Voice hoarseness in a patient with underlying Eisenmenger's syndrome: a case report.

Background: The natural history of patients diagnosed with Eisenmenger's Syndrome typically revolve around the pediatric population. Medical advances have allowed these patients to live longer and present with a different subset of symptoms as a result of the progression of their disease process.

Case Presentation: In this case report, we discuss a 77-year-old Caucasian female with Eisenmenger's Syndrome presenting with hoarseness.

A Road Map to Personalizing Targeted Cancer Therapies Using Synthetic Lethality.

Targeted therapies rely on the genetic and epigenetic status of the tumor cells and are seen as the most promising approach to treat cancer today. However, current targeted therapies focus on directly inhibiting those molecules that are altered in tumor cells. Unfortunately, targeting these molecules, even with specific inhibitors, is challenging as tumor cells rewire their genetic circuitry to eliminate genetic dependency on these targets.

Molecular characterization of an MLL1 fusion and its role in chromosomal instability.

Chromosomal rearrangements involving the mixed-lineage leukemia (MLL1) gene are common in a unique group of acute leukemias, with more than 100 fusion partners in this malignancy alone. However, do these fusions occur or have a role in solid tumors? We performed extensive network analyses of MLL1-fusion partners in patient datasets, revealing that multiple MLL1-fusion partners exhibited significant interactions with the androgen-receptor signaling pathway. Further exploration of tumor sequence data from TCGA predicts the presence of MLL1 fusions with truncated SET domain in prostate tumors.

Expression-based analyses indicate a central role for hypoxia in driving tumor plasticity through microenvironment remodeling and chromosomal instability.

Can transcriptomic alterations drive the evolution of tumors? We asked if changes in gene expression found in all patients arise earlier in tumor development and can be relevant to tumor progression. Our analyses of non-mutated genes from the non-amplified regions of the genome of 158 triple-negative breast cancer (TNBC) cases identified 219 exclusively expression-altered (EEA) genes that may play important role in TNBC. Phylogenetic analyses of these genes predict a "punctuated burst" of multiple gene upregulation events occurring at early stages of tumor development, followed by minimal subsequent changes later in tumor progression.

Calmodulin-binding proteins: A journey of 40 years.

The proteins which bind to calmodulin in a Ca-dependent and reversible manner are known as calmodulin-binding proteins. These proteins are involved in a multitude of processes in which Ca and calmodulin play crucial roles. Our group elucidated the mechanism and importance of these proteins in normal and diseased conditions.

An integrated computational and experimental study uncovers FUT9 as a metabolic driver of colorectal cancer.

Metabolic alterations play an important role in cancer and yet, few metabolic cancer driver genes are known. Here we perform a combined genomic and metabolic modeling analysis searching for metabolic drivers of colorectal cancer. Our analysis predicts FUT9, which catalyzes the biosynthesis of Ley glycolipids, as a driver of advanced-stage colon cancer.

Insulin Cannot Induce Adipogenic Differentiation in Primary Cardiac Cultures.

Cardiac tissue contains a heterogeneous population of cardiomyocytes and nonmyocyte population especially fibroblasts. Fibroblast differentiation into adipogenic lineage is important for fat accumulation around the heart which is important in cardiac pathology. The differentiation in fibroblast has been observed both spontaneously and due to increased insulin stimulation.

Therapeutic relevance of the protein phosphatase 2A in cancer.

Chromosomal Instability (CIN) is regarded as a unifying feature of heterogeneous tumor populations, driving intratumoral heterogeneity. Polo-Like Kinase 1 (PLK1), a serine-threonine kinase that is often overexpressed across multiple tumor types, is one of the key regulators of CIN and is considered as a potential therapeutic target. However, targeting PLK1 has remained a challenge due to the off-target effects caused by the inhibition of other members of the polo-like family.

Novel myristoylation of the sperm-specific hexokinase 1 isoform regulates its atypical localization.

The hexokinase 1 variant in mammalian spermatozoa (HK1S) has a unique N-terminus and this isoform atypically localizes to the plasma membrane. However, the mechanism of this process currently remains ambiguous. In this report, we show that fatty acylation underlies the specific sorting of HK1S.

Expression of calcineurin, calpastatin and heat shock proteins during ischemia and reperfusion.

Objective: Calcineurin (CaN) interacts with calpains (Calpn) and causes cellular damage eventually leading to cell death. Calpastatin (Calp) is a specific Calpn inhibitor, along with CaN stimulation has been implicated in reduced cell death and self-repair. Molecular chaperones, heat shock proteins (Hsp70 and Hsp90) acts as regulators in Calpn signaling.

Enhanced protective immunity derived from dendritic cells with phagocytosis of CD40 ligand transgene-engineered apoptotic tumor cells via increased dendritic cell maturation.

Aims And Background: Dendritic cells (DCs) play a pivotal role in regulating CD8+ cytotoxic T-lymphocyte (CTL) responses. Currently, DC vaccines have been used in experimental animal models and clinical trials for evaluation of antitumor immunity. However, their efficacy is limited, warranting the improvement of DC-based cancer vaccines.

Enrichment of cardiomyocytes in primary cultures of murine neonatal hearts.

In vitro culture of neonatal murine cardiomyocytes is vital for understanding the functions of the heart. Cardiomyocyte cultures are difficult to maintain because they do not proliferate after birth. The maintenance of primary cultures of viable and functional cardiomyocytes is considerably affected by the yield from initial steps of isolation procedures.

Regulation of N-myristoyltransferase by the calpain and caspase systems.

N-myristoyltransferase (NMT) is an essential eukaryotic enzyme which catalyzes the transfer of the myristoyl group to the terminal glycine residue of a number of proteins including those involved in signal transduction and apoptotic pathways. In higher eukaryotes, two isoforms of NMT have been identified (NMT1 and NMT2) which share about 76% amino acid sequence identity in humans. Protein-protein interactions of NMTs reveal that m-calpain interacts with NMT1 whereas caspase-3 interacts with NMT2.

Ischemia and reperfusion induce differential expression of calpastatin and its homologue high molecular weight calmodulin-binding protein in murine cardiomyocytes.

In the heart, calpastatin (Calp) and its homologue high molecular weight calmodulin-binding protein (HMWCaMBP) regulate calpains (Calpn) by inhibition. A rise in intracellular myocardial Ca2+ during cardiac ischemia activates Calpn thereby causing damage to myocardial proteins, which leads to myocyte death and consequently to loss of myocardial structure and function. The present study aims to elucidate expression of Calp and HMWCaMBP with respect to Calpn during induced ischemia and reperfusion in primary murine cardiomyocyte cultures.

Altered expression of calcineurin, calpain, calpastatin and HMWCaMBP in cardiac cells following ischemia and reperfusion.

A rise in intracellular myocardial Ca(2+) during cardiac ischemia activates calpain (Calpn) thereby causing damage to myocardial proteins, which leads to myocyte death and consequently to loss of myocardial structure and function. Calcineurin (CaN) interacts with Calpn and causes cellular damage eventually leading to cell death. Calpastatin (Calp) and high molecular weight calmodulin-binding protein (HMWCaMBP) (homolog of Calp), inhibit Calpn activity and thus prevent cell death.

Cardiomyocyte culture - an update on the in vitro cardiovascular model and future challenges.

The success of any work with isolated cardiomyocytes depends on the reproducibility of cell isolation, because the cells do not divide. To date, there is no suitable in vitro model to study human adult cardiac cell biology. Although embryonic stem cells and induced pluripotent stem cells are able to differentiate into cardiomyocytes in vitro, the efficiency of this process is low.

Proton-gated ion channels in mouse bone marrow stromal cells.

A variety of ion channels like acid sensing ion channels (ASICs) and several members of the transient receptor potential (TRP) cation channel family are known to be activated by protons. The present study describes proton-gated current in mouse bone marrow stromal cells (BMSCs), by using whole cell patch clamp. Rapid application of extracellular solution of pH ≤ 6.

High molecular weight calmodulin-binding protein: 20 years onwards-a potential therapeutic calpain inhibitor.

Apoptosis in cardiovascular diseases is considered to be a major reason for heart failure. Caspase-independent apoptosis due to calpains and other proteases occurs due to increase in intracellular Ca(2+) levels which act on a feed-forward mechanism. Calpains are Ca(2+)-activated cysteine proteases present in the cytosol as inactive proenzymes.

Scanning electron microscopy preparation protocol for differentiated stem cells.

The lack of an established protocol for scanning electron microscopy (SEM) studies on stem cells differentiating into adipogenic lineage led us to develop a protocol for the preparation of differentiated adult bone marrow-derived mesenchymal stem cells (BMSC) for SEM. This protocol describes the procedure to maintain and preserve the structural organization of cellular components following differentiation, for morphological and physical characterization. The fixation of the differentiated cells was followed by dehydration using methanol, and vacuum desiccation before microscopy.