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Laura Rué, Mónica Bañez-Coronel, Jordi Creus-Muncunill, Albert Giralt, Rafael Alcalá-Vida, Gartze Mentxaka, Birgit Kagerbauer, M Teresa Zomeño-Abellán, Zeus Aranda, Veronica Venturi, Esther Pérez-Navarro, Xavier Estivill, Eulàlia Martí
Huntington's disease (HD) is a polyglutamine disorder caused by a CAG expansion in the Huntingtin (HTT) gene exon 1. This expansion encodes a mutant protein whose abnormal function is traditionally associated with HD pathogenesis; however, recent evidence has also linked HD pathogenesis to RNA stable hairpins formed by the mutant HTT expansion. Here, we have shown that a locked nucleic acid-modified antisense oligonucleotide complementary to the CAG repeat (LNA-CTG) preferentially binds to mutant HTT without affecting HTT mRNA or protein levels...
October 10, 2016: Journal of Clinical Investigation
Zeus A De Los Santos, Christian Wolf
The self-assembly of a stereodynamic phosphine ligand, Pd(II) and a chiral amine, amino alcohol or amino acid gen-erates characteristic UV and CD signals that can be used for quantitative stereochemical analysis of the bound substrate. A robust mix-and-measure chiroptical sensing protocol has been developed and used for the determination of the abso-lute configuration, ee and yield of an amine produced by iridium catalyzed asymmetric hydrogenation of an iminium salt. The analysis requires only 1 mg of the crude reaction mixture and minimizes cost, labor, time and waste...
October 3, 2016: Journal of the American Chemical Society
Zeus Saldaña-Ahuactzi, Gerardo E Rodea, Ariadnna Cruz-Córdova, Viridiana Rodríguez-Ramírez, Karina Espinosa-Mazariego, Martín A González-Montalvo, Sara A Ochoa, Bertha González-Pedrajo, Carlos A Eslava-Campos, Edgar O López-Villegas, Rigoberto Hernández-Castro, José Arellano-Galindo, Genaro Patiño-López, Juan Xicohtencatl-Cortes
Enterotoxigenic Escherichia coli (ETEC) is a major cause of morbidity in children under 5 years of age in low- and middle-income countries and a leading cause of traveler's diarrhea worldwide. The ability of ETEC to colonize the intestinal epithelium is mediated by fimbrial adhesins, such as CS21 (Longus). This adhesin is a type IVb pilus involved in adherence to intestinal cells in vitro and bacterial self-aggregation. Fourteen open reading frames have been proposed to be involved in CS21 assembly, hitherto only the lngA and lngB genes, coding for the major (LngA) and minor (LngB) structural subunit, have been characterized...
2016: Frontiers in Microbiology
Lisa Dannenberg, Vladimir Erschoff, Florian Bönner, Michael Gliem, Sebastian Jander, Bodo Levkau, Malte Kelm, Thomas Hohlfeld, Tobias Zeus, Amin Polzin
BACKGROUND: >50% of stroke patients rely on analgesic medication to control pain. Aspirin is the mainstay of medical treatment of stroke patients; however analgesic medication with dipyrone impairs aspirin antiplatelet effects ex-vivo. The clinical impact of this impairment is unknown. Therefore, we aimed to determine aspirin antiplatelet effects and neurological outcome in stroke patients with aspirin and dipyrone comedication. METHODS: We conducted a prospective cohort study in 41 patients with stroke...
June 11, 2016: Vascular Pharmacology
Lisa Dannenberg, Amin Polzin, Roland Bullens, Malte Kelm, Tobias Zeus
No abstract text is available yet for this article.
July 15, 2016: International Journal of Cardiology
Verena Veulemans, Tobias Zeus, Laura Kleinebrecht, Jan Balzer, Katharina Hellhammer, Amin Polzin, Patrick Horn, Alexander Blehm, Jan-Philipp Minol, Patric Kröpil, Ralf Westenfeld, Tienush Rassaf, Artur Lichtenberg, Malte Kelm
BACKGROUND: Preprocedural manual multi-slice-CT-segmentation tools (MSCT-ST) define the gold standard for planning transcatheter aortic valve replacement (TAVR). They are able to predict the perpendicular line of the aortic annulus (PPL) and to indicate the corresponding C-arm angulation (CAA). Fully automated planning-tools and their clinical relevance have not been systematically evaluated in a real world setting so far. METHODS AND RESULTS: The study population consists of an all-comers cohort of 160 consecutive TAVR patients with a drop out of 35 patients for technical and anatomical reasons...
2016: PloS One
Patrick Horn, Gülsüm Erkilet, Verena Veulemans, Patric Kröpil, Leon Schurgers, Tobias Zeus, Christian Heiss, Malte Kelm, Ralf Westenfeld
BACKGROUND: Circulating microparticles (MPs) derived from endothelial cells and blood cells bear procoagulant activity and promote thrombin generation. Thrombin exerts proinflammatory effects mediating the progression of atherosclerosis. Aortic valve stenosis may represent an atherosclerosis-like process involving both the aortic valve and the vascular system. The aim of this study was to investigate whether MP-induced thrombin generation is related to coronary atherosclerosis and aortic valve calcification...
2016: PloS One
Christos Rammos, Tobias Zeus, Jan Balzer, Laura Kubatz, Ulrike B Hendgen-Cotta, Verena Veulemans, Katharina Hellhammer, Matthias Totzeck, Peter Luedike, Malte Kelm, Tienush Rassaf
BACKGROUND AND OBJECTIVE: Endothelial dysfunction is predictive for cardiovascular events and may be caused by decreased bioavailability of nitric oxide (NO). NO is scavenged by cell-free hemoglobin with reduction of bioavailable NO up to 70% subsequently deteriorating vascular function. While patients with mitral regurgitation (MR) suffer from an impaired prognosis, mechanisms relating to coexistent vascular dysfunctions have not been described yet. Therapy of MR using a percutaneous mitral valve repair (PMVR) approach has been shown to lead to significant clinical benefits...
2016: PloS One
Katharina Hellhammer, Tobias Zeus, Pablo E Verde, Verena Veulemanns, Lisa Kahlstadt, Georg Wolff, Ralf Erkens, Ralf Westenfeld, Eliano P Navarese, Marc W Merx, Tienush Rassaf, Malte Kelm
AIM: To determine the impact of red blood cell distribution width on outcome in anemic patients undergoing transcatheter aortic valve implantation (TAVI). METHODS: In a retrospective single center cohort study we determined the impact of baseline red cell distribution width (RDW) and anemia on outcome in 376 patients with aortic stenosis undergoing TAVI. All patients were discussed in the institutional heart team and declined for surgical aortic valve replacement due to high operative risk...
February 26, 2016: World Journal of Cardiology
Małgorzata Kasprowicz-Potocka, Anita Zaworska, Sebastian Andrzej Kaczmarek, Andrzej Rutkowski
The aim of this study was to determine the nutrient digestibility of seeds of four varieties of narrow-leafed lupines (Lupinus angustifolius) and the possibility of soya bean meal (SBM) substitution by lupine seeds alone and in combination with rapeseed meal (RSM) in the diets of pigs. The seeds of the lupine varieties Kalif, Sonet, Zeus and Boruta were analysed. The apparent total tract digestibility (ATTD) was determined on 50 cross-bred pigs using the difference method with titanium dioxide as a marker. The substitution of SBM by lupine seeds alone (at 0 - 100%) was tested on 60 pigs (20-105 kg body weight (BW)) and by a combination of lupine seeds and RSM on 180 fattening pigs (35-80 kg BW)...
2016: Archives of Animal Nutrition
Sara Ariotti, Marianna Adamo, Francesco Costa, Athanasios Patialiakas, Carlo Briguori, Attila Thury, Salvatore Colangelo, Gianluca Campo, Matteo Tebaldi, Imre Ungi, Stefano Tondi, Marco Roffi, Alberto Menozzi, Nicoletta de Cesare, Roberto Garbo, Emanuele Meliga, Luca Testa, Henrique Mesquita Gabriel, Marco Ferlini, Pascal Vranckx, Marco Valgimigli
OBJECTIVES: This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease. BACKGROUND: DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns...
March 14, 2016: JACC. Cardiovascular Interventions
Claudia Sommerer, Klemens Budde, Martin Zeier, Rudolf P Wüthrich, Petra Reinke, Ute Eisenberger, Anja Mühlfeld, Wolfgang Arns, Rolf Stahl, Katharina Heller, Heiner H Wolters, Barbara Suwelack, Hans Ulrich Klehr, Ingeborg A Hauser, Manfred Stangl, Silvio Nadalin, Michael Dürr, Martina Porstner, Christoph May, Peter Wimmer, Oliver Witzke, Frank Lehner
AIMS: To assess 5-year efficacy, renal, and safety outcomes following early conversion from cyclosporine to everolimus vs. a standard cyclosporine-based regimen in living-donor kidney transplant (LDKT) recipients. MATERIALS AND METHODS: The ZEUS study was a randomized, open-label, 1-year, multicenter study in which 300 de novo kidney transplant recipients continued to receive cyclosporine or converted to everolimus at 4.5 months post-transplant, with annual follow-up visits to 5 years post-transplant...
April 2016: Clinical Nephrology
Franz Oswald, Patrick Rodriguez, Benedetto Daniele Giaimo, Zeus A Antonello, Laura Mira, Gerhard Mittler, Verena N Thiel, Kelly J Collins, Nassif Tabaja, Wiebke Cizelsky, Melanie Rothe, Susanne J Kühl, Michael Kühl, Francesca Ferrante, Kerstin Hein, Rhett A Kovall, Maria Dominguez, Tilman Borggrefe
The transcriptional shift from repression to activation of target genes is crucial for the fidelity of Notch responses through incompletely understood mechanisms that likely involve chromatin-based control. To activate silenced genes, repressive chromatin marks are removed and active marks must be acquired. Histone H3 lysine-4 (H3K4) demethylases are key chromatin modifiers that establish the repressive chromatin state at Notch target genes. However, the counteracting histone methyltransferase required for the active chromatin state remained elusive...
June 2, 2016: Nucleic Acids Research
Tobias Zeus, Ulrike Ketterer, Daniela Leuf, Lisa Dannenberg, Rabea Wagstaff, Florian Bönner, Michael Gliem, Sebastian Jander, Malte Kelm, Amin Polzin
Troponin T (TnT) elevation above the 99th percentile upper reference limit (URL) is considered diagnostic of acute myocardial infarction (MI). Non-specific increases of TnT are frequent in acute stroke patients. However, in these patients, correct diagnosis of MI is crucial because the antithrombotic medications used to treat acute MI might be harmful and produce intracranial bleeding. In this study, we aimed to associate enhanced TnT levels defined by different cutoff values with occurrence of culprit lesion coronary artery disease (CAD) as well as 1-year major adverse cerebral and cardiovascular events (MACCEs)...
June 2016: Translational Stroke Research
Zeus A De Los Santos, Ransheng Ding, Christian Wolf
A stereodynamic chemosensor that can be used for simultaneous determination of the absolute configuration, enantiomeric composition and total concentration of chiral amines and amino alcohols based on two fast optical measurements was prepared and tested. The free sensor is CD-silent and produces characteristic blue-shifted UV and CD signals upon substrate binding via Schiff base formation. The potential in high-throughput screening applications and for rational sensor developments are discussed.
February 14, 2016: Organic & Biomolecular Chemistry
Zeus A Antonello, Tobias Reiff, Maria Dominguez
Stem cells are responsible for preserving morphology and function of adult tissues. Stem cells divide to self-renew and to generate progenitor cells to sustain cell demand from the tissue throughout the organism's life. Unlike stem cells, the progenitor cells have limited proliferation potential but have the capacity to terminally differentiate and thereby to substitute older or damaged mature cells. Recent findings indicate that adult stem cells can adapt their division kinetics dynamically to match changes in tissue demand during homeostasis and regeneration...
2015: Fly
A Polzin, L Dannenberg, R Sansone, B Levkau, M Kelm, T Hohlfeld, T Zeus
UNLABELLED: ESSENTIALS: Chronic kidney disease (CKD) patients have a high risk of cardiovascular events. A pharmacodynamic evaluation of the effects of aspirin in 116 patients was carried out. The antiplatelet effects of aspirin are associated with impaired renal function. The optimal antithrombotic regimen in CKD patients must be investigated on a larger scale. BACKGROUND: The pharmacodynamic response to aspirin varies significantly between individuals. Insufficient antiplatelet effects of aspirin are associated with increased risk of ischemic events...
February 2016: Journal of Thrombosis and Haemostasis: JTH
Mark Duquette, Peter M Sadow, Amjad Husain, Jennifer N Sims, Zeus A Antonello, Andrew H Fischer, Chen Song, Elena Castellanos-Rizaldos, G Mike Makrigiorgos, Junichi Kurebayashi, Vania Nose, Paul Van Hummelen, Roderick T Bronson, Michelle Vinco, Thomas J Giordano, Dora Dias-Santagata, Pier Paolo Pandolfi, Carmelo Nucera
BRAF(V600E) mutation exerts an essential oncogenic function in many tumors, including papillary thyroid carcinoma (PTC). Although BRAF(V600E) inhibitors are available, lack of response has been frequently observed. To study the mechanism underlying intrinsic resistance to the mutant BRAF(V600E) selective inhibitor vemurafenib, we established short-term primary cell cultures of human metastatic/recurrent BRAF(V600E)-PTC, intrathyroidal BRAF(V600E)-PTC, and normal thyroid (NT). We also generated an early intervention model of human BRAF(V600E)-PTC orthotopic mouse...
December 15, 2015: Oncotarget
Kerstin Fischer, Veronika Zeus, Linda Kwasnitschka, Gerald Kerth, Martin Haase, Martin H Groschup, Anne Balkema-Buschmann
Recently several infectious agents with a zoonotic potential have been detected in different bat species. However, there is still a lack of knowledge on the transmission dynamics within and between bat species, as well as from bats to other mammals. To better understand these processes, it is important to compare the phylogenetic relationships between different agents to that of their respective hosts. In this study, we analysed more than 950 urine, faeces and oral swab samples collected from 653 bats from mainly four species (Myotis nattereri, Myotis bechsteinii, Myotis daubentonii, and Plecotus auritus) for the presence of coronavirus, paramyxovirus and astrovirus related nucleic acids located in three different regions of Germany...
January 2016: Infection, Genetics and Evolution
Dong-In Shin, Marc W Merx, Christian Meyer, Kiriakos Kirmanoglou, Katharina Hellhammer, Jan Ohlig, Dimitra Katsani, Tobias Zeus, Ralf Westenfeld, Christian Eickholt, Axel Linke, Malte Kelm
PURPOSE: Development of AV-block is a frequent complication associated with transcatheter aortic valve implantation (TAVI). To date little is known about the predictive value of the HV-interval prior to TAVI with respect to the risk of AV-block development. METHODS AND RESULTS: HV-interval was determined in 25 consecutive elderly patients with severe aortic valve stenosis (AS) before and immediately after TAVI. All patients subsequently underwent TAVI and 8 of these 25 patients (32%) developed complete AV-block during the TAVI procedure requiring permanent pacemaker implantation...
October 2015: Acta Cardiologica
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