Socioeconomic and Political Initiators of Pay Comparison (original) (raw)
C-kit+ cardiac progenitors exhibit mesenchymal markers and preferential cardiovascular commitment
Cardiovascular research, 2011
The heart contains c-kit(+) progenitors that maintain cardiac homeostasis. Cardiac c-kit(+) cells are multipotent and give rise to myocardial, endothelial and smooth muscle cells, both in vitro and in vivo. C-kit(+) cells have been thoroughly investigated for their stem cell activity, susceptibility to stress conditions and ageing, as well as for their ability to repair the infarcted heart. Recently, expression of mesenchymal stem cell (MSC) markers and MSC differentiation potency have been reported in cardiac progenitor cells. Based on this evidence, we hypothesized that c-kit(+) cells may have phenotypic and functional features in common with cardiac MSCs. Culture of cells obtained from enzymatic dissociation of heart auricle fragments produced a fast-growing fibroblast-like population expressing mesenchymal markers. C-kit(+) cells co-expressing MSC markers were identified in this population, sorted by flow cytometry and cultured in the presence or the absence of unselected cardia...
Post-activation Turn-off of NF-kappa B-dependent Transcription Is Regulated by Acetylation of p65
Journal of Biological Chemistry, 2003
NF-κB represents a family of eukaryotic transcription factors participating in the regulation of various cellular genes involved in the immediate early processes of immune, acute-phase, and inflammatory responses. Cellular localization and consequently the transcriptional activity of NF-κB is tightly regulated by its partner IκBα. Here, we show that the p65 subunit of NF-κB is acetylated by both p300 and PCAF on lysines 122 and 123. Both HDAC2 and HDAC3 interact with p65 although only HDAC3 was able to deacetylate p65. Acetylation of p65 reduces its ability to bind κΒ-DNA. Finally, acetylation of p65 facilitated its removal from DNA and consequently its ΙκΒα-mediated export from the nucleus. We propose that acetylation of p65 plays a key role in ΙκΒα-mediated attenuation of NF-κΒ transcriptional activity which is an important process that restores the latent state in post-induced cells.
Journal of Biological Chemistry, 2005
Flotillin-1 is a lipid raft-associated protein that has been implicated in various cellular processes. We examine the subcellular distribution of flotillin-1 in different cell types, and find that localization is cell type-specific. Flotillin-1 relocates from a cytoplasmic compartment to the plasma membrane upon the differentiation of 3T3-L1 adipocytes. To delineate the structural determinants necessary for its localization, we generated a series of truncation mutants of flotillin-1. Wild-type flotillin-1 has two putative hydrophobic domains, and is localized to lipid raft microdomains at the plasma membrane. Flotillin-1 fragments lacking the N-terminal hydrophobic stretch are excluded from the lipid raft compartments, but remain at the plasma membrane. On the other hand, mutants with the second hydrophobic region deleted fail to traffic to the plasma membrane, but are instead found in intracellular granule-like structures. Flotillin-1 specifically interacts with the adapter protein CAP, the Src family kinase Fyn, and cortical F-actin in lipid raft microdomains in adipocytes. Furthermore, CAP and Fyn associate with different regions in the amino terminal sequences of flotillin-1. These results further our understanding for how flotillin-1 can function as a molecular link between lipid rafts of the plasma membrane and a multimeric signaling complex at the actin cytoskeleton.
Journal of Biological Chemistry, 2003
Human Von Willebrand factor (VWF) gene sequences +155 to +247 contain cisacting elements that contribute towards endothelial specific activation of the VWF promoter. Analyses of this region demonstrated the presence of a GATA binding site that is necessary for the promoter activation in endothelial cells. We have recently reported the presence of a novel NFY binding sequence in this region that does not conform to the consensus NFY binding sequence CCAAT. NFY was shown to function as a repressor of the VWF promoter through interaction with this novel binding site. Here we report that the NFY interacts with histone deacetylases (HDACs) in a cell-type specific manner and recruits them to the VWF promoter to inhibit the promoter activity in non-endothelial cells. Analyses of the acetylation status of histones in the chromatin region containing the VWF promoter sequences demonstrated that these sequences are associated with acetylated histone H4 specifically in endothelial cells. It was also demonstrated that HDACs are specifically recruited to the same chromatin region in nonendothelial cells. We also demonstrated that GATA6 is the GATA family member that interacts with the VWF promoter and that GATA6 is associated with NFY specifically in non-endothelial cells. We propose that NFY recruits HDACs to the VWF promoter, which may result in deacetylation of GATA6 as well as of histones in non-endothelial cells, thus leading to promoter inactivation. In endothelial cells however, association of HDACs, NFY and GATA6 is interrupted potentially through endothelial-cell specific signaling/mechanism, thus favoring the balance towards acetylation and activation of the VWF promoter. 2 by guest on April 2, 2016 http://www.jbc.org/ Downloaded from
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2015
Rocky Mountain spotted fever (RMSF) has emerged as a significant cause of morbidity and mortality since 2002 on tribal lands in Arizona. The explosive nature of this outbreak and the recognition of an unexpected tick vector, Rhipicephalus sanguineus, prompted an investigation to characterize RMSF in this unique setting, and compare RMSF cases to similar illnesses. We compared medical records of 205 RMSF cases and 175 non-RMSF illnesses that prompted RMSF testing during 2002-2011 from two Indian reservations in Arizona. RMSF cases occurred year-round and peaked later (July-September) than RMSF cases reported from other U.S regions. Cases were younger (median age 11 years) and reported fever and rash less frequently as well as less tick exposure compared to other U.S. cases. Fever was present in 81% of cases but not significantly different from that in non-RMSF illnesses. Classic laboratory abnormalities such as low sodium and platelet counts had small and subtle differences betwee...
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2014
Invasive fungal infection (IFI) following liver transplant is associated with significant morbidity and mortality. Antifungal prophylaxis is rational for liver transplant patients at high IFI risk. In this open-label, noninferiority study, patients were randomized 1:1 to receive intravenous micafungin 100 mg or center-specific standard care (fluconazole, liposomal amphotericin B, or caspofungin) posttransplant. The primary endpoint was clinical success (absence of a proven/probable IFI and no need for additional antifungals) at end of prophylaxis (EOP). Noninferiority (10% margin) of micafungin vs standard care was assessed in the per protocol and full analysis sets. Safety assessments included adverse events and liver and kidney function tests. The full analysis set comprised 344 patients (172 micafungin; 172 standard care). Mean age was 51.2 years; 48.0% had a Model for End-Stage Liver Disease score ≥20. At EOP (mean treatment duration, 17 days), clinical success was 98.6% for ...
Circulation. Heart failure, 2014
We sought to determine whether empirical nesiritide or milrinone would improve the early postoperative course after Fontan surgery. We hypothesized that compared with milrinone or placebo, patients assigned to receive nesiritide would have improved early postoperative outcomes. In a single-center, randomized, double-blinded, placebo-controlled, multi-arm parallel-group clinical trial, patients undergoing primary Fontan surgery were assigned to receive nesiritide, milrinone, or placebo. A loading dose of study drug was administered on cardiopulmonary bypass followed by a continuous infusion for ≥12 hours and ≤5 days after cardiac intensive care unit admission. The primary outcome was days alive and out of the hospital within 30 days of surgery. Secondary outcomes included measures of cardiovascular function, renal function, resource use, and adverse events. Among 106 enrolled subjects, 35, 36, and 35 were randomized to the nesiritide, milrinone, and placebo groups, respectively, and ...