@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{MuellerKrennSchindleretal.1993, author = {M{\"u}ller, J. G. and Krenn, V. and Schindler, C. and Czub, S. and Stahl-Henning, C. and Coulibaly, C. and Hunsmann, G. and Kneitz, C. and Kerkau, T. and Rethwilm, A. and ter Meulen, V. and M{\"u}ller-Hermelink, H. K.}, title = {Alterations of Thymus Cortical Epithelium and Interdigitating Dendritic Cells but No Increase of Thymocyte Cell Death in the Early Course of Simian Immunodeficiency Virus Infection}, series = {American Journal of Pathology}, volume = {143}, journal = {American Journal of Pathology}, number = {3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128250}, pages = {699-713}, year = {1993}, abstract = {The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low « 1 in 1 04 T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate andflow cytometry showed a reduction of the immature \(CD4^+/CD8^+\) double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, andfinally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis.}, language = {en} } @article{MuellerKrennCzubetal.1993, author = {M{\"u}ller, J. and Krenn, V. and Czub, S. and Schindler, C. and Kneitz, C. and Kerkau, T. and Stahl-Henning, C. and Coulibaly, C. and Hunsmann, G. and Rethwilm, Axel and ter Meulen, Volker and M{\"u}ller-Hermelink, H. K.}, title = {The thymus in SIV infection}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-80265}, year = {1993}, abstract = {no abstract available}, subject = {HIV-Infektion}, language = {en} } @article{MuellerCzubRethwilmetal.1994, author = {M{\"u}ller, J. G. and Czub, S. and Rethwilm, Axel and M{\"u}ller-Hermelink, H. K.}, title = {Korrelation von Organpathologie und Verteilung virusreplizierenderZellen, nachgewiesen mit der RNA in situ Hybridisierungw{\"a}hrend der SIVmac-Infektion von Macaca mulatta}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-47331}, year = {1994}, abstract = {No abstract available}, subject = {Virologie}, language = {de} } @article{ZeinerPreusseGolebiewskaetal.2019, author = {Zeiner, Pia S. and Preusse, Corinna and Golebiewska, Anna and Zinke, Jenny and Iriondo, Ane and Muller, Arnaud and Kaoma, Tony and Filipski, Katharina and M{\"u}ller-Eschner, Monika and Bernatz, Simon and Blank, Anna-Eva and Baumgarten, Peter and Ilina, Elena and Grote, Anne and Hansmann, Martin L. and Verhoff, Marcel A. and Franz, Kea and Feuerhake, Friedrich and Steinbach, Joachim P. and Wischhusen, J{\"o}rg and Stenzel, Werner and Niclou, Simone P. and Harter, Patrick N. and Mittelbronn, Michel}, title = {Distribution and prognostic impact of microglia/macrophage subpopulations in gliomas}, series = {Brain Pathology}, volume = {29}, journal = {Brain Pathology}, doi = {10.1111/bpa.12690}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233897}, pages = {513-529}, year = {2019}, abstract = {While the central nervous system is considered an immunoprivileged site and brain tumors display immunosuppressive features, both innate and adaptive immune responses affect glioblastoma (GBM) growth and treatment resistance. However, the impact of the major immune cell population in gliomas, represented by glioma-associated microglia/macrophages (GAMs), on patients' clinical course is still unclear. Thus, we aimed at assessing the immunohistochemical expression of selected microglia and macrophage markers in 344 gliomas (including gliomas from WHO grade I-IV). Furthermore, we analyzed a cohort of 241 IDH1R132H-non-mutant GBM patients for association of GAM subtypes and patient overall survival. Phenotypical properties of GAMs, isolated from high-grade astrocytomas by CD11b-based magnetic cell sorting, were analyzed by immunocytochemistry, mRNA microarray, qRT-PCR and bioinformatic analyses. A higher amount of CD68-, CD163- and CD206-positive GAMs in the vital tumor core was associated with beneficial patient survival. The mRNA expression profile of GAMs displayed an upregulation of factors that are considered as pro-inflammatory M1 (eg, CCL2, CCL3L3, CCL4, PTGS2) and anti-inflammatory M2 polarization markers (eg, MRC1, LGMN, CD163, IL10, MSR1), the latter rather being associated with phagocytic functions in the GBM microenvironment. In summary, we present evidence that human GBMs contain mixed M1/M2-like polarized GAMs and that the levels of different GAM subpopulations in the tumor core are positively associated with overall survival of patients with IDH1R132H-non-mutant GBMs.}, 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{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{GattenloehnerJoerissenHuhnetal.2010, author = {Gattenloehner, Stefan and Joerissen, H. and Huhn, M. and Vincent, A. and Beeson, D. and Tzartos, S. and Mamalaki, A. and Etschmann, B. and Muller-Hermelink, H. K. and Koscielniak, E. and Barth, S. and Marx, A.}, title = {A Human Recombinant Autoantibody-Based Immunotoxin Specific for the Fetal Acetylcholine Receptor Inhibits Rhabdomyosarcoma Growth In Vitro and in a Murine Transplantation Model [Research Article]}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-68200}, year = {2010}, abstract = {Rhabdomyosarcoma (RMS) is the most common malignant soft tissue tumor in children and is highly resistant to all forms of treatment currently available once metastasis or relapse has commenced. As it has recently been determined that the acetylcholine receptor (AChR) γ-subunit, which defines the fetal AChR (fAChR) isoform, is almost exclusively expressed in RMS post partum, we recombinantly fused a single chain variable fragment (scFv) derived from a fully human anti-fAChR Fab-fragment to Pseudomonas exotoxin A to generate an anti-fAChR immunotoxin (scFv35-ETA).While scFv35-ETA had no damaging effect on fAChR-negative control cell lines, it killed human embryonic and alveolar RMS cell lines in vitro and delayed RMS development in a murine transplantation model. These results indicate that scFv35-ETA may be a valuable new therapeutic tool as well as a relevant step towards the development of a fully human immunotoxin directed against RMS. Moreover, as approximately 20\% of metastatic malignant melanomas (MMs) display rhabdoid features including the expression of fAChR, the immunotoxin we developed may also prove to be of significant use in the treatment of these more common and most often fatal neoplasms.}, subject = {Medizin}, language = {en} } @article{HoubenHesbacherSchmidetal.2011, author = {Houben, Roland and Hesbacher, Sonja and Schmid, Corinna P. and Kauczok, Claudia S. and Flohr, Ulrike and Haferkamp, Sebastian and M{\"u}ller, Cornelia S. L. and Schrama, David and Wischhusen, J{\"o}rg and Becker, J{\"u}rgen C.}, title = {High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69012}, year = {2011}, abstract = {Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5-8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.}, subject = {Krebs }, 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} }