue. We highlight a conse ...
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Journal ArticleCell Stem Cell · January 5, 2023
The efficacy and safety of gene-therapy strategies for indications like tissue damage hinge on precision; yet, current methods afford little spatial or temporal control of payload delivery. Here, we find that tissue-regeneration enhancer elements (TREEs) i ...
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Journal ArticleFront Cardiovasc Med · 2023
BACKGROUND: Reliable biomarkers for assessing the viability of the donor hearts undergoing ex vivo perfusion remain elusive. A unique feature of normothermic ex vivo perfusion on the TransMedics® Organ Care System (OCS™) is that the donor heart is maintain ...
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Journal ArticleFront Cardiovasc Med · 2023
Ex situ organ preservation by machine perfusion can improve preservation of organs for transplantation. Furthermore, machine perfusion opens up the possibilities for selective immunomodulation, creation of tolerance to ischemia-reperfusion injury and/or co ...
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Journal ArticleSci Transl Med · November 2, 2022
Pyruvate kinase M2 (PKM2) is a glycolytic enzyme that translocates to the nucleus to regulate transcription factors in different tissues or pathologic states. Although studied extensively in cancer, its biological role in the heart remains unresolved. PKM1 ...
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Journal ArticleLife Sci Space Res (Amst) · November 2022
Future lunar missions and beyond will require new and innovative approaches to radiation countermeasures. The Translational Research Institute for Space Health (TRISH) is focused on identifying and supporting unique approaches to reduce risks to human heal ...
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Journal ArticleRedox Biol · November 2022
Diastolic dysfunction (DD) underlies heart failure with preserved ejection fraction (HFpEF), a clinical syndrome associated with aging that is becoming more prevalent. Despite extensive clinical studies, no effective treatment exists for HFpEF. Recent find ...
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Journal ArticleBiology (Basel) · October 15, 2022
ATTR amyloidosis comprises a spectrum of multiple clinical presentations, including, predominantly, neuropathy and cardiomyopathy. The common triggering pathogenic protein is misfolded transthyretin, a carrier protein that destabilizes misfolds and assembl ...
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Journal ArticleCirc Res · September 30, 2022
BACKGROUND: Cardiac involvement is an important determinant of mortality among sarcoidosis patients. Although granulomatous inflammation is a hallmark finding in cardiac sarcoidosis, the precise immune cell populations that comprise the granuloma remain un ...
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Journal ArticleiScience · April 15, 2022
The complex and inaccessible space radiation environment poses an unresolved risk to astronaut cardiovascular health during long-term space exploration missions. To model this risk, healthy male c57BL/6 mice aged six months (corresponding to an astronaut o ...
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Journal ArticleJ Vis Exp · February 14, 2022
Cardiac transplantation is the gold standard treatment for end-stage heart failure. However, it remains limited by the number of available donor hearts and complications such as primary graft dysfunction and graft rejection. The recent clinical use of an e ...
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Journal ArticleFront Cardiovasc Med · 2022
BACKGROUND: The optimal delivery route to enhance effectiveness of regenerative therapeutics to the human heart is poorly understood. Direct intra-myocardial (IM) injection is the gold standard, however, it is relatively invasive. We thus compared targeted ...
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Journal ArticleMethods Mol Biol · 2022
Recent advances in ex vivo perfusion have enabled an extended preservation time for solid organs prior to transplantation allowing for possible resuscitation of the donor organ during the preservation period. Opportunities to provide viral vector-mediated ...
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Journal ArticleJ Heart Lung Transplant · December 2021
PURPOSE: Clinical models to identify patients at high risk of primary graft dysfunction (PGD) after heart transplantation (HT) are limited, and the underlying pathophysiology of this common post-transplant complication remains poorly understood. We sought ...
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Journal ArticleCell Death Discov · October 23, 2021
Heart failure (HF) has reached epidemic proportions in developed countries, affecting over 20 million people worldwide. Despite modern medical and device therapies, 60-70% of HF patients still die within 5 years of diagnosis as it relentlessly progresses t ...
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Journal ArticleComput Struct Biotechnol J · 2021
Several factors in Western society, including widespread use of antibiotics, chronic inflammation, and loss of complex eukaryotic symbionts such as helminths, have a dramatic impact on the ecosystem of the gut, affecting the microbiota hosted there. In add ...
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Journal ArticleCardiovasc Pathol · 2021
Programmed death-ligand 1 (PD-L1), a transmembrane protein and member of the CD28 T cell family is associated with lymphocyte activation.1 PD-L1 expression is upregulated on activated antigen presenting cells such as monocytes, myeloid and dendritic cells. ...
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Journal ArticleJ Environ Sci Health C Toxicol Carcinog · 2021
Staying longer in outer space will inevitably increase the health risks of astronauts due to the exposures to galactic cosmic rays and solar particle events. Exposure may pose a significant hazard to space flight crews not only during the mission but also ...
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Journal ArticleBiotechniques · July 2020
The generation of an experimental animal model often requires considerable investment of both time and money. Typically, investigators are interested in specific organs and when experimental animals are euthanized, tissues that are not the focus of the res ...
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ConferenceThe Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · April 1, 2020
PURPOSE: Cardiac gene therapy remains limited by inefficient transgene delivery with currently available methods (intravenous infusion, transcatheter coronary artery infusion, direct myocardial injection). We previously demonstrated in a porcine heterotopi ...
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Journal ArticleAntioxid Redox Signal · July 1, 2019
Aims: Oxidative stress is implicated in cardiomyocyte cell death and cardiac remodeling in the failing heart. The role of NADPH oxidase 4 (NOX4) in cardiac adaptation to pressure overload is controversial, but its function in myocardial ischemic stress has ...
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Journal ArticleSci Rep · May 29, 2019
Clinically, both percutaneous and surgical approaches to deliver viral vectors to the heart either have resulted in therapeutically inadequate levels of transgene expression or have raised safety concerns associated with extra-cardiac delivery. Recent deve ...
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Journal ArticleExp Biol Med (Maywood) · April 2019
The composition of the microbiota is of critical importance for health and disease, and is receiving increased scientific and medical scrutiny. Of particular interest is the role of changing diets as a function of agriculture and, perhaps to an even greate ...
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Journal ArticleAm J Physiol Heart Circ Physiol · January 1, 2019
The nuclear receptor retinoic acid-related orphan receptor-α (RORα) regulates numerous critical biological processes, including central nervous system development, lymphocyte differentiation, and lipid metabolism. RORα has been recently identified in the h ...
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Journal ArticleJ Card Surg · June 2018
BACKGROUND: Patients with end-stage heart failure on left ventricular assist devices (LVADs) are predisposed to a high incidence of stroke. Preoperative factors associated with increased stroke risk are poorly understood. METHODS: We performed a single-cen ...
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Journal ArticleJ Vis Exp · May 11, 2018
Mechanical circulatory support (MCS) has been introduced as a viable alternative to heart transplantation primarily through the use of intracorporeal ventricular assist devices (VADs) for support of the left ventricle. However, certain clinical scenarios w ...
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Journal ArticleMol Cell · May 3, 2018
Most G protein-coupled receptors (GPCRs) signal through both heterotrimeric G proteins and β-arrestins (βarr1 and βarr2). Although synthetic ligands can elicit biased signaling by G protein- vis-à-vis βarr-mediated transduction, endogenous mechanisms for b ...
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Journal ArticleJCI Insight · September 7, 2017
The oncoprotein Mdm2 is a RING domain-containing E3 ubiquitin ligase that ubiquitinates G protein-coupled receptor kinase 2 (GRK2) and β-arrestin2, thereby regulating β-adrenergic receptor (βAR) signaling and endocytosis. Previous studies showed that cardi ...
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Journal ArticlePhysiol Rep · August 2017
Creatine (Cr), phosphocreatine (PCr), and creatine kinases (CK) comprise an energy shuttle linking ATP production in mitochondria with cellular consumption sites. Myocytes cannot synthesize Cr: these cells depend on uptake across the cell membrane by a spe ...
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Journal ArticleInt J Clin Exp Med · 2017
The cellular environment of the mammalian heart constantly is challenged with environmental and intrinsic pathological insults, which affect the proper folding of proteins in heart failure. The effects of damaged or misfolded proteins on the cell can be pr ...
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Journal ArticleASAIO J · 2017
Left ventricular assist device (LVAD) therapy unloads the failing heart but exposes the human body to unique pathophysiologic demands such as continuous blood flow and complete univentricular support, which are associated with increased risk of adverse cli ...
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Journal ArticleSci Rep · September 27, 2016
On Earth, biological systems have evolved in response to environmental stressors, interactions dictated by physical forces that include gravity. The absence of gravity is an extreme stressor and the impact of its absence on biological systems is ill-define ...
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Journal ArticleJ Card Fail · February 2016
BACKGROUND: Although primary graft dysfunction (PGD) is a leading cause of mortality and morbidity early post-heart transplant, relatively little is known regarding mechanisms involved in PGD development. METHODS AND RESULTS: We examined the relationship b ...
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Journal ArticleJ Am Coll Cardiol · January 26, 2016
BACKGROUND: Heart failure (HF) is characterized by perturbations in energy homeostasis and metabolism. The reversibility and prognostic value of circulating markers associated with these changes remain unclear. OBJECTIVES: This study sought to describe the ...
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Journal ArticleAddict Biol · January 2016
Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. ...
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Journal ArticleStem Cells Dev · November 15, 2015
Cardiovascular disease is the leading cause of death in the United States. Heart failure is a common, costly, and potentially fatal condition that is inadequately managed by pharmaceuticals. Cardiac repair therapies are promising alternative options. A pot ...
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Journal ArticleJ Vis Exp · June 11, 2014
Since its introduction in the late 19(th) century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease(1-15). Although th ...
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Journal ArticlePLoS One · 2014
The molecular differences between ischemic (IF) and non-ischemic (NIF) heart failure are poorly defined. A better understanding of the molecular differences between these two heart failure etiologies may lead to the development of more effective heart fail ...
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Journal ArticleTransl Res · April 2013
Ischemic cardiovascular disease remains the leading cause of death worldwide. Despite advances in the medical management of atherosclerosis over the past several decades, many patients require arterial revascularization to reduce mortality and alleviate is ...
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Journal ArticleHum Gene Ther · October 2012
Adeno-associated virus type 3b (AAV3b) has been largely ignored by gene therapists because of the inability of vectors based on this serotype to transduce target tissues efficiently. Here we describe a phenomenon unique to AAV3b in that vectors based on th ...
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Journal ArticleJ Virol · August 2012
Adeno-associated virus (AAV) vectors have the potential to promote long-term gene expression. Unfortunately, humoral immunity restricts patient treatment and in addition provides an obstacle to the potential option of vector readministration. In this study ...
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Journal ArticleHum Gene Ther · June 2012
Successful amelioration of cardiac dysfunction and heart failure through gene therapy approaches will require a transgene effective at attenuating myocardial injury, and subsequent remodeling, using an efficient and safe delivery vehicle. Our laboratory ha ...
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Journal ArticleMol Ther · February 2012
Efficient and widespread gene transfer is required for successful treatment of Duchenne muscular dystrophy (DMD). Here, we performed the first clinical trial using a chimeric adeno-associated virus (AAV) capsid variant (designated AAV2.5) derived from a ra ...
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Journal ArticleProc Natl Acad Sci U S A · September 20, 2011
Physiological sensing of O(2) tension (partial O(2) pressure, pO(2)) plays an important role in some mammalian cellular systems, but striated muscle generally is not considered to be among them. Here we describe a molecular mechanism in skeletal muscle tha ...
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Journal ArticleAm J Physiol Endocrinol Metab · May 2011
Profound alterations in myocellular creatine and phosphocreatine levels are observed during human heart failure. To maintain its intracellular creatine stores, cardiomyocytes depend upon a cell membrane creatine transporter whose regulation is not clearly ...
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Journal ArticleJ Thorac Cardiovasc Surg · December 2010
OBJECTIVE: Achieving transmural tissue ablation might be necessary for successful treatment of atrial fibrillation. The purpose of this study was to evaluate the reproducibility of transmural left atrial ablation using a high-intensity focused ultrasound e ...
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Journal ArticleJ Biol Chem · November 26, 2010
The molecular pathways regulating signal transducer and activator of transcription 1 (STAT1) levels in states of inflammation are incompletely understood. The suppressor of cytokine signaling, protein inhibitor of STAT, and SHP-1/2 tyrosine phosphatases ul ...
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Journal ArticleN Engl J Med · October 7, 2010
We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne's muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional ...
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Journal ArticleAnn Thorac Surg · October 2010
BACKGROUND: Bleeding is a major cause of morbidity in recipients of continuous-flow left ventricular assist devices (CF-LVAD). A better understanding of the impact of CF-LVAD support on the hemostatic profile is necessary to establish better strategies for ...
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Journal ArticleBiochemistry · July 6, 2010
Several lines of evidence point strongly toward the importance of highly alpha-helical intermediates in the folding of all globular proteins, regardless of their native structure. However, experimental refolding studies demonstrate no observable alpha-heli ...
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Journal ArticleAppl Environ Microbiol · July 2010
Although mice associated with a single bacterial species have been used to provide a simple model for analysis of host-bacteria relationships, bacteria have been shown to display adaptability when grown in a variety of novel environments. In this study, ch ...
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Journal ArticleASAIO J · 2010
A higher rate of nonsurgical bleeding has been observed in nonpulsatile left ventricular assist device (LVAD) recipients. von Willebrand factor (vWF) profiles were compared for nonpulsatile and pulsatile LVAD recipients to explore mechanisms that may contr ...
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Journal ArticleProc Natl Acad Sci U S A · April 14, 2009
Despite substantial evidence that nitric oxide (NO) and/or endogenous S-nitrosothiols (SNOs) exert protective effects in a variety of cardiovascular diseases, the molecular details are largely unknown. Here we show that following left coronary artery ligat ...
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Journal ArticleCancer Gene Ther · December 2005
Augmenting cancer treatment by protein and gene delivery continues to gain momentum based on success in animal models. The primary hurdle of fully exploiting the arsenal of molecular targets and therapeutic transgenes continues to be efficient delivery. Ve ...
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Journal ArticleJ Virol · May 2004
For all adeno-associated virus (AAV) serotypes, 60 monomers of the Vp1, Vp2, and Vp3 structural proteins assemble via an unknown mechanism to form an intact capsid. In an effort to better understand the properties of the capsid monomers and their role in v ...
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Journal ArticleJ Virol · January 2003
Marker rescue, the restoration of gene function by replacement of a defective gene with a normal one by recombination, has been utilized to produce novel adeno-associated virus (AAV) vectors. AAV serotype 2 (AAV2) clones containing wild-type terminal repea ...
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Journal ArticleJ Virol · February 2000
The EICP0 protein of equine herpesvirus 1 (EHV-1) is an early, viral regulatory protein that independently trans-activates EHV-1 immediate-early (IE), early, gamma1 late, and gamma2 late promoters. To assess whether this powerful trans-activator functions ...
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Journal ArticleVirology · April 10, 1999
The equine herpesvirus 1 immediate-early (IE) phosphoprotein is essential for the activation of transcription from viral early and late promoters and trans-represses its own promoter. Transient-transfection assays showed that the IE protein trans-represses ...
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Journal ArticleJ Virol · July 1997
To assess the role of the equine herpesvirus type 1 (EHV-1) ICP0 protein (EICP0) in gene regulation, a variety of molecular studies on the EICP0 gene and gene products of both the attenuated cell culture-adapted Kentucky A (KyA) strain and the Ab4p strain ...
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Journal ArticleJournal of Clinical Ultrasound · March 1982
AbstractThe peak frequency ratio (PFR) between the internal carotid and common carotid artery Fast Fourier Transform Spectral Analysis patterns has been used to identify patients with internal carotid artery stenosis. To ev ...
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