Search

Your search keyword '"Wolf, Eckhard"' showing total 2,313 results
Start Over Author "Wolf, Eckhard"
2,313 results on '"Wolf, Eckhard"'

2. Xenotransplantation von Organen

Author

Schmoeckel, Michael, Längin, Matthias, Reichart, Bruno, Abicht, Jan-Michael, Bender, Martin, Denner, Joachim, Marckmann, Georg, Brenner, Paolo, Wolf, Eckhard, and Hagl, Christian

Published
2024
Full Text
View/download PDF

7. Parapoxvirus species revisited by whole genome sequencing: A retrospective analysis of bovine virus isolates

Author

Graf Alexander, Rziha Hanns-Joachim, Krebs Stefan, Wolf Eckhard, Blum Helmut, and Büttner Mathias

Subjects
Parapoxvirus, Phylogenetic analysis, Species classification, Nanopore sequencing, Whole genome sequencing, Gene variation, Microbiology, QR1-502, Infectious and parasitic diseases, RC109-216
Abstract

Parapoxviruses (PPV) of animals are spread worldwide. While the Orf virus (ORFV) species is a molecularly well-characterized prototype pathogen of small ruminants, the genomes of virus species affecting large ruminants, namely Bovine papular stomatitis virus (BPSV) and Pseudocowpox virus (PCPV), are less well known. Using Nanopore sequencing we retrospectively show the whole genome sequences (WGS) of six BPSV, three PCPV isolates and an attenuated ORFV strain, originating from different geographic locations. A phylogenetic tree shows that the de novo assembled genomes belong to PPV species including WGS of reference PPV. Remarkably, Nanopore sequencing allowed the molecular resolution of inverted terminal repeats (ITR) and the hairpin loop within the de novo assembled WGS. Additionally, peculiarities regarding map location of two genes and the heterogeneity of a genomic region were noted. Details for the molecular variability of an interferon response modulatory gene (ORF116) and the PCPV specificity of gene 073.5 are reported. In summary, WGS gained by Nanopore sequencing allowed analysis of complete PPV genomes and confident virus species attribution within a phylogenetic tree avoiding uncertainty of limited gene-based diagnostics. Nanopore-based WGS provides robust comparison of PPV genomes and reliable identity determination of new Poxviruses.

Published
2024
Full Text
View/download PDF

16. Xenografts Show Signs of Concentric Hypertrophy and Dynamic Left Ventricular Outflow Tract Obstruction After Orthotopic Pig-to-baboon Heart Transplantation

Author

Längin, Matthias, Buttgereit, Ines, Reichart, Bruno, Panelli, Alessandro, Radan, Julia, Mokelke, Maren, Neumann, Elisabeth, Bender, Martin, Michel, Sebastian, Ellgass, Reinhard, Ying, Jiawei, Fresch, Ann Kathrin, Mayr, Tanja, Steen, Stig, Paskevicius, Audrius, Egerer, Stefanie, Bähr, Andrea, Kessler, Barbara, Klymiuk, Nikolai, Binder, Uli, Skerra, Arne, Ledderose, Stephan, Müller, Susanna, Walz, Christoph, Hagl, Christian, Wolf, Eckhard, Ayares, David, Brenner, Paolo, and Abicht, Jan-Michael

Published
2023
Full Text
View/download PDF

17. Phenotypic features of dystrophin gene knockout pigs harboring a human artificial chromosome containing the entire dystrophin (DMD) gene

Author

Watanabe, Masahito, Miyamoto, Hitomaru, Okamoto, Kazutoshi, Nakano, Kazuaki, Matsunari, Hitomi, Kazuki, Kanako, Hasegawa, Koki, Uchikura, Ayuko, Takayanagi, Shuko, Umeyama, Kazuhiro, Hiramuki, Yosuke, Kemter, Elisabeth, Klymuik, Nikolai, Kurome, Mayuko, Kessler, Barbara, Wolf, Eckhard, Kazuki, Yasuhiro, and Nagashima, Hiroshi

Published
2023
Full Text
View/download PDF

20. Pig models for Duchenne muscular dystrophy – from disease mechanisms to validation of new diagnostic and therapeutic concepts

Author

Stirm, Michael, Fonteyne, Lina Marie, Shashikadze, Bachuki, Stöckl, Jan B., Kurome, Mayuko, Keßler, Barbara, Zakhartchenko, Valeri, Kemter, Elisabeth, Blum, Helmut, Arnold, Georg J., Matiasek, Kaspar, Wanke, Rüdiger, Wurst, Wolfgang, Nagashima, Hiroshi, Knieling, Ferdinand, Walter, Maggie C., Kupatt, Christian, Fröhlich, Thomas, Klymiuk, Nikolai, Blutke, Andreas, and Wolf, Eckhard

Published
2022
Full Text
View/download PDF

21. Migratory and anti-fibrotic programmes define the regenerative potential of human cardiac progenitors

Author

Poch, Christine M., Foo, Kylie S., De Angelis, Maria Teresa, Jennbacken, Karin, Santamaria, Gianluca, Bähr, Andrea, Wang, Qing-Dong, Reiter, Franziska, Hornaschewitz, Nadja, Zawada, Dorota, Bozoglu, Tarik, My, Ilaria, Meier, Anna, Dorn, Tatjana, Hege, Simon, Lehtinen, Miia L., Tsoi, Yat Long, Hovdal, Daniel, Hyllner, Johan, Schwarz, Sascha, Sudhop, Stefanie, Jurisch, Victoria, Sini, Marcella, Fellows, Mick D., Cummings, Matthew, Clarke, Jonathan, Baptista, Ricardo, Eroglu, Elif, Wolf, Eckhard, Klymiuk, Nikolai, Lu, Kun, Tomasi, Roland, Dendorfer, Andreas, Gaspari, Marco, Parrotta, Elvira, Cuda, Giovanni, Krane, Markus, Sinnecker, Daniel, Hoppmann, Petra, Kupatt, Christian, Fritsche-Danielson, Regina, Moretti, Alessandra, Chien, Kenneth R., and Laugwitz, Karl-Ludwig

Published
2022
Full Text
View/download PDF

25. Deep phenotyping and lifetime trajectories reveal limited effects of longevity regulators on the aging process in C57BL/6J mice

Author

Xie, Kan, Fuchs, Helmut, Scifo, Enzo, Liu, Dan, Aziz, Ahmad, Aguilar-Pimentel, Juan Antonio, Amarie, Oana Veronica, Becker, Lore, da Silva-Buttkus, Patricia, Calzada-Wack, Julia, Cho, Yi-Li, Deng, Yushuang, Edwards, A. Cole, Garrett, Lillian, Georgopoulou, Christina, Gerlini, Raffaele, Hölter, Sabine M., Klein-Rodewald, Tanja, Kramer, Michael, Leuchtenberger, Stefanie, Lountzi, Dimitra, Mayer-Kuckuk, Phillip, Nover, Lena L., Oestereicher, Manuela A., Overkott, Clemens, Pearson, Brandon L., Rathkolb, Birgit, Rozman, Jan, Russ, Jenny, Schaaf, Kristina, Spielmann, Nadine, Sanz-Moreno, Adrián, Stoeger, Claudia, Treise, Irina, Bano, Daniele, Busch, Dirk H., Graw, Jochen, Klingenspor, Martin, Klopstock, Thomas, Mock, Beverly A., Salomoni, Paolo, Schmidt-Weber, Carsten, Weiergräber, Marco, Wolf, Eckhard, Wurst, Wolfgang, Gailus-Durner, Valérie, Breteler, Monique M. B., Hrabě de Angelis, Martin, and Ehninger, Dan

Published
2022
Full Text
View/download PDF

26. Cas9-expressing chickens and pigs as resources for genome editing in livestock

Author

Rieblinger, Beate, Sid, Hicham, Duda, Denise, Bozoglu, Tarik, Klinger, Romina, Schlickenrieder, Antonina, Lengyel, Kamila, Flisikowski, Krzysztof, Flisikowska, Tatiana, Simm, Nina, Grodziecki, Alessandro, Perleberg, Carolin, Bähr, Andrea, Carrier, Lucie, Kurome, Mayuko, Zakhartchenko, Valeri, Kessler, Barbara, Wolf, Eckhard, Kettler, Lutz, Luksch, Harald, Hagag, Ibrahim T., Wise, Daniel, Kaufman, Jim, Kaufer, Benedikt B., Kupatt, Christian, Schnieke, Angelika, and Schusser, Benjamin

Published
2021

28. Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy

Author

Spielmann, Nadine, Miller, Gregor, Oprea, Tudor I., Hsu, Chih-Wei, Fobo, Gisela, Frishman, Goar, Montrone, Corinna, Haseli Mashhadi, Hamed, Mason, Jeremy, Munoz Fuentes, Violeta, Leuchtenberger, Stefanie, Ruepp, Andreas, Wagner, Matias, Westphal, Dominik S., Wolf, Cordula, Görlach, Agnes, Sanz-Moreno, Adrián, Cho, Yi-Li, Teperino, Raffaele, Brandmaier, Stefan, Sharma, Sapna, Galter, Isabella Rikarda, Östereicher, Manuela A., Zapf, Lilly, Mayer-Kuckuk, Philipp, Rozman, Jan, Teboul, Lydia, Bunton-Stasyshyn, Rosie K. A., Cater, Heather, Stewart, Michelle, Christou, Skevoulla, Westerberg, Henrik, Willett, Amelia M., Wotton, Janine M., Roper, Willson B., Christiansen, Audrey E., Ward, Christopher S., Heaney, Jason D., Reynolds, Corey L., Prochazka, Jan, Bower, Lynette, Clary, David, Selloum, Mohammed, Bou About, Ghina, Wendling, Olivia, Jacobs, Hugues, Leblanc, Sophie, Meziane, Hamid, Sorg, Tania, Audain, Enrique, Gilly, Arthur, Rayner, Nigel W., Hitz, Marc-Phillip, Zeggini, Eleftheria, Wolf, Eckhard, Sedlacek, Radislav, Murray, Steven A., Svenson, Karen L., Braun, Robert E., White, Jaqueline K., Kelsey, Lois, Gao, Xiang, Shiroishi, Toshihiko, Xu, Ying, Seong, Je Kyung, Mammano, Fabio, Tocchini-Valentini, Glauco P., Beaudet, Arthur L., Meehan, Terrence F., Parkinson, Helen, Smedley, Damian, Mallon, Ann-Marie, Wells, Sara E., Grallert, Harald, Wurst, Wolfgang, Marschall, Susan, Fuchs, Helmut, Brown, Steve D. M., Flenniken, Ann M., Nutter, Lauryl M. J., McKerlie, Colin, Herault, Yann, Lloyd, K. C. Kent, Dickinson, Mary E., Gailus-Durner, Valerie, and Hrabe de Angelis, Martin

Published
2022
Full Text
View/download PDF

29. Animal models of obesity and diabetes mellitus

Author

Kleinert, Maximilian, Clemmensen, Christoffer, Hofmann, Susanna M, Moore, Mary C, Renner, Simone, Woods, Stephen C, Huypens, Peter, Beckers, Johannes, de Angelis, Martin Hrabe, Schürmann, Annette, Bakhti, Mostafa, Klingenspor, Martin, Heiman, Mark, Cherrington, Alan D, Ristow, Michael, Lickert, Heiko, Wolf, Eckhard, Havel, Peter J, Müller, Timo D, and Tschöp, Matthias H

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Biotechnology, Nutrition, Obesity, Neurodegenerative, Diabetes, Metabolic and endocrine, Animals, Body Mass Index, Diabetes Mellitus, Type 2, Disease Models, Animal, Dogs, Fishes, Haplorhini, Humans, Mice, Rats, Risk Assessment, Sensitivity and Specificity, Swine, Endocrinology & Metabolism, Clinical sciences
Abstract

More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models.

Published
2018

30. Identification of genetic elements in metabolism by high-throughput mouse phenotyping

Author

Rozman, Jan, Rathkolb, Birgit, Oestereicher, Manuela A, Schütt, Christine, Ravindranath, Aakash Chavan, Leuchtenberger, Stefanie, Sharma, Sapna, Kistler, Martin, Willershäuser, Monja, Brommage, Robert, Meehan, Terrence F, Mason, Jeremy, Haselimashhadi, Hamed, IMPC Consortium, Hough, Tertius, Mallon, Ann-Marie, Wells, Sara, Santos, Luis, Lelliott, Christopher J, White, Jacqueline K, Sorg, Tania, Champy, Marie-France, Bower, Lynette R, Reynolds, Corey L, Flenniken, Ann M, Murray, Stephen A, Nutter, Lauryl MJ, Svenson, Karen L, West, David, Tocchini-Valentini, Glauco P, Beaudet, Arthur L, Bosch, Fatima, Braun, Robert B, Dobbie, Michael S, Gao, Xiang, Herault, Yann, Moshiri, Ala, Moore, Bret A, Kent Lloyd, KC, McKerlie, Colin, Masuya, Hiroshi, Tanaka, Nobuhiko, Flicek, Paul, Parkinson, Helen E, Sedlacek, Radislav, Seong, Je Kyung, Wang, Chi-Kuang Leo, Moore, Mark, Brown, Steve D, Tschöp, Matthias H, Wurst, Wolfgang, Klingenspor, Martin, Wolf, Eckhard, Beckers, Johannes, Machicao, Fausto, Peter, Andreas, Staiger, Harald, Häring, Hans-Ulrich, Grallert, Harald, Campillos, Monica, Maier, Holger, Fuchs, Helmut, Gailus-Durner, Valerie, Werner, Thomas, and Hrabe de Angelis, Martin

Subjects
Biochemistry and Cell Biology, Bioinformatics and Computational Biology, Genetics, Biological Sciences, Human Genome, Nutrition, 2.1 Biological and endogenous factors, Generic health relevance, Animals, Area Under Curve, Basal Metabolism, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, Gene Regulatory Networks, Genome-Wide Association Study, High-Throughput Screening Assays, Humans, Metabolic Diseases, Mice, Mice, Knockout, Obesity, Oxygen Consumption, Phenotype, Triglycerides, IMPC Consortium
Abstract

Metabolic diseases are a worldwide problem but the underlying genetic factors and their relevance to metabolic disease remain incompletely understood. Genome-wide research is needed to characterize so-far unannotated mammalian metabolic genes. Here, we generate and analyze metabolic phenotypic data of 2016 knockout mouse strains under the aegis of the International Mouse Phenotyping Consortium (IMPC) and find 974 gene knockouts with strong metabolic phenotypes. 429 of those had no previous link to metabolism and 51 genes remain functionally completely unannotated. We compared human orthologues of these uncharacterized genes in five GWAS consortia and indeed 23 candidate genes are associated with metabolic disease. We further identify common regulatory elements in promoters of candidate genes. As each regulatory element is composed of several transcription factor binding sites, our data reveal an extensive metabolic phenotype-associated network of co-regulated genes. Our systematic mouse phenotype analysis thus paves the way for full functional annotation of the genome.

Published
2018

32. Functional maturation and longitudinal imaging of intraportal neonatal porcine islet grafts in genetically diabetic pigs

Author

Pilz, Johanna, primary, Gloddek, Nicol, additional, Lindheimer, Felix, additional, Lindner, Magdalena J., additional, Puhr-Westerheide, Daniel, additional, Ümütlü, Muzzafer, additional, Cyran, Clemens, additional, Seidensticker, Max, additional, Lindner, Richard, additional, Kraetzl, Martin, additional, Renner, Simone, additional, Merkus, Daphne, additional, Teupser, Daniel, additional, Bartenstein, Peter, additional, Ziegler, Sibylle I., additional, Wolf, Eckhard, additional, and Kemter, Elisabeth, additional

Published
2024
Full Text
View/download PDF

34. Use of Xenogeneic Cells

Author

Kemter, Elisabeth, Kind, Alexander, Reichart, Bruno, Wolf, Eckhard, Gimble, Jeffrey M., editor, Marolt Presen, Darja, editor, Oreffo, Richard O. C., editor, Wolbank, Susanne, editor, and Redl, Heinz, editor

Published
2020
Full Text
View/download PDF

35. Publisher Correction: Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy

Author

Spielmann, Nadine, Miller, Gregor, Oprea, Tudor I., Hsu, Chih-Wei, Fobo, Gisela, Frishman, Goar, Montrone, Corinna, Haseli Mashhadi, Hamed, Mason, Jeremy, Munoz Fuentes, Violeta, Leuchtenberger, Stefanie, Ruepp, Andreas, Wagner, Matias, Westphal, Dominik S., Wolf, Cordula, Görlach, Agnes, Sanz-Moreno, Adrián, Cho, Yi-Li, Teperino, Raffaele, Brandmaier, Stefan, Sharma, Sapna, Galter, Isabella Rikarda, Östereicher, Manuela A., Zapf, Lilly, Mayer-Kuckuk, Philipp, Rozman, Jan, Teboul, Lydia, Bunton-Stasyshyn, Rosie K. A., Cater, Heather, Stewart, Michelle, Christou, Skevoulla, Westerberg, Henrik, Willett, Amelia M., Wotton, Janine M., Roper, Willson B., Christiansen, Audrey E., Ward, Christopher S., Heaney, Jason D., Reynolds, Corey L., Prochazka, Jan, Bower, Lynette, Clary, David, Selloum, Mohammed, Bou About, Ghina, Wendling, Olivia, Jacobs, Hugues, Leblanc, Sophie, Meziane, Hamid, Sorg, Tania, Audain, Enrique, Gilly, Arthur, Rayner, Nigel W., Hitz, Marc-Phillip, Zeggini, Eleftheria, Wolf, Eckhard, Sedlacek, Radislav, Murray, Steven A., Svenson, Karen L., Braun, Robert E., White, Jaqueline K., Kelsey, Lois, Gao, Xiang, Shiroishi, Toshihiko, Xu, Ying, Seong, Je Kyung, Mammano, Fabio, Tocchini-Valentini, Glauco P., Beaudet, Arthur L., Meehan, Terrence F., Parkinson, Helen, Smedley, Damian, Mallon, Ann-Marie, Wells, Sara E., Grallert, Harald, Wurst, Wolfgang, Marschall, Susan, Fuchs, Helmut, Brown, Steve D. M., Flenniken, Ann M., Nutter, Lauryl M. J., McKerlie, Colin, Herault, Yann, Lloyd, K. C. Kent, Dickinson, Mary E., Gailus-Durner, Valerie, and Hrabe de Angelis, Martin

Published
2022
Full Text
View/download PDF

38. Identifying novel genetic determinants of Indirect Genetic Effects

Author

Hrabě de Angelis, Martin (Prof. Dr. Dr. h.c. mult.), Hrabě de Angelis, Martin (Prof. Dr. Dr. h.c. mult.);Wolf, Eckhard (Prof. Dr.), Tomar, Archana, Hrabě de Angelis, Martin (Prof. Dr. Dr. h.c. mult.), Hrabě de Angelis, Martin (Prof. Dr. Dr. h.c. mult.);Wolf, Eckhard (Prof. Dr.), and Tomar, Archana

Abstract

This study explored the genotype-phenotype association resource of the International Mouse Phenotyping Consortium (IMPC) with the aim of understanding whether Indirect Genetic Effects are detectable and how common they are in mammalian genetics, what are the underlying genetic determinants of Indirect Genetic Effects in mammals and which relevance they may have for human physiology and susceptibility to complex diseases., Diese Studie untersuchte die Genotyp-Phänotyp-Assoziation Ressource des International Mouse Phenotyping Consortium (IMPC) untersucht, um zu verstehen, ob indirekte genetische Effekte nachweisbar sind und wie häufig sie in der Säugetiere Genetik vorkommen. Zudem habe ich untersucht welche genetischen Determinanten den indirekten genetischen Effekten bei Säugetieren zugrunde liegen und welche Bedeutung diese für die menschliche Physiologie und die Anfälligkeit für komplexe Krankheiten haben könnten.

Published
2024

39. 414.7: The Perioperative Cardiac Xenograft Dysfunction (PCXD) Has A Major Impact in (Life-Supporting) Orthotopic (oXTx) Cardiac Xenotransplantation, but Not in the Heterotopic Thoracic (htXTx) Xenotransplantation

Author

Brenner, Paolo, Reichart, Bruno, Längin, Matthias, Bender, Martin, Mayr, Tanja, Güthoff, Sonja, Michel, Sebastian, Buchholz, Stefan, Radan, Julia, Mokelke, Maren, Buttgereit, Ines, Neumann, Elisabeth, Bauer, Andreas, Klymiuk, Nikolai, Wolf, Eckhard, Walz, Christoph, Reimann, Keith, Ayares, David, Hagl, Christian, Steen, Stig, and Abicht, Jan-Michael

Published
2022
Full Text
View/download PDF

40. Immunoprotection Strategies in β‐Cell Replacement Therapy: A Closer Look at Porcine Islet Xenotransplantation.

Author

Grimus, Sarah, Sarangova, Victoria, Welzel, Petra B., Ludwig, Barbara, Seissler, Jochen, Kemter, Elisabeth, Wolf, Eckhard, and Ali, Asghar

Subjects
ISLANDS of Langerhans, ORGANS (Anatomy), ISLANDS, XENOTRANSPLANTATION, TYPE 1 diabetes, ANTIGEN presenting cells
Abstract

Type 1 diabetes mellitus (T1DM) is characterized by absolute insulin deficiency primarily due to autoimmune destruction of pancreatic β‐cells. The prevailing treatment for T1DM involves daily subcutaneous insulin injections, but a substantial proportion of patients face challenges such as severe hypoglycemic episodes and poorly controlled hyperglycemia. For T1DM patients, a more effective therapeutic option involves the replacement of β‐cells through allogeneic transplantation of either the entire pancreas or isolated pancreatic islets. Unfortunately, the scarcity of transplantable human organs has led to a growing list of patients waiting for an islet transplant. One potential alternative is xenotransplantation of porcine pancreatic islets. However, due to inter‐species molecular incompatibilities, porcine tissues trigger a robust immune response in humans, leading to xenograft rejection. Several promising strategies aim to overcome this challenge and enhance the long‐term survival and functionality of xenogeneic islet grafts. These strategies include the use of islets derived from genetically modified pigs, immunoisolation of islets by encapsulation in biocompatible materials, and the creation of an immunomodulatory microenvironment by co‐transplanting islets with accessory cells or utilizing immunomodulatory biomaterials. This review concentrates on delineating the primary obstacles in islet xenotransplantation and elucidates the fundamental principles and recent breakthroughs aimed at addressing these challenges. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

41. Comparative Phenotyping of Mice Reveals Canonical and Noncanonical Physiological Functions of TRα and TRβ.

Author

Hönes, Georg Sebastian, Geist, Daniela, Wenzek, Christina, Pfluger, Paul Thomas, Müller, Timo Dirk, Aguilar-Pimentel, Juan Antonio, Amarie, Oana Veronica, Becker, Lore, Dragano, Natalia, Garrett, Lillian, Hölter, Sabine Maria, Rathkolb, Birgit, Rozman, Jan, Spielmann, Nadine, Treise, Irina, Wolf, Eckhard, Wurst, Wolfgang, Fuchs, Helmut, Gailus-Durner, Valerie, and Angelis, Martin Hrabe de

Subjects
ACTION spectrum, THYROID hormone receptors, MICE, MUSCLE metabolism, KNOCKOUT mice
Abstract

Thyroid hormone (TH) effects are mediated through TH receptors (TRs), TRα1, TRβ1, and TRβ2. The TRs bind to the DNA and regulate expression of TH target genes (canonical signaling). In addition, they mediate activation of signaling pathways (noncanonical signaling). Whether noncanonical TR action contributes to the spectrum of TH effects is largely unknown. The aim of this study was to attribute physiological effects to the TR isoforms and their canonical and noncanonical signaling. We conducted multiparameter phenotyping in male and female TR knockout mice (TRαKO, TRβKO), mice with disrupted canonical signaling due to mutations in the TR DNA binding domain (TRαGS, TRβGS), and their wild-type littermates. Perturbations in senses, especially hearing (mainly TRβ with a lesser impact of TRα), visual acuity, retinal thickness (TRα and TRβ), and in muscle metabolism (TRα) highlighted the role of canonical TR action. Strikingly, selective abrogation of canonical TR action often had little phenotypic consequence, suggesting that noncanonical TR action sufficed to maintain the wild-type phenotype for specific effects. For instance, macrocytic anemia, reduced retinal vascularization, or increased anxiety-related behavior were only observed in TRαKO but not TRαGS mice. Noncanonical TRα action improved energy utilization and prevented hyperphagia observed in female TRαKO mice. In summary, by examining the phenotypes of TRα and TRβ knockout models alongside their DNA binding–deficient mutants and wild-type counterparts, we could establish that the noncanonical actions of TRα and TRβ play a crucial role in modulating sensory, behavioral, and metabolic functions and, thus, contribute to the spectrum of physiological TH effects. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

42. Structural and proteomic repercussions of growth hormone receptor deficiency on the pituitary gland: Lessons from a translational pig model.

Author

Shashikadze, Bachuki, Franzmeier, Sophie, Hofmann, Isabel, Kraetzl, Martin, Flenkenthaler, Florian, Blutke, Andreas, Fröhlich, Thomas, Wolf, Eckhard, and Hinrichs, Arne

Subjects
SOMATOTROPIN receptors, PITUITARY dwarfism, PITUITARY gland, SOMATOMEDIN C, PROTEOMICS
Abstract

Growth hormone receptor deficiency (GHRD) results in low serum insulin‐like growth factor 1 (IGF1) and high, but non‐functional serum growth hormone (GH) levels in human Laron syndrome (LS) patients and animal models. This study investigated the quantitative histomorphological and molecular alterations associated with GHRD. Pituitary glands from 6 months old growth hormone receptor deficient (GHR‐KO) and control pigs were analyzed using a quantitative histomorphological approach in paraffin (9 GHR‐KO [5 males, 4 females] vs. 11 controls [5 males, 6 females]), ultrathin sections tissue sections (3 male GHR‐KO vs. 3 male controls) and label‐free proteomics (4 GHR‐KO vs. 4 control pigs [2 per sex]). GHR‐KO pigs displayed reduced body weights (60% reduction in comparison to controls; p <.0001) and decreased pituitary volumes (54% reduction in comparison to controls; p <.0001). The volume proportion of the adenohypophysis did not differ in GHR‐KO and control pituitaries (65% vs. 71%; p =.0506) and GHR‐KO adenohypophyses displayed a reduced absolute volume but an unaltered volume density of somatotrophs in comparison to controls (21% vs. 18%; p =.3164). In GHR‐KO pigs, somatotroph cells displayed a significantly reduced volume density of granules (23.5%) as compared to controls (67.7%; p <.0001). Holistic proteome analysis of adenohypophysis samples identified 4660 proteins, of which 592 were differentially abundant between the GHR‐KO and control groups. In GHR‐KO samples, the abundance of somatotropin precursor was decreased, whereas increased abundances of proteins involved in protein production, transport and endoplasmic reticulum (ER) stress were revealed. Increased protein production and secretion as well as significantly reduced proportion of GH‐storing granules in somatotroph cells of the adenohypophysis without an increase in volume density of somatotroph cells in the adenohypophysis could explain elevated serum GH levels in GHR‐KO pigs. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

43. Non-invasive in vivo imaging of porcine islet xenografts in a preclinical model with [68Ga]Ga-exendin-4.

Author

Lindheimer, Felix, Lindner, Magdalena Julia, Oos, Rosel, Honarpisheh, Mohsen, Yichen Zhang, Yutian Lei, Buerck, Lelia Wolf-van, Gildehaus, Franz Josef, Lindner, Simon, Bartenstein, Peter, Kemter, Elisabeth, Wolf, Eckhard, Seissler, Jochen, and Ziegler, Sibylle

Subjects
ISLANDS of Langerhans transplantation, LIGANDS (Chemistry), RESEARCH funding, GLUCAGON-like peptide 1, XENOGRAFTS, POSITRON emission tomography, DESCRIPTIVE statistics, MICE, ANIMAL experimentation, STAINS & staining (Microscopy), EMISSION-computed tomography, DATA analysis software
Abstract

Introduction: Islet xenotransplantation may be a therapeutic option in type 1 diabetes. Recent advances in generating genetically modified source pigs offer advantages as immune suppressants can potentially be eliminated after the transplantation. Therapy monitoring would greatly benefit from noninvasive methods for assessing the viability of transplanted islets. Peptide-based positron emission tomography (PET) targeting the glucagon-like peptide-1 receptor (GLP1R) expression on beta cells may offer a procedure that can directly be translated from an experimental setting to the clinic. The aim of this study was to establish the labeling of the GLP1R ligand [68Ga]Ga-exendin-4, to demonstrate the feasibility of imaging porcine islet xenografts in vivo and to compare signal quality for three different transplantation sites in a mouse model. Materials and methods: Mice with engrafted neonatal porcine islet cell clusters (NPICCs) under the kidney capsule, into the inguinal fold, or the lower hindlimb muscle were studied. After reaching normoglycemia, the mice were injected with [68Ga]Ga-exendin-4 for PET data acquisition. Subsequent autoradiography (AR) was used for comparing ex vivo data with in vivo uptake. Results: NPICCs in the lower right hindlimb muscle could be detected in vivo and in AR. Due to the high background in the kidney and urinary bladder, islets could not be detected in the PET data at transplantation sites close to these organs, while AR showed a clear signal for the islets in the inguinal fold. Discussion: PET with [68Ga]Ga-exendin-4 detects islets transplanted in the hindlimb muscle tissue of mice, offering the potential of longitudinal monitoring of viable porcine islets. Other sites are not suitable for in vivo imaging owing to high activity accumulation of Exendin-4 in kidney and bladder. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

44. Current Status of Cardiac Xenotransplantation: Report of a Workshop of the German Heart Transplant Centers, Martinsried, March 3, 2023.

Author

Schmoeckel, Michael, Längin, Matthias, Reichart, Bruno, Abicht, Jan-Michael, Bender, Martin, Michel, Sebastian, Kamla, Christine-Elena, Denner, Joachim, Tönjes, Ralf Reinhard, Schwinzer, Reinhard, Marckmann, Georg, Wolf, Eckhard, Brenner, Paolo, and Hagl, Christian

Subjects
HEART transplantation, XENOTRANSPLANTATION, CLINICAL medicine, COMPETENT authority, CARDIAC patients
Abstract

This report comprises the contents of the presentations and following discussions of a workshop of the German Heart Transplant Centers in Martinsried, Germany on cardiac xenotransplantation. The production and current availability of genetically modified donor pigs, preservation techniques during organ harvesting, and immunosuppressive regimens in the recipient are described. Selection criteria for suitable patients and possible solutions to the problem of overgrowth of the xenotransplant are discussed. Obviously microbiological safety for the recipient and close contacts is essential, and ethical considerations to gain public acceptance for clinical applications are addressed. The first clinical trial will be regulated and supervised by the Paul-Ehrlich-Institute as the National Competent Authority for Germany, and the German Heart Transplant Centers agreed to cooperatively select the first patients for cardiac xenotransplantation. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

45. The Endothelial Glycocalyx in Pig-to-Baboon Cardiac Xenotransplantation—First Insights.

Author

Bender, Martin, Abicht, Jan-Michael, Reichart, Bruno, Leuschen, Maria, Wall, Felicia, Radan, Julia, Neumann, Elisabeth, Mokelke, Maren, Buttgereit, Ines, Michel, Sebastian, Ellgass, Reinhard, Gieseke, Katja, Steen, Stig, Paskevicius, Audrius, Denner, Joachim, Godehardt, Antonia W., Tönjes, Ralf R., Hagl, Christian, Ayares, David, and Wolf, Eckhard

Subjects
GLYCOCALYX, XENOTRANSPLANTATION, HEPARAN sulfate, XENOGRAFTS, PRESERVATION of organs, tissues, etc., ENDOTHELIAL cells
Abstract

Cardiac xenotransplantation has seen remarkable success in recent years and is emerging as the most promising alternative to human cardiac allotransplantation. Despite these achievements, acute vascular rejection still presents a challenge for long-term xenograft acceptance and new insights into innate and adaptive immune responses as well as detailed characterizations of signaling pathways are necessary. In allotransplantation, endothelial cells and their sugar-rich surface—the endothelial glycocalyx—are known to influence organ rejection. In xenotransplantation, however, only in vitro data exist on the role of the endothelial glycocalyx so far. Thus, in the current study, we analyzed the changes of the endothelial glycocalyx components hyaluronan, heparan sulfate and syndecan-1 after pig-to-baboon cardiac xenotransplantations in the perioperative (n = 4) and postoperative (n = 5) periods. These analyses provide first insights into changes of the endothelial glycocalyx after pig-to-baboon cardiac xenotransplantation and show that damage to the endothelial glycocalyx seems to be comparable or even less pronounced than in similar human settings when current strategies of cardiac xenotransplantation are applied. At the same time, data from the experiments where current strategies, like non-ischemic preservation, growth inhibition or porcine cytomegalovirus (a porcine roseolovirus (PCMV/PRV)) elimination could not be applied indicate that damage of the endothelial glycocalyx also plays an important role in cardiac xenotransplantation. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

47. Pig-to-non-human primate heart transplantation: The final step toward clinical xenotransplantation?

Author

Reichart, Bruno, Längin, Matthias, Radan, Julia, Mokelke, Maren, Buttgereit, Ines, Ying, Jiawei, Fresch, Ann Kathrin, Mayr, Tanja, Issl, Lara, Buchholz, Stefan, Michel, Sebastian, Ellgass, Reinhard, Mihalj, Maks, Egerer, Stefanie, Baehr, Andrea, Kessler, Barbara, Kemter, Elisabeth, Kurome, Mayuko, Zakhartchenko, Valeri, Steen, Stig, Sjöberg, Trygve, Paskevicius, Audrius, Krüger, Luise, Fiebig, Uwe, Denner, Joachim, Godehardt, Antonia W., Tönjes, Ralf R., Milusev, Anastasia, Rieben, Robert, Sfriso, Riccardo, Walz, Christoph, Kirchner, Thomas, Ayares, David, Lampe, Karen, Schönmann, Uwe, Hagl, Christian, Wolf, Eckhard, Klymiuk, Nikolai, Abicht, Jan-Michael, and Brenner, Paolo

Published
2020
Full Text
View/download PDF

49. Functional changes of the liver in the absence of growth hormone (GH) action – Proteomic and metabolomic insights from a GH receptor deficient pig model

Author

Riedel, Evamaria O., Hinrichs, Arne, Kemter, Elisabeth, Dahlhoff, Maik, Backman, Mattias, Rathkolb, Birgit, Prehn, Cornelia, Adamski, Jerzy, Renner, Simone, Blutke, Andreas, de Angelis, Martin Hrabĕ, Bidlingmaier, Martin, Schopohl, Jochen, Arnold, Georg J., Fröhlich, Thomas, and Wolf, Eckhard

Published
2020
Full Text
View/download PDF

50. In-depth phenotyping reveals common and novel disease symptoms in a hemizygous knock-in mouse model (Mut-ko/ki) of mut-type methylmalonic aciduria

Author

Lucienne, Marie, Aguilar-Pimentel, Juan Antonio, Amarie, Oana V., Becker, Lore, Calzada-Wack, Julia, da Silva-Buttkus, Patricia, Garrett, Lillian, Hölter, Sabine M., Mayer-Kuckuk, Philipp, Rathkolb, Birgit, Rozman, Jan, Spielmann, Nadine, Treise, Irina, Busch, Dirk H., Klopstock, Thomas, Schmidt-Weber, Carsten, Wolf, Eckhard, Wurst, Wolfgang, Forny, Merima, Mathis, Déborah, Fingerhut, Ralph, Froese, D. Sean, Gailus-Durner, Valerie, Fuchs, Helmut, de Angelis, Martin Hrabě, and Baumgartner, Matthias R.

Published
2020
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results