96 results on '"Endres, T."'
Search Results
2. PReS-FINAL-2331: Low-penetrance NLRP3 variants
- Author
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Endres, T, Hofer, F, Goldbach-Mansky, R, Hoffman, HM, Blank, N, Krause, K, Rietschel, C, Horneff, G, Lohse, P, and Kuemmerle-Deschner, J
- Published
- 2013
3. PW02-040 - Low-penetrance NLRP3 variants
- Author
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Endres, T, Hofer, F, Goldbach-Mansky, R, Hoffman, HM, Blank, N, Krause, K, Rietschel, C, Horneff, G, Lohse, P, and Kuemmerle-Deschner, J
- Published
- 2013
4. Water-film thickness imaging based on time-multiplexed near-infrared absorption with up to 500 Hz repetition rate
- Author
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Lubnow, M., primary, Dreier, T., additional, Schulz, C., additional, and Endres, T., additional
- Published
- 2023
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5. Improving Lifelong Learning by Fostering Students' Learning Strategies at University
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Endres, T., Endres, T., Leber, J., Bottger, C., Rovers, S., Renkl, A., Endres, T., Endres, T., Leber, J., Bottger, C., Rovers, S., and Renkl, A.
- Abstract
The foundation of how students usually learn is laid early in their academic lives. However, many or even most students do not primarily rely on those learning strategies that are most favorable from a scientific point of view. To change students' learning behavior when they start their university education, we developed a computer-based adaptive learning environment to train favorable learning strategies and change students' habits using them. This learning environment pursues three main goals: acquiring declarative and conditional knowledge about learning strategies, consolidating that knowledge, and applying these learning strategies in practice. In this report, we describe four experimental studies conducted to optimize this learning environment (n = 336). With those studies, we improved the learning environment with respect to how motivating it is, investigated an efficient way to consolidate knowledge, and explored how to facilitate the formation of effective implementation intentions for applying learning strategies and changing learning habits. Our strategy-training module is implemented in the curriculum for freshman students at the Department of Psychology, University of Freiburg (Germany). Around 120 students take part in our program every year. An open version of this training intervention is freely available to everyone.
- Published
- 2021
6. Brief Report: Clinical and Molecular Phenotypes of Low‐Penetrance Variants of NLRP3: Diagnostic and Therapeutic Challenges
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Kuemmerle‐Deschner, J. B., Verma, D., Endres, T., Broderick, L., de Jesus, A. A., Hofer, F., Blank, N., Krause, K., Rietschel, C., Horneff, G., Aksentijevich, I., Lohse, P., Goldbach‐Mansky, R., Hoffman, H. M., and Benseler, S. M.
- Published
- 2017
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7. Simultaneous measurement of liquid-film thickness and solute concentration of aqueous solutions of two urea derivatives using NIR absorption
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Lubnow, M., primary, Dreier, T., additional, Schulz, C., additional, and Endres, T., additional
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- 2021
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8. Context and trade-offs characterize real-world threat detection systems: A review and comprehensive framework to improve research practice and resolve the translational crisis
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Fendt, M., Parsons, M.H., Apfelbach, R., Carthey, A.J.R., Dickman, C.R., Endres, T., Frank, A.S.K., Heinz, D.E., Jones, M.E., Kiyokawa, Y., Kreutzmann, J.C., Roelofs, K., Schneider, M., Sulger, J., Wotjak, C.T., Blumstein, D.T., Fendt, M., Parsons, M.H., Apfelbach, R., Carthey, A.J.R., Dickman, C.R., Endres, T., Frank, A.S.K., Heinz, D.E., Jones, M.E., Kiyokawa, Y., Kreutzmann, J.C., Roelofs, K., Schneider, M., Sulger, J., Wotjak, C.T., and Blumstein, D.T.
- Abstract
Contains fulltext : 219339.pdf (Publisher’s version ) (Closed access), A better understanding of context in decision-making - that is, the internal and external conditions that modulate decisions - is required to help bridge the gap between natural behaviors that evolved by natural selection and more arbitrary laboratory models of anxiety and fear. Because anxiety and fear are mechanisms evolved to manage threats from predators and other exigencies, the large behavioral, ecological and evolutionary literature on predation risk is useful for re-framing experimental research on human anxiety-related disorders. We review the trade-offs that are commonly made during antipredator decision-making in wild animals along with the context under which the behavior is performed and measured, and highlight their relevance for focused laboratory models of fear and anxiety. We then develop an integrative mechanistic model of decision-making under risk which, when applied to laboratory and field settings, should improve studies of the biological basis of normal and pathological anxiety and may therefore improve translational outcomes.
- Published
- 2020
9. Postsynaptic BDNF signalling regulates long-term potentiation at thalamo-amygdala afferents
- Author
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Meis, S., Endres, T., and Lessmann, V.
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- 2012
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10. FTY720 treatment starting after onset of symptoms reverses synaptic and memory deficits in an AD mouse model
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Kartalou G-I, Salgueiro Pereira SP, Endres T, Lesnikova A, Casarotto P, Pousinha P, Delanoe K, Edelmann E, Castrén E, Gottmann K, Marie H, Lessmann V.
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- 2019
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11. Highly replicated sampling reveals no diurnal vertical migration but stable species-specific vertical habitats in planktonic foraminifera
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Meilland, J., Siccha, M., Weinkauf, M.F.G., Jonkers, L., Morard, R., Baranowski, U., Baumeister, A., Bertlich, J., Brummer, G.-J. A., Debray, P., Fritz-Endres, T., Groeneveld, J., Magerl, L., Munz, P., Rillo, M.C., Schmidt, C., Takagi, H., Theara, G., Kucera, M., Meilland, J., Siccha, M., Weinkauf, M.F.G., Jonkers, L., Morard, R., Baranowski, U., Baumeister, A., Bertlich, J., Brummer, G.-J. A., Debray, P., Fritz-Endres, T., Groeneveld, J., Magerl, L., Munz, P., Rillo, M.C., Schmidt, C., Takagi, H., Theara, G., and Kucera, M.
- Abstract
Diurnal vertical migration (DVM) is a widespread phenomenon in the upper ocean, but it remains unclear to what degree it also involves passively transported micro- and meso-zooplankton. These organisms are difficult to monitor by in situ sensing and observations from discrete samples are often inconclusive. Prime examples of such ambiguity are planktonic foraminifera, where contradictory evidence for DVM continues to cast doubt on the stability of species vertical habitats, which introduces uncertainties in geochemical proxy interpretation. To provide a robust answer, we carried out highly replicated randomized sampling with 41 vertically resolved plankton net hauls taken within 26 hours in a confined area of 400 km2 in the tropical North Atlantic, where DVM in larger plankton occurs. Manual enumeration of planktonic foraminifera cell density consistently reveals the highest total cell concentrations in the surface mixed layer (top 50 m) and analysis of cell density in seven individual species representing different shell sizes, life strategies and presumed depth habitats reveals consistent vertical habitats not changing over the 26 hours sampling period. These observations robustly reject the existence of DVM in planktonic foraminifera in a setting where DVM occurs in other organisms.
- Published
- 2019
12. The Relation Between Long-Term Synaptic Plasticity at Glutamatergic Synapses in the Amygdala and Fear Learning in Adult Heterozygous BDNF-Knockout Mice
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Meis, S, primary, Endres, T, additional, Munsch, T, additional, and Lessmann, V, additional
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- 2017
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13. Ernst Cassirers Wahrnehmungs- und Repräsentationstheorie
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Endres, T. (Tobias) and Universitäts- und Landesbibliothek Münster
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Philosophie ,Geschichte ,Gesellschaft ,Geltung ,DGPhil ,ddc:100 ,Philosophy, parapsychology and occultism, psychology - Published
- 2014
14. The Relation Between Long-Term Synaptic Plasticity at Glutamatergic Synapses in the Amygdala and Fear Learning in Adult Heterozygous BDNF-Knockout Mice.
- Author
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Meis, S., Endres, T., Munsch, T., and Lessmann, V.
- Published
- 2018
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15. Clinical and Molecular Phenotypes of Low-Penetrance Variants of NLRP3: Diagnostic and Therapeutic Challenges.
- Author
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Kuemmerle‐Deschner, J. B., Verma, D., Endres, T., Broderick, L., Jesus, A. A., Hofer, F., Blank, N., Krause, K., Rietschel, C., Horneff, G., Aksentijevich, I., Lohse, P., Goldbach‐Mansky, R., Hoffman, H. M., and Benseler, S. M.
- Subjects
ENZYME metabolism ,TREATMENT effectiveness ,CELL death ,EYE diseases ,FEVER ,GENETIC disorders ,HEARING disorders ,INFLAMMATION ,INTERLEUKINS ,KIDNEYS ,MEDICAL cooperation ,RESEARCH ,SKIN diseases ,PHENOTYPES ,DNA-binding proteins ,STATISTICAL significance ,DESCRIPTIVE statistics ,CHEMICAL inhibitors - Abstract
Objective Cryopyrin-associated periodic syndromes ( CAPS) result from gain-of-function mutations in the NLRP3 gene, which causes excessive release of interleukin-1β ( IL-1β) and systemic inflammation. While pathogenetic NLRP3 variant phenotypes are well-characterized, low-penetrance NLRP3 variants represent a significant clinical challenge. The aims of this study were to determine the clinical phenotype, the in vitro biologic phenotype, and the effect of anti- IL-1 treatment in patients with low-penetrance NLRP3 variants. Methods A multicenter study of consecutive symptomatic patients with low-penetrance NLRP3 variants recruited from 7 centers between May 2012 and May 2013 was performed. The observed findings were transferred into a study database, from which they were extracted for analysis. Controls were patients with a known pathogenetic NLRP3 variant. Clinical presentation and CAPS markers of inflammation were captured. Functional assays of inflammasome activation, including caspase 1 activity, NF-κB release, cell death, and IL-1β release, were performed. Treatment effects of IL-1 were determined. Comparisons between low-penetrance and pathogenetic NLRP3 variants were performed. Results The study included 45 patients, 21 of which were female (47%); 26 of the patients (58%) were children. NLRP3 low-penetrance variants identified in the patients were Q703K (n = 19), R488K (n = 6), and V198M (n = 20). In the controls, 28 had pathogenetic NLRP3 variants. Patients with low-penetrance NLRP3 variants had significantly more fever (76%) and gastrointestinal symptoms (73%); eye disease, hearing loss, and renal involvement were less common. Functional inflammasome testing identified an intermediate phenotype in low-penetrance NLRP3 variants as compared to wild-type and pathogenetic NLRP3 variants. All treated patients responded to IL-1 inhibition, with complete response documented in 50% of patients. Conclusion Patients with low-penetrance NLRP3 variants display a distinct clinical phenotype and an intermediate biologic phenotype, including IL-1β and non- IL-1β-mediated inflammatory pathway activation. [ABSTRACT FROM AUTHOR]
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- 2017
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16. RFID based patient registration in mass casualty incidents
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Nestler, S, Artinger, E, Coskun, T, Endres, T, and Klinker, G
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ddc: 610 ,lcsh:R858-859.7 ,lcsh:RC109-216 ,610 Medical sciences ,Medicine ,lcsh:Computer applications to medicine. Medical informatics ,lcsh:Infectious and parasitic diseases - Abstract
In MCIs (mass casualty incidents) the EMC (emergency medical chief) has to gain an overview on all patients at the scene. When using paper based patient tags the patient-related information remains at the patients themselves and the information relay is complex. We propose a mobile, RFID based solution, which makes the local patient-related information available to all relief workers at the scene. As a consequence all processes in an MCI are more transparent and the resulting medication and transport of the injured is more efficient. The introduction of RFID enhanced patient tags leads to various usability challenges which are discussed in this paper. Furthermore, three different implementations show, how these challenges can be solved in the future. These solutions have been evaluated in a disaster control exercise in order to get an impression of the practical suitability of the proposed solutions. The future introduction of RFID tags in rescue and emergency services can be based on this work., GMS Medizinische Informatik, Biometrie und Epidemiologie; 7(1):Doc02; ISSN 1860-9171
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- 2011
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17. Funktionelle Langzeitergebnisse nach tarsaler Kahnbeinfraktur
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Coulibaly, M., Sietsema, D., Ringler, J., Endres, T., and Jones, C.
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Tarsale Kahnbeinfrakturen (TKF) sind selten und die funktionellen Heilungsergebnisse sind weitgehend unbestimmt. Zielsetzung dieser Studie war die Evaluation funktioneller Ergebnisse nach erlittener TKF. Methodik: Eine prospektive Analyse wurde an einer Kohorte von 64 Patienten durchgeführt,[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 51. Tagung des Berufsverbandes der Fachärzte für Orthopädie
- Published
- 2010
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18. A functional inflammasome activation assaydifferentiates patients with pathogenic NLRP3mutations and symptomatic patients with lowpenetrance variants
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Rieber, N, primary, Gavrilov, A, additional, Hofer, L, additional, Singh, A, additional, Öz, H, additional, Endres, T, additional, Schäfer, I, additional, Handgretinger, R, additional, Hartl, D, additional, and Kümmerle-Deschner, J, additional
- Published
- 2015
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19. Canakinumab treat-to target strategies increase complete response rate in CAPS
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Kuemmerle-Deschner, J, primary, Hofer, F, additional, Endres, T, additional, Kortus-Goetze, B, additional, Blank, N, additional, Weißbarth-Riedel, E, additional, Schuetz, C, additional, Kallinich, T, additional, Krause, K, additional, Rietschel, C, additional, Horneff, G, additional, and Benseler, SM, additional
- Published
- 2015
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20. Results and functional outcome of femoral neck fractures in young adults
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Jones, C, Sietsema, D, Ringler, J, Endres, T, and Coulibaly, M
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Objective: The purpose of this study was to evaluate long-term functional outcome, results and complications after operative treatment of femoral neck fracture (FNF) in young adults. Methods: Over a five-year period, 2002–2007, 87 skeletally mature patients were retrospectively identified [for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 51. Tagung des Berufsverbandes der Fachärzte für Orthopädie
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- 2010
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21. Funktionelle Ergebnisse nach Frakturen des Os cuboideum
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Coulibaly, M, Sietsema, D, Ringler, J, Endres, T, and Jones, C
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Fragestellung: Cuboid-Frakturen (CF) sind seltene Verletzungen des Fußgewölbes und die funktionellen Heilungsergebnisse sind unterrepräsentiert. Zielsetzung dieser Studie war die Evaluation funktioneller Ergebnisse nach erlittener CF. Methodik: Eine prospektive Analyse wurde an einer[for full text, please go to the a.m. URL], Deutscher Kongress für Orthopädie und Unfallchirurgie; 74. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie, 96. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie, 51. Tagung des Berufsverbandes der Fachärzte für Orthopädie
- Published
- 2010
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22. Formation of the Troodos Ophiolite at a triple junction: Evidence from trace elements in volcanic glass
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Regelous, M., Haase, K.M., Freund, S., Keith, M., Weinzierl, C.G., Beier, Christoph, Brandl, Philipp A., Endres, T., Schmidt, H., Regelous, M., Haase, K.M., Freund, S., Keith, M., Weinzierl, C.G., Beier, Christoph, Brandl, Philipp A., Endres, T., and Schmidt, H.
- Abstract
Fresh volcanic glasses from the extrusive section of the Troodos Ophiolite in Akaki Canyon are tholeiitic and basaltic to dacitic in composition. Compared to normal MORB they have extremely low fractionation corrected Na8, Fe8 and Ti8 and are enriched in fluid-mobile trace elements, including U, Ba, Rb, Sr and Pb, relative to non-fluid mobile elements of similar incompatibility. Trace element compositions of Akaki lavas define an array extending between ‘back-arc lava’-like compositions, and the field defined by Troodos boninites from the upper part of the lava sequence. Troodos lavas were derived from a mantle source that underwent early melt depletion, and later enrichment by both fluids and small degree melts. These processes can explain the unusual negative correlation of Pb/Ce with Zr/Nb and Ba/Nb in Troodos extrusives. Although some Troodos lavas are similar in composition to lavas from back-arc spreading centres, the boninites from the upper parts of the lava pile do not appear to have exact compositional equivalents among lavas from fore-arcs, back-arcs or other tectonic settings where similar rocktypes have been recovered. We suggest that the geochemical evolution inferred for the mantle source of Troodos lavas, together with geological evidence is most consistent with an origin for the Troodos Ophiolite at a spreading centre close to a ridge–trench–trench, or ridge–trench–transform triple junction, where highly depleted, subduction-modified, fluid-enriched mantle wedge material was able to upwell and decompress to shallow depths in a ‘fore-arc’ location. In such a tectonic setting, arc volcanism is captured by the spreading centre, explaining the lack of evidence for subaerial arc magmatism in Troodos. Rapid lateral migration of the triple junction could account for the similar ages of other Tethyan supra-subduction zone ophiolites.
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- 2014
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23. 6-Jahres-Ergebnisse der 4-Schrauben-OSG-Arthrodese
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Endres, T, Amlang, M, Rammelt, S, and Zwipp, H
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ddc: 610 - Published
- 2007
24. Spätergebnisse der OSG-Arthrodese
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Endres, T, Rammelt, S, Grass, R, and Zwipp, H
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ddc: 610 - Published
- 2003
25. PReS-FINAL-2224: Canakinumab treatment regimens in CAPS-patients
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Hofer, F, primary, Endres, T, additional, Kortus-Götze, B, additional, Blank, N, additional, Weißbarth-Riedel, E, additional, Schütz, C, additional, Kallinich, T, additional, Krause, K, additional, Rietschel, C, additional, Horneff, G, additional, and Kuemmerle-Deschner, J, additional
- Published
- 2013
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26. PW02-041 - Canakinumab treatment regimens in CAPS-patients
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Hofer, F, primary, Endres, T, additional, Kortus-Götze, B, additional, Blank, N, additional, Weißbarth-Riedel, E, additional, Schuetz, C, additional, Kallinich, T, additional, Krause, K, additional, Rietschel, C, additional, Horneff, G, additional, and Kuemmerle-Deschner, J, additional
- Published
- 2013
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27. Long-Term Functional Outcome of Midfoot Fractures
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Jones, C, Sietsema, D, Ringler, J, Endres, T, Coulibaly, M, Jones, C, Sietsema, D, Ringler, J, Endres, T, and Coulibaly, M
- Published
- 2010
28. Funktionelle Langzeitergebnisse nach tarsaler Kahnbeinfraktur
- Author
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Coulibaly, M, Sietsema, D, Ringler, J, Endres, T, Jones, C, Coulibaly, M, Sietsema, D, Ringler, J, Endres, T, and Jones, C
- Published
- 2010
29. Building communities that promote successful aging
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Fried, L. P., Freedman, M., Endres, T. E., and Barbara A. Wasik
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Male ,Aging ,Life Expectancy ,Health Services for the Aged ,Humans ,Female ,Health Promotion ,Community Networks ,United States ,Research Article ,Aged - Abstract
Despite the fact that, in a few years, a fifth of the US population will be older than 65 years and people will be living a third of their lives after retirement, we have developed few avenues that would permit older adults to play meaningful roles as they age and few institutions to harness the experience that older adults could contribute to society. In fact, older adults constitute this country's only increasing natural resource--and the least used one. In this article we consider the rationale for developing institutions that harness the abilities and time of older adults, rather than focusing solely on their needs. Such an approach would decrease the structural lag between a social concept of retirement as unproductive leisure and an aging population that is larger, healthier, and with a need for more productive opportunities. Gerontologically designed opportunities for contribution on a large social scale could well provide a national approach to primary prevention to maintain health and function in older adults.
- Published
- 1997
30. Postsynaptic BDNF signalling regulates long-term potentiation at thalamo-amygdala afferents
- Author
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Meis, S., primary, Endres, T., additional, and Lessmann, V., additional
- Published
- 2011
- Full Text
- View/download PDF
31. Robustness to fractionally-spaced equalizer length using the constant modulus criterion
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Endres, T J, Anderson, Brian, Johnson, C Richard, Green, M, Endres, T J, Anderson, Brian, Johnson, C Richard, and Green, M
- Abstract
This correspondence studies robustness properties of the constant modulus (CM) criterion and the constant modulus algorithm (CMA) to the suboptimal but practical situation where the number of fractionally spaced equalizer coefficients is less than what is needed to remove all intersymbol interference (ISI). Hence, there necessarily exists an error in the equalized signal. Relationships between CM and mean squared error cost functions are established.
- Published
- 1999
32. A Data Broadcasting System Expanding the Information Capacity of Existing Analog Communication Systems
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Chung, W., primary, Endres, T., additional, and Long, C.D., additional
- Published
- 2005
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33. Robustness of Fractionally-Spaced Equalizer Length Using the Constant Modulus Criterion.
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Endres, T. J. and Anderson, B. D. O.
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- *
ALGORITHMS , *SIGNAL processing - Abstract
Provides information on a study which examined the robustness properties of fractionally spaced constant modulus algorithm (CMA) and constant modulus criterion. Description of the fractionally spaced CMA; Two algebraic analysis approaches; Conclusion.
- Published
- 1999
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34. In vivo impact of tubulin polymerization promoting protein (Tppp) knockout to the airway inflammatory response.
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Endres T, Duesler L, Corey DA, and Kelley TJ
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- Animals, Mice, Microtubules metabolism, Polymerization, Cystic Fibrosis metabolism, Nerve Tissue Proteins metabolism, Tubulin metabolism
- Abstract
Microtubule dysfunction has been implicated as a mediator of inflammation in multiple diseases such as disorders of the cardiovascular and neurologic systems. Tubulin polymerization promoting protein (Tppp) facilitates microtubule elongation and regulates tubulin acetylation through inhibition of cytosolic deacetylase enzymes. Pathologic alterations in microtubule structure and dynamics have been described in cystic fibrosis (CF) and associated with inflammation, however the causality and mechanism remain unclear. Likewise, Tppp has been identified as a potential modifier of CF airway disease severity. Here we directly assess the impact of microtubule dysfunction on infection and inflammation by interrogating wild type and a Tppp knockout mouse model (Tppp - / -). Mice are challenged with a clinical isolate of Pseudomonas aeruginosa-laden agarose beads and assessed for bacterial clearance and inflammatory markers. Tppp - / - mouse model demonstrate impaired bacterial clearance and an elevated inflammatory response compared to control mice. These data are consistent with the hypothesis microtubule dysregulation is sufficient to lead to CF-like airway responses in mice., (© 2023. The Author(s).)
- Published
- 2023
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35. Spatially resolved measurement of the distribution of solid and liquid Si nanoparticles in plasma synthesis through line-of-sight extinction spectroscopy.
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Liu G, Wollny P, Menser J, Dreier T, Endres T, Wlokas I, Daun KJ, and Schulz C
- Abstract
In many high-temperature gas-phase nanoparticle synthesis processes, freshly nucleated particles are liquid and solidify during growth and cooling. This study presents an approach to determine the location of the liquid-to-solid phase transition and the volume fraction and number density of particles of both phases within a gas phase reactor. Spectrally-resolved line-of-sight attenuation (LOSA) measurements are applied to a silicon nanoparticle aerosol generated from monosilane in a microwave plasma reactor. A phantom-based analysis using particle number density, particle size, and temperature distribution from direct numerical simulation (DNS) of the reacting flow indicates that the contributions from the two particle phases can be decoupled under practical conditions, even with noisy data. The approach was applied to analyze spatially and spectrally resolved LOSA measurements from the hot gas flow downstream of the plasma zone where both solid and liquid silicon particles coexist. Extinction spectra were recorded along a line perpendicular to the flow direction by a spectrometer with an electron-multiplying charge-coupled device (EMCCD) camera, and two-dimensional projections were deconvolved to obtain radial extinction coefficient distributions of solid and liquid particles across the cross-section of the flow. Particle number densities of both particle phases were retrieved simultaneously based on the size-dependent extinction cross-sections of the nanoparticles. The particle-size distribution was determined via thermophoretic sampling at the same location with subsequent transmission electron microscopy (TEM) analysis. The particle temperature distribution was determined from the particle's thermal radiation based on line-of-sight emission (LOSE) measurements. The approach for phase-selective data analysis can be transferred to other materials aerosol systems as long as significant differences exist in extinction spectra for the related different particle classes.
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- 2023
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36. MYC multimers shield stalled replication forks from RNA polymerase.
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Solvie D, Baluapuri A, Uhl L, Fleischhauer D, Endres T, Papadopoulos D, Aziba A, Gaballa A, Mikicic I, Isaakova E, Giansanti C, Jansen J, Jungblut M, Klein T, Schülein-Völk C, Maric H, Doose S, Sauer M, Beli P, Rosenwald A, Dobbelstein M, Wolf E, and Eilers M
- Subjects
- Humans, Chromatin genetics, Promoter Regions, Genetic genetics, RNA Polymerase II metabolism, Transcription, Genetic, Tumor Suppressor Proteins metabolism, Ubiquitin-Protein Ligases metabolism, DNA Breaks, Double-Stranded, S Phase, Binding Sites, RNA, Messenger biosynthesis, DNA-Directed RNA Polymerases metabolism
- Abstract
Oncoproteins of the MYC family drive the development of numerous human tumours
1 . In unperturbed cells, MYC proteins bind to nearly all active promoters and control transcription by RNA polymerase II2,3 . MYC proteins can also coordinate transcription with DNA replication4,5 and promote the repair of transcription-associated DNA damage6 , but how they exert these mechanistically diverse functions is unknown. Here we show that MYC dissociates from many of its binding sites in active promoters and forms multimeric, often sphere-like structures in response to perturbation of transcription elongation, mRNA splicing or inhibition of the proteasome. Multimerization is accompanied by a global change in the MYC interactome towards proteins involved in transcription termination and RNA processing. MYC multimers accumulate on chromatin immediately adjacent to stalled replication forks and surround FANCD2, ATR and BRCA1 proteins, which are located at stalled forks7,8 . MYC multimerization is triggered in a HUWE16 and ubiquitylation-dependent manner. At active promoters, MYC multimers block antisense transcription and stabilize FANCD2 association with chromatin. This limits DNA double strand break formation during S-phase, suggesting that the multimerization of MYC enables tumour cells to proliferate under stressful conditions., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2022
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37. MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling.
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Zimmerli D, Brambillasca CS, Talens F, Bhin J, Linstra R, Romanens L, Bhattacharya A, Joosten SEP, Da Silva AM, Padrao N, Wellenstein MD, Kersten K, de Boo M, Roorda M, Henneman L, de Bruijn R, Annunziato S, van der Burg E, Drenth AP, Lutz C, Endres T, van de Ven M, Eilers M, Wessels L, de Visser KE, Zwart W, Fehrmann RSN, van Vugt MATM, and Jonkers J
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- Animals, Humans, Mice, Cell Line, Tumor, Interferons, Lymphocytes, Tumor-Infiltrating, Signal Transduction, Tumor Microenvironment genetics, Proto-Oncogene Proteins c-myc metabolism, Triple Negative Breast Neoplasms metabolism
- Abstract
The limited efficacy of immune checkpoint inhibitor treatment in triple-negative breast cancer (TNBC) patients is attributed to sparse or unresponsive tumor-infiltrating lymphocytes, but the mechanisms that lead to a therapy resistant tumor immune microenvironment are incompletely known. Here we show a strong correlation between MYC expression and loss of immune signatures in human TNBC. In mouse models of TNBC proficient or deficient of breast cancer type 1 susceptibility gene (BRCA1), MYC overexpression dramatically decreases lymphocyte infiltration in tumors, along with immune signature remodelling. MYC-mediated suppression of inflammatory signalling induced by BRCA1/2 inactivation is confirmed in human TNBC cell lines. Moreover, MYC overexpression prevents the recruitment and activation of lymphocytes in both human and mouse TNBC co-culture models. Chromatin-immunoprecipitation-sequencing reveals that MYC, together with its co-repressor MIZ1, directly binds promoters of multiple interferon-signalling genes, resulting in their downregulation. MYC overexpression thus counters tumor growth inhibition by a Stimulator of Interferon Genes (STING) agonist via suppressing induction of interferon signalling. Together, our data reveal that MYC suppresses innate immunity and facilitates tumor immune escape, explaining the poor immunogenicity of MYC-overexpressing TNBCs., (© 2022. The Author(s).)
- Published
- 2022
- Full Text
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38. ProBDNF Dependence of LTD and Fear Extinction Learning in the Amygdala of Adult Mice.
- Author
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Ma X, Vuyyuru H, Munsch T, Endres T, Lessmann V, and Meis S
- Subjects
- Amygdala metabolism, Animals, Learning physiology, Mice, Neuronal Plasticity, Extinction, Psychological physiology, Fear physiology
- Abstract
Neurotrophins are secreted proteins that control survival, differentiation, and synaptic plasticity. While mature neurotrophins regulate these functions via tyrosine kinase signaling (Trk), uncleaved pro-neurotrophins bind preferentially to the p75 neurotrophin receptor (p75NTR) and often exert opposite effects to those of mature neurotrophins. In the amygdala, brain-derived neurotrophic factor (BDNF) enables long-term potentiation as well as fear and fear extinction learning. In the present study, we focused on the impact of mature BDNF and proBDNF signaling on long-term depression (LTD) in the lateral amygdala (LA). Hence, we conducted extracellular field potential recordings in an in vitro slice preparation and recorded LTD in cortical and thalamic afferents to the LA. LTD was unchanged by acute block of BDNF/TrkB signaling. In contrast, LTD was inhibited by blocking p75NTR signaling, by disinhibition of the proteolytic cleavage of proBDNF into mature BDNF, and by preincubation with a function-blocking anti-proBDNF antibody. Since LTD-like processes in the amygdala are supposed to be related to fear extinction learning, we locally inhibited p75NTR signaling in the amygdala during or after fear extinction training, resulting in impaired fear extinction memory. Overall, these results suggest that in the amygdala proBDNF/p75NTR signaling plays a pivotal role in LTD and fear extinction learning., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
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39. A Novel Aminomethacrylate-Based Copolymer for Solubility Enhancement-From Radical Polymer Synthesis to Manufacture and Characterization of Amorphous Solid Dispersions.
- Author
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Schmied FP, Bernhardt A, Moers C, Meier C, Endres T, and Klein S
- Abstract
The present study covers the synthesis, purification and evaluation of a novel aminomethacrylate-based copolymer in terms of its suitability for improving the solubility and in vitro release of poorly water-soluble drug compounds. The new copolymer was synthesized by solvent polymerization with radical initiation and by use of a chain transfer agent. Based on its composition, it can be considered as a modified type of dimethylaminoethyl methacrylate-butyl methacrylate-methyl methacrylate "EUDRAGIT
® E PO" (ModE). ModE was specifically developed to provide a copolymer with processing and application properties that exceed those of commercially available (co-)polymers in solubility enhancement technologies where possible. By varying the concentration of the chain transfer agent in the radical polymerization process, the molecular weight of ModE was varied in a range of 173-305 kDa. To evaluate the solubility-enhancing properties of ModE, a series of drug-loaded extrudates were prepared by hot melt extrusion using the novel-as well as several commercially available-(co-)polymers. These extrudates were then subjected to comparative tests for amorphousness, solubility-enhancing properties, storage stability, and drug release. Celecoxib, efavirenz, and fenofibrate were used as model drugs in all experiments. Of all the (co-)polymers included in the study, ModE with a molecular weight of 173 kDa showed the best performance in terms of desired properties and was shown to be particularly suitable for preparing amorphous solid dispersions (ASDs) of the three model drugs, which in a first set of dissolution experiments showed better release behavior under pH conditions of the fasting stomach than higher molecular weight ModE types, as well as a variety of commercially available (co-)polymers. Therefore, the results demonstrate the successful synthesis of a new copolymer, which in future studies will be investigated in more detail for universal application in the field of solubility enhancement.- Published
- 2022
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- View/download PDF
40. A Compact Fiber-Coupled NIR/MIR Laser Absorption Instrument for the Simultaneous Measurement of Gas-Phase Temperature and CO, CO 2 , and H 2 O Concentration.
- Author
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Shi L, Endres T, Jeffries JB, Dreier T, and Schulz C
- Abstract
A fiber-coupled, compact, remotely operated laser absorption instrument is developed for CO, CO
2 , and H2 O measurements in reactive flows at the elevated temperatures and pressures expected in gas turbine combustor test rigs with target pressures from 1-25 bar and temperatures of up to 2000 K. The optical engineering for solutions of the significant challenges from the ambient acoustic noise (~120 dB) and ambient test rig temperatures (60 °C) are discussed in detail. The sensor delivers wavelength-multiplexed light in a single optical fiber from a set of solid-state lasers ranging from diodes in the near-infrared (~1300 nm) to quantum cascade lasers in the mid-infrared (~4900 nm). Wavelength-multiplexing systems using a single optical fiber have not previously spanned such a wide range of laser wavelengths. Gas temperature is inferred from the ratio of two water vapor transitions. Here, the design of the sensor, the optical engineering required for simultaneous fiber delivery of a wide range of laser wavelengths on a single optical line-of-sight, the engineering required for sensor survival in the harsh ambient environment, and laboratory testing of sensor performance in the exhaust gas of a flat flame burner are presented.- Published
- 2022
- Full Text
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41. MYCN recruits the nuclear exosome complex to RNA polymerase II to prevent transcription-replication conflicts.
- Author
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Papadopoulos D, Solvie D, Baluapuri A, Endres T, Ha SA, Herold S, Kalb J, Giansanti C, Schülein-Völk C, Ade CP, Schneider C, Gaballa A, Vos S, Fischer U, Dobbelstein M, Wolf E, and Eilers M
- Subjects
- Animals, Ataxia Telangiectasia Mutated Proteins genetics, Ataxia Telangiectasia Mutated Proteins metabolism, BRCA1 Protein genetics, BRCA1 Protein metabolism, Cell Line, Tumor, Cell Nucleus genetics, DNA Breaks, Double-Stranded, Exoribonucleases genetics, Exoribonucleases metabolism, Exosomes genetics, Female, Gene Expression Regulation, Neoplastic, HEK293 Cells, Humans, Male, Mice, N-Myc Proto-Oncogene Protein genetics, NIH 3T3 Cells, Neuroblastoma genetics, Neuroblastoma pathology, Promoter Regions, Genetic, RNA Caps genetics, RNA Caps metabolism, RNA Polymerase II genetics, Transcription Termination, Genetic, Cell Nucleus enzymology, Cell Proliferation, DNA Replication, Exosomes enzymology, N-Myc Proto-Oncogene Protein metabolism, Neuroblastoma enzymology, RNA Polymerase II metabolism, Transcription, Genetic
- Abstract
The MYCN oncoprotein drives the development of numerous neuroendocrine and pediatric tumors. Here we show that MYCN interacts with the nuclear RNA exosome, a 3'-5' exoribonuclease complex, and recruits the exosome to its target genes. In the absence of the exosome, MYCN-directed elongation by RNA polymerase II (RNAPII) is slow and non-productive on a large group of cell-cycle-regulated genes. During the S phase of MYCN-driven tumor cells, the exosome is required to prevent the accumulation of stalled replication forks and of double-strand breaks close to the transcription start sites. Upon depletion of the exosome, activation of ATM causes recruitment of BRCA1, which stabilizes nuclear mRNA decapping complexes, leading to MYCN-dependent transcription termination. Disruption of mRNA decapping in turn activates ATR, indicating transcription-replication conflicts. We propose that exosome recruitment by MYCN maintains productive transcription elongation during S phase and prevents transcription-replication conflicts to maintain the rapid proliferation of neuroendocrine tumor cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021. Published by Elsevier Inc.)
- Published
- 2022
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42. Phase-sensitive detection of gas-borne Si nanoparticles via line-of-sight UV/VIS attenuation.
- Author
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Asif M, Menser J, Endres T, Dreier T, Daun K, and Schulz C
- Abstract
The distinct optical properties of solid and liquid silicon nanoparticles are exploited to determine the distribution of gas-borne solid and liquid particles in situ using line-of-sight attenuation measurements carried out across a microwave plasma reactor operated at 100 mbar. The ratio between liquid and solid particles detected downstream of the plasma varied with measurement location, microwave power, and flow rate. Temperatures of the liquid particles were pyrometrically-inferred using a spectroscopic model based on Drude theory. The phase-sensitive measurement supports the understanding of nanoparticle formation and interaction and thus the overall gas-phase synthesis process.
- Published
- 2021
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- View/download PDF
43. Characterization of tracers for two-color laser-induced fluorescence thermometry of liquid-phase temperature in ethanol, 2-ethylhexanoic-acid/ethanol mixtures, 1-butanol, and o-xylene.
- Author
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Prenting MM, Shilikhin M, Dreier T, Schulz C, and Endres T
- Abstract
The fluorescence spectra of dye solutions change their spectral signature with temperature. This effect is frequently used for temperature imaging in liquids and sprays based on two-color laser-induced fluorescence (2cLIF) measurements by simultaneously detecting the fluorescence intensity in two separate wavelength channels resulting in a temperature-sensitive ratio. In this work, we recorded temperature-dependent absorption and fluorescence spectra of solutions of five laser dyes (coumarin 152, coumarin 153, rhodamine B, pyrromethene 597, and DCM) dissolved in ethanol, a 35/65 vol.% mixture of ethanol/2-ethylhexanoic acid, ethanol/hexamethylsiloxane, o-xylene, and 1-butanol to investigate their potential as temperature tracers in evaporating and burning sprays. The dissolved tracers were excited at either 266, 355, and 532 nm (depending on the tracer) for temperatures between 296 and 393 K (depending on the solvent) and for concentrations ranging between 0.1 and 10 mg/l. Absorption and fluorescence spectra of the tracers were investigated for their temperature dependence, the magnitude of signal re-absorption, the impact of different solvents, and varying two-component solvent compositions. Based on the measured fluorescence spectra, the tracers were analyzed for their 2cLIF temperature sensitivity in the respective solvents. Coumarin 152 showed for single-component solvents the overall best spectroscopic properties for our specific measurement situation related to temperature imaging measurements in spray-flame synthesis of nanoparticles as demonstrated previously in ethanol spray flames [Exp. Fluids61, 77 (2020)10.1007/s00348-020-2909-9].
- Published
- 2021
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- View/download PDF
44. BDNF haploinsufficiency induces behavioral endophenotypes of schizophrenia in male mice that are rescued by enriched environment.
- Author
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Harb M, Jagusch J, Durairaja A, Endres T, Leßmann V, and Fendt M
- Subjects
- Animals, Endophenotypes, Haploinsufficiency, Male, Mice, Mice, Inbred C57BL, Reflex, Startle, Brain-Derived Neurotrophic Factor genetics, Schizophrenia genetics
- Abstract
Brain-derived neurotrophic factor (BDNF) is implicated in a number of processes that are crucial for healthy functioning of the brain. Schizophrenia is associated with low BDNF levels in the brain and blood, however, not much is known about BDNF's role in the different symptoms of schizophrenia. Here, we used BDNF-haploinsufficient (BDNF
+/- ) mice to investigate the role of BDNF in different mouse behavioral endophenotypes of schizophrenia. Furthermore, we assessed if an enriched environment can prevent the observed changes. In this study, male mature adult wild-type and BDNF+/- mice were tested in mouse paradigms for cognitive flexibility (attentional set shifting), sensorimotor gating (prepulse inhibition), and associative emotional learning (safety and fear conditioning). Before these tests, half of the mice had a 2-month exposure to an enriched environment, including running wheels. After the tests, BDNF brain levels were quantified. BDNF+/- mice had general deficits in the attentional set-shifting task, increased startle magnitudes, and prepulse inhibition deficits. Contextual fear learning was not affected but safety learning was absent. Enriched environment housing completely prevented the observed behavioral deficits in BDNF+/- mice. Notably, the behavioral performance of the mice was negatively correlated with BDNF protein levels. These novel findings strongly suggest that decreased BDNF levels are associated with several behavioral endophenotypes of schizophrenia. Furthermore, an enriched environment increases BDNF protein to wild-type levels and is thereby able to rescue these behavioral endophenotypes.- Published
- 2021
- Full Text
- View/download PDF
45. Spatial distribution of gas-phase synthesized germanium nanoparticle volume-fraction and temperature using combined in situ line-of-sight emission and extinction spectroscopy.
- Author
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Liu G, Asif M, Menser J, Dreier T, Mohri K, Schulz C, and Endres T
- Abstract
In this study, emission and extinction spectroscopy were combined to in situ measure temperature and volume fraction distributions of liquid germanium nanoparticle gas-phase synthesized in an argon/hydrogen/germane flow through a microwave plasma. Emission of the hot particles and extinction against a continuous background were recorded by a spectrometer in the 380-703 nm and 230-556 nm ranges, respectively, selected based on the specific optical properties of the material. Absorption coefficients were deconvoluted from line-of-sight attenuation (LOSA) measurements by a least-square algorithm and then used to determine the local volume fraction distribution. The temperature field was derived from the line-of-sight emission (LOSE) spectra with the prior knowledge of absorption coefficients. A multi-wavelength reconstruction model was developed for the determination of the spatially-resolved distribution of the measured quantities assuming a stationary axisymmetric flow. Advantages of the method include experimental simplicity, low cost, and adaptability to up-scaled reactor sizes.
- Published
- 2021
- Full Text
- View/download PDF
46. Ubiquitylation of MYC couples transcription elongation with double-strand break repair at active promoters.
- Author
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Endres T, Solvie D, Heidelberger JB, Andrioletti V, Baluapuri A, Ade CP, Muhar M, Eilers U, Vos SM, Cramer P, Zuber J, Beli P, Popov N, Wolf E, Gallant P, and Eilers M
- Subjects
- ATPases Associated with Diverse Cellular Activities genetics, ATPases Associated with Diverse Cellular Activities metabolism, Cell Line, Tumor, Histones genetics, Histones metabolism, Humans, Proto-Oncogene Proteins c-myc genetics, RNA Polymerase II genetics, RNA Polymerase II metabolism, Tumor Suppressor Proteins genetics, Tumor Suppressor Proteins metabolism, Ubiquitin-Protein Ligases genetics, Ubiquitin-Protein Ligases metabolism, Ubiquitination, DNA Breaks, Double-Stranded, DNA Repair, Promoter Regions, Genetic, Proto-Oncogene Proteins c-myc metabolism, Transcription Elongation, Genetic
- Abstract
The MYC oncoprotein globally affects the function of RNA polymerase II (RNAPII). The ability of MYC to promote transcription elongation depends on its ubiquitylation. Here, we show that MYC and PAF1c (polymerase II-associated factor 1 complex) interact directly and mutually enhance each other's association with active promoters. PAF1c is rapidly transferred from MYC onto RNAPII. This transfer is driven by the HUWE1 ubiquitin ligase and is required for MYC-dependent transcription elongation. MYC and HUWE1 promote histone H2B ubiquitylation, which alters chromatin structure both for transcription elongation and double-strand break repair. Consistently, MYC suppresses double-strand break accumulation in active genes in a strictly PAF1c-dependent manner. Depletion of PAF1c causes transcription-dependent accumulation of double-strand breaks, despite widespread repair-associated DNA synthesis. Our data show that the transfer of PAF1c from MYC onto RNAPII efficiently couples transcription elongation with double-strand break repair to maintain the genomic integrity of MYC-driven tumor cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2021
- Full Text
- View/download PDF
47. Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model.
- Author
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Kartalou GI, Salgueiro-Pereira AR, Endres T, Lesnikova A, Casarotto P, Pousinha P, Delanoe K, Edelmann E, Castrén E, Gottmann K, Marie H, and Lessmann V
- Subjects
- Alzheimer Disease genetics, Alzheimer Disease metabolism, Alzheimer Disease pathology, Amyloid beta-Peptides genetics, Animals, Anti-Inflammatory Agents pharmacology, Astrocytes metabolism, Astrocytes pathology, Disease Models, Animal, Fingolimod Hydrochloride pharmacology, Hippocampus drug effects, Hippocampus metabolism, Humans, Inflammation genetics, Inflammation metabolism, Inflammation pathology, Memory Disorders genetics, Memory Disorders metabolism, Memory Disorders pathology, Mice, Mice, Transgenic, Microglia drug effects, Microglia metabolism, Synapses genetics, Synapses pathology, Alzheimer Disease drug therapy, Amyloid beta-Protein Precursor genetics, Inflammation drug therapy, Memory Disorders drug therapy, Presenilin-1 genetics
- Abstract
Therapeutic approaches providing effective medication for Alzheimer's disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes.
- Published
- 2020
- Full Text
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48. Cytosolic, but not matrix, calcium is essential for adjustment of mitochondrial pyruvate supply.
- Author
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Szibor M, Gizatullina Z, Gainutdinov T, Endres T, Debska-Vielhaber G, Kunz M, Karavasili N, Hallmann K, Schreiber F, Bamberger A, Schwarzer M, Doenst T, Heinze HJ, Lessmann V, Vielhaber S, Kunz WS, and Gellerich FN
- Subjects
- Animals, Aspartic Acid metabolism, Brain metabolism, Calcium Channels deficiency, Calcium Channels genetics, Glutamic Acid chemistry, Glutamic Acid metabolism, Heart physiology, Malates chemistry, Malates metabolism, Membrane Potential, Mitochondrial, Mice, Mice, Inbred C57BL, Mice, Knockout, Myocardium metabolism, Oxidative Phosphorylation, Rats, Substrate Specificity, Synaptosomes metabolism, Calcium metabolism, Cytosol metabolism, Mitochondria metabolism, Pyruvic Acid metabolism
- Abstract
Mitochondrial oxidative phosphorylation (OXPHOS) and cellular workload are tightly balanced by the key cellular regulator, calcium (Ca
2+ ). Current models assume that cytosolic Ca2+ regulates workload and that mitochondrial Ca2+ uptake precedes activation of matrix dehydrogenases, thereby matching OXPHOS substrate supply to ATP demand. Surprisingly, knockout (KO) of the mitochondrial Ca2+ uniporter (MCU) in mice results in only minimal phenotypic changes and does not alter OXPHOS. This implies that adaptive activation of mitochondrial dehydrogenases by intramitochondrial Ca2+ cannot be the exclusive mechanism for OXPHOS control. We hypothesized that cytosolic Ca2+ , but not mitochondrial matrix Ca2+ , may adapt OXPHOS to workload by adjusting the rate of pyruvate supply from the cytosol to the mitochondria. Here, we studied the role of malate-aspartate shuttle (MAS)-dependent substrate supply in OXPHOS responses to changing Ca2+ concentrations in isolated brain and heart mitochondria, synaptosomes, fibroblasts, and thymocytes from WT and MCU KO mice and the isolated working rat heart. Our results indicate that extramitochondrial Ca2+ controls up to 85% of maximal pyruvate-driven OXPHOS rates, mediated by the activity of the complete MAS, and that intramitochondrial Ca2+ accounts for the remaining 15%. Of note, the complete MAS, as applied here, included besides its classical NADH oxidation reaction the generation of cytosolic pyruvate. Part of this largely neglected mechanism has previously been described as the "mitochondrial gas pedal." Its implementation into OXPHOS control models integrates seemingly contradictory results and warrants a critical reappraisal of metabolic control mechanisms in health and disease., (© 2020 Szibor et al.)- Published
- 2020
- Full Text
- View/download PDF
49. Impact of Chronic BDNF Depletion on GABAergic Synaptic Transmission in the Lateral Amygdala.
- Author
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Meis S, Endres T, Munsch T, and Lessmann V
- Subjects
- Animals, Brain-Derived Neurotrophic Factor genetics, Female, Long-Term Potentiation genetics, Mice, Mice, Knockout, Neuronal Plasticity genetics, Neuronal Plasticity physiology, Patch-Clamp Techniques, Synaptic Transmission genetics, Synaptic Transmission physiology, gamma-Aminobutyric Acid metabolism, Amygdala metabolism, Brain-Derived Neurotrophic Factor metabolism, Long-Term Potentiation physiology
- Abstract
Brain-derived neurotrophic factor (BDNF) has previously been shown to play an important role in glutamatergic synaptic plasticity in the amygdala, correlating with cued fear learning. While glutamatergic neurotransmission is facilitated by BDNF signaling in the amygdala, its mechanism of action at inhibitory synapses in this nucleus is far less understood. We therefore analyzed the impact of chronic BDNF depletion on GABA
A -mediated synaptic transmission in BDNF heterozygous knockout mice (BDNF+/- ). Analysis of miniature and evoked inhibitory postsynaptic currents (IPSCs) in the lateral amygdala (LA) revealed neither pre- nor postsynaptic differences in BDNF+/- mice compared to wild-type littermates. In addition, long-term potentiation (LTP) of IPSCs was similar in both genotypes. In contrast, facilitation of spontaneous IPSCs (sIPSCs) by norepinephrine (NE) was significantly reduced in BDNF+/- mice. These results argue against a generally impaired efficacy and plasticity at GABAergic synapses due to a chronic BDNF deficit. Importantly, the increase in GABAergic tone mediated by NE is reduced in BDNF+/- mice. As release of NE is elevated during aversive behavioral states in the amygdala, effects of a chronic BDNF deficit on GABAergic inhibition may become evident in response to states of high arousal, leading to amygdala hyper-excitability and impaired amygdala function.- Published
- 2019
- Full Text
- View/download PDF
50. Clinical Indications of Computed Tomography (CT) of the Head in Patients With Low-Energy Geriatric Hip Fractures: A Follow-Up Study at a Community Hospital.
- Author
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Danielson K, Hall T, Endres T, Jones C, and Sietsema D
- Abstract
Introduction: A seemingly large percentage of geriatric patients with isolated low-energy femur fractures undergo a head computed tomography (CT) scans during initial work up in the emergency department. This study aimed to evaluate the pertinent clinical variables that are associated with positive CT findings with the objective to decrease the number of unnecessary CT scans performed., Methods: A retrospective review performed at a level II trauma center including 713 patients over the age of 65 sustaining a femur fracture following a low-energy fall. The main outcome measure was pertinent clinical variables that are associated with CT scans that yielded positive findings., Results: A total of 713 patients over the age of 65 were included, with a low-energy fall, of which 76.2% (543/713) underwent a head CT scan as part of their evaluation. The most common presenting symptom reported was the patient hitting their head, 13% (93/713), and 1.8% (13/713) were unsure if they had hit their head. Of those evaluated with a head CT scan, only 3 (0.4%) had acute findings and none required acute neurosurgical intervention. All three patients with acute changes on the head CT scan had an Injury Severity Score (ISS) greater than 9, Glasgow Coma Scale (GCS) less than 15, and evidence of trauma above the clavicles., Discussion: None of the patients with a traumatic injury required a neurosurgical intervention after sustaining a low-energy fall (0/713)., Conclusion: Head CT scans should have a limited role in the workup of this patient population and should be reserved for patients with a history and physical exam findings that support head trauma, an ISS > 9 and GCS < 15., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2019
- Full Text
- View/download PDF
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