1,347 results on '"Borchert T"'
Search Results
2. List of Contributors
- Author
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Alcock, J., primary, Aoki, K., additional, Arunkumar, G., additional, Austad, S.N., additional, Ayala, F.J., additional, Bailey, D.H., additional, Balloux, F., additional, Bar-Yosef, O., additional, Barrett, H.C., additional, Baum, W.M., additional, Bilbao Leis, A., additional, Borchert, T., additional, Boyle, E., additional, Cabral, L.G., additional, Canfield, A.L., additional, Cela-Conde, C.J., additional, Cervantes, B.G., additional, Deacon, T.W., additional, DeGregori, J., additional, Dubreuil, B., additional, Feldman, M.W., additional, Finch, C.E., additional, Flinn, M.V., additional, Fumagalli, M., additional, Gagneux, P., additional, Gaudieri, S., additional, Greer, L.F., additional, Hameroff, S., additional, Henneberg, M., additional, Hill, A.K., additional, John, M., additional, Kingstone, A., additional, Kronfeldner, M., additional, Laidlaw, K.E.W., additional, Lordkipanidze, D., additional, Mallal, S., additional, McDermott, R., additional, McKenzie, K., additional, Monroe, K.R., additional, Murphy, J., additional, Nasiopoulos, E., additional, Oakley, B., additional, Peters, T., additional, Pitchappan, R.M., additional, Preuss, T.M., additional, Puts, D.A., additional, Reimers, M., additional, Risko, E.F., additional, Roland, A., additional, Rose, M.R., additional, Roughgarden, J., additional, Rozhok, A.I., additional, Rühli, F., additional, Ruse, M., additional, Rutledge, G.A., additional, Stoneking, M., additional, Templeton, A.R., additional, Tibayrenc, M., additional, Varki, A., additional, Verschuuren, G.M., additional, Wakano, J.Y., additional, Wood, B., additional, and Zampieri, F., additional
- Published
- 2017
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3. Characterizing the transition from immune response to tissue repair after myocardial infarction by multiparametric imaging.
- Author
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Hess A, Borchert T, Ross TL, Bengel FM, and Thackeray JT
- Subjects
- Animals, Immunity, Mice, Myocardium pathology, Positron-Emission Tomography methods, Myocardial Infarction pathology, Ventricular Remodeling physiology
- Abstract
Persistent inflammation following myocardial infarction (MI) precipitates adverse outcome including acute ventricular rupture and chronic heart failure. Molecular imaging allows longitudinal assessment of immune cell activity in the infarct territory and predicts severity of remodeling. We utilized a multiparametric imaging platform to assess the immune response and cardiac healing following MI in mice. Suppression of circulating macrophages prior to MI paradoxically resulted in higher total leukocyte content in the heart, demonstrated by increased CXC motif chemokine receptor 4 (CXCR4) positron emission tomography imaging. This supported the formation of a thrombus overlying the injured region, as identified by magnetic resonance imaging. The injured and thrombotic region in macrophage depeleted mice subsequently showed active calcification, as evidenced by accumulation of
18 F-fluoride and by cardiac computed tomography. Importantly, macrophage suppression triggered a prolonged inflammatory response confirmed by post-mortem tissue analysis that was associated with higher mortality from ventricular rupture early after occlusion and with increased infarct size and worse chronic contractile function at 6 weeks after reperfusion. These findings establish a molecular imaging toolbox for monitoring the interplay between adverse immune response and tissue repair after MI. This may serve as a foundation for development and monitoring of novel targeted therapies that may include immune modulation and endogenous healing support., (© 2022. The Author(s).)- Published
- 2022
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4. Identification of molecular markers for the flower type in the ornamental crop Calluna vulgaris
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Borchert, T. and Hohe, A.
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- 2009
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5. Role of phosphodiesterases in the development of takotsubo syndrome
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Huebscher, D, primary, Borchert, T, additional, Hasenfuss, G, additional, Nikolaev, V.O, additional, and Streckfuss-Boemeke, K, additional
- Published
- 2020
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6. Problems or prospects? Being a parent in the early phase of the COVID-19 pandemic in Germany.
- Author
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Ecker A, Jarvers I, Schleicher D, Kandsperger S, Schelhorn I, Meyer M, Borchert T, Lüdtke M, and Shiban Y
- Abstract
Background: In the early phase of the COVID-19 pandemic, many restrictions hit people in ways never seen before. Mental wellbeing was affected and burden was high, especially for high-risk groups such as parents. However, to our knowledge no research has yet examined whether being a parent was not only a risk for psychological burden but also a way to cope with the COVID-19 pandemic., Methods: An online survey was used to collect data from 1,121 participants from April to June 2020. In addition to demographic variables, risk factors (financial burden, problems complying with COVID-19 restrictions, and pre-treatment due to mental health problems) and protective factors (emotion regulation, humor, and crisis self-efficacy) were collected. The dataset was divided into three groups: parents whose children lived at home ( n = 395), parents whose children did not (no longer) live at home ( n = 165), and people who were not parents ( n = 561)., Results: A linear mixed effect model showed that parents had no higher burden than non-parents, and even less when children did not live at home. Expected risk factors were generally less important, and there were no differences between parents and non-parents. In contrast, parents had advantages in protective factors., Conclusion: In the early phase of the COVID-19 pandemic, it was shown that parents (with and without their children at home) were not necessarily at risk due to additional burden, but also had prospects of coping better with the situation than people without children., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ecker, Jarvers, Schleicher, Kandsperger, Schelhorn, Meyer, Borchert, Lüdtke and Shiban.)
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- 2022
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7. Interrogating Cardio-Renal Crosstalk After Acute Myocardial Infarction by Use of TSPO-Targeted PET/CT
- Author
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Werner, R, additional, Thackeray, JT, additional, Hess, A, additional, Borchert, T, additional, Wollert, KC, additional, Melk, A, additional, Ross, TL, additional, and Bengel, FM, additional
- Published
- 2020
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8. 3074Analyzing the regulation of a catecholamine-dependent altered cAMP signaling in a patient-specific induced pluripotent stem cell takotsubo-model
- Author
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Huebscher, D, primary, Borchert, T, additional, Hasenfuss, G, additional, Nikolaev, V, additional, and Streckfuss-Boemeke, K, additional
- Published
- 2019
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9. 2163Molecular imaging of cardiac and neuroinflammation early after myocardial infarction and in progressive heart failure
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Borchert, T, primary, Hess, A, additional, Lukacevic, M, additional, Ross, T L, additional, Bengel, F M, additional, and Thackeray, J T, additional
- Published
- 2019
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10. Identifying Two Family Members in Jacob Cornelisz’s Amsterdam Workshop: Cornelis Buys and Cornelis Anthonisz
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Meuwissen, D., Faries, Molly, Dubois, A., Couvert, J., Borchert, T.-H., Art and Culture, History, Antiquity, and CLUE+
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Workshop practice ,Cornelis Buys ,Amsterdam ,Jacob Cornelisz van Oostsanen - Abstract
The Amsterdam painter, Jacob Cornelisz, established one of the largest and most diversified workshops of his time – as has been made abundantly clear by the exhibitions in Alkmaar and Amsterdam in the spring of 2014. In this paper, the authors build on the research associated with the exhibitions as well as discoveries made by Amsterdam archivist, S.A.C. (Bas) Dudok van Heel, in publishing the genealogy that included Jacob Cornelisz along with other painters known as Cornelis Buys. These insights open up possibilities for new attributions, allowing the identification of one workshop assistant as Cornelis Jacobsz alias Cornelis Buys, Jacob Cornelisz’s eldest son, and the identification of another assistant, the Berlin Sketchbook Master, as Jacob’s grandson, Cornelis Anthonisz. This, in turn, reveals hitherto unknown contributions made to Jacob’s shop by Jan van Scorel after his return from Italy in 1524.
- Published
- 2018
11. 249Serial 11C-methionine PET detects involvement of astroglia in neuroinflammation following acute myocardial infarction
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Bascunana Almarcha, P, primary, Hess, A, additional, Borchert, T, additional, Wang, Y, additional, Wollert, K C, additional, Bengel, F M, additional, and Thackeray, J T, additional
- Published
- 2019
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12. Dissecting the target leukocyte subpopulations of clinically relevant inflammation radiopharmaceuticals.
- Author
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Borchert T, Beitar L, Langer LBN, Polyak A, Wester HJ, Ross TL, Hilfiker-Kleiner D, Bengel FM, and Thackeray JT
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- Animals, Cell Culture Techniques, Coordination Complexes pharmacokinetics, Fibroblasts metabolism, Fluorine Radioisotopes pharmacokinetics, Fluorodeoxyglucose F18 pharmacokinetics, Humans, Indoles pharmacokinetics, Myocytes, Cardiac metabolism, Octreotide analogs & derivatives, Octreotide pharmacokinetics, Organometallic Compounds pharmacokinetics, Peptides, Cyclic pharmacokinetics, Rats, Leukocytes metabolism, Macrophages metabolism, Radiopharmaceuticals pharmacokinetics
- Abstract
Background: Leukocyte subtypes bear distinct pro-inflammatory, reparative, and regulatory functions. Imaging inflammation provides information on disease prognosis and may guide therapy, but the cellular basis of the signal remains equivocal. We evaluated leukocyte subtype specificity of characterized clinically relevant inflammation-targeted radiotracers., Methods and Results: Leukocyte populations were purified from blood- and THP-1-derived macrophages were polarized into M1-, reparative M2a-, or M2c-macrophages. In vitro uptake assays were conducted using tracers of enhanced glucose or amino acid metabolism and molecular markers of inflammatory cells. Both
18 F-deoxyglucose (18 F-FDG) and the labeled amino acid11 C-methionine (11 C-MET) displayed higher uptake in neutrophils and monocytes compared to other leukocytes (P = 0.005), and markedly higher accumulation in pro-inflammatory M1-macrophages compared to reparative M2a-macrophages (P < 0.001). Molecular tracers68 Ga-DOTATATE targeting the somatostatin receptor type 2 and68 Ga-pentixafor targeting the chemokine receptor type 4 (CXCR4) exhibited broad uptake by leukocyte subpopulations and polarized macrophages with highest uptake in T-cells/natural killer cells and B-cells compared to neutrophils. Mitochondrial translocator protein (TSPO)-targeted18 F-flutriciclamide selectively accumulated in monocytes and pro-inflammatory M1 macrophages (P < 0.001). Uptake by myocytes and fibroblasts tended to be higher for metabolic radiotracers., Conclusions: The different in vitro cellular uptake profiles may allow isolation of distinct phases of the inflammatory pathway with specific inflammation-targeted radiotracers. The pathogenetic cell population in specific inflammatory diseases should be considered in the selection of an appropriate imaging agent., (© 2019. American Society of Nuclear Cardiology.)- Published
- 2021
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13. P1851Catecholamine-dependent cAMP signaling in a patient-specific induced pluripotent stem cell takotsubo-model
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Streckfuss-Boemeke, K, primary, Huebscher, D, additional, Borchert, T, additional, Nikolaev, V O, additional, Sossalla, S T, additional, Templin, C, additional, and Hasenfuss, G, additional
- Published
- 2018
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14. AntimiR-132 Attenuates Myocardial Hypertrophy in an Animal Model of Percutaneous Aortic Constriction.
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Hinkel R, Batkai S, Bähr A, Bozoglu T, Straub S, Borchert T, Viereck J, Howe A, Hornaschewitz N, Oberberger L, Jurisch V, Kozlik-Feldmann R, Freudenthal F, Ziegler T, Weber C, Sperandio M, Engelhardt S, Laugwitz KL, Moretti A, Klymiuk N, Thum T, and Kupatt C
- Subjects
- Animals, Aorta, Thoracic surgery, Cardiomegaly complications, Cardiomegaly diagnosis, Constriction, Constriction, Pathologic complications, Coronary Vessels, Disease Models, Animal, Heart Failure etiology, Heart Failure physiopathology, Heart Failure prevention & control, Injections, Intra-Arterial, MicroRNAs genetics, MicroRNAs metabolism, Stents adverse effects, Swine, Treatment Outcome, Antagomirs administration & dosage, Aortic Diseases complications, Cardiomegaly drug therapy, MicroRNAs antagonists & inhibitors, Ventricular Remodeling drug effects
- Abstract
Background: Pathological cardiac hypertrophy is a result of afterload-increasing pathologies including untreated hypertension and aortic stenosis. It features progressive adverse cardiac remodeling, myocardial dysfunction, capillary rarefaction, and interstitial fibrosis often leading to heart failure., Objectives: This study aimed to establish a novel porcine model of pressure-overload-induced heart failure and to determine the effect of inhibition of microribonucleic acid 132 (miR-132) on heart failure development in this model., Methods: This study developed a novel porcine model of percutaneous aortic constriction by implantation of a percutaneous reduction stent in the thoracic aorta, inducing progressive remodeling at day 56 (d56) after pressure-overload induction. In this study, an antisense oligonucleotide specifically inhibiting miR-132 (antimiR-132), was regionally applied via intracoronary injection at d0 (percutaneous transverse aortic constriction induction) and d28., Results: At d56, antimiR-132 treatment diminished cardiomyocyte cross-sectional area (188.9 ± 2.8 vs. 258.4 ± 9.0 μm
2 in untreated hypertrophic hearts) and improved global cardiac function (ejection fraction 48.9 ± 1.0% vs. 36.1 ± 1.7% in control hearts). Moreover, at d56 antimiR-132-treated hearts displayed less increase of interstitial fibrosis compared with sham-operated hearts (Δsham 1.8 ± 0.5%) than control hearts (Δsham 10.8 ± 0.6%). Of note, cardiac platelet and endothelial cell adhesion molecule 1+ capillary density was higher in the antimiR-132-treated hearts (647 ± 20 cells/mm2 ) compared with in the control group (485 ± 23 cells/mm2 )., Conclusions: The inhibition of miR-132 is a valid strategy in prevention of heart failure progression in hypertrophic heart disease and may be developed as a treatment for heart failure of nonischemic origin., Competing Interests: FUNDING SUPPORT AND AUTHOR DISCLOSURES This study was supported by the Deutsches Zentrum für Herz-Kreislauf-Forschung (German Centre for Cardiovascular Research) (to Drs. Hinkel, Weber, Engelhardt, Laugwitz, Moretti, and Kupatt) and, with regard to model development, by the Deutsche Forschungsgemeinschaft (German Research Foundation) (TRR 267 to Drs. Thum, Weber, Engelhardt, Laugwitz, and Kupatt.; and KFO311 to Dr. Thum.). Drs. Baktai and Thum are founders of Cardior Pharmaceuticals GmbH and hold shares. Dr. Thum filed and licensed patents in the field of noncoding ribonucleic acids including miR-132. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2021
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15. CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure.
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Batkai S, Genschel C, Viereck J, Rump S, Bär C, Borchert T, Traxler D, Riesenhuber M, Spannbauer A, Lukovic D, Zlabinger K, Hašimbegović E, Winkler J, Garamvölgyi R, Neitzel S, Gyöngyösi M, and Thum T
- Subjects
- Animals, Diastole, Disease Models, Animal, Swine, Ventricular Remodeling, Heart Failure drug therapy, Myocardial Infarction drug therapy
- Abstract
Aims: Cardiac miR-132 activation leads to adverse remodelling and pathological hypertrophy. CDR132L is a synthetic lead-optimized oligonucleotide inhibitor with proven preclinical efficacy and safety in heart failure (HF) early after myocardial infarction (MI), and recently completed clinical evaluation in a Phase 1b study (NCT04045405). The aim of the current study was to assess safety and efficacy of CDR132L in a clinically relevant large animal (pig) model of chronic heart failure following MI., Methods and Results: In a chronic model of post-MI HF, slow-growing pigs underwent 90 min left anterior descending artery occlusion followed by reperfusion. Animals were randomized and treatment started 1-month post-MI. Monthly intravenous (IV) treatments of CDR132L over 3 or 5 months (3× or 5×) were applied in a blinded randomized placebo-controlled fashion. Efficacy was evaluated based on serial magnetic resonance imaging, haemodynamic, and biomarker analyses. The treatment regime provided sufficient tissue exposure and CDR132L was well tolerated. Overall, CDR132L treatment significantly improved cardiac function and reversed cardiac remodelling. In addition to the systolic recovery, diastolic function was also ameliorated in this chronic model of HF., Conclusion: Monthly repeated dosing of CDR132L is safe and adequate to provide clinically relevant exposure and therapeutic efficacy in a model of chronic post-MI HF. CDR132L thus should be explored as treatment for the broad area of chronic heart failure., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)
- Published
- 2021
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16. 11 C-Methionine PET Identifies Astroglia Involvement in Heart-Brain Inflammation Networking After Acute Myocardial Infarction.
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Bascuñana P, Hess A, Borchert T, Wang Y, Wollert KC, Bengel FM, and Thackeray JT
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- Acute Disease, Animals, Male, Mice, Inbred C57BL, Myocardial Infarction complications, Myocardial Infarction pathology, Whole Body Imaging, Astrocytes pathology, Carbon Radioisotopes, Encephalitis complications, Methionine, Microglia pathology, Myocardial Infarction diagnostic imaging, Positron-Emission Tomography
- Abstract
Acute myocardial infarction (MI) triggers a local and systemic inflammatory response. We recently showed microglia involvement using translocator protein imaging. Here, we evaluated whether
11 C-methionine provides further insight into heart-brain inflammation networking. Methods: Male C57BL/6 mice underwent permanent coronary artery ligation followed by11 C-methionine PET at 3 and 7 d ( n = 3). In subgroups, leukocyte homing was blocked by integrin antibodies ( n = 5). The cellular substrate for PET signal was identified using brain section immunostaining. Results:11 C-methionine uptake (percentage injected dose/cm3 ) peaked in the MI region on day 3 (5.9 ± 0.9 vs. 2.4 ± 0.5), decreasing to the control level by day 7 (4.3 ± 0.6). Brain uptake was proportional to cardiac uptake ( r = 0.47, P < 0.05), peaking also on day 3 (2.9 ± 0.4 vs. 2.4 ± 0.3) and returning to baseline on day 7 (2.3 ± 0.4). Integrin blockade reduced uptake at every time point. Immunostaining on day 3 revealed colocalization of the l-type amino acid transporter, with glial fibrillary acidic protein-positive astrocytes but not CD68-positive microglia. Conclusion: PET imaging with11 C-methionine specifically identifies an astrocyte component, enabling further dissection of the heart-brain axis in post-MI inflammation., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)- Published
- 2020
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17. Angiotensin-converting enzyme inhibitor treatment early after myocardial infarction attenuates acute cardiac and neuroinflammation without effect on chronic neuroinflammation.
- Author
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Borchert T, Hess A, Lukačević M, Ross TL, Bengel FM, and Thackeray JT
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- Acute Disease, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Animals, Chronic Disease, Mice, Mice, Inbred C57BL, Enalapril pharmacology, Enalapril therapeutic use, Heart diagnostic imaging, Heart drug effects, Inflammation diagnostic imaging, Inflammation drug therapy, Myocardial Infarction complications, Myocardial Infarction diagnostic imaging, Myocardial Infarction drug therapy, Nervous System Diseases diagnostic imaging, Nervous System Diseases drug therapy
- Abstract
Purpose: Myocardial infarction (MI) triggers a local inflammatory response which orchestrates cardiac repair and contributes to concurrent neuroinflammation. Angiotensin-converting enzyme (ACE) inhibitor therapy not only attenuates cardiac remodeling by interfering with the neurohumoral system, but also influences acute leukocyte mobilization from hematopoietic reservoirs. Here, we seek to dissect the anti-inflammatory and anti-remodeling contributions of ACE inhibitors to the benefit of heart and brain outcomes after MI., Methods: C57BL/6 mice underwent permanent coronary artery ligation (n = 41) or sham surgery (n = 9). Subgroups received ACE inhibitor enalapril (20 mg/kg, oral) either early (anti-inflammatory strategy; 10 days treatment beginning 3 days prior to surgery; n = 9) or delayed (anti-remodeling; continuous from 7 days post-MI; n = 16), or no therapy (n = 16). Cardiac and neuroinflammation were serially investigated using whole-body macrophage- and microglia-targeted translocator protein (TSPO) PET at 3 days, 7 days, and 8 weeks. In vivo PET signal was validated by autoradiography and histopathology., Results: Myocardial infarction evoked higher TSPO signal in the infarct region at 3 days and 7 days compared with sham (p < 0.001), with concurrent elevation in brain TSPO signal (+ 18%, p = 0.005). At 8 weeks after MI, remote myocardium TSPO signal was increased, consistent with mitochondrial stress, and corresponding to recurrent neuroinflammation. Early enalapril treatment lowered the acute TSPO signal in the heart and brain by 55% (p < 0.001) and 14% (p = 0.045), respectively. The acute infarct signal predicted late functional outcome (r = 0.418, p = 0.038). Delayed enalapril treatment reduced chronic myocardial TSPO signal, consistent with alleviated mitochondrial stress. Early enalapril therapy tended to lower TSPO signal in the failing myocardium at 8 weeks after MI (p = 0.090) without an effect on chronic neuroinflammation., Conclusions: Whole-body TSPO PET identifies myocardial macrophage infiltration and neuroinflammation after MI, and altered cardiomyocyte mitochondrial density in chronic heart failure. Improved chronic cardiac outcome by enalapril treatment derives partially from acute anti-inflammatory activity with complementary benefits in later stages. Whereas early ACE inhibitor therapy lowers acute neuroinflammation, chronic alleviation is not achieved by early or delayed ACE inhibitor therapy, suggesting a more complex mechanism underlying recurrent neuroinflammation in ischemic heart failure.
- Published
- 2020
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18. Non-Human Primate iPSC Generation, Cultivation, and Cardiac Differentiation under Chemically Defined Conditions.
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Stauske M, Rodriguez Polo I, Haas W, Knorr DY, Borchert T, Streckfuss-Bömeke K, Dressel R, Bartels I, Tiburcy M, Zimmermann WH, and Behr R
- Subjects
- Animals, Cell Shape, Cells, Cultured, Cellular Reprogramming, Feeder Cells cytology, Fibroblasts cytology, Humans, Macaca mulatta, Myocytes, Cardiac cytology, Papio, Time Factors, Tissue Engineering, Transgenes, Cell Culture Techniques methods, Cell Differentiation, Induced Pluripotent Stem Cells cytology, Myocardium cytology
- Abstract
Non-human primates (NHP) are important surrogate models for late preclinical development of advanced therapy medicinal products (ATMPs), including induced pluripotent stem cell (iPSC)-based therapies, which are also under development for heart failure repair. For effective heart repair by remuscularization, large numbers of cardiomyocytes are required, which can be obtained by efficient differentiation of iPSCs. However, NHP-iPSC generation and long-term culture in an undifferentiated state under feeder cell-free conditions turned out to be problematic. Here we describe the reproducible development of rhesus macaque ( Macaca mulatta ) iPSC lines. Postnatal rhesus skin fibroblasts were reprogrammed under chemically defined conditions using non-integrating vectors. The robustness of the protocol was confirmed using another NHP species, the olive baboon ( Papio anubis ). Feeder-free maintenance of NHP-iPSCs was essentially dependent on concurrent Wnt-activation by GSK-inhibition (Gi) and Wnt-inhibition (Wi). Generated NHP-iPSCs were successfully differentiated into cardiomyocytes using a combined growth factor/GiWi protocol. The capacity of the iPSC-derived cardiomyocytes to self-organize into contractile engineered heart muscle (EHM) was demonstrated. Collectively, this study establishes a reproducible protocol for the robust generation and culture of NHP-iPSCs, which are useful for preclinical testing of strategies for cell replacement therapies in NHP.
- Published
- 2020
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19. Left Ventricular Remodelling Associated with the Transient Elevated [ 68 Ga]Ga-Pentixafor Activity in the Remote Myocardium Following Acute Myocardial Infarction.
- Author
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Wu P, Xu L, Wang Q, Ma X, Wang X, Wang H, He S, Ru H, Zhao Y, Xiao Y, Zhang J, Wang X, An S, Hacker M, Li X, Zhang X, Wang Y, Yang M, Wu Z, and Li S
- Subjects
- Animals, Male, Coordination Complexes chemistry, Coordination Complexes pharmacology, Rats, Sprague-Dawley, Peptides, Cyclic pharmacology, Peptides, Cyclic chemistry, Rats, Positron-Emission Tomography, Myocardial Infarction diagnostic imaging, Myocardial Infarction metabolism, Myocardial Infarction drug therapy, Myocardial Infarction pathology, Ventricular Remodeling drug effects, Myocardium metabolism, Myocardium pathology
- Abstract
Background: Previous studies have initially reported accompanying elevated 2-deoxy-2[
18 F]fluoro-D-glucose ([18 F]F-FDG) inflammatory activity in the remote area and its prognostic value after acute myocardial infarction (AMI). Non-invasive characterization of the accompanying inflammation in the remote myocardium may be of potency in guiding future targeted theranostics. [68 Ga]Ga-Pentixafor targeting chemokine receptor 4 (CXCR4) on the surface of inflammatory cells is currently one of the promising inflammatory imaging agents. In this study, we sought to focus on the longitudinal evolution of [68 Ga]Ga-Pentixafor activities in the remote myocardium following AMI and its association with cardiac function., Methods: Twelve AMI rats and six Sham rats serially underwent [68 Ga]Ga-Pentixafor imaging at pre-operation, and 5, 7, 14 days post-operation. Maximum and mean standard uptake value (SUV) and target-to-background ratio (TBR) were assessed to indicate the uptake intensity. Gated [18 F]F-FDG imaging and immunofluorescent staining were performed to obtain cardiac function and responses of pro-inflammatory and reparative macrophages, respectively., Results: The uptake of [68 Ga]Ga-Pentixafor in the infarcted myocardium peaked at day 5 (all P = 0.003), retained at day 7 (all P = 0.011), and recovered at day 14 after AMI (P > 0.05), paralleling with the rise-fall pro-inflammatory M1 macrophages (P < 0.05). Correlated with the peak activity in the infarct territory, [68 Ga]Ga-Pentixafor uptake in the remote myocardium on day 5 early after AMI significantly increased (AMI vs. Sham: SUVmean, SUVmax, and TBRmean: all P < 0.05), and strongly correlated with contemporaneous EDV and/or ESV (SUVmean and TBRmean: both P < 0.05). The transitory remote activity recovered as of day 7 post-AMI (AMI vs. Sham: P > 0.05)., Conclusions: Corresponding with the peaked [68 Ga]Ga-Pentixafor activity in the infarcted myocardium, the activity in the remote region elevated accordingly and led to contemporaneous left ventricular remodelling early after AMI. Further studies are warranted to clarify its clinical application potential., (© 2024. The Author(s), under exclusive licence to World Molecular Imaging Society.)- Published
- 2024
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20. Staging the court of Burgundy. Proceedings of the conference 'The Splendour of Burgundy'
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Blockmans, W., Borchert, T.-H., Gabriëls, N., Oosterman, J.B., and Oosterwijk, A. van
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Cultural and Religious Identities [Memory] - Abstract
Item does not contain fulltext The Splendour of Burgundy 394 p.
- Published
- 2013
21. A High-Throughput Method as a Diagnostic Tool for HIV Detection in Patient-Specific Induced Pluripotent Stem Cells Generated by Different Reprogramming Methods.
- Author
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Hübscher D, Rebs S, Haupt L, Borchert T, Guessoum CI, Treu F, Köhne S, Maus A, Hambrecht M, Sossalla S, Dressel R, Uy A, Jakob M, Hasenfuss G, and Streckfuss-Bömeke K
- Abstract
Induced pluripotent stem cells (iPSCs) provide a unique opportunity for generation of patient-specific cells for use in translational purposes. We aimed to compare iPSCs generated by different reprogramming methods regarding their reprogramming efficiency, pluripotency capacity, and the possibility to use high-throughput PCR-based methods for detection of human pathogenic viruses. iPSCs from skin fibroblasts (FB), peripheral blood mononuclear cells (PBMCs), or mesenchymal stem cells (MSCs) were generated by using three different reprogramming systems including chromosomal integrating and nonintegrating methods. Reprogramming efficiencies were in accordance with the literature, indicating that the parental cell type and the reprogramming method play a major role for the reprogramming efficiencies (FB: STEMCCA: 1.30 ± 0.18, Sendai virus: 1.37 ± 0.01, and episomal plasmids: 0.04 ± 0.02; PBMCs: Sendai virus: 0.002 ± 0.001, episomal plasmids: 0) but result in the same characteristics of pluripotency. We found the highest reprogramming efficiencies for MSC with 3.32 ± 1.2 by using episomal plasmids. Since GMP standard working procedures and screening units need virus contamination-free cell lines, we studied HIV-1 contamination in the generated iPSCs. We used the high-throughput cobas® 6800/8800 system, which is normally used for detection of HIV-1 in plasma of patients, and found that footprint-free reprogramming methods as episomal plasmids and Sendai virus are useful for the described virus detection method. This fast, cost-effective, robust, and reliable assay demonstrates the feasibility to use high-throughput PCR-based methods for detection of human pathogenic viruses in ps-iPSC lines that were generated with nongenome integrating reprogramming methods., Competing Interests: The authors declare no conflicts of interest.
- Published
- 2019
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22. Malformation of gynoecia impedes fertilisation in bud-flowering Calluna vulgaris.
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Behrend, A., Borchert, T., Müller, A., Tänzer, J., and Hohe, A.
- Subjects
ANGIOSPERMS ,BUDS ,PLANT fertilization ,PLANT abnormalities ,HEATHER ,GYNOECIUM ,GERMINATION - Abstract
In Calluna vulgaris, a common bedding plant during autumn in the northern hemisphere, the bud-blooming mutation of flower morphology is of high economic importance. Breeding of new bud-blooming cultivars suffers from poor seed set in some of the desirable bud-flowering crossing partners. In the current study, fertilisation and seed development in genotypes with good or poor seed set were monitored in detail in order to examine pre- and post-zygotic cross breeding incompatibilities. Whereas no distinct differences were detected in seed development, pollen tube growth was impeded in the pistils of genotypes characterised by poor seed set. Detailed microscopic analysis revealed malformations of the gynoecia due to imperfect fusion of carpels. Hence, a pre-zygotic mechanism hindering pollen tube growth due to malformation of gynoecia was deduced. An interaction of putative candidate genes involved in malformation of gynoecia with floral organ identity genes controlling the flower architecture is discussed. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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23. Enkele modellen uit het atelier van Bernard van Orley
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Hendrikman, L.I., van den Brink, P B R, and Borchert, T H
- Published
- 1999
24. Malformation of gynoecia impedes fertilisation in bud‐flowering Calluna vulgaris
- Author
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Behrend, A., primary, Borchert, T., additional, Müller, A., additional, Tänzer, J., additional, and Hohe, A., additional
- Published
- 2012
- Full Text
- View/download PDF
25. ON THE GENETICS OF THE 'BUD-FLOWERING' TRAIT IN THE ORNAMENTAL CROP CALLUNA VULGARIS
- Author
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Borchert, T., primary, Behrend, A., additional, and Hohe, A., additional
- Published
- 2012
- Full Text
- View/download PDF
26. Monastic Labor: Thinking about the Work of Monks in Contemporary Theravada Communities
- Author
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Borchert, T., primary
- Published
- 2010
- Full Text
- View/download PDF
27. The Abbot's New House: Thinking about How Religion Works among Buddhists and Ethnic Minorities in Southwest China
- Author
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Borchert, T., primary
- Published
- 2010
- Full Text
- View/download PDF
28. Structure and mechanism of rhamnogalacturonan lyases
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Otten, H., primary, Jensen, M.H., additional, Christensen, U., additional, Borchert, T., additional, Christensen, L.L.H., additional, Larsen, S., additional, and Lo Leggio, L., additional
- Published
- 2008
- Full Text
- View/download PDF
29. New insight into catalytic mechanism of serine proteases from ultra-high resolution X-ray studies
- Author
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Raczynska, J., primary, Dauter, M., additional, Borchert, T., additional, and Rypniewski, W., additional
- Published
- 2008
- Full Text
- View/download PDF
30. Crystallographic and kinetic studies of rhamnogalacturonan lyase fromAspergillus aculeatus
- Author
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Larsen, S., primary, Jensen, M. H., additional, Christensen, U., additional, Lo Leggio, L., additional, Borchert, T., additional, and Christensen, L. L. H., additional
- Published
- 2007
- Full Text
- View/download PDF
31. Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial.
- Author
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Bauersachs J, Solomon SD, Anker SD, Antorrena-Miranda I, Batkai S, Viereck J, Rump S, Filippatos G, Granzer U, Ponikowski P, de Boer RA, Vardeny O, Hauke W, and Thum T
- Subjects
- Humans, Male, Female, Heart Failure drug therapy, Heart Failure physiopathology, Ventricular Dysfunction, Left drug therapy, Ventricular Dysfunction, Left physiopathology, Ventricular Dysfunction, Left etiology, Treatment Outcome, MicroRNAs, Ventricular Remodeling drug effects, Middle Aged, Aged, Oligonucleotides, Antisense therapeutic use, Oligonucleotides, Antisense administration & dosage, Double-Blind Method, Ventricular Function, Left physiology, Ventricular Function, Left drug effects, Myocardial Infarction drug therapy, Myocardial Infarction physiopathology, Myocardial Infarction complications, Stroke Volume physiology
- Abstract
Aim: Inhibition of microRNA (miR)-132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR-132, demonstrated beneficial effects on left ventricular (LV) structure and function in relevant preclinical models, and was safe and well tolerated in a Phase 1b study in stable chronic HF patients. Patients with acute myocardial infarction (MI) and subsequent LV dysfunction and remodelling have limited therapeutic options, and may profit from early CDR132L treatment., Methods: The HF-REVERT (Phase 2, multicenter, randomized, parallel, 3-arm, placebo-controlled Study to Assess Efficacy and Safety of CDR132L in Patients with Reduced Left Ventricular Ejection Fraction after Myocardial Infarction) evaluates the efficacy and safety of CDR132L in HF patients post-acute MI (n = 280), comparing the effect of 5 and 10 mg/kg CDR132L, administered as three single intravenous doses 28 days apart, in addition to standard of care. Key inclusion criteria are the diagnosis of acute MI, the development of systolic dysfunction (LV ejection fraction ≤45%) and elevated N-terminal pro-B-type natriuretic peptide. The study consists of a 6-month double-blinded treatment period with the primary endpoint LV end-systolic volume index and relevant secondary endpoints, followed by a 6-month open-label observation period., Conclusion: The HF-REVERT trial may underpin the concept of miR-132 inhibition to prevent or reverse cardiac remodelling in post-MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)
- Published
- 2024
- Full Text
- View/download PDF
32. Catecholamine-Dependent β-Adrenergic Signaling in a Pluripotent Stem Cell Model of Takotsubo Cardiomyopathy.
- Author
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Borchert T, Hübscher D, Guessoum CI, Lam TD, Ghadri JR, Schellinger IN, Tiburcy M, Liaw NY, Li Y, Haas J, Sossalla S, Huber MA, Cyganek L, Jacobshagen C, Dressel R, Raaz U, Nikolaev VO, Guan K, Thiele H, Meder B, Wollnik B, Zimmermann WH, Lüscher TF, Hasenfuss G, Templin C, and Streckfuss-Bömeke K
- Subjects
- Adult, Cell Differentiation, Cells, Cultured, Female, Humans, Induced Pluripotent Stem Cells pathology, Middle Aged, Myocytes, Cardiac metabolism, Myocytes, Cardiac pathology, Signal Transduction, Takotsubo Cardiomyopathy pathology, Catecholamines pharmacology, Induced Pluripotent Stem Cells metabolism, Receptors, Adrenergic, beta metabolism, Takotsubo Cardiomyopathy metabolism
- Abstract
Background: Takotsubo syndrome (TTS) is characterized by an acute left ventricular dysfunction and is associated with life-threating complications in the acute phase. The underlying disease mechanism in TTS is still unknown. A genetic basis has been suggested to be involved in the pathogenesis., Objectives: The aims of the study were to establish an in vitro induced pluripotent stem cell (iPSC) model of TTS, to test the hypothesis of altered β-adrenergic signaling in TTS iPSC-cardiomyocytes (CMs), and to explore whether genetic susceptibility underlies the pathophysiology of TTS., Methods: Somatic cells of patients with TTS and control subjects were reprogrammed to iPSCs and differentiated into CMs. Three-month-old CMs were subjected to catecholamine stimulation to simulate neurohumoral overstimulation. We investigated β-adrenergic signaling and TTS cardiomyocyte function., Results: Enhanced β-adrenergic signaling in TTS-iPSC-CMs under catecholamine-induced stress increased expression of the cardiac stress marker NR4A1; cyclic adenosine monophosphate levels; and cyclic adenosine monophosphate-dependent protein kinase A-mediated hyperphosphorylation of RYR2-S2808, PLN-S16, TNI-S23/24, and Cav1.2-S1928, and leads to a reduced calcium time to transient 50% decay. These cellular catecholamine-dependent responses were mainly mediated by β
1 -adrenoceptor signaling in TTS. Engineered heart muscles from TTS-iPSC-CMs showed an impaired force of contraction and a higher sensitivity to isoprenaline-stimulated inotropy compared with control subjects. In addition, altered electrical activity and increased lipid accumulation were detected in catecholamine-treated TTS-iPSC-CMs, and were confirmed by differentially expressed lipid transporters CD36 and CPT1C. Furthermore, we uncovered genetic variants in different key regulators of cardiac function., Conclusions: Enhanced β-adrenergic signaling and higher sensitivity to catecholamine-induced toxicity were identified as mechanisms associated with the TTS phenotype. (International Takotsubo Registry [InterTAK Registry] [InterTAK]; NCT01947621)., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2017
- Full Text
- View/download PDF
33. Effect of prebreeding maintenance diet on subsequent reproduction by artificial insemination in alpine and saanen goats
- Author
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Goonewardene, L.A., primary, Whitmore, W., additional, Jaeger, S., additional, Borchert, T., additional, Okine, E., additional, Ashmawy, O., additional, and Emond, S., additional
- Published
- 1997
- Full Text
- View/download PDF
34. Identification of a Bacillus subtilis secretion mutant using a -galactosidase screening procedure
- Author
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Jacobs, M. F., primary, Andersen, J. B., additional, Borchert, T. V., additional, and Kontinen, V. P., additional
- Published
- 1995
- Full Text
- View/download PDF
35. Design, creation, and characterization of a stable,monomeric triosephosphate isomerase.
- Author
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Borchert, T V, primary, Abagyan, R, additional, Jaenicke, R, additional, and Wierenga, R K, additional
- Published
- 1994
- Full Text
- View/download PDF
36. Effect of signal sequence alterations on export of levansucrase in Bacillus subtilis
- Author
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Borchert, T V, primary and Nagarajan, V, additional
- Published
- 1991
- Full Text
- View/download PDF
37. "The usual suspects"- analysis of transcriptome sequences reveals deviating B gene activity in C. vulgaris bud bloomers.
- Author
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Behrend A, Borchert T, and Hohe A
- Subjects
- Base Sequence, Contig Mapping, Gene Expression Profiling, Gene Expression Regulation, Plant, Gene Library, Gene Ontology, MADS Domain Proteins metabolism, Molecular Sequence Annotation, Plant Proteins genetics, Plant Proteins metabolism, Real-Time Polymerase Chain Reaction, Calluna genetics, Flowers genetics, Genes, Plant, MADS Domain Proteins genetics, Transcriptome genetics
- Abstract
Background: The production of heather (Calluna vulgaris) in Germany is highly dependent on cultivars with mutated flower morphology, the so-called diplocalyx bud bloomers. So far, this unique flower type of C. vulgaris has not been reported in any other plant species. The flowers are characterised by an extremely extended flower attractiveness, since the flower buds remain closed throughout the complete flowering season. The flowers of C. vulgaris bud bloomers are male sterile, because the stamens are absent. Furthermore, petals are converted into sepals. Therefore the diplocalyx bud bloomer flowers consist of two whorls of sepals directly followed by the gynoecium., Results: A broad comparison was undertaken to identify genes differentially expressed in the bud flowering phenotype and in the wild type of C. vulgaris. Transcriptome sequence reads were generated using 454 sequencing of two flower type specific cDNA libraries. In total, 360,000 sequence reads were obtained, assembled to 12,200 contigs, functionally mapped, and annotated. Transcript abundances were compared and 365 differentially expressed genes detected. Among these differentially expressed genes, Calluna vulgaris PISTILLATA (CvPI) which is the orthologue of the Arabidopsis B gene PISTILLATA (PI) was considered as the most promising candidate gene. Quantitative Reverse Transcription Polymerase Chain Reaction (qRT PCR) was performed to analyse the gene expression levels of two C. vulgaris B genes CvPI and Calluna vulgaris APETALA 3 (CvAP3) in both flower types. CvAP3 which is the orthologue of the Arabidopsis B gene APETALA 3 (AP3) turned out to be ectopically expressed in sepals of wild type and bud bloomer flowers. CvPI expression was proven to be reduced in the bud blooming flowers., Conclusions: Differential expression patterns of the B-class genes CvAP3 and CvPI were identified to cause the characteristic morphology of C. vulgaris flowers leading to the following hypotheses: ectopic expression of CvAP3 is a convincing explanation for the formation of a completely petaloid perianth in both flower types. In C. vulgaris, CvPI is essential for determination of petal and stamen identity. The characteristic transition of petals into sepals potentially depends on the observed deficiency of CvPI and CvAP3 expression in bud blooming flowers.
- Published
- 2015
- Full Text
- View/download PDF
38. A multi-disciplinary analysis of the Portrait of Philip the Good in Dijon.
- Author
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Verheyen, Jan, Buti, David, Cartechini, Laura, Fontana, Raffaella, Iwanicka, Magdalena, Raffaelli, Marco, and Targowski, Piotr
- Subjects
OPTICAL coherence tomography ,ART historians ,REFLECTANCE spectroscopy ,INFRARED imaging ,RESEARCH methodology ,SPECTRAL imaging ,MULTISPECTRAL imaging - Abstract
One of the finest fifteenth-century portraits of the Burgundian Duke Philip the Good resides in the Musée des Beaux-Arts in Dijon. This small yet exceptionally crafted panel holds significance for both historians and art historians alike. Surprisingly, prior to this study, the context, the dating and the authorship of the piece remained obscure, and the widely circulated hypothesis of it being "a copy of a lost portrait by Rogier van der Weyden" has never been corroborated by convincing arguments. Clarifying the context, dating and authorship of the painting were the primary objectives of the investigations discussed in the article. Therefore, this painting underwent a multidisciplinary investigation spanning both the positive and human sciences. Macro-XRF scans were conducted alongside hyperspectral reflectance scans, multispectral imaging in the visible and infrared range, and optical coherence tomography. These analyses were complemented by an art historical study. As a result, a precise delineation between authentic and retouched sections was achieved. This article does not merely present the various perspectives separately but constructs a coherent narrative based on all these foundations. This holistic multidisciplinary research methodology produced a clear account, albeit with some scope for future inquiry. The involvement of the painter Pieter Cristus was conclusively demonstrated. This painter, whether himself personally, an assistant in the workshop or a contemporary follower, is attributed to the genesis of this work, which is presumed to be not the original portrait but a contemporaneous copy, possibly commissioned by the Burgundian Duke himself. While we no longer remain in the dark and have lifted some veils, this study also paves the way for further investigation into this panel and the numerous other portraits of Philip the Good. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
39. Tregs delivered post-myocardial infarction adopt an injury-specific phenotype promoting cardiac repair via macrophages in mice.
- Author
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Alshoubaki, Yasmin K., Nayer, Bhavana, Lu, Yen-Zhen, Salimova, Ekaterina, Lau, Sin Nee, Tan, Jean L., Amann-Zalcenstein, Daniela, Hickey, Peter F., del Monte-Nieto, Gonzalo, Vasanthakumar, Ajithkumar, and Martino, Mikaël M.
- Abstract
Regulatory T cells (Tregs) are key immune regulators that have shown promise in enhancing cardiac repair post-MI, although the mechanisms remain elusive. Here, we show that rapidly increasing Treg number in the circulation post-MI via systemic administration of exogenous Tregs improves cardiac function in male mice, by limiting cardiomyocyte death and reducing fibrosis. Mechanistically, exogenous Tregs quickly home to the infarcted heart and adopt an injury-specific transcriptome that mediates repair by modulating monocytes/macrophages. Specially, Tregs lead to a reduction in pro-inflammatory Ly6C
Hi CCR2+ monocytes/macrophages accompanied by a rapid shift of macrophages towards a pro-repair phenotype. Additionally, exogenous Treg-derived factors, including nidogen-1 and IL-10, along with a decrease in cardiac CD8+ T cell number, mediate the reduction of the pro-inflammatory monocyte/macrophage subset in the heart. Supporting the pivotal role of IL-10, exogenous Tregs knocked out for IL-10 lose their pro-repair capabilities. Together, this study highlights the beneficial use of a Treg-based therapeutic approach for cardiac repair with important mechanistic insights that could facilitate the development of novel immunotherapies for MI.After myocardial infarction, excessive inflammation impairs heart repair, leading to reduced cardiac function. Here, the authors show that treatment with anti-inflammatory immune cells (regulatory T cells) improves cardiac repair by modulating the activity of a specific subset of macrophages in the heart. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
40. The Efficiency of In Vitro Differentiation of Primate iPSCs into Cardiomyocytes Depending on Their Cell Seeding Density and Cell Line Specificity.
- Author
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Tereshchenko, Yuliia, Petkov, Stoyan G., and Behr, Rüdiger
- Subjects
INDUCED pluripotent stem cells ,RHESUS monkeys ,CELL lines ,CELLULAR therapy ,PRIMATES - Abstract
A thorough characterization of induced pluripotent stem cells (iPSCs) used with in vitro models or therapeutics is essential. Even iPSCs derived from a single donor can exhibit variability within and between cell lines, which can lead to heterogeneity in results and hinder the promising future of cell replacement therapies. In this study, the cell seeding density of human and rhesus monkey iPSCs was tested to maximize the cell line-specific yield of the generated cardiomyocytes. We found that, despite using the same iPSC generation and differentiation protocols, the cell seeding density for the cell line-specific best differentiation efficiency could differ by a factor of four for the four cell lines used here. In addition, the cell lines showed differences in the range of cell seeding densities that they could tolerate without the severe loss of differentiation efficiency. Overall, our data show that the cell seeding density is a critical parameter for the differentiation inefficiency of primate iPSCs to cardiomyocytes and that iPSCs generated with the same episomal approach still exhibit considerable heterogeneity. Therefore, individual characterization of iPSC lines is required, and functional comparability with in vivo processes must be ensured to warrant the translatability of in vitro research with iPSCs. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Emerging Trends and Innovations in the Treatment and Diagnosis of Atherosclerosis and Cardiovascular Disease: A Comprehensive Review towards Healthier Aging.
- Author
-
Alradwan, Ibrahim, AL Fayez, Nojoud, Alomary, Mohammad N., Alshehri, Abdullah A., Aodah, Alhassan H., Almughem, Fahad A., Alsulami, Khulud A., Aldossary, Ahmad M., Alawad, Abdullah O., Tawfik, Yahya M. K., and Tawfik, Essam A.
- Subjects
PERIPHERAL vascular diseases ,TECHNOLOGICAL innovations ,CARDIOVASCULAR diseases risk factors ,CARDIOVASCULAR disease diagnosis ,GENE therapy - Abstract
Cardiovascular diseases (CVDs) are classed as diseases of aging, which are associated with an increased prevalence of atherosclerotic lesion formation caused by such diseases and is considered as one of the leading causes of death globally, representing a severe health crisis affecting the heart and blood vessels. Atherosclerosis is described as a chronic condition that can lead to myocardial infarction, ischemic cardiomyopathy, stroke, and peripheral arterial disease and to date, most pharmacological therapies mainly aim to control risk factors in patients with cardiovascular disease. Advances in transformative therapies and imaging diagnostics agents could shape the clinical applications of such approaches, including nanomedicine, biomaterials, immunotherapy, cell therapy, and gene therapy, which are emerging and likely to significantly impact CVD management in the coming decade. This review summarizes the current anti-atherosclerotic therapies' major milestones, strengths, and limitations. It provides an overview of the recent discoveries and emerging technologies in nanomedicine, cell therapy, and gene and immune therapeutics that can revolutionize CVD clinical practice by steering it toward precision medicine. CVD-related clinical trials and promising pre-clinical strategies that would significantly impact patients with CVD are discussed. Here, we review these recent advances, highlighting key clinical opportunities in the rapidly emerging field of CVD medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. Deciphering Structural Traits for Thermal and Kinetic Stability across Protein Family Evolution through Ancestral Sequence Reconstruction.
- Author
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Cea, Pablo A, Pérez, Myriam, Herrera, Sixto M, Muñoz, Sebastián M, Fuentes-Ugarte, Nicolás, Coche-Miranda, José, Maturana, Pablo, Guixé, Victoria, and Castro-Fernandez, Victor
- Subjects
ENZYME stability ,PROTEIN structure ,AMINO acid sequence ,MOLECULAR dynamics ,PROTEIN engineering - Abstract
Natural proteins are frequently marginally stable, and an increase in environmental temperature can easily lead to unfolding. As a result, protein engineering to improve protein stability is an area of intensive research. Nonetheless, since there is usually a high degree of structural homology between proteins from thermophilic organisms and their mesophilic counterparts, the identification of structural determinants for thermoadaptation is challenging. Moreover, in many cases, it has become clear that the success of stabilization strategies is often dependent on the evolutionary history of a protein family. In the last few years, the use of ancestral sequence reconstruction (ASR) as a tool for elucidation of the evolutionary history of functional traits of a protein family has gained strength. Here, we used ASR to trace the evolutionary pathways between mesophilic and thermophilic kinases that participate in the biosynthetic pathway of vitamin B
1 in bacteria. By combining biophysics approaches, X-ray crystallography, and molecular dynamics simulations, we found that the thermal stability of these enzymes correlates with their kinetic stability, where the highest thermal/kinetic stability is given by an increase in small hydrophobic amino acids that allow a higher number of interatomic hydrophobic contacts, making this type of interaction the main support for stability in this protein architecture. The results highlight the potential benefits of using ASR to explore the evolutionary history of protein sequence and structure to identify traits responsible for the kinetic and thermal stability of any protein architecture. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF
43. Radiology of fibrosis part III: genitourinary system.
- Author
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Tarchi, Sofia Maria, Salvatore, Mary, Lichtenstein, Philip, Sekar, Thillai, Capaccione, Kathleen, Luk, Lyndon, Shaish, Hiram, Makkar, Jasnit, Desperito, Elise, Leb, Jay, Navot, Benjamin, Goldstein, Jonathan, Laifer, Sherelle, Beylergil, Volkan, Ma, Hong, Jambawalikar, Sachin, Aberle, Dwight, D'Souza, Belinda, Bentley-Hibbert, Stuart, and Marin, Monica Pernia
- Subjects
CONNECTIVE tissues ,WOUND healing ,RADIOLOGY ,CANCER invasiveness ,FIBROSIS ,QUALITY of life - Abstract
Fibrosis is a pathological process involving the abnormal deposition of connective tissue, resulting from improper tissue repair in response to sustained injury caused by hypoxia, infection, or physical damage. It can impact any organ, leading to their dysfunction and eventual failure. Additionally, tissue fibrosis plays an important role in carcinogenesis and the progression of cancer. Early and accurate diagnosis of organ fibrosis, coupled with regular surveillance, is essential for timely disease-modifying interventions, ultimately reducing mortality and enhancing quality of life. While extensive research has already been carried out on the topics of aberrant wound healing and fibrogenesis, we lack a thorough understanding of how their relationship reveals itself through modern imaging techniques. This paper focuses on fibrosis of the genito-urinary system, detailing relevant imaging technologies used for its detection and exploring future directions. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
44. Non-human primate studies for cardiomyocyte transplantation--ready for translation?
- Author
-
von Bibra, Constantin and Hinkel, Rabea
- Subjects
MACAQUES ,PRIMATES ,CARDIAC regeneration ,CELL transplantation ,HEART failure patients ,CELLULAR therapy - Abstract
Non-human primates (NHP) are valuable models for late translational pre-clinical studies, often seen as a last step before clinical application. The unique similarity between NHPs and humans is often the subject of ethical concerns. However, it is precisely this analogy in anatomy, physiology, and the immune system that narrows the translational gap to other animal models in the cardiovascular field. Cell and gene therapy approaches are two dominant strategies investigated in the research field of cardiac regeneration. Focusing on the cell therapy approach, several xeno- and allogeneic cell transplantation studies with a translational motivation have been realized in macaque species. This is based on the pressing need for novel therapeutic options for heart failure patients. Stem cell-based remuscularization of the injured heart can be achieved via direct injection of cardiomyocytes (CMs) or patch application. Both CM delivery approaches are in the late preclinical stage, and the first clinical trials have started. However, are we already ready for the clinical area? The present review concentrates on CM transplantation studies conducted in NHPs, discusses the main sources and discoveries, and provides a perspective about human translation. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
45. Post deployment recycling of machine learning models.
- Author
-
Patel, Harsh, Adams, Bram, and Hassan, Ahmed E.
- Published
- 2024
- Full Text
- View/download PDF
46. You have how many spreadsheets?
- Author
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Rux E and Borchert T
- Published
- 2010
47. Conformational Averaging in pK Calculations: Improvement and Limitations in Prediction of Ionization Properties of Proteins
- Author
-
Koumanov, A., Karshikoff, A., Friis, E. P., and Borchert, T. V.
- Abstract
Calculations of pK values of individual titratable groups in one structure of Bacillus circulans xylanase and two similar structures of Bacillus agaradhaerens xylanase were performed by combination of molecular dynamics simulation and a continuum electrostatic model. The influence of the starting structure and the simulation length was investigated. The results agree well with the observations of other authors that calculations using an ensemble of structures describe titration properties of proteins more accurately than calculations based on a single structure. This study emphasizes the features of the collected ensemble rather than the precision of the finally obtained values. The evolution along the trajectory of individual averaged pK
a values and their components, such as contribution of desolvation penalty and interactions with protein permanent charges, were analyzed. For the majority of titratable sites, it was shown that simulation time shorter than 500 ps is insufficient to represent their ionization behavior. Calculations based on slightly different initial structures of Bacillus agaradhaerens xylanase demonstrated that the averaged pKa value for some groups is correlated to the initial structure, even for a long molecular dynamic trajectory.- Published
- 2001
48. Design and synthesis of triglyceride analogue biotinylated suicide inhibitors for directed molecular evolution of lipolytic enzymes
- Author
-
Deussen, H. J., Danielsen, S., Breinholt, J., and Borchert, T. V.
- Published
- 2000
- Full Text
- View/download PDF
49. AFLP-based genetic mapping of the "bud-flowering" trait in heather (Calluna vulgaris).
- Author
-
Behrend A, Borchert T, Spiller M, and Hohe A
- Subjects
- Algorithms, Calluna physiology, Genetic Linkage, Likelihood Functions, Amplified Fragment Length Polymorphism Analysis, Calluna genetics, Flowers
- Abstract
Background: Calluna vulgaris is one of the most important landscaping plants produced in Germany. Its enormous economic success is due to the prolonged flower attractiveness of mutants in flower morphology, the so-called bud-bloomers. In this study, we present the first genetic linkage map of C. vulgaris in which we mapped a locus of the economically highly desired trait "flower type"., Results: The map was constructed in JoinMap 4.1. using 535 AFLP markers from a single mapping population. A large fraction (40%) of markers showed distorted segregation. To test the effect of segregation distortion on linkage estimation, these markers were sorted regarding their segregation ratio and added in groups to the data set. The plausibility of group formation was evaluated by comparison of the "two-way pseudo-testcross" and the "integrated" mapping approach. Furthermore, regression mapping was compared to the multipoint-likelihood algorithm. The majority of maps constructed by different combinations of these methods consisted of eight linkage groups corresponding to the chromosome number of C. vulgaris., Conclusions: All maps confirmed the independent inheritance of the most important horticultural traits "flower type", "flower colour", and "leaf colour". An AFLP marker for the most important breeding target "flower type" was identified. The presented genetic map of C. vulgaris can now serve as a basis for further molecular marker selection and map-based cloning of the candidate gene encoding the unique flower architecture of C. vulgaris bud-bloomers.
- Published
- 2013
- Full Text
- View/download PDF
50. 'Who's who' in two different flower types of Calluna vulgaris (Ericaceae): morphological and molecular analyses of flower organ identity.
- Author
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Borchert T, Eckardt K, Fuchs J, Krüger K, and Hohe A
- Subjects
- Calluna anatomy & histology, DNA, Plant genetics, Flowers genetics, Gene Expression Regulation, Developmental, Gene Expression Regulation, Plant, Genome, Plant, MADS Domain Proteins genetics, Microscopy, Electron, Scanning, Phenotype, Plant Proteins genetics, Sequence Analysis, DNA, Calluna genetics, Flowers ultrastructure
- Abstract
Background: The ornamental crop Calluna vulgaris is of increasing importance to the horticultural industry in the northern hemisphere due to a flower organ mutation: the flowers of the 'bud-flowering' phenotype remain closed i.e. as buds throughout the total flowering period and thereby maintain more colorful flowers for a longer period of time than the wild-type. This feature is accompanied and presumably caused by the complete lack of stamens. Descriptions of this botanical particularity are inconsistent and partially conflicting. In order to clarify basic questions of flower organ identity in general and stamen loss in detail, a study of the wild-type and the 'bud-flowering' flower type of C. vulgaris was initiated., Results: Flowers were examined by macro- and microscopic techniques. Organ development was investigated comparatively in both the wild-type and the 'bud-flowering' type by histological analyses. Analysis of epidermal cell surface structure of vegetative tissues and perianth organs using scanning electron microscopy revealed that in wild-type flowers the outer whorls of colored organs may be identified as sepals, while the inner ones may be identified as petals. In the 'bud-flowering' type, two whorls of sepals are directly followed by the gynoecium. Both, petals and stamens, are completely missing in this flower type. The uppermost whorl of green leaves represents bracts in both flower types. In addition, two MADS-box genes (homologs of AP3/DEF and SEP1/2) were identified in C. vulgaris using RACE-PCR. Expression analysis by qRT-PCR was conducted for both genes in leaves, bracts, sepals and petals. These experiments revealed an expression pattern supporting the organ classification based on morphological characteristics., Conclusions: Organ identity in both wild-type and 'bud-flowering' C. vulgaris was clarified using a combination of microscopic and molecular methods. Our results for bract, sepal and petal organ identity are supported by the 'ABCDE model'. However, loss of stamens in the 'bud-flowering' phenotype is an exceptional flower organ modification that cannot be explained by modified spatial expression of known organ identity genes.
- Published
- 2009
- Full Text
- View/download PDF
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