TY - JOUR A1 - Degenkolbe, Elisa A1 - König, Jana A1 - Zimmer, Julia A1 - Walther, Maria A1 - Reißner, Carsten A1 - Nickel, Joachim A1 - Plöger, Frank A1 - Raspopovic, Jelena A1 - Sharpe, James A1 - Dathe, Katharina A1 - Hecht, Jacqueline T. A1 - Mundlos, Stefan A1 - Doelken, Sandra C. A1 - Seemann, Petra T1 - A GDF5 Point Mutation Strikes Twice - Causing BDA1 and SYNS2 JF - PLOS Genetics N2 - Growth and Differentiation Factor 5 (GDF5) is a secreted growth factor that belongs to the Bone Morphogenetic Protein (BMP) family and plays a pivotal role during limb development. GDF5 is a susceptibility gene for osteoarthritis (OA) and mutations in GDF5 are associated with a wide variety of skeletal malformations ranging from complex syndromes such as acromesomelic chondrodysplasias to isolated forms of brachydactylies or multiple synostoses syndrome 2 (SYNS2). Here, we report on a family with an autosomal dominant inherited combination of SYNS2 and additional brachydactyly type A1 (BDA1) caused by a single point mutation in GDF5 (p.W414R). Functional studies, including chondrogenesis assays with primary mesenchymal cells, luciferase reporter gene assays and Surface Plasmon Resonance analysis, of the GDF5 W-414R variant in comparison to other GDF5 mutations associated with isolated BDA1 (p.R399C) or SYNS2 (p.E491K) revealed a dual pathomechanism characterized by a gain-and loss-of-function at the same time. On the one hand insensitivity to the main GDF5 antagonist NOGGIN (NOG) leads to a GDF5 gain of function and subsequent SYNS2 phenotype. Whereas on the other hand, a reduced signaling activity, specifically via the BMP receptor type IA (BMPR1A), is likely responsible for the BDA1 phenotype. These results demonstrate that one mutation in the overlapping interface of antagonist and receptor binding site in GDF5 can lead to a GDF5 variant with pathophysiological relevance for both, BDA1 and SYNS2 development. Consequently, our study assembles another part of the molecular puzzle of how loss and gain of function mutations in GDF5 affect bone development in hands and feet resulting in specific types of brachydactyly and SYNS2. These novel insights into the biology of GDF5 might also provide further clues on the pathophysiology of OA. KW - dominant-negative mutatio KW - morphogenetic protein receptors KW - brachtydacyly type A2 KW - BMP KW - gene encoding noggin KW - growth factor beta KW - signal tranduction KW - molecular mechanism KW - crystal-structure KW - differentiation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127556 SN - 1553-7404 VL - 9 IS - 10 ER - TY - JOUR A1 - Brehm, Klaus A1 - Haas, Albert A1 - Goebel, Werner A1 - Kreft, Jürgen T1 - A gene encoding a superoxide dismutase of the facultative intracellular bacterium Listeria monocytogenes N2 - A gene (Imsod) encoding superoxide dismutase (SOD; EC 1.15.1.1) of the facultative intracellular pathogen, Listeria monocytogenes, was cloned by functional complementation of an SOD-deficient Escherichia coli mutant. The nucleotide sequence was determined and the deduced amino acid (aa) sequence (202 aa) showed close similarity to manganese-containing SOD's from other organisms. Subunits of the recombinant L. monocytogenes SOD (re-SOD) and of both E. coli SODs formed enzymatically active hybrid enzymes in vivo. DNA/DNA-hybridization experiments showed that this type of recombinant re-sod gene is conserved within the genus Listeria. KW - Biologie Y1 - 1992 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60515 ER - TY - JOUR A1 - Luis, Werner A1 - Horrer, Günther A1 - Philipp, Michael A1 - Lubitz, Katharina A1 - Kuntze‐Fechner, Maximilian W. A1 - Radius, Udo T1 - A General Synthetic Route to NHC‐Phosphinidenes: NHC‐mediated Dehydrogenation of Primary Phosphines JF - Zeitschrift für anorganische und allgemeine Chemie N2 - The dehydrocoupling of primary phosphines with N-heterocyclic carbenes (NHCs) to yield NHC-phosphinidenes is reported. The reaction of two equivalents of the NHCs Me\(_2\)Im (1,3-dimethylimidazolin-2-ylidene), Me\(_4\)Im (1,3,4,5-tetramethylimidazolin-2-ylidene), iPr\(_2\)Im (1,3-di-iso-propylimidazolin-2-ylidene) and Mes\(_2\)Im (2,4,6-trimethylphenylimidazolin-2-ylidene) with PhPH\(_2\) and MesPH\(_2\) led to the NHC stabilized phosphinidenes (NHC)PAr: (iPr\(_2\)Im)PPh (1), (Mes\(_2\)Im)PPh (2), (Me\(_4\)Im)PPh (3), (Mes\(_2\)Im)PMes (4), (Me\(_2\)Im)PMes (5), (Me\(_4\)Im)PMes (6) and (iPr\(_2\)Im)PMes (7). The reaction of tBuPH\(_2\) with two equivalents of the NHCs afforded the corresponding NHC stabilized parent phosphinidenes (NHC)PH: (iPr\(_2\)Im)PH (8), (Mes\(_2\)Im)PH (9) and (Me\(_4\)Im)PH (10). Reaction of 1 with oxygen and sulfur led to isolation of iPr\(_2\)Im-P(O)\(_2\)Ph (11) and iPr\(_2\)Im-P(S)\(_2\)Ph (12), whereas the reaction with elemental selenium and tellurium gave (NHC)PPh cleavage with formation of (iPr\(_2\)Im)Se (13), iPr\(_2\)ImTe (14) and different cyclo-oligophosphines. Furthermore, the complexes [{(iPr\(_2\)Im)PPh}W(CO)\(_5\)] (15), [Co(CO)\(_2\)(NO){(iPr\(_2\)Im)PPh}] (16) and [(η\(^5\)-C\(_5\)Me\(_2\))Co(η\(^2\)-C\(_2\)H\(_4\)){(iPr\(_2\)Im)PPh}] (17) have been prepared starting from 1 and a suitable transition metal complex precursor. The complexes 16 and 17 decompose in solution upon heating to ca. 80 °C to yield the NHC complexes [Co(iPr\(_2\)Im)(CO)\(_2\)(NO)] and [(η\(^5\)-C\(_5\)Me\(_5\))Co(iPr\(_2\)Im)(η\(^2\)-C\(_2\)H\(_4\))] with formation of cyclo-oligophosphines. The reaction of 1 with [Ni(COD)\(_2\)] afforded the diphosphene complex [Ni(iPr\(_2\)Im)\(_2\)(trans-PhP=PPh)] 18. KW - transition metal complexes KW - N-heterocyclic carbenes KW - phosphinidenes KW - dehydrocoupling Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258016 VL - 647 IS - 8 ER - TY - JOUR A1 - Rayner, Christopher A1 - Coleman, Jonathan R. I. A1 - Purves, Kirstin L. A1 - Hodsoll, John A1 - Goldsmith, Kimberley A1 - Alpers, Georg W. A1 - Andersson, Evelyn A1 - Arolt, Volker A1 - Boberg, Julia A1 - Bögels, Susan A1 - Creswell, Cathy A1 - Cooper, Peter A1 - Curtis, Charles A1 - Deckert, Jürgen A1 - Domschke, Katharina A1 - El Alaoui, Samir A1 - Fehm, Lydia A1 - Fydrich, Thomas A1 - Gerlach, Alexander L. A1 - Grocholewski, Anja A1 - Hahlweg, Kurt A1 - Hamm, Alfons A1 - Hedman, Erik A1 - Heiervang, Einar R. A1 - Hudson, Jennifer L. A1 - Jöhren, Peter A1 - Keers, Robert A1 - Kircher, Tilo A1 - Lang, Thomas A1 - Lavebratt, Catharina A1 - Lee, Sang-hyuck A1 - Lester, Kathryn J. A1 - Lindefors, Nils A1 - Margraf, Jürgen A1 - Nauta, Maaike A1 - Pané-Farré, Christiane A. A1 - Pauli, Paul A1 - Rapee, Ronald M. A1 - Reif, Andreas A1 - Rief, Winfried A1 - Roberts, Susanna A1 - Schalling, Martin A1 - Schneider, Silvia A1 - Silverman, Wendy K. A1 - Ströhle, Andreas A1 - Teismann, Tobias A1 - Thastum, Mikael A1 - Wannemüller, Andre A1 - Weber, Heike A1 - Wittchen, Hans-Ulrich A1 - Wolf, Christiane A1 - Rück, Christian A1 - Breen, Gerome A1 - Eley, Thalia C. T1 - A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders JF - Translational Psychiatry N2 - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits. KW - Human behaviour KW - Personalized medicine KW - Prognostic markers KW - Psychiatric disorders Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225048 VL - 9 IS - 150 ER - TY - JOUR A1 - Huestegge, Lynn A1 - Pieczykolan, Aleks A1 - Koch, Iring T1 - A Gestalt account of human behavior is supported by evidence from switching between single and dual actions JF - Scientific Reports N2 - The question of how behavior is represented in the mind lies at the core of psychology as the science of mind and behavior. While a long-standing research tradition has established two opposing fundamental views of perceptual representation, Structuralism and Gestalt psychology, we test both accounts with respect to action representation: Are multiple actions (characterizing human behavior in general) represented as the sum of their component actions (Structuralist view) or holistically (Gestalt view)? Using a single-/dual-response switch paradigm, we analyzed switches between dual ([A + B]) and single ([A], [B]) responses across different effector systems and revealed comparable performance in partial repetitions and full switches of behavioral requirements (e.g., in [A + B] → [A] vs. [B] → [A], or [A] → [A + B] vs. [B] → [A + B]), but only when the presence of dimensional overlap between responses allows for Gestalt formation. This evidence for a Gestalt view of behavior in our paradigm challenges some fundamental assumptions in current (tacitly Structuralist) action control theories (in particular the idea that all actions are represented compositionally with reference to their components), provides a novel explanatory angle for understanding complex, highly synchronized human behavior (e.g., dance), and delimitates the degree to which complex behavior can be analyzed in terms of its basic components. KW - cognitive neuroscience KW - human behaviour KW - learning and memory Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357862 VL - 13 ER - TY - JOUR A1 - Herrmann, Thomas A1 - Karunakaran, Mohindar Murugesh A1 - Fichtner, Alina Suzann T1 - A glance over the fence: Using phylogeny and species comparison for a better understanding of antigen recognition by human γδ T‐cells JF - Immunological Reviews N2 - Both, jawless and jawed vertebrates possess three lymphocyte lineages defined by highly diverse antigen receptors: Two T‐cell‐ and one B‐cell‐like lineage. In both phylogenetic groups, the theoretically possible number of individual antigen receptor specificities can even outnumber that of lymphocytes of a whole organism. Despite fundamental differences in structure and genetics of these antigen receptors, convergent evolution led to functional similarities between the lineages. Jawed vertebrates possess αβ and γδ T‐cells defined by eponymous αβ and γδ T‐cell antigen receptors (TCRs). “Conventional” αβ T‐cells recognize complexes of Major Histocompatibility Complex (MHC) class I and II molecules and peptides. Non‐conventional T‐cells, which can be αβ or γδ T‐cells, recognize a large variety of ligands and differ strongly in phenotype and function between species and within an organism. This review describes similarities and differences of non‐conventional T‐cells of various species and discusses ligands and functions of their TCRs. A special focus is laid on Vγ9Vδ2 T‐cells whose TCRs act as sensors for phosphorylated isoprenoid metabolites, so‐called phosphoantigens (PAg), associated with microbial infections or altered host metabolism in cancer or after drug treatment. We discuss the role of butyrophilin (BTN)3A and BTN2A1 in PAg‐sensing and how species comparison can help in a better understanding of this human Vγ9Vδ2 T‐cell subset. KW - antigen presentation KW - BTN2 KW - BTN3 KW - butyrophilin KW - evolution KW - γδ TCR Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218373 VL - 298 IS - 1 SP - 218 EP - 236 ER - TY - JOUR A1 - Bar-Yosef, Hagit A1 - Gildor, Tsvia A1 - Ramírez-Zavala, Bernardo A1 - Schmauch, Christian A1 - Weissman, Ziva A1 - Pinsky, Mariel A1 - Naddaf, Rawi A1 - Morschhäuser, Joachim A1 - Arkowitz, Robert A. A1 - Kornitzer, Daniel T1 - A global analysis of kinase function in Candida albicans hyphal morphogenesis reveals a role for the endocytosis regulator Akl1 JF - Frontiers in Cellular and Infection Microbiology N2 - The human pathogenic fungus Candida albicans can switch between yeast and hyphal morphologies as a function of environmental conditions and cellular physiology. The yeast-to-hyphae morphogenetic switch is activated by well-established, kinase-based signal transduction pathways that are induced by extracellular stimuli. In order to identify possible inhibitory pathways of the yeast-to-hyphae transition, we interrogated a collection of C. albicans protein kinases and phosphatases ectopically expressed under the regulation of the TETon promoter. Proportionately more phosphatases than kinases were identified that inhibited hyphal morphogenesis, consistent with the known role of protein phosphorylation in hyphal induction. Among the kinases, we identified AKL1 as a gene that significantly suppressed hyphal morphogenesis in serum. Akl1 specifically affected hyphal elongation rather than initiation: overexpression of AKL1 repressed hyphal growth, and deletion of AKL1 resulted in acceleration of the rate of hyphal elongation. Akl1 suppressed fluid-phase endocytosis, probably via Pan1, a putative clathrin-mediated endocytosis scaffolding protein. In the absence of Akl1, the Pan1 patches were delocalized from the sub-apical region, and fluid-phase endocytosis was intensified. These results underscore the requirement of an active endocytic pathway for hyphal morphogenesis. Furthermore, these results suggest that under standard conditions, endocytosis is rate-limiting for hyphal elongation. KW - hyphae KW - endocytosis KW - Pan1 KW - functional genomics Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197204 SN - 2235-2988 VL - 8 ER - TY - JOUR A1 - Carradec, Quentin A1 - Pelletier, Eric A1 - Da Silva, Corinne A1 - Alberti, Adriana A1 - Seeleuthner, Yoann A1 - Blanc-Mathieu, Romain A1 - Lima-Mendez, Gipsi A1 - Rocha, Fabio A1 - Tirichine, Leila A1 - Labadie, Karine A1 - Kirilovsky, Amos A1 - Bertrand, Alexis A1 - Engelen, Stefan A1 - Madoui, Mohammed-Amin A1 - Méheust, Raphaël A1 - Poulain, Julie A1 - Romac, Sarah A1 - Richter, Daniel J. A1 - Yoshikawa, Genki A1 - Dimier, Céline A1 - Kandels-Lewis, Stefanie A1 - Picheral, Marc A1 - Searson, Sarah A1 - Jaillon, Olivier A1 - Aury, Jean-Marc A1 - Karsenti, Eric A1 - Sullivan, Matthew B. A1 - Sunagawa, Shinichi A1 - Bork, Peer A1 - Not, Fabrice A1 - Hingamp, Pascal A1 - Raes, Jeroen A1 - Guidi, Lionel A1 - Ogata, Hiroyuki A1 - de Vargas, Colomban A1 - Iudicone, Daniele A1 - Bowler, Chris A1 - Wincker, Patrick T1 - A global ocean atlas of eukaryotic gene JF - Nature Communications N2 - While our knowledge about the roles of microbes and viruses in the ocean has increased tremendously due to recent advances in genomics and metagenomics, research on marine microbial eukaryotes and zooplankton has benefited much less from these new technologies because of their larger genomes, their enormous diversity, and largely unexplored physiologies. Here, we use a metatranscriptomics approach to capture expressed genes in open ocean Tara Oceans stations across four organismal size fractions. The individual sequence reads cluster into 116 million unigenes representing the largest reference collection of eukaryotic transcripts from any single biome. The catalog is used to unveil functions expressed by eukaryotic marine plankton, and to assess their functional biogeography. Almost half of the sequences have no similarity with known proteins, and a great number belong to new gene families with a restricted distribution in the ocean. Overall, the resource provides the foundations for exploring the roles of marine eukaryotes in ocean ecology and biogeochemistry. KW - genomics KW - marine biology KW - microbial ecology KW - water microbiology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222250 VL - 9 ER - TY - JOUR A1 - Zillober, Christian T1 - A globally convergent version of the method of moving asymptotes N2 - No abstract available Y1 - 1993 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-31984 ER - TY - JOUR A1 - Adeyemo, O. M. A1 - Shapira, S. A1 - Tombaccini, D. A1 - Pollard, H. A1 - Feuerstein, G. A1 - Sirén, Anna-Leena T1 - A goldfish model for evaluation of the neurotoxicit of \(\omega\)-conotoxin GVIA and screening of monoclonal antibodies N2 - A Goldfish Model for Evaluation of the Neurotaxicity of \(\omega\)-Conotoxin GVI A and Screening of Monoclonal Antibodies. ADEYEMO, 0. M .. SHAPIRA, S., TOMBACCINI, D., POLLARD, H. 8 .• FEUERSTEIN, G .. AND SIREN, A-L. ( 1991 ). Toxicol. App/. Pharmaco/. 108, 489-496. The neurotoxicity of \(\omega\)-conotoxin (\(\omega\)-CgTx), a potent neuronal voltage-sensitive calcium channel blocker, was measured using a new bioassay. \(\omega\)-CgTx was administered intraperitoneally (ip) to goldfish weighing approximately 1.6 g, and dose-related changes were observed over a 2-hr period. \(\omega\)CgTx induced time- and dose-dependent abnormal swimming behavior (ASB) and mortality. The antitoxin activity of the antiborlies was investigated in vivo by either ( l) preincubation of the antibody with w-CgTx at 4°C overnight, or (2) pretreatment with antibody, 30 min before \(\omega\)CgTx injection in a 10:1 antibody/\(\omega\)-CgTx molar ratio. The LD50 dose of \(\omega\)-CgTx in goldfish was 5 nmol/kg ip, and preincubation of monoclonal antibody (50 nmol/kg ip) with \(\omega\)-CgTx (5 nmol/kg ip) significantly (p < 0.05) reduced mortality. ASB, and toxicity time. The antitoxin activity of the monoclonal antiborlies evidenced in the goldfish bioassay was further tested in the conscious rat. In the rat, the increases in mean arterial pressure and heart rate induced by \(\omega\)-CgTx (0.03 nmol/rat icv) were significantly (p < 0.02 and p < 0.0 l, respectively) attenuated by preincubation of the toxin with the antibody (0.3 nmol/rat). We conclude that the goldfish bioassay provides a simple. accurate, and inexpensive in vivo model for the study of the toxicity of \(\omega\)CgTx KW - Neurobiologie Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63087 ER - TY - JOUR A1 - Gerova, Milan A1 - Wicke, Laura A1 - Chihara, Kotaro A1 - Schneider, Cornelius A1 - Lavigne, Rob A1 - Vogel, Jörg T1 - A grad-seq view of RNA and protein complexes in Pseudomonas aeruginosa under standard and bacteriophage predation conditions JF - mbio N2 - The Gram-negative rod-shaped bacterium Pseudomonas aeruginosa is not only a major cause of nosocomial infections but also serves as a model species of bacterial RNA biology. While its transcriptome architecture and posttranscriptional regulation through the RNA-binding proteins Hfq, RsmA, and RsmN have been studied in detail, global information about stable RNA-protein complexes in this human pathogen is currently lacking. Here, we implement gradient profiling by sequencing (Grad-seq) in exponentially growing P. aeruginosa cells to comprehensively predict RNA and protein complexes, based on glycerol gradient sedimentation profiles of >73% of all transcripts and ∼40% of all proteins. As to benchmarking, our global profiles readily reported complexes of stable RNAs of P. aeruginosa, including 6S RNA with RNA polymerase and associated product RNAs (pRNAs). We observe specific clusters of noncoding RNAs, which correlate with Hfq and RsmA/N, and provide a first hint that P. aeruginosa expresses a ProQ-like FinO domain-containing RNA-binding protein. To understand how biological stress may perturb cellular RNA/protein complexes, we performed Grad-seq after infection by the bacteriophage ΦKZ. This model phage, which has a well-defined transcription profile during host takeover, displayed efficient translational utilization of phage mRNAs and tRNAs, as evident from their increased cosedimentation with ribosomal subunits. Additionally, Grad-seq experimentally determines previously overlooked phage-encoded noncoding RNAs. Taken together, the Pseudomonas protein and RNA complex data provided here will pave the way to a better understanding of RNA-protein interactions during viral predation of the bacterial cell. IMPORTANCE Stable complexes by cellular proteins and RNA molecules lie at the heart of gene regulation and physiology in any bacterium of interest. It is therefore crucial to globally determine these complexes in order to identify and characterize new molecular players and regulation mechanisms. Pseudomonads harbor some of the largest genomes known in bacteria, encoding ∼5,500 different proteins. Here, we provide a first glimpse on which proteins and cellular transcripts form stable complexes in the human pathogen Pseudomonas aeruginosa. We additionally performed this analysis with bacteria subjected to the important and frequently encountered biological stress of a bacteriophage infection. We identified several molecules with established roles in a variety of cellular pathways, which were affected by the phage and can now be explored for their role during phage infection. Most importantly, we observed strong colocalization of phage transcripts and host ribosomes, indicating the existence of specialized translation mechanisms during phage infection. All data are publicly available in an interactive and easy to use browser. KW - Grad-seq KW - Pseudomonas KW - UKZ KW - bacteriophage KW - infection KW - Pseudomonas aeruginosa KW - RNA-binding proteins KW - noncoding RNA KW - phage Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259054 VL - 12 IS - 1 ER - TY - JOUR A1 - Schmid, Benjamin A1 - Schindelin, Johannes A1 - Cardona, Albert A1 - Longair, Martin A1 - Heisenberg, Martin T1 - A high-level 3D visualization API for Java and ImageJ N2 - Background: Current imaging methods such as Magnetic Resonance Imaging (MRI), Confocal microscopy, Electron Microscopy (EM) or Selective Plane Illumination Microscopy (SPIM) yield three-dimensional (3D) data sets in need of appropriate computational methods for their analysis. The reconstruction, segmentation and registration are best approached from the 3D representation of the data set. Results: Here we present a platform-independent framework based on Java and Java 3D for accelerated rendering of biological images. Our framework is seamlessly integrated into ImageJ, a free image processing package with a vast collection of community-developed biological image analysis tools. Our framework enriches the ImageJ software libraries with methods that greatly reduce the complexity of developing image analysis tools in an interactive 3D visualization environment. In particular, we provide high-level access to volume rendering, volume editing, surface extraction, and image annotation. The ability to rely on a library that removes the low-level details enables concentrating software development efforts on the algorithm implementation parts. Conclusions: Our framework enables biomedical image software development to be built with 3D visualization capabilities with very little effort. We offer the source code and convenient binary packages along with extensive documentation at http://3dviewer.neurofly.de. KW - Visualisierung KW - Java 3D KW - ImageJ KW - framework Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67851 ER - TY - JOUR A1 - Farrell, Jeffrey M. A1 - Grande, Vincenzo A1 - Schmidt, David A1 - Würthner, Frank T1 - A Highly Warped Heptagon-Containing sp\(^2\) Carbon Scaffold via Vinylnaphthyl π-Extension JF - Angewandte Chemie International Edition N2 - A new strategy is demonstrated for the synthesis of warped, negatively curved, all‐sp\(^2\)‐carbon π‐scaffolds. Multifold C−C coupling reactions are used to transform a polyaromatic borinic acid into a saddle‐shaped polyaromatic hydrocarbon (2 ) bearing two heptagonal rings. Notably, this Schwarzite substructure is synthesized in only two steps from an unfunctionalized alkene. A highly warped structure of 2 was revealed by X‐ray crystallographic studies and pronounced flexibility of this π‐scaffold was ascertained by experimental and computational studies. Compound 2 exhibits excellent solubility, visible range absorption and fluorescence, and readily undergoes two reversible one‐electron oxidations at mild potentials. KW - arenes KW - carbon KW - C-C coupling KW - curvature KW - polycyclic aromatic hydrocarbons Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206682 VL - 58 IS - 46 ER - TY - JOUR A1 - Amoretti, Andrea A1 - Areán, Daniel A1 - Argurio, Riccardo A1 - Musso, Daniele A1 - Zayas, Leopoldo A. Pando T1 - A holographic perspective on phonons and pseudo-phonons JF - Journal of High Energy Physics N2 - We analyze the concomitant spontaneous breaking of translation and conformal symmetries by introducing in a CFT a complex scalar operator that acquires a spatially dependent expectation value. The model, inspired by the holographic Q-lattice, provides a privileged setup to study the emergence of phonons from a spontaneous translational symmetry breaking in a conformal field theory and offers valuable hints for the treatment of phonons in QFT at large. We first analyze the Ward identity structure by means of standard QFT techniques, considering both spontaneous and explicit symmetry breaking. Next, by implementing holographic renormalization, we show that the same set of Ward identities holds in the holographic Q-lattice. Eventually, relying on the holographic and QFT results, we study the correlators realizing the symmetry breaking pattern and how they encode information about the low-energy spectrum. KW - AdS-CFT correspondence KW - effective field theories KW - holography and condensed matter physics (AdS/CMT) Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170882 VL - 5 IS - 51 ER - TY - JOUR A1 - Claus, Heike A1 - Hubert, Kerstin A1 - Becher, Dörte A1 - Otto, Andreas A1 - Pawlik, Marie-Christin A1 - Lappann, Ines A1 - Strobel, Lea A1 - Vogel, Ulrich A1 - Johswich, Kay T1 - A homopolymeric adenosine tract in the promoter region of nspA influences factor H-mediated serum resistance in Neisseria meningitidis JF - Scientific Reports N2 - Although usually asymptomatically colonizing the human nasopharynx, the Gram-negative bacterium Neisseria meningitidis (meningococcus) can spread to the blood stream and cause invasive disease. For survival in blood, N. meningitidis evades the complement system by expression of a polysaccharide capsule and surface proteins sequestering the complement regulator factor H (fH). Meningococcal strains belonging to the sequence type (ST-) 41/44 clonal complex (cc41/44) cause a major proportion of serogroup B meningococcal disease worldwide, but they are also common in asymptomatic carriers. Proteome analysis comparing cc41/44 isolates from invasive disease versus carriage revealed differential expression levels of the outer membrane protein NspA, which binds fH. Deletion of nspA reduced serum resistance and NspA expression correlated with fH sequestration. Expression levels of NspA depended on the length of a homopolymeric tract in the nspA promoter: A 5-adenosine tract dictated low NspA expression, whereas a 6-adenosine motif guided high NspA expression. Screening German cc41/44 strain collections revealed the 6-adenosine motif in 39% of disease isolates, but only in 3.4% of carriage isolates. Thus, high NspA expression is associated with disease, but not strictly required. The 6-adenosine nspA promoter is most common to the cc41/44, but is also found in other hypervirulent clonal complexes. KW - Meningitis KW - Pathogens Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200956 VL - 9 ER - TY - JOUR A1 - Walz, Nora A1 - Mühlberger, Andreas A1 - Pauli, Paul T1 - A human open field test reveals thigmotaxis related to agoraphobic fear JF - Biological Psychiatry N2 - BACKGROUND: Thigmotaxis refers to a specific behavior of animals (i.e., to stay close to walls when exploring an open space). Such behavior can be assessed with the open field test (OFT), which is a well-established indicator of animal fear. The detection of similar open field behavior in humans may verify the translational validity of this paradigm. Enhanced thigmotaxis related to anxiety may suggest the relevance of such behavior for anxiety disorders, especially agoraphobia. METHODS: A global positioning system was used to analyze the behavior of 16 patients with agoraphobia and 18 healthy individuals with a risk for agoraphobia (i.e., high anxiety sensitivity) during a human OFT and compare it with appropriate control groups (n = 16 and n = 19). We also tracked 17 patients with agoraphobia and 17 control participants during a city walk that involved walking through an open market square. RESULTS: Our human OFT triggered thigmotaxis in participants; patients with agoraphobia and participants with high anxiety sensitivity exhibited enhanced thigmotaxis. This behavior was evident in increased movement lengths along the wall of the natural open field and fewer entries into the center of the field despite normal movement speed and length. Furthermore, participants avoided passing through the market square during the city walk, indicating again that thigmotaxis is related to agoraphobia. CONCLUSIONS: This study is the first to our knowledge to verify the translational validity of the OFT and to reveal that thigmotaxis, an evolutionarily adaptive behavior shown by most species, is related to agoraphobia, a pathologic fear of open spaces, and anxiety sensitivity, a risk factor for agoraphobia. KW - Agoraphobia KW - Animal models KW - Anxiety sensitivity KW - Avoidance behavior KW - Openfield test KW - Thigmotaxis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187607 VL - 80 IS - 5 ER - TY - JOUR A1 - Gattenloehner, Stefan A1 - Joerissen, H. A1 - Huhn, M. A1 - Vincent, A. A1 - Beeson, D. A1 - Tzartos, S. A1 - Mamalaki, A. A1 - Etschmann, B. A1 - Muller-Hermelink, H. K. A1 - Koscielniak, E. A1 - Barth, S. A1 - Marx, A. T1 - 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] N2 - 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. KW - Medizin Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-68200 ER - TY - JOUR A1 - Koenig, Leopold A1 - Ramme, Anja Patricia A1 - Faust, Daniel A1 - Mayer, Manuela A1 - Flötke, Tobias A1 - Gerhartl, Anna A1 - Brachner, Andreas A1 - Neuhaus, Winfried A1 - Appelt-Menzel, Antje A1 - Metzger, Marco A1 - Marx, Uwe A1 - Dehne, Eva-Maria T1 - A human stem cell-derived brain-liver chip for assessing blood-brain-barrier permeation of pharmaceutical drugs JF - Cells N2 - Significant advancements in the field of preclinical in vitro blood-brain barrier (BBB) models have been achieved in recent years, by developing monolayer-based culture systems towards complex multi-cellular assays. The coupling of those models with other relevant organoid systems to integrate the investigation of blood-brain barrier permeation in the larger picture of drug distribution and metabolization is still missing. Here, we report for the first time the combination of a human induced pluripotent stem cell (hiPSC)-derived blood-brain barrier model with a cortical brain and a liver spheroid model from the same donor in a closed microfluidic system (MPS). The two model compounds atenolol and propranolol were used to measure permeation at the blood–brain barrier and to assess metabolization. Both substances showed an in vivo-like permeation behavior and were metabolized in vitro. Therefore, the novel multi-organ system enabled not only the measurement of parent compound concentrations but also of metabolite distribution at the blood-brain barrier. KW - blood-brain barrier (BBB) model KW - human induced pluripotent stem cells (hiPSCs) KW - microphysiological systems (MPS) KW - multi-organ chip KW - brain–liver chip Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290375 SN - 2073-4409 VL - 11 IS - 20 ER - TY - JOUR A1 - Wilhelm, Gernot T1 - A Hurrian Letter from Tell Brak N2 - No abstract available. KW - Tell Brak Y1 - 1991 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-85972 ER - TY - JOUR A1 - Stange, Katja A1 - Désir, Julie A1 - Kakar, Naseebullah A1 - Mueller, Thomas D. A1 - Budde, Birgit S. A1 - Gordon, Christopher T. A1 - Horn, Denise A1 - Seemann, Petra A1 - Borck, Guntram T1 - A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia JF - Orphanet Journal of Rare Diseases N2 - Background: Grebe dysplasia, Hunter-Thompson dysplasia, and du Pan dysplasia constitute a spectrum of skeletal dysplasias inherited as an autosomal recessive trait characterized by short stature, severe acromesomelic shortening of the limbs, and normal axial skeleton. The majority of patients with these disorders have biallelic loss-of-function mutations of GDF5. In single instances, Grebe dysplasia and a Grebe dysplasia-like phenotype with genital anomalies have been shown to be caused by mutations in BMPR1B, encoding a GDF5 receptor. Methods: We clinically and radiologically characterised an acromesomelic chondrodysplasia in an adult woman born to consanguineous parents. We sequenced GDF5 and BMPR1B on DNA of the proposita. We performed 3D structural analysis and luciferase reporter assays to functionally investigate the identified BMPR1B mutation. Results: We extend the genotype-phenotype correlation in the acromesomelic chondrodysplasias by showing that the milder du Pan dysplasia can be caused by a hypomorphic BMPR1B mutation. We show that the homozygous c.91C>T, p.(Arg31Cys) mutation causing du Pan dysplasia leads to a significant loss of BMPR1B function, but to a lesser extent than the previously reported p.Cys53Arg mutation that results in the more severe Grebe dysplasia. Conclusions: The phenotypic severity gradient of the clinically and radiologically related acromesomelic chondrodysplasia spectrum of skeletal disorders may be due to the extent of functional impairment of the ligand-receptor pair GDF5-BMPR1B. KW - linkage analysis KW - chondrodysplasia KW - specificity KW - Grebe dysplasia KW - BMPR1B KW - du Pan dysplasia KW - tool KW - missense KW - grebe KW - protein-1 CDMP1 gene KW - Acromesomelic dysplasias Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151650 VL - 10 IS - 84 ER -