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991.
Tomá? Venit Rastislav Dzijak Al?běta Kalendová Michal Kahle Jana Roho?ková Volker Schmidt Thomas Rülicke Birgit Rathkolb Wolfgang Hans Alexander Bohla Oliver Eickelberg Tobias Stoeger Eckhard Wolf Ali ?nder Yildirim Valérie Gailus-Durner Helmut Fuchs Martin Hrabě de Angelis Pavel Hozák 《PloS one》2013,8(4)
992.
We introduce an electromechanical model for human cardiac tissue which couples a biophysical model of cardiac excitation (Tusscher, Noble, Noble, Panfilov, 2006) and tension development (adjusted Niederer, Hunter, Smith, 2006 model) with a discrete elastic mass-lattice model. The equations for the excitation processes are solved with a finite difference approach, and the equations of the mass-lattice model are solved using Verlet integration. This allows the coupled problem to be solved with high numerical resolution. Passive mechanical properties of the mass-lattice model are described by a generalized Hooke''s law for finite deformations (Seth material). Active mechanical contraction is initiated by changes of the intracellular calcium concentration, which is a variable of the electrical model. Mechanical deformation feeds back on the electrophysiology via stretch-activated ion channels whose conductivity is controlled by the local stretch of the medium. We apply the model to study how stretch-activated currents affect the action potential shape, restitution properties, and dynamics of spiral waves, under constant stretch, and dynamic stretch caused by active mechanical contraction. We find that stretch conditions substantially affect these properties via stretch-activated currents. In constantly stretched medium, we observe a substantial decrease in conduction velocity, and an increase of action potential duration; whereas, with dynamic stretch, action potential duration is increased only slightly, and the conduction velocity restitution curve becomes biphasic. Moreover, in constantly stretched medium, we find an increase of the core size and period of a spiral wave, but no change in rotation dynamics; in contrast, in the dynamically stretching medium, we observe spiral drift. Our results may be important to understand how altered stretch conditions affect the heart''s functioning. 相似文献
993.
Xiangli Cui Erin E. Witalison Alena P. Chumanevich Alexander A. Chumanevich Deepak Poudyal Venkataraman Subramanian Aaron J. Schetter Curtis C. Harris Paul R. Thompson Lorne J. Hofseth 《PloS one》2013,8(1)
Protein Arginine Deiminases (PADs) catalyze the post-translational conversion of peptidyl-Arginine to peptidyl-Citrulline in a calcium-dependent, irreversible reaction. Evidence is emerging that PADs play a role in carcinogenesis. To determine the cancer-associated functional implications of PADs, we designed a small molecule PAD inhibitor (called Chor-amidine or Cl-amidine), and tested the impact of this drug on the cell cycle. Data derived from experiments in colon cancer cells indicate that Cl-amidine causes a G1 arrest, and that this was p53-dependent. In a separate set of experiments, we found that Cl-amidine caused a significant increase in microRNA-16 (miRNA-16), and that this increase was also p53-dependent. Because miRNA-16 is a putative tumor suppressor miRNA, and others have found that miRNA-16 suppresses proliferation, we hypothesized that the p53-dependent G1 arrest associated with PAD inhibition was, in turn, dependent on miRNA-16 expression. Results are consistent with this hypothesis. As well, we found the G1 arrest is at least in part due to the ability of Cl-amidine-mediated expression of miRNA-16 to suppress its'' G1-associated targets: cyclins D1, D2, D3, E1, and cdk6. Our study sheds light into the mechanisms by which PAD inhibition can protect against or treat colon cancer. 相似文献
994.
Annemarie Voorberg-van der Wel Anne-Marie Zeeman Sandra M. van Amsterdam Alexander van den Berg Els J. Klooster Shiroh Iwanaga Chris J. Janse Geert-Jan van Gemert Robert Sauerwein Niels Beenhakker Gerrit Koopman Alan W. Thomas Clemens H. M. Kocken 《PloS one》2013,8(1)
A major challenge for strategies to combat the human malaria parasite Plasmodium vivax is the presence of hypnozoites in the liver. These dormant forms can cause renewed clinical disease after reactivation through unknown mechanisms. The closely related non-human primate malaria P. cynomolgi is a frequently used model for studying hypnozoite-induced relapses. Here we report the generation of the first transgenic P. cynomolgi parasites that stably express fluorescent markers in liver stages by transfection with novel DNA-constructs containing a P. cynomolgi centromere. Analysis of fluorescent liver stages in culture identified, in addition to developing liver-schizonts, uninucleate persisting parasites that were atovaquone resistant but primaquine sensitive, features associated with hypnozoites. We demonstrate that these hypnozoite-forms could be isolated by fluorescence-activated cell sorting. The fluorescently-tagged parasites in combination with FACS-purification open new avenues for a wide range of studies for analysing hypnozoite biology and reactivation. 相似文献
995.
Barbara Messner Johann Kern Dominik Wiedemann Stefan Schwaiger Adrian Türkcan Christian Ploner Alexander Trockenbacher Klaus Aumayr Nikolaos Bonaros Günther Laufer Hermann Stuppner Gerold Untergasser David Bernhard 《PloS one》2013,8(3)
Background
Insufficient angiogenesis and arteriogenesis in cardiac tissue after myocardial infarction (MI) is a significant factor hampering the functional recovery of the heart. To overcome this problem we screened for compounds capable of stimulating angiogenesis, and herein investigate the most active molecule, 5-Methoxyleoligin (5ML), in detail.Methods and Results
5ML potently stimulated endothelial tube formation, angiogenic sprouting, and angiogenesis in a chicken chorioallantoic membrane assay. Further, microarray- and knock down- based analyses revealed that 5ML induces angiogenesis by upregulation of CYP26B1. In an in vivo rat MI model 5ML potently increased the number of arterioles in the peri-infarction and infarction area, reduced myocardial muscle loss, and led to a significant increase in LV function (plus 21% 28 days after MI).Conclusion
The present study shows that 5ML induces CYP26B1-dependent angiogenesis in vitro, and arteriogenesis in vivo. Whether or not CYP26B1 is relevant for in vivo arteriogenesis is not clear at the moment. Importantly, 5ML-induced arteriogenesis in vivo makes the compound even more interesting for a post MI therapy. 5ML may constitute the first low molecular weight compound leading to an improvement of myocardial function after MI. 相似文献996.
Souriya Vang Hsin-Ta Wu Andrew Fischer Daniel H. Miller Shannon MacLaughlan Elijah Douglass Margaret Steinhoff Colin Collins Peter J. S. Smith Laurent Brard Alexander S. Brodsky 《PloS one》2013,8(3)
Serous epithelial ovarian cancer (EOC) patients often succumb to aggressive metastatic disease, yet little is known about the behavior and genetics of ovarian cancer metastasis. Here, we aim to understand how omental metastases differ from primary tumors and how these differences may influence chemotherapy. We analyzed the miRNA expression profiles of primary EOC tumors and their respective omental metastases from 9 patients using miRNA Taqman qPCR arrays. We find 17 miRNAs with differential expression in omental lesions compared to primary tumors. miR-21, miR-150, and miR-146a have low expression in most primary tumors with significantly increased expression in omental lesions, with concomitant decreased expression of predicted mRNA targets based on mRNA expression. We find that miR-150 and miR-146a mediate spheroid size. Both miR-146a and miR-150 increase the number of residual surviving cells by 2–4 fold when challenged with lethal cisplatin concentrations. These observations suggest that at least two of the miRNAs, miR-146a and miR-150, up-regulated in omental lesions, stimulate survival and increase drug tolerance. Our observations suggest that cancer cells in omental tumors express key miRNAs differently than primary tumors, and that at least some of these microRNAs may be critical regulators of the emergence of drug resistant disease. 相似文献
997.
998.
Leonie E. Paulis Alexandra M. Klein Alexander Ghanem Tessa Geelen Bram F. Coolen Martin Breitbach Katrin Zimmermann Klaas Nicolay Bernd K. Fleischmann Wilhelm Roell Gustav J. Strijkers 《PloS one》2013,8(4)
Aims
Controversy exists in regard to the beneficial effects of transplanting cardiac or somatic progenitor cells upon myocardial injury. We have therefore investigated the functional short- and long-term consequences after intramyocardial transplantation of these cell types in a murine lesion model.Methods and Results
Myocardial infarction (MI) was induced in mice (n = 75), followed by the intramyocardial injection of 1−2×105 luciferase- and GFP-expressing embryonic cardiomyocytes (eCMs), skeletal myoblasts (SMs), mesenchymal stem cells (MSCs) or medium into the infarct. Non-treated healthy mice (n = 6) served as controls. Bioluminescence and fluorescence imaging confirmed the engraftment and survival of the cells up to seven weeks postoperatively. After two weeks MRI was performed, which showed that infarct volume was significantly decreased by eCMs only (14.8±2.2% MI+eCM vs. 26.7±1.6% MI). Left ventricular dilation was significantly decreased by transplantation of any cell type, but most efficiently by eCMs. Moreover, eCM treatment increased the ejection fraction and cardiac output significantly to 33.4±2.2% and 22.3±1.2 ml/min. In addition, this cell type exclusively and significantly increased the end-systolic wall thickness in the infarct center and borders and raised the wall thickening in the infarct borders. Repetitive echocardiography examinations at later time points confirmed that these beneficial effects were accompanied by better survival rates.Conclusion
Cellular cardiomyoplasty employing contractile and electrically coupling embryonic cardiomyocytes (eCMs) into ischemic myocardium provoked significantly smaller infarcts with less adverse remodeling and improved cardiac function and long-term survival compared to transplantation of somatic cells (SMs and MSCs), thereby proving that a cardiomyocyte phenotype is important to restore myocardial function. 相似文献999.
Brenda Alexander Ann Marie Hart Kathleen Austin D. Enette Larson‐Meyer 《Obesity (Silver Spring, Md.)》2013,21(7):1451-1458
Objective: The presence of appetite hormones, namely glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY), and leptin in breast milk may be important in infant feeding regulation and infant growth. This study evaluated whether concentrations of GLP‐1, PYY, and leptin change across a single feeding (from fore‐ to hindmilk), and are associated with maternal and infant anthropometrics. Design and Methods: Thirteen postpartum women (mean ± SD: 25.6 ± 4.5 years, 72.0 ± 11.9 kg) provided fore‐ and hindmilk samples 4‐5 weeks after delivery and underwent measurements of body weight and composition by Dual X‐ray Absorptiometry. GLP‐1, PYY, and leptin concentrations were measured using radioimmunoassay, and milk fat content was determined by creamatocrit. Results: Concentration of GLP‐1 and content of milk fat was higher in hindmilk than foremilk (P ≤ 0.05). PYY and leptin concentrations did not change between fore‐ and hindmilk. Both leptin concentration and milk fat content were correlated with indices of maternal adiposity, including body mass index (r = 0.65‐0.85, P < 0.02), and fat mass (r = 0.65‐0.84, P < 0.02). Hindmilk GLP‐1 was correlated with infant weight gain from birth to 6 months (r = ?0.67, P = 0.034). Conclusion: The presence of appetite hormones in breast milk may be important in infant appetite and growth regulation. 相似文献