TY  - JOUR
A1  - Antoniou, Antonis C.
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Beesley, Jonathan
A1  - Chen, Xiaoqing
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Barrowdale, Daniel
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Caligo, Maria A.
A1  - Loman, Niklas
A1  - Harbst, Katja
A1  - Lindblom, Annika
A1  - Arver, Brita
A1  - Rosenquist, Richard
A1  - Karlsson, Per
A1  - Nathanson, Kate
A1  - Domchek, Susan
A1  - Rebbeck, Tim
A1  - Jakubowska, Anna
A1  - Lubinski, Jan
A1  - Jaworska, Katarzyna
A1  - Durda, Katarzyna
A1  - Zlowowcka-Perłowska, Elżbieta
A1  - Osorio, Ana
A1  - Durán, Mercedes
A1  - Andrés, Raquel
A1  - Benítez, Javier
A1  - Hamann, Ute
A1  - Hogervorst, Frans B.
A1  - van Os, Theo A.
A1  - Verhoef, Senno
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Wijnen, Juul
A1  - Garcia, Encarna B. Gómez
A1  - Ligtenberg, Marjolijn J.
A1  - Kriege, Mieke
A1  - Collée, Margriet
A1  - Ausems, Margreet G. E. M.
A1  - Oosterwijk, Jan C.
A1  - Peock, Susan
A1  - Frost, Debra
A1  - Ellis, Steve D.
A1  - Platte, Radka
A1  - Fineberg, Elena
A1  - Evans, D. Gareth
A1  - Lalloo, Fiona
A1  - Jacobs, Chris
A1  - Eeles, Ros
A1  - Adlard, Julian
A1  - Davidson, Rosemarie
A1  - Cole, Trevor
A1  - Cook, Jackie
A1  - Paterson, Joan
A1  - Douglas, Fiona
A1  - Brewer, Carole
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Walker, Lisa
A1  - Rogers, Mark T.
A1  - Donaldson, Alan
A1  - Dorkins, Huw
A1  - Godwin, Andrew K.
A1  - Bove, Betsy
A1  - Stoppa-Lyonnet, Dominique
A1  - Houdayer, Claude
A1  - Buecher, Bruno
A1  - de Pauw, Antoine
A1  - Mazoyer, Sylvie
A1  - Calender, Alain
A1  - Léoné, Mélanie
A1  - Bressac-de Paillerets, Brigitte
A1  - Caron, Olivier
A1  - Sobol, Hagay
A1  - Frenay, Marc
A1  - Prieur, Fabienne
A1  - Ferrer, Sandra Fert
A1  - Mortemousque, Isabelle
A1  - Buys, Saundra
A1  - Daly, Mary
A1  - Miron, Alexander
A1  - Terry, Mary Beth
A1  - Hopper, John L.
A1  - John, Esther M.
A1  - Southey, Melissa
A1  - Goldgar, David
A1  - Singer, Christian F.
A1  - Fink-Retter, Anneliese
A1  - Muy-Kheng, Tea
A1  - Geschwantler Kaulich, Daphne
A1  - Hansen, Thomas V. O.
A1  - Nielsen, Finn C.
A1  - Barkardottir, Rosa B.
A1  - Gaudet, Mia
A1  - Kirchhoff, Tomas
A1  - Joseph, Vijai
A1  - Dutra-Clarke, Ana
A1  - Offit, Kenneth
A1  - Piedmonte, Marion
A1  - Kirk, Judy
A1  - Cohn, David
A1  - Hurteau, Jean
A1  - Byron, John
A1  - Fiorica, James
A1  - Toland, Amanda E.
A1  - Montagna, Marco
A1  - Oliani, Cristina
A1  - Imyanitov, Evgeny
A1  - Isaacs, Claudine
A1  - Tihomirova, Laima
A1  - Blanco, Ignacio
A1  - Lazaro, Conxi
A1  - Teulé, Alex
A1  - Del Valle, J.
A1  - Gayther, Simon A.
A1  - Odunsi, Kunle
A1  - Gross, Jenny
A1  - Karlan, Beth Y.
A1  - Olah, Edith
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Beattie, Mary S.
A1  - Dorfling, Cecelia M.
A1  - Jansen van Rensburg, Elizabeth
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Schmutzler, Rita K.
A1  - Wappenschmidt, Barbara
A1  - Engel, Christoph
A1  - Meindl, Alfons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Heidemann, Simone
A1  - Niederacher, Dieter
A1  - Preisler-Adams, Sabine
A1  - Gadzicki, Dorothea
A1  - Varon-Mateeva, Raymonda
A1  - Deissler, Helmut
A1  - Gehrig, Andrea
A1  - Sutter, Christian
A1  - Kast, Karin
A1  - Fiebig, Britta
A1  - Schäfer, Dieter
A1  - Caldes, Trinidad
A1  - de la Hoya, Miguel
A1  - Nevanlinna, Heli
A1  - Muranen, Taru A.
A1  - Lespérance, Bernard
A1  - Spurdle, Amanda B.
A1  - Neuhausen, Susan L.
A1  - Ding, Yuan C.
A1  - Wang, Xianshu
A1  - Fredericksen, Zachary
A1  - Pankratz, Vernon S.
A1  - Lindor, Noralane M.
A1  - Peterlongo, Paulo
A1  - Manoukian, Siranoush
A1  - Peissel, Bernard
A1  - Zaffaroni, Daniela
A1  - Bonanni, Bernardo
A1  - Bernard, Loris
A1  - Dolcetti, Riccardo
A1  - Papi, Laura
A1  - Ottini, Laura
A1  - Radice, Paolo
A1  - Greene, Mark H.
A1  - Loud, Jennifer T.
A1  - Andrulis, Irene L.
A1  - Ozcelik, Hilmi
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Thomassen, Mads
A1  - Gerdes, Anne-Marie
A1  - Jensen, Uffe B.
A1  - Skytte, Anne-Bine
A1  - Kruse, Torben A.
A1  - Chenevix-Trench, Georgia
A1  - Couch, Fergus J.
A1  - Simard, Jacques
A1  - Easton, Douglas F.
T1  - Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
JF  - Breast Cancer Research
N2  - Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). 
Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. 
Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10\(^{-4}\)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10\(^{-5}\), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10\(^{-5}\)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). 
Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
KW  - investigators
KW  - genetic modifiers
KW  - mammographic density
KW  - susceptibility loci
KW  - ovarian cancer
KW  - hormone-related protein
KW  - genome-wide association
KW  - tumor subtypes
KW  - alleles
KW  - consortium
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130449
VL  - 14
IS  - R33
ER  - 
TY  - JOUR
A1  - Eckardt, Jan-Niklas
A1  - Stasik, Sebastian
A1  - Kramer, Michael
A1  - Röllig, Christoph
A1  - Krämer, Alwin
A1  - Scholl, Sebastian
A1  - Hochhaus, Andreas
A1  - Crysandt, Martina
A1  - Brümmendorf, Tim H.
A1  - Naumann, Ralph
A1  - Steffen, Björn
A1  - Kunzmann, Volker
A1  - Einsele, Hermann
A1  - Schaich, Markus
A1  - Burchert, Andreas
A1  - Neubauer, Andreas
A1  - Schäfer-Eckart, Kerstin
A1  - Schliemann, Christoph
A1  - Krause, Stefan W.
A1  - Herbst, Regina
A1  - Hänel, Mathias
A1  - Frickhofen, Norbert
A1  - Noppeney, Richard
A1  - Kaiser, Ulrich
A1  - Baldus, Claudia D.
A1  - Kaufmann, Martin
A1  - Rácil, Zdenek
A1  - Platzbecker, Uwe
A1  - Berdel, Wolfgang E.
A1  - Mayer, Jiří
A1  - Serve, Hubert
A1  - Müller-Tidow, Carsten
A1  - Ehninger, Gerhard
A1  - Stölzel, Friedrich
A1  - Kroschinsky, Frank
A1  - Schetelig, Johannes
A1  - Bornhäuser, Martin
A1  - Thiede, Christian
A1  - Middeke, Jan Moritz
T1  - Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia
JF  - Cancers
N2  - Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.
KW  - acute myeloid leukemia
KW  - BCOR
KW  - BCORL1
KW  - loss-of-function
KW  - risk stratification
KW  - survival
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236735
SN  - 2072-6694
VL  - 13
IS  - 9
ER  - 
TY  - JOUR
A1  - Alepee, Natalie
A1  - Bahinski, Anthony
A1  - Daneshian, Mardas
A1  - De Weyer, Bart
A1  - Fritsche, Ellen
A1  - Goldberg, Alan
A1  - Hansmann, Jan
A1  - Hartung, Thomas
A1  - Haycock, John
A1  - Hogberg, Helena T.
A1  - Hoelting, Lisa
A1  - Kelm, Jens M.
A1  - Kadereit, Suzanne
A1  - McVey, Emily
A1  - Landsiedel, Robert
A1  - Leist, Marcel
A1  - Lübberstedt, Marc
A1  - Noor, Fozia
A1  - Pellevoisin, Christian
A1  - Petersohn, Dirk
A1  - Pfannenbecker, Uwe
A1  - Reisinger, Kerstin
A1  - Ramirez, Tzutzuy
A1  - Rothen-Rutishauser, Barbara
A1  - Schäfer-Korting, Monika
A1  - Zeilinger, Katrin
A1  - Zurich, Marie-Gabriele
T1  - State-of-the-Art of 3D Cultures (Organs-on-a-Chip) in Safety Testing and Pathophysiology
JF  - ALTEX - Alternatives to Animal Experimentation
N2  - Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs liver, lung, skin, brain are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.
KW  - 3D models
KW  - organotypic
KW  - organ-on-a-chip
KW  - multicellular tumor spheroids
KW  - primary human hepatocytes
KW  - embryonic stem cell
KW  - reconstructed human epidermis
KW  - in-vitro models
KW  - full thickness skin
KW  - necrosis-factor-alpha
KW  - metabolic flux analysis
KW  - long-term
KW  - human liver cells
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117826
VL  - 31
IS  - 4
ER  - 
TY  - THES
A1  - Schäfer, Jan
T1  - Die klinische Relevanz des optokinetischen Afternystagmus in der Schwindeldiagnostik
T1  - Clinical relevance of optokinetic afternystagmus in vertigo diagnosis
N2  - In der vorliegenden Arbeit sind 200 unausgelesene Patienten der neurootologischen Abteilung der Universitätsklinik und – poliklinik für Hals-, Nasen- und Ohrenkranke in Würzburg untersucht worden. Neben den bewährten äquilibriometrischen Untersuchungsmethoden wie z.B. kalorische Vestibularisprüfung (Schmetterlingskalorigramm) und rotatorischer Intensitätsdämpfungstest (RIDT) wurden die Patienten auch einer optokinetischen Untersuchung unterzogen und dabei der optokinetische Afternystagmus bestimmt. Hierbei wird an unserer Klinik die programmierbare Drehstuhlmethode angewendet, die sich durch eine Umkehr der Bezugssysteme, der Patient wird hier gegen seine Umwelt gedreht, von der weitverbreiteten Trommelmethode unterscheidet. Zunächst wurden Durchschnittswerte für das gesamte Kollektiv ermittelt. Es fielen keine aussagekräftigen Parameter auf; wie zu erwarten stellten sich die Afternystagmus-Frequenzen in Drehrichtung gegenüber denen in Gegenrichtung erhöht dar. Anschließend wurden Untergruppierungen gebildet um Bezüge zwischen Afternystagmusreaktion und Schwindelanamnese nachzuweisen. Die Patienten wurden hinsichtlich des Alters, des Geschlechtes, und des kalorischen Hemmungsverhaltens selektiert. Des weiteren wurden Unterkollektive verschiedener vegetativer Symptome, des vestibulären-Reiz-Reaktionsstärke-Versuchs (VRRSV) und einzelner optokinetischer Untersuchungen gebildet. Es zeigte sich, dass die optokinetische Afternystagmusfrequenz im männlichen Kollektiv geringfügig gegenüber der des weiblichen Kollektives erhöht war. In den verschiedenen Altersgruppen nimmt die optokinetische Afternystagmusfrequenz in Drehrichtung mit dem Alter tendenziell ab; um geschlechtsspezifische altersabhängige Tendenzen zu untersuchen wurden entsprechende weitere Untergruppen gebildet. Auch hier konnte eine geringe Frequenzabnahme mit dem Alter, in der weiblichen Untersuchungsgruppe deutlicher als in der männlichen, festgestellt werden. Bei der Untersuchung der einzelnen Kalorik-Patientengruppen ergaben sich für die Gruppe der zentral gestörten Patienten eine tendenziell erhöhte optokinetische Afternystagmusfrequenz, welche deutlicher bei der Afternystagmusreaktion in Drehrichtung darzustellen war. Die Patienten mit einer „Schweißausbruch“-Anamnese wiesen im Kollektiv der Patienten mit vegetativen Symptomen die höchste optokinetische Afternystagmusfrequenz auf. Im VRRSV konnte keine Tendenz erkannt werden, erhöhte Werte im Kollektiv „recruitment“ lassen keine schlüssige Aussage zu. Auch die nach verschieden stark ausfallender optokinetische Afternystagmusreaktion selektierten Patienten ließen keine deutliche Aussage über Zusammenhänge in der Schwindelanamnese im Vergleich zum Gesamtkollektiv zu. Eine statistisch signifikante Absicherung war in keinem der Fälle möglich. Als typische Beispiele werden Einzelfälle in einer Kasuistik demonstriert. In der Diskussion werden die gewonnenen Ergebnisse mit Literaturwerten verglichen. Eine herausragende klinische Relevanz des Untersuchungsparameters „optokinetischer Afternystagmus“ konnte hierbei nicht ermittelt werden. Im Einzelfall stellt die Afternystagmusprüfung, insbesondere bei der Differenzierung vestibulärer Seitendifferenzen und Hyperreaktionen jedoch sicherlich eine interessante Untersuchungsmethode dar.
N2  - 200 unselected patients of the neurootological department of Hals- Nasen- und Ohren clinic of the wuerzburg university hospital have been inspected. Besides the usual aequilibriometric examinations such as e.g. caloric testing the patients underwent an optokinetic test including measurement of optokinetic afternystagmus. The collected data was analyzed statistically. At first average values were being built. To detect relations between afternystagmus reaction and vertigo anamnesis subcollectives concerning age, sex, caloric-inhibition behavior, various vegetative symptoms and different optokinetic tests were being examined. None of the examined subcollectives showed any statistically significance for the investigated parameters. Typical patient examples are being presented in a casuistical manner. Accordingly the mesurement of OKAN shows no additional relevant information in vertigo-dizziness anamnesis; admittedly in differentiation of vestibular side differences and hyperreaktions OKAN seems to be an interesting investigation parameter.
KW  - OKAN
KW  - Schwindeldiagnostik
KW  - Afternystagmus
KW  - OKAN
KW  - vertigo
KW  - afternystagmus
Y1  - 2005
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-17927
ER  - 
TY  - JOUR
A1  - Bonig, Halvard
A1  - Kuçi, Zyrafete
A1  - Kuçi, Selim
A1  - Bakhtiar, Shahrzad
A1  - Basu, Oliver
A1  - Bug, Gesine
A1  - Dennis, Mike
A1  - Greil, Johann
A1  - Barta, Aniko
A1  - Kállay, Krisztián M.
A1  - Lang, Peter
A1  - Lucchini, Giovanna
A1  - Pol, Raj
A1  - Schulz, Ansgar
A1  - Sykora, Karl-Walter
A1  - Teichert von Luettichau, Irene
A1  - Herter-Sprie, Grit
A1  - Ashab Uddin, Mohammad
A1  - Jenkin, Phil
A1  - Alsultan, Abdulrahman
A1  - Buechner, Jochen
A1  - Stein, Jerry
A1  - Kelemen, Agnes
A1  - Jarisch, Andrea
A1  - Soerensen, Jan
A1  - Salzmann-Manrique, Emilia
A1  - Hutter, Martin
A1  - Schäfer, Richard
A1  - Seifried, Erhard
A1  - Paneesha, Shankara
A1  - Novitzky-Basso, Igor
A1  - Gefen, Aharon
A1  - Nevo, Neta
A1  - Beutel, Gernot
A1  - Schlegel, Paul-Gerhardt
A1  - Klingebiel, Thomas
A1  - Bader, Peter
T1  - Children and adults with Refractory acute Graft-versus-Host Disease respond to treatment with the Mesenchymal Stromal cell preparation “MSC-FFM”—Outcome report of 92 patients
JF  - Cells
N2  - (1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
KW  - graft-versus host
KW  - transplantation
KW  - mesenchymal stromal cell
KW  - cell therapy
KW  - hospital exemption
KW  - steroid-resistant aGvHD
KW  - refractory aGvHD
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193878
SN  - 2073-4409
VL  - 8
IS  - 12
ER  - 
TY  - JOUR
A1  - Le Provost, Gaëtane
A1  - Thiele, Jan
A1  - Westphal, Catrin
A1  - Penone, Caterina
A1  - Allan, Eric
A1  - Neyret, Margot
A1  - van der Plas, Fons
A1  - Ayasse, Manfred
A1  - Bardgett, Richard D.
A1  - Birkhofer, Klaus
A1  - Boch, Steffen
A1  - Bonkowski, Michael
A1  - Buscot, Francois
A1  - Feldhaar, Heike
A1  - Gaulton, Rachel
A1  - Goldmann, Kezia
A1  - Gossner, Martin M.
A1  - Klaus, Valentin H.
A1  - Kleinebecker, Till
A1  - Krauss, Jochen
A1  - Renner, Swen
A1  - Scherreiks, Pascal
A1  - Sikorski, Johannes
A1  - Baulechner, Dennis
A1  - Blüthgen, Nico
A1  - Bolliger, Ralph
A1  - Börschig, Carmen
A1  - Busch, Verena
A1  - Chisté, Melanie
A1  - Fiore-Donno, Anna Maria
A1  - Fischer, Markus
A1  - Arndt, Hartmut
A1  - Hoelzel, Norbert
A1  - John, Katharina
A1  - Jung, Kirsten
A1  - Lange, Markus
A1  - Marzini, Carlo
A1  - Overmann, Jörg
A1  - Paŝalić, Esther
A1  - Perović, David J.
A1  - Prati, Daniel
A1  - Schäfer, Deborah
A1  - Schöning, Ingo
A1  - Schrumpf, Marion
A1  - Sonnemann, Ilja
A1  - Steffan-Dewenter, Ingolf
A1  - Tschapka, Marco
A1  - Türke, Manfred
A1  - Vogt, Juliane
A1  - Wehner, Katja
A1  - Weiner, Christiane
A1  - Weisser, Wolfgang
A1  - Wells, Konstans
A1  - Werner, Michael
A1  - Wolters, Volkmar
A1  - Wubet, Tesfaye
A1  - Wurst, Susanne
A1  - Zaitsev, Andrey S.
A1  - Manning, Peter
T1  - Contrasting responses of above- and belowground diversity to multiple components of land-use intensity
JF  - Nature Communications
N2  - Land-use intensification is a major driver of biodiversity loss. However, understanding how different components of land use drive biodiversity loss requires the investigation of multiple trophic levels across spatial scales. Using data from 150 agricultural grasslands in central Europe, we assess the influence of multiple components of local- and landscape-level land use on more than 4,000 above- and belowground taxa, spanning 20 trophic groups. Plot-level land-use intensity is strongly and negatively associated with aboveground trophic groups, but positively or not associated with belowground trophic groups. Meanwhile, both above- and belowground trophic groups respond to landscape-level land use, but to different drivers: aboveground diversity of grasslands is promoted by diverse surrounding land-cover, while belowground diversity is positively related to a high permanent forest cover in the surrounding landscape. These results highlight a role of landscape-level land use in shaping belowground communities, and suggest that revised agroecosystem management strategies are needed to conserve whole-ecosystem biodiversity.
KW  - biodiversity
KW  - community ecology
KW  - grassland ecology
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-371552
VL  - 12
ER  - 
TY  - JOUR
A1  - Steimle, Alex
A1  - Menz, Sarah
A1  - Bender, Annika
A1  - Ball, Brianna
A1  - Weber, Alexander N. R.
A1  - Hagemann, Thomas
A1  - Lange, Anna
A1  - Maerz, Jan K.
A1  - Perusel, Raphael
A1  - Michaelis, Lena
A1  - Schäfer, Andrea
A1  - Yao, Hans
A1  - Löw, Hanna-Christine
A1  - Beier, Sina
A1  - Mebrhatu, Mehari Tesfazgi
A1  - Gronbach, Kerstin
A1  - Wagner, Samuel
A1  - Voehringer, David
A1  - Schaller, Martin
A1  - Fehrenbacher, Birgit
A1  - Autenrieth, Ingo B.
A1  - Oelschlaeger, Tobias A.
A1  - Frick, Julia-Stefanie
T1  - Flagellin hypervariable region determinessymbiotic properties of commensalEscherichia coli strains
JF  - PLoS Biology
N2  - Escherichia coli represents a classical intestinal gram-negative commensal. Despite this commensalism, different E. coli strains can mediate disparate immunogenic properties in a given host. Symbiotic E. coli strains such as E. coli Nissle 1917 (EcN) are attributed beneficial properties, e.g., promotion of intestinal homeostasis. Therefore, we aimed to identify molecular features derived from symbiotic bacteria that might help to develop innovative therapeutic alternatives for the treatment of intestinal immune disorders. This study was performed using the dextran sodium sulphate (DSS)-induced colitis mouse model, which is routinely used to evaluate potential therapeutics for the treatment of Inflammatory Bowel Diseases (IBDs). We focused on the analysis of flagellin structures of different E. coli strains. EcN flagellin was found to harbor a substantially longer hypervariable region (HVR) compared to other commensal E. coli strains, and this longer HVR mediated symbiotic properties through stronger activation of Toll-like receptor (TLR)5, thereby resulting in interleukin (IL)-22–mediated protection of mice against DSS-induced colitis. Furthermore, using bone-marrow–chimeric mice (BMCM), CD11c+ cells of the colonic lamina propria (LP) were identified as the main mediators of these flagellin-induced symbiotic effects. We propose flagellin from symbiotic E. coli strains as a potential therapeutic to restore intestinal immune homeostasis, e.g., for the treatment of IBD patients.
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-239501
VL  - 17
ER  -