@article{DavisYuKeenanetal.2013, author = {Davis, Lea K. and Yu, Dongmei and Keenan, Clare L. and Gamazon, Eric R. and Konkashbaev, Anuar I. and Derks, Eske M. and Neale, Benjamin M. and Yang, Jian and Lee, S. Hong and Evans, Patrick and Barr, Cathy L. and Bellodi, Laura and Benarroch, Fortu and Berrio, Gabriel Bedoya and Bienvenu, Oscar J. and Bloch, Michael H. and Blom, Rianne M. and Bruun, Ruth D. and Budman, Cathy L. and Camarena, Beatriz and Campbell, Desmond and Cappi, Carolina and Cardona Silgado, Julio C. and Cath, Danielle C. and Cavallini, Maria C. and Chavira, Denise A. and Chouinard, Sylvian and Conti, David V. and Cook, Edwin H. and Coric, Vladimir and Cullen, Bernadette A. and Deforce, Dieter and Delorme, Richard and Dion, Yves and Edlund, Christopher K. and Egberts, Karin and Falkai, Peter and Fernandez, Thomas V. and Gallagher, Patience J. and Garrido, Helena and Geller, Daniel and Girard, Simon L. and Grabe, Hans J. and Grados, Marco A. and Greenberg, Benjamin D. and Gross-Tsur, Varda and Haddad, Stephen and Heiman, Gary A. and Hemmings, Sian M. J. and Hounie, Ana G. and Illmann, Cornelia and Jankovic, Joseph and Jenike, Micheal A. and Kennedy, James L. and King, Robert A. and Kremeyer, Barbara and Kurlan, Roger and Lanzagorta, Nuria and Leboyer, Marion and Leckman, James F. and Lennertz, Leonhard and Liu, Chunyu and Lochner, Christine and Lowe, Thomas L. and Macciardi, Fabio and McCracken, James T. and McGrath, Lauren M. and Restrepo, Sandra C. Mesa and Moessner, Rainald and Morgan, Jubel and Muller, Heike and Murphy, Dennis L. and Naarden, Allan L. and Ochoa, William Cornejo and Ophoff, Roel A. and Osiecki, Lisa and Pakstis, Andrew J. and Pato, Michele T. and Pato, Carlos N. and Piacentini, John and Pittenger, Christopher and Pollak, Yehunda and Rauch, Scott L. and Renner, Tobias J. and Reus, Victor I. and Richter, Margaret A. and Riddle, Mark A. and Robertson, Mary M. and Romero, Roxana and Ros{\`a}rio, Maria C. and Rosenberg, David and Rouleau, Guy A. and Ruhrmann, Stephan and Ruiz-Linares, Andreas and Sampaio, Aline S. and Samuels, Jack and Sandor, Paul and Sheppard, Broke and Singer, Harvey S. and Smit, Jan H. and Stein, Dan J. and Strengman, E. and Tischfield, Jay A. and Valencia Duarte, Ana V. and Vallada, Homero and Van Nieuwerburgh, Flip and Veenstra-VanderWeele, Jeremy and Walitza, Susanne and Wang, Ying and Wendland, Jens R. and Westenberg, Herman G. M. and Shugart, Yin Yao and Miguel, Euripedes C. and McMahon, William and Wagner, Michael and Nicolini, Humberto and Posthuma, Danielle and Hanna, Gregory L. and Heutink, Peter and Denys, Damiaan and Arnold, Paul D. and Oostra, Ben A. and Nestadt, Gerald and Freimer, Nelson B. and Pauls, David L. and Wray, Naomi R. and Stewart, S. Evelyn and Mathews, Carol A. and Knowles, James A. and Cox, Nancy J. and Scharf, Jeremiah M.}, title = {Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture}, series = {PLoS Genetics}, volume = {9}, journal = {PLoS Genetics}, number = {10}, issn = {1553-7390}, doi = {10.1371/journal.pgen.1003864}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127377}, pages = {e1003864}, year = {2013}, abstract = {The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5\% accounted for 21\% of the TS heritability and 0\% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.}, language = {en} } @article{RostMuellerKelleretal.2014, author = {Rost, Simone and M{\"u}ller, Elisabeth and Keller, Alexander and Fregin, Andreas and M{\"u}ller, Clemens R.}, title = {Confirmation of warfarin resistance of naturally occurring VKORC1 variants by coexpression with coagulation factor IX and in silico protein modelling}, doi = {10.1186/1471-2156-15-17}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-110095}, year = {2014}, abstract = {Background VKORC1 has been identified some years ago as the gene encoding vitamin K epoxide reductase (VKOR) - the target protein for coumarin derivates like warfarin or phenprocoumon. Resistance against warfarin and other coumarin-type anticoagulants has been frequently reported over the last 50 years in rodents due to problems in pest control as well as in thrombophilic patients showing variable response to anticoagulant treatment. Many different mutations have already been detected in the VKORC1 gene leading to warfarin resistance in rats, mice and in humans. Since the conventional in vitro dithiothreitol (DTT)-driven VKOR enzymatic assay often did not reflect the in vivo status concerning warfarin resistance, we recently developed a cell culture-based method for coexpression of VKORC1 with coagulation factor IX and subsequent measurement of secreted FIX in order to test warfarin inhibition in wild-type and mutated VKORC1. Results In the present study, we coexpressed wild-type factor IX with 12 different VKORC1 variants which were previously detected in warfarin resistant rats and mice. The results show that amino acid substitutions in VKORC1 maintain VKOR activity and are associated with warfarin resistance. When we projected in silico the amino acid substitutions onto the published three-dimensional model of the bacterial VKOR enzyme, the predicted effects matched well the catalytic mechanism proposed for the bacterial enzyme. Conclusions The established cell-based system for coexpression of VKORC1 and factor IX uses FIX activity as an indicator of carboxylation efficiency. This system reflects the warfarin resistance status of VKORC1 mutations from anticoagulant resistant rodents more closely than the traditional DTT-driven enzyme assay. All mutations studied were also predicted to be involved in the reaction mechanism.}, language = {en} } @article{BaeHeidrichLevicketal.2020, author = {Bae, Soyeon and Heidrich, Lea and Levick, Shaun R. and Gossner, Martin M. and Seibold, Sebastian and Weisser, Wolfgang W. and Magdon, Paul and Serebryanyk, Alla and B{\"a}ssler, Claus and Sch{\"a}fer, Deborah and Schulze, Ernst-Detlef and Doerfler, Inken and M{\"u}ller, J{\"o}rg and Jung, Kirsten and Heurich, Marco and Fischer, Markus and Roth, Nicolas and Schall, Peter and Boch, Steffen and W{\"o}llauer, Stephan and Renner, Swen C. and M{\"u}ller, J{\"o}rg}, title = {Dispersal ability, trophic position and body size mediate species turnover processes: Insights from a multi-taxa and multi-scale approach}, series = {Diversity and Distribution}, volume = {27}, journal = {Diversity and Distribution}, number = {3}, doi = {10.1111/ddi.13204}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236117}, pages = {439-453}, year = {2020}, abstract = {Aim: Despite increasing interest in β-diversity, that is the spatial and temporal turnover of species, the mechanisms underlying species turnover at different spatial scales are not fully understood, although they likely differ among different functional groups. We investigated the relative importance of dispersal limitations and the environmental filtering caused by vegetation for local, multi-taxa forest communities differing in their dispersal ability, trophic position and body size. Location: Temperate forests in five regions across Germany. Methods: In the inter-region analysis, the independent and shared effects of the regional spatial structure (regional species pool), landscape spatial structure (dispersal limitation) and environmental factors on species turnover were quantified with a 1-ha grain across 11 functional groups in up to 495 plots by variation partitioning. In the intra-region analysis, the relative importance of three environmental factors related to vegetation (herb and tree layer composition and forest physiognomy) and spatial structure for species turnover was determined. Results: In the inter-region analysis, over half of the explained variation in community composition (23\% of the total explained 35\%) was explained by the shared effects of several factors, indicative of spatially structured environmental filtering. Among the independent effects, environmental factors were the strongest on average over 11 groups, but the importance of landscape spatial structure increased for less dispersive functional groups. In the intra-region analysis, the independent effect of plant species composition had a stronger influence on species turnover than forest physiognomy, but the relative importance of the latter increased with increasing trophic position and body size. Main conclusions: Our study revealed that the mechanisms structuring assemblage composition are associated with the traits of functional groups. Hence, conservation frameworks targeting biodiversity of multiple groups should cover both environmental and biogeographical gradients. Within regions, forest management can enhance β-diversity particularly by diversifying tree species composition and forest physiognomy.}, language = {en} } @article{UlrichsNoethlingKelleretal.1987, author = {Ulrichs, Karin and N{\"o}thling, R. and Keller, R. and Heusermann, U. and M{\"u}ller-Buchholtz, W.}, title = {Genetically determined variation of constitutive major histocompatibility complex class II antigen expression in various rat strains and cell types}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-44769}, year = {1987}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{KochDegerKlotzetal.1986, author = {Koch, R. and Deger, A. and Klotz, Karl-Norbert and Schenzle, D. and Kr{\"a}mer, H. and Kelm, S. and M{\"u}ller, G. and Rapp, R. and Weber, U.}, title = {Characterization of solubilized insulin receptors from rat liver microsomes. Existence of two receptor species with different binding properties}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60215}, year = {1986}, abstract = {Insulin receptors were solubilized from rat liver microsomes by the nonionic detergent Triton X-100. After gel filtration of the extract on Sepharose CL-6B, two insulin-binding species (peak I and peak li) were obtained. The structure and binding properties of both peaks were characterized. Gel filtration yielded Stokes radii of 9.2 nm (peak I) and 8.0 nm (peak Il). Both peaks were glycoproteins. At 4°C peak 1 showed optimal insulin binding at pH 8.0 and high ionic strength. In contrast, peak li bad its binding optimum at pH 7.0 and low ionic strength, where peak I bindingwas minimal. For peak I the change in insulin binding under different conditions of pH and ionic strength was due to a change in receptor affinity only. For peak 11 an additional change in receptor number was found. Both peaks yielded non-linear Scatchard plots under most of the buffer conditions examined. At their binding optima at 4 oc the high affinity dissociation constants were 0.50 nM (peak I) and 0.55 nM (peak II). Sodium dodecyl sulfatejpolyacrylamide gel electrophoresis of peak I revealed five receptor bands with Mr 400000, 365000, 320000, 290000, and 245000 under non-reducing conditions. For peak II two major receptor bands with M\(_r\) 210000 and 115000 were found. The peak II receptor bands were also obtained aftermild reduction of peak I. After complete reduction both peaks showed one major receptor band with M\(_r\) 130000. The reductive generation of the peak II receptor together with molecular mass estimations suggest that the peak I receptor is the disulfide-linked dimer of the peak II receptor. Thus, Triton extracts from rat liver microsomes contain two receptor species, which are related, but differ considerably in their size and insulin-binding properties.}, subject = {Toxikologie}, language = {en} } @article{BrinkmannSchwinnMuelleretal.1993, author = {Brinkmann, R. and Schwinn, A. and M{\"u}ller, J. and Stahl-Hennig, C. and Coulibaly, C. and Hunsmann, G. and Czub, S. and Rethwilm, Axel and D{\"o}rries, R. and ter Meulen, Volker}, title = {In vitro and in vivo infection of rhesus monkey microglial cells by simian immunodeficiency virus}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-61415}, year = {1993}, abstract = {The observation that microglial cells in brain tissue are probably a major target for human immunodeficiency virus (HIV) infection has raised interest in the pathogenic role of this cell population for the development of neuro-AIOS. Since it is very difficult to obtain microglia from normal or diseased human brain we studied microglial cells isolated from fresh brain tissue of uninfected and simian immunodeficiency virus (SIV) infected rhesus monkeys (Macacca mulatta) in comparison to peripheral blood macrophages. Besides the characterization of the phenotypes of these two cell populations, we examined the replication of SIV in the cells in addition to the effect of viral infection on the expression of cell surface molecules. We found that microglia and macrophages support replication of the wild-type SIV\(_{mac25}\), strain as well as the infectious clone (SIV\(_239\)). Infectious viruswas produced and a CPE developed. Isolated microglial cells from SIV-infected monkeys were latently infected independent of the presence of neuropathological lesions and produced infectious virus after 20-25 days in culture. In situ hybridization revealed that only a small percentage of isolated microglial cells are productively infected in vivo, yet the majority of these expressed MHC class II molecules. This indicated a state of activation that is acquired in vivo. These findings indicate that microglia are a prime target cell for SIV infection in CNS tissue.}, subject = {Virologie}, language = {en} } @article{GratwohlPfirrmannZanderetal.2016, author = {Gratwohl, A and Pfirrmann, M and Zander, A and Kr{\"o}ger, N and Beelen, D and Novotny, J and Nerl, C and Scheid, C and Spiekermann, K and Mayer, J and Sayer, HG and Falge, C and Bunjes, D and D{\"o}hner, H and Ganser, A and Schmidt-Wolf, I and Schwerdtfeger, R and Baurmann, H and Kuse, R and Schmitz, N and Wehmeier, A and Fischer, J Th and Ho, AD and Wilhelm, M and Goebeler, M-E and Lindemann, HW and Bormann, M and Hertenstein, B and Schlimok, G and Baerlocher, GM and Aul, C and Pfreundschuh, M and Fabian, M and Staib, P and Edinger, M and Schatz, M and Fauser, A and Arnold, R and Kindler, T and Wulf, G and Rosselet, A and Hellmann, A and Sch{\"a}fer, E and Pr{\"u}mmer, O and Schenk, M and Hasford, J and Heimpel, H and Hossfeld, DK and Kolb, H-J and B{\"u}sche, G and Haferlach, C and Schnittger, S and M{\"u}ller, MC and Reiter, A and Berger, U and Saußele, S and Hochhaus, A and Hehlmann, R}, title = {Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment}, series = {Leukemia}, volume = {30}, journal = {Leukemia}, doi = {10.1038/leu.2015.281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-150368}, pages = {562-569}, year = {2016}, abstract = {Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95\% confidence interval (CI): 0.69-0.82) vs 0.69 (95\% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56\% vs 39\%; P = 0.005) and free of drug treatment (56\% vs 6\%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.}, language = {en} } @article{LausUlrichsMuellerRuchholtz1986, author = {Laus, R. and Ulrichs, Karin and M{\"u}ller-Ruchholtz, W.}, title = {Molecular Specificity of Human Heterophile Antibodies (HHA) in Normal Human Serum (NHS) Reacting with Xenogeneic Cells.}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72921}, year = {1986}, abstract = {No abstract available}, subject = {Immunobiologie}, language = {en} } @article{UlrichsKellerMuellerRuchholtz1985, author = {Ulrichs, Karin and Keller, R. and M{\"u}ller-Ruchholtz, W.}, title = {Serological demonstration and manipulation of passenger cells (PC) in pancreas islet grafts}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-72944}, year = {1985}, abstract = {No abstract available}, subject = {Immunobiologie}, language = {en} } @article{AdamAhrweilerSahaMoelleretal.1993, author = {Adam, W. and Ahrweiler, M. and Saha-M{\"o}ller, C. R. and Sauter, M. and Sch{\"o}nberger, A. and Epe, B. and M{\"u}ller, E. and Schiffmann, D. and Stopper, Helga and Wild, D.}, title = {Genotoxicity studies of benzofuran dioxetanes and epoxides with isolated DNA, bacteria and mammalian cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63420}, year = {1993}, abstract = {1.2-Dioxetanes, very reactive and high energy molecules. are involved as labile intermediates in dioxygenase- activated aerobic metabolism and in physiological processes. Various toxico1ogica1 tests reveal that dioxetanes are indeed genotoxic. In supercoiled DNA of bacteriophage PM2 they induce endonucleasesensitive sites, most of them are FPG protein-sensitive base modifications (8-hydroxyguanine, fonnamidopyrimidines). Pyrimidinedimersand sites ofbase loss (AP sites) which were probed by UV endonuclease and exonuclease 111 are minor lesions in this system. While the alky1-substituted dioxetanes do not show any significant mutagenic activity in different Salmonella typhimurium strains, heteroarene dioxetanes such as benzofuran and furocoumarin dioxetanes are strongly mutagenic in S. typhimurium strain TA I 00. DNA adducts formed with an intermediary alkyJating agent appear to be responsible for the mutagenic activity of benzofuran dioxetane. We assume that the benzofuran epoxides, generated in situ from benzofuran dioxetanes by deoxygenation are the ultimate mutagens of the latter. since benzofuran epoxides are highly mutagenic in the S. typhimurium strain TAIOO and they form DNA adducts. as detected by the 212Ppostlabelling technique. Our results imply that the type of D NA darnage promoted by dioxetanes is dependent on the structural feature of dioxetanes. Furthermore, the direct photochemical DNA darnage by energy transfer. i.e., pyrimidine dimers, plays a minor role in the genotoxicity of dioxetanes. Instead, photooxidation dominates in isolated DNA. while radical darnage and alkylation prevail in the cellular system.}, subject = {Toxikologie}, language = {en} } @article{UlrichsSchangKelleretal.1984, author = {Ulrichs, Karin and Schang, T. and Keller, R. and M{\"u}ller-Ruchholtz, W.}, title = {Reactivity of pancreas islet cells with antisera of known specificity}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45466}, year = {1984}, abstract = {No abstract available}, language = {en} } @article{EngemannUlrichsThiedeetal.1990, author = {Engemann, R. and Ulrichs, Karin and Thiede, A. and M{\"u}ller-Ruchholtz, W. and Hamelmann, H.}, title = {Value of a physiological liver transplant model in rats. Induction of specific graft tolerance in a fully allogeneic strain combination}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45622}, year = {1990}, abstract = {No abstract available}, language = {en} } @article{KueblerReutherKirchneretal.1994, author = {K{\"u}bler, N. and Reuther, J. and Kirchner, T. and Pfaff, M. and M{\"u}ller-Hermelink, H. K. and Albert, R. and Sebald, Walter}, title = {IgG monoclonal antibodies that inhibit osteoinductivity of human bone matrix-derived proteins (hBMP/NCP)}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-62388}, year = {1994}, abstract = {Monoclonal hBMP/NCP (human bone morphogenetic protein anrl associaterl noncollagenous proteins) antiborlies of the lgG class were prorlucerl. In vitro, 12 of 19 hBMP/NCP antiborlies showerl functional inhibition of hBMP/ NCP-induced chondroneogenesis in a neonatal muscle tissue assay. Inducing factors were characterized by their inhibiting antibodies with immunoblotting. Several peptide factors seem to be involved in the cascade of inducerl chondro- and osteogenesis.}, subject = {Biochemie}, language = {en} } @article{KorthMuellerSustmannetal.1987, author = {Korth, H.-G. and M{\"u}ller, W. and Sustmann, R. and Christl, Manfred}, title = {Rearrangement of Free Radicals, XII. ESR Spectroscopic Study of the Ring Opening of the Homobenzvalenyl Radical}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-58376}, year = {1987}, abstract = {Abstraction of an allylic hydrogen atom in homobenzvalene (4) either in solurion by photolyticaßy generated tert-butoxyl radicals or in an adamantane matrix by X-rays produces the homobcnzvalenyl radical (5). which tbennally rearranps · to tbe tropylium ndical (1). In solution tbe activation cnergy for the rate determined step of the reaction sequence was detennined· to be 13.4 ± O.S kcal/mol.}, subject = {Organische Chemie}, language = {en} } @article{SpinelliMuellerFriedeletal.2013, author = {Spinelli, Simona and M{\"u}ller, Tanja and Friedel, Miriam and Sigrist, Hannes and Lesch, Klaus-Peter and Henkelman, Mark and Rudin, Markus and Seifritz, Erich and Pryce, Christopher R.}, title = {Effects of repeated adolescent stress and serotonin transporter gene partial knockout in mice on behaviors and brain structures relevant to major depression}, series = {Frontiers in Behavioral Neuroscience}, volume = {7}, journal = {Frontiers in Behavioral Neuroscience}, doi = {10.3389/fnbeh.2013.00215}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-122240}, pages = {215}, year = {2013}, abstract = {In humans, exposure to stress during development is associated with structural and functional alterations of the prefrontal cortex (PFC), amygdala (AMY), and hippocampus (HC) and their circuits of connectivity, and with an increased risk for developing major depressive disorder particularly in carriers of the short (s) variant of the serotonin transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR). Although changes in these regions are found in carriers of the s allele and/or in depressed patients, evidence for a specific genotype x developmental stress effect on brain structure and function is limited. Here, we investigated the effect of repeated stress exposure during adolescence in mice with partial knockout of the 5-HIT gene (HET) vs. wildtype (WT) on early-adulthood behavioral measures and brain structure [using magnetic resonance imaging (MRI)] relevant to human major depression. Behaviorally, adolescent stress (AS) increased anxiety and decreased activity and did so to a similar degree in HET and WT. In a probabilistic reversal learning task, HET-AS mice achieved fewer reversals than did HET-No-AS mice. 5-HIT genotype and AS were without effect on corticosterone stress response. In terms of structural brain differences, AS reduced the volume of two long-range white matter tracts, the optic tract (OT) and the cerebral peduncle (CP), in WT mice specifically. In a region-of-interest analysis, AS was associated with increased HC volume and HET genotype with a decreased frontal lobe volume. In conclusion, we found that 5-HIT and AS genotype exerted long-term effects on behavior and development of brain regions relevant to human depression.}, language = {en} } @article{ErhardtAkulaSchumacheretal.2012, author = {Erhardt, A. and Akula, N. and Schumacher, J. and Czamara, D. and Karbalai, N. and M{\"u}ller-Myhsok, B. and Mors, O. and Borglum, A. and Kristensen, A. S. and Woldbye, D. P. D. and Koefoed, P. and Eriksson, E. and Maron, E. and Metspalu, A. and Nurnberger, J. and Philibert, R. A. and Kennedy, J. and Domschke, K. and Reif, A. and Deckert, J. and Otowa, T. and Kawamura, Y. and Kaiya, H. and Okazaki, Y. and Tanii, H. and Tokunaga, K. and Sasaki, T. and Ioannidis, J. P. A. and McMahon, F. J. and Binder, E. B.}, title = {Replication and meta-analysis of TMEM132D gene variants in panic disorder}, series = {Translational Psychiatry}, volume = {2}, journal = {Translational Psychiatry}, number = {e156}, doi = {10.1038/tp.2012.85}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133324}, year = {2012}, abstract = {A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case-control samples (n = 1670 cases and n 2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n 1038 cases and n 2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P = 1.4e-8 and P = 1.1e-8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations.}, language = {en} } @article{LudwigSaemannAlexanderetal.2013, author = {Ludwig, K. U. and S{\"a}mann, P. and Alexander, M. and Becker, J. and Bruder, J. and Moll, K. and Spieler, D. and Czisch, M. and Warnke, A. and Docherty, S. J. and Davis, O. S. P. and Plomin, R. and N{\"o}then, M. M. and Landerl, K. and M{\"u}ller-Myhsok, B. and Hoffmann, P. and Schumacher, J. and Schulte-K{\"o}rne, G. and Czamara, D.}, title = {A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults}, series = {Translational Psychiatry}, volume = {3}, journal = {Translational Psychiatry}, number = {e229}, doi = {10.1038/tp.2012.148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131513}, year = {2013}, abstract = {The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87\%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.}, language = {en} } @article{LausUlrichsMuellerRuchholtz1988, author = {Laus, R. and Ulrichs, Karin and M{\"u}ller-Ruchholtz, W.}, title = {Carbohydrate-specific human heterophile antibodies in normal human sera that react with xenogeneic cells}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-78271}, year = {1988}, abstract = {Human heterophile antibodies (HHA) that are present in normal human sera (NHS)play an important role in hyperacute xenograft rejection. The aim of this study was to analyze the occurrence, mode of action and molecular specificity of HHA in NHS that are directed against xenogeneic Iymphocytes (isolated from mouse, rat, guinea pig, rabbit, cattle and pig) and isolated rat pancreatic islets. All sera contained variable amounts of HHA that killed the target cells via the classical complement pathway. The cytotoxic activity of these HHA was specifically inhibited by certain carbohydrates (a-D-melibiose, ß-Iactose, ß-gentiobiose, ß-cellobiose, D-mannose, N-acetyl-ß-D-mannosamine and a-D-rhamnose) and by rat IgM. By means of affinity chromatography with immobilized inhibitors we obtained an antibody preparation of mainly IgG type from NHS (up to 3.5 mg/IO ml serum) that reacted strongly with rat lymphocytes and isolated rat pancreatic islets. Though thus far residual xenospecific antibody activity has remained in the sera even after multiple affinity chromatography, these data suggest that specific elimination of HHA is feasible and that it may be thus possible to overcome a major obstacle to xenotransplantation.}, subject = {Immunobiologie}, language = {de} } @article{MuellerScheer1970, author = {M{\"u}ller, R. and Scheer, Ulrich}, title = {Klangspektrographische Untersuchungen der Laut{\"a}ußerung beim Krallenfrosch, Xenopus laevis}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-40529}, year = {1970}, abstract = {No abstract available}, language = {de} } @article{UlrichsKaitschickBartlettetal.1992, author = {Ulrichs, Karin and Kaitschick, J. and Bartlett, R. and M{\"u}ller-Ruchholtz, W.}, title = {Suppression of natural xenophile antibodies with the novel immunomodulating drug leflunomide}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45202}, year = {1992}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{UlrichsKellerMuellerRuchholtz1986, author = {Ulrichs, Karin and Keller, R. and M{\"u}ller-Ruchholtz, W.}, title = {Vorkommen und Manipulation von MHC Klasse II Antigenen auf Zellen isolierter Langerhans-Inseln}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-45499}, year = {1986}, abstract = {No abstract available}, subject = {Langerhans-Inseln}, language = {de} } @article{UhlerHaaseHoffmannetal.2022, author = {Uhler, Johannes and Haase, Peter and Hoffmann, Lara and Hothorn, Torsten and Schmidl, J{\"u}rgen and Stoll, Stefan and Welti, Ellen A. R. and Buse, J{\"o}rn and M{\"u}ller, J{\"o}rg}, title = {A comparison of different Malaise trap types}, series = {Insect Conservation and Diversity}, volume = {15}, journal = {Insect Conservation and Diversity}, number = {6}, doi = {10.1111/icad.12604}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-293694}, pages = {666 -- 672}, year = {2022}, abstract = {Recent reports on insect decline have highlighted the need for long-term data on insect communities towards identifying their trends and drivers. With the launch of many new insect monitoring schemes to investigate insect communities over large spatial and temporal scales, Malaise traps have become one of the most important tools due to the broad spectrum of species collected and reduced capture bias through passive sampling of insects day and night. However, Malaise traps can vary in size, shape, and colour, and it is unknown how these differences affect biomass, species richness, and composition of trap catch, making it difficult to compare results between studies. We compared five Malaise trap types (three variations of the Townes and two variations of the Bartak Malaise trap) to determine their effects on biomass and species richness as identified by metabarcoding. Insect biomass varied by 20\%-55\%, not strictly following trap size but varying with trap type. Total species richness was 20\%-38\% higher in the three Townes trap models compared to the Bartak traps. Bartak traps captured lower richness of highly mobile taxa but increased richness of ground-dwelling taxa. The white roofed Townes trap captured a higher richness of pollinators. We find that biomass, total richness, and taxa group specific richness are all sensitive to Malaise trap type. Trap type should be carefully considered and aligned to match monitoring and research questions. Additionally, our estimates of trap type effects can be used to adjust results to facilitate comparisons across studies.}, language = {en} } @article{GrausLiRathjeetal.2023, author = {Graus, Dorothea and Li, Kunkun and Rathje, Jan M. and Ding, Meiqi and Krischke, Markus and M{\"u}ller, Martin J. and Cuin, Tracey Ann and Al-Rasheid, Khaled A. S. and Scherzer, S{\"o}nke and Marten, Irene and Konrad, Kai R. and Hedrich, Rainer}, title = {Tobacco leaf tissue rapidly detoxifies direct salt loads without activation of calcium and SOS signaling}, series = {New Phytologist}, volume = {237}, journal = {New Phytologist}, number = {1}, doi = {10.1111/nph.18501}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312152}, pages = {217 -- 231}, year = {2023}, abstract = {Salt stress is a major abiotic stress, responsible for declining agricultural productivity. Roots are regarded as hubs for salt detoxification, however, leaf salt concentrations may exceed those of roots. How mature leaves manage acute sodium chloride (NaCl) stress is mostly unknown. To analyze the mechanisms for NaCl redistribution in leaves, salt was infiltrated into intact tobacco leaves. It initiated pronounced osmotically-driven leaf movements. Leaf downward movement caused by hydro-passive turgor loss reached a maximum within 2 h. Salt-driven cellular water release was accompanied by a transient change in membrane depolarization but not an increase in cytosolic calcium ion (Ca\(^{2+}\)) level. Nonetheless, only half an hour later, the leaves had completely regained turgor. This recovery phase was characterized by an increase in mesophyll cell plasma membrane hydrogen ion (H\(^{+}\)) pumping, a salt uptake-dependent cytosolic alkalization, and a return of the apoplast osmolality to pre-stress levels. Although, transcript numbers of abscisic acid- and Salt Overly Sensitive pathway elements remained unchanged, salt adaptation depended on the vacuolar H\(^{+}\)/Na\(^{+}\)-exchanger NHX1. Altogether, tobacco leaves can detoxify sodium ions (Na\(^{+}\)) rapidly even under massive salt loads, based on pre-established posttranslational settings and NHX1 cation/H+ antiport activity. Unlike roots, signaling and processing of salt stress in tobacco leaves does not depend on Ca\(^{2+}\) signaling.}, language = {en} } @article{MatthesSchoenfeldZottnicketal.2015, author = {Matthes, Philipp R. and Sch{\"o}nfeld, Fabian and Zottnick, Sven H. and M{\"u}ller-Buschbaum, Klaus}, title = {Post-synthetic shaping of porosity and crystal structure of Ln-Bipy-MOFs by thermal treatment}, series = {Molecules}, volume = {20}, journal = {Molecules}, doi = {10.3390/molecules200712125}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148404}, pages = {12125-12153}, year = {2015}, abstract = {The reaction of anhydrous lanthanide chlorides together with 4,4'-bipyridine yields the MOFs \(^{2}\)\(_{∞}\)[Ln\(_{2}\)Cl\(_{6}\)(bipy)\(_{3}\)]*2bipy, with Ln = Pr-Yb, bipy = 4,4'-bipyridine, and \(^{3}\)\(_{∞}\)[La\(_{2}\)Cl\(_{6}\)(bipy)\(_{5}\)]*4bipy. Post-synthetic thermal treatment in combination with different vacuum conditions was successfully used to shape the porosity of the MOFs. In addition to the MOFs microporosity, a tuneable mesoporosity can be implemented depending on the treatment conditions as a surface morphological modification. Furthermore, thermal treatment without vacuum results in several identifiable crystalline high-temperature phases. Instead of collapse of the frameworks upon heating, further aggregation under release of bipy is observed. \(^{3}\)\(_{∞}\)[LaCl\(_{3}\)(bipy)] and \(^{2}\)\(_{∞}\)[Ln\(_{3}\)Cl\(_{9}\)(bipy)\(_{3}\)], with Ln = La, Pr, Sm, and \(^{1}\)\(_{∞}\)[Ho\(_{2}\)Cl\(_{6}\)(bipy)\(_{2}\)] were identified and characterized, which can also exhibit luminescence. Besides being released upon heating, the linker 4,4'-bipyridine can undergo activation of C-C bonding in ortho-position leading to the in-situ formation of 4,4':2',2 '':4 '',4'''-quaterpyridine (qtpy). qtpy can thereby function as linker itself, as shown for the formation of the network \(^{2}\)\(_{∞}\)[Gd\(_{2}\)Cl\(_{6}\)(qtpy)\(_{2}\)(bipy)\(_{2}\)]*bipy. Altogether, the manuscript elaborates the influence of thermal treatment beyond the usual activation procedures reported for MOFs.}, language = {en} } @article{WeberLassalleHaukeRamseretal.2018, author = {Weber-Lassalle, Nana and Hauke, Jan and Ramser, Juliane and Richters, Lisa and Groß, Eva and Bl{\"u}mcke, Britta and Gehrig, Andrea and Kahlert, Anne-Karin and M{\"u}ller, Clemens R. and Hackmann, Karl and Honisch, Ellen and Weber-Lassalle, Konstantin and Niederacher, Dieter and Borde, Julika and Thiele, Holger and Ernst, Corinna and Altm{\"u}ller, Janine and Neidhardt, Guido and N{\"u}rnberg, Peter and Klaschik, Kristina and Schroeder, Christopher and Platzer, Konrad and Volk, Alexander E. and Wang-Gohrke, Shan and Just, Walter and Auber, Bernd and Kubisch, Christian and Schmidt, Gunnar and Horvath, Judit and Wappenschmidt, Barbara and Engel, Christoph and Arnold, Norbert and Dworniczak, Bernd and Rhiem, Kerstin and Meindl, Alfons and Schmutzler, Rita K. and Hahnen, Eric}, title = {BRIP1 loss-of-function mutations confer high risk for familial ovarian cancer, but not familial breast cancer}, series = {Breast Cancer Research}, volume = {20}, journal = {Breast Cancer Research}, doi = {10.1186/s13058-018-0935-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233433}, year = {2018}, abstract = {Background Germline mutations in the BRIP1 gene have been described as conferring a moderate risk for ovarian cancer (OC), while the role of BRIP1 in breast cancer (BC) pathogenesis remains controversial. Methods To assess the role of deleterious BRIP1 germline mutations in BC/OC predisposition, 6341 well-characterized index patients with BC, 706 index patients with OC, and 2189 geographically matched female controls were screened for loss-of-function (LoF) mutations and potentially damaging missense variants. All index patients met the inclusion criteria of the German Consortium for Hereditary Breast and Ovarian Cancer for germline testing and tested negative for pathogenic BRCA1/2 variants. Results BRIP1 LoF mutations confer a high OC risk in familial index patients (odds ratio (OR) = 20.97, 95\% confidence interval (CI) = 12.02-36.57, P < 0.0001) and in the subgroup of index patients with late-onset OC (OR = 29.91, 95\% CI = 14.99-59.66, P < 0.0001). No significant association of BRIP1 LoF mutations with familial BC was observed (OR = 1.81 95\% CI = 1.00-3.30, P = 0.0623). In the subgroup of familial BC index patients without a family history of OC there was also no apparent association (OR = 1.42, 95\% CI = 0.70-2.90, P = 0.3030). In 1027 familial BC index patients with a family history of OC, the BRIP1 mutation prevalence was significantly higher than that observed in controls (OR = 3.59, 95\% CI = 1.43-9.01; P = 0.0168). Based on the negative association between BRIP1 LoF mutations and familial BC in the absence of an OC family history, we conclude that the elevated mutation prevalence in the latter cohort was driven by the occurrence of OC in these families. Compared with controls, predicted damaging rare missense variants were significantly more prevalent in OC (P = 0.0014) but not in BC (P = 0.0693) patients. Conclusions To avoid ambiguous results, studies aimed at assessing the impact of candidate predisposition gene mutations on BC risk might differentiate between BC index patients with an OC family history and those without. In familial cases, we suggest that BRIP1 is a high-risk gene for late-onset OC but not a BC predisposition gene, though minor effects cannot be excluded.}, language = {en} } @article{SteinMarufMuelleretal.2021, author = {Stein, Kiera and Maruf, Abdullah Al and M{\"u}ller, Daniel J. and Bishop, Jeffrey R. and Bousman, Chad A.}, title = {Serotonin transporter genetic variation and antidepressant response and tolerability: a systematic review and meta-analysis}, series = {Journal of Personalized Medicine}, volume = {11}, journal = {Journal of Personalized Medicine}, number = {12}, issn = {2075-4426}, doi = {10.3390/jpm11121334}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252294}, year = {2021}, abstract = {Antidepressants are used to treat several psychiatric disorders; however, a large proportion of patients do not respond to their first antidepressant therapy and often experience adverse drug reactions (ADR). A common insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter (SLC6A4) gene has been frequently investigated for its association with antidepressant outcomes. Here, we performed a systematic review and meta-analysis to assess 5-HTTLPR associations with antidepressants: (1) response in psychiatric disorders other than major depressive disorder (MDD) and (2) tolerability across all psychiatric disorders. Literature searches were performed up to January 2021, yielding 82 studies that met inclusion criteria, and 16 of these studies were included in the meta-analyses. Carriers of the 5-HTTLPR LL or LS genotypes were more likely to respond to antidepressant therapy, compared to the SS carriers in the total and European ancestry-only study populations. Long (L) allele carriers taking selective serotonin reuptake inhibitors (SSRIs) reported fewer ADRs relative to short/short (SS) carriers. European L carriers taking SSRIs had lower ADR rates than S carriers. These results suggest the 5-HTTLPR polymorphism may serve as a marker for antidepressant outcomes in psychiatric disorders and may be particularly relevant to SSRI treatment among individuals of European descent.}, language = {en} } @article{SchererFallerFriedrichetal.2015, author = {Scherer, Reinhold and Faller, Josef and Friedrich, Elisabeth V. C. and Opisso, Eloy and Costa, Ursula and K{\"u}bler, Andrea and M{\"u}ller-Putz, Gernot R.}, title = {Individually Adapted Imagery Improves Brain-Computer Interface Performance in End-Users with Disability}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0123727}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143021}, pages = {e0123727}, year = {2015}, abstract = {Brain-computer interfaces (BCIs) translate oscillatory electroencephalogram (EEG) patterns into action. Different mental activities modulate spontaneous EEG rhythms in various ways. Non-stationarity and inherent variability of EEG signals, however, make reliable recognition of modulated EEG patterns challenging. Able-bodied individuals who use a BCI for the first time achieve - on average - binary classification performance of about 75\%. Performance in users with central nervous system (CNS) tissue damage is typically lower. User training generally enhances reliability of EEG pattern generation and thus also robustness of pattern recognition. In this study, we investigated the impact of mental tasks on binary classification performance in BCI users with central nervous system (CNS) tissue damage such as persons with stroke or spinal cord injury (SCI). Motor imagery (MI), that is the kinesthetic imagination of movement (e.g. squeezing a rubber ball with the right hand), is the "gold standard" and mainly used to modulate EEG patterns. Based on our recent results in able-bodied users, we hypothesized that pair- wise combination of "brain-teaser" (e.g. mental subtraction and mental word association) and "dynamic imagery" (e. g. hand and feet MI) tasks significantly increases classification performance of induced EEG patterns in the selected end-user group. Within- day (How stable is the classification within a day?) and between-day (How well does a model trained on day one perform on unseen data of day two?) analysis of variability of mental task pair classification in nine individuals confirmed the hypothesis. We found that the use of the classical MI task pair hand vs. feed leads to significantly lower classification accuracy - in average up to 15\% less - in most users with stroke or SCI. User-specific selection of task pairs was again essential to enhance performance. We expect that the gained evidence will significantly contribute to make imagery-based BCI technology become accessible to a larger population of users including individuals with special needs due to CNS damage.}, language = {en} } @article{FuchsYoussefSeheretal.2019, author = {Fuchs, A. and Youssef, A. and Seher, A. and Hochleitner, G. and Dalton, P. D. and Hartmann, S. and Brands, R. C. and M{\"u}ller-Richter, U. D. A. and Linz, C,}, title = {Medical-grade polycaprolactone scaffolds made by melt electrospinning writing for oral bone regeneration - a pilot study in vitro}, series = {BMC Oral Health}, volume = {19}, journal = {BMC Oral Health}, doi = {10.1186/s12903-019-0717-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200274}, pages = {28}, year = {2019}, abstract = {Background The spectrum of indications for the use of membranes and scaffolds in the field of oral and maxillofacial surgery includes, amongst others, guided bone regeneration (GBR). Currently available membrane systems face certain disadvantages such as difficult clinical handling, inconsistent degradation, undirected cell growth and a lack of stability that often complicate their application. Therefore, new membranes which can overcome these issues are of great interest in this field. Methods In this pilot study, we investigated polycaprolactone (PCL) scaffolds intended to enhance oral wound healing by means of melt electrospinning writing (MEW), which allowed for three-dimensional (3D) printing of micron scale fibers and very exact fiber placement. A singular set of box-shaped scaffolds of different sizes consisting of medical-grade PCL was examined and the scaffolds' morphology was evaluated via scanning electron microscopy (SEM). Each prototype sample with box sizes of 225 μm, 300 μm, 375 μm, 450 μm and 500 μm was assessed for cytotoxicity and cell growth by seeding each scaffold with human osteoblast-like cell line MG63. Results All scaffolds demonstrated good cytocompatibility according to cell viability, protein concentration, and cell number. SEM analysis revealed an exact fiber placement of the MEW scaffolds and the growth of viable MG63 cells on them. For the examined box-shaped scaffolds with pore sizes between 225 μm and 500 μm, a preferred box size for initial osteoblast attachment could not be found. Conclusions These well-defined 3D scaffolds consisting of medical-grade materials optimized for cell attachment and cell growth hold the key to a promising new approach in GBR in oral and maxillofacial surgery.}, language = {en} } @article{McLaughlinSchmulensonTeplytskaetal.2021, author = {Mc Laughlin, Anna M. and Schmulenson, Eduard and Teplytska, Olga and Zimmermann, Sebastian and Opitz, Patrick and Groenland, Stefanie L. and Huitema, Alwin D. R. and Steeghs, Neeltje and M{\"u}ller, Lothar and Fuxius, Stefan and Illerhaus, Gerald and Joerger, Markus and Mayer, Frank and Fuhr, Uwe and Holdenrieder, Stefan and Hempel, Georg and Scherf-Clavel, Oliver and Jaehde, Ulrich and Kloft, Charlotte}, title = {Developing a nationwide infrastructure for therapeutic drug monitoring of targeted oral anticancer drugs: the ON-TARGET study protocol}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {24}, issn = {2072-6694}, doi = {10.3390/cancers13246281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252196}, year = {2021}, abstract = {Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80\% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.}, language = {en} } @article{TymoshenkoOnykiienkoMuelleretal.2017, author = {Tymoshenko, Y. V. and Onykiienko, Y. A. and M{\"u}ller, T. and Thomale, R. and Rachel, S. and Cameron, A. S. and Portnichenko, P. Y. and Efremov, D. V. and Tsurkan, V. and Abernathy, D. L. and Ollivier, J. and Schneidewind, A. and Piovano, A. and Felea, V. and Loidl, A. and Inosov, D. S.}, title = {Pseudo-Goldstone magnons in the frustrated \(S=3/2\) Heisenberg helimagnet \(ZnCr_2Se_4\) with a pyrochlore magnetic sublattice}, series = {Physical Review X}, volume = {7}, journal = {Physical Review X}, number = {4}, doi = {10.1103/PhysRevX.7.041049}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172770}, year = {2017}, abstract = {Low-energy spin excitations in any long-range ordered magnetic system in the absence of magnetocrystalline anisotropy are gapless Goldstone modes emanating from the ordering wave vectors. In helimagnets, these modes hybridize into the so-called helimagnon excitations. Here we employ neutron spectroscopy supported by theoretical calculations to investigate the magnetic excitation spectrum of the isotropic Heisenberg helimagnet \({ZnCr_2Se_4}\) with a cubic spinel structure, in which spin\(-3/2\) magnetic \({Cr^{3+}}\) ions are arranged in a geometrically frustrated pyrochlore sublattice. Apart from the conventional Goldstone mode emanating from the \((0~ 0~ {q_h})\) ordering vector, low-energy magnetic excitations in the single-domain proper-screw spiral phase show soft helimagnon modes with a small energy gap of \({∼0.17~ meV}\), emerging from two orthogonal wave vectors \(({q_h}~ 0~ 0)\) and \({(0~ {q_h}~ 0)}\) where no magnetic Bragg peaks are present. We term them pseudo-Goldstone magnons, as they appear gapless within linear spinwave theory and only acquire a finite gap due to higher-order quantum-fluctuation corrections. Our results are likely universal for a broad class of symmetric helimagnets, opening up a new way of studying weak magnon-magnon interactions with accessible spectroscopic methods.}, language = {en} } @article{HankeRauschSosnowskietal.2022, author = {Hanke, Kathrin and Rausch, Tanja K. and Sosnowski, Runa and Paul, Pia and Spiegler, Juliane and M{\"u}ller, Mirja and K{\"o}nig, Inke R. and G{\"o}pel, Wolfgang and Herting, Egbert and H{\"a}rtel, Christoph}, title = {Early skin-to-skin contact does not affect cerebral tissue oxygenation in preterm infants <32 weeks of gestation}, series = {Children}, volume = {9}, journal = {Children}, number = {2}, issn = {2227-9067}, doi = {10.3390/children9020211}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262290}, year = {2022}, abstract = {Aim: It was the aim of our study to determine the regional cerebral tissue oxygenation saturation (rcSO\(_2\)) as an additional monitoring parameter during early skin-to-skin contact (SSC) in preterm infants with a gestational age of <32 gestational weeks. Methods: We conducted two observational convenience sample studies using additional monitoring with near-infrared spectroscopy (NIRS) in the first 120 h of life: (a) NIRS 1 (gestational age of 26 0/7 to 31 6/7 weeks) and (b) NIRS 2 (gestational age of 24 0/7 to 28 6/7 weeks). The rcSO\(_2\) values were compared between resting time in the incubator (period I), SSC (period II) and handling nursing care (period III). For the comparison, we separated the sequential effects by including a "wash-out phase" of 1 h between each period. Results: During the first 120 h of life 38/53 infants in NIRS 1 and 15/23 infants in NIRS 2 received SSC, respectively. We found no remarkable differences for rcSO\(_2\) values of NIRS 1 patients between SSC time and period I (95\% confidence interval (CI) for the difference in \%: SSC vs. period I [1; 3]). In NIRS 2, rcSO\(_2\) values during SSC were only 2\% lower compared with period I [median [1. quartile; 3. quartile] in \%; 78 [73; 82] vs. 80 [74; 85]] but were similar to period III [78 [72; 83]]. In a combined analysis, a small difference in rcSO\(_2\) values between SSC and resting times was found using a generalized linear mixed model that included gender and gestational age (OR 95\% CI; 1.178 [1.103; 1.253], p < 0.0001). Episodes below the cut-off for "hypoxia"; e.g., <55\%, were comparable during SSC and periods I and III (0.3-2.1\%). No FiO\(_2\) adjustment was required in the vast majority of SSC episodes. Conclusions: Our observational data indicate that rcSO\(_2\) values of infants during SSC were comparable to rcSO\(_2\) values during incubator care and resting time. This additional monitoring supports a safe implementation of early SSC in extremely preterm infants in NICUs.}, language = {en} } @article{GenslerLeikeimMoellmannetal.2020, author = {Gensler, Marius and Leikeim, Anna and M{\"o}llmann, Marc and Komma, Miriam and Heid, Susanne and M{\"u}ller, Claudia and Boccaccini, Aldo R. and Salehi, Sahar and Groeber-Becker, Florian and Hansmann, Jan}, title = {3D printing of bioreactors in tissue engineering: A generalised approach}, series = {PLoS One}, volume = {15}, journal = {PLoS One}, number = {11}, doi = {10.1371/journal.pone.0242615}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231368}, year = {2020}, abstract = {3D printing is a rapidly evolving field for biological (bioprinting) and non-biological applications. Due to a high degree of freedom for geometrical parameters in 3D printing, prototype printing of bioreactors is a promising approach in the field of Tissue Engineering. The variety of printers, materials, printing parameters and device settings is difficult to overview both for beginners as well as for most professionals. In order to address this problem, we designed a guidance including test bodies to elucidate the real printing performance for a given printer system. Therefore, performance parameters such as accuracy or mechanical stability of the test bodies are systematically analysed. Moreover, post processing steps such as sterilisation or cleaning are considered in the test procedure. The guidance presented here is also applicable to optimise the printer settings for a given printer device. As proof of concept, we compared fused filament fabrication, stereolithography and selective laser sintering as the three most used printing methods. We determined fused filament fabrication printing as the most economical solution, while stereolithography is most accurate and features the highest surface quality. Finally, we tested the applicability of our guidance by identifying a printer solution to manufacture a complex bioreactor for a perfused tissue construct. Due to its design, the manufacture via subtractive mechanical methods would be 21-fold more expensive than additive manufacturing and therefore, would result in three times the number of parts to be assembled subsequently. Using this bioreactor we showed a successful 14-day-culture of a biofabricated collagen-based tissue construct containing human dermal fibroblasts as the stromal part and a perfusable central channel with human microvascular endothelial cells. Our study indicates how the full potential of biofabrication can be exploited, as most printed tissues exhibit individual shapes and require storage under physiological conditions, after the bioprinting process.}, language = {en} } @article{ZeinerZinkeKowalewskietal.2018, author = {Zeiner, P. S. and Zinke, J. and Kowalewski, D. J. and Bernatz, S. and Tichy, J. and Ronellenfitsch, M. W. and Thorsen, F. and Berger, A. and Forster, M. T. and Muller, A. and Steinbach, J. P. and Beschorner, R. and Wischhusen, J. and Kvasnicka, H. M. and Plate, K. H. and Stefanović, S. and Weide, B. and Mittelbronn, M. and Harter, P. N.}, title = {CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival}, series = {Acta Neuropathologica Communications}, volume = {6}, journal = {Acta Neuropathologica Communications}, doi = {10.1186/s40478-018-0521-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233882}, year = {2018}, abstract = {Abstract Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity. We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line. We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74\(^{high}\) and TIL\(^{high}\) tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected. In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.}, language = {en} } @article{WurmbSchorscherJusticeetal.2018, author = {Wurmb, T and Schorscher, N and Justice, P and Dietz, S and Schua, R and Jarausch, T and Kinstle, U and Greiner, J and M{\"o}ldner, G and M{\"u}ller, J and Kraus, M and Simon, S and Wagenh{\"a}user, U and Hemm, J and Roewer, N and Helm, M}, title = {Structured analysis, evaluation and report of the emergency response to a terrorist attack in Wuerzburg, Germany using a new template of standardised quality indicators}, series = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine}, volume = {26}, journal = {Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine}, number = {87}, doi = {10.1186/s13049-018-0555-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177054}, year = {2018}, abstract = {Background: Until now there has been a reported lack of systematic reports and scientific evaluations of rescue missions during terror attacks. This however is urgently required in order to improve the performance of emergency medical services and to be able to compare different missions with each other. Aim of the presented work was to report the systematic evaluation and the lessons learned from the response to a terror attack that happened in Wuerzburg, Germany in 2016. Methods: A team of 14 experts developed a template of quality indicators and operational characteristics, which allow for the description, assessment and comparison of civil emergency rescue missions during mass killing incidents. The entire systematic evaluation process consisted of three main steps. The first step was the systematic data collection according to the quality indicators and operational characteristics. Second was the systematic stratification and assessment of the data. The last step was the prioritisation of the identified weaknesses and the definition of the lessons learned. Results: Five important "lessons learned" have been defined. First of all, a comprehensive concept for rescue missions during terror attacks is essential. Furthermore, the establishment of a defined high priority communication infrastructure between the different dispatch centres ("red phone") is vital. The goal is to secure the continuity of information between a few well-defined individuals. Thirdly, the organization of the incident scene needs to be commonly decided and communicated between police, medical services and fire services during the mission. A successful mission tactic requires continuous flux of reports to the on-site command post. Therefore, a predefined and common communication infrastructure for all operational forces is a crucial point. Finally, all strategies need to be extensively trained before the real life scenario hits. Conclusion: According to a systematic evaluation, we defined the lessons learned from a terror attack in 2016. Further systematic reports and academic work surrounding life threatening rescue missions and mass killing incidents are needed in order to ultimately improve such mission outcomes. In the future, a close international collaboration might help to find the best database to report and evaluate major incidents but also mass killing events.}, language = {en} }