@article{FarrellGrandeSchmidtetal.2019, author = {Farrell, Jeffrey M. and Grande, Vincenzo and Schmidt, David and W{\"u}rthner, Frank}, title = {A Highly Warped Heptagon-Containing sp\(^2\) Carbon Scaffold via Vinylnaphthyl π-Extension}, series = {Angewandte Chemie International Edition}, volume = {58}, journal = {Angewandte Chemie International Edition}, number = {46}, doi = {10.1002/anie.201909975}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-206682}, pages = {16504-16507}, year = {2019}, abstract = {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.}, language = {en} } @article{SchmidSchindelinCardonaetal.2010, author = {Schmid, Benjamin and Schindelin, Johannes and Cardona, Albert and Longair, Martin and Heisenberg, Martin}, title = {A high-level 3D visualization API for Java and ImageJ}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-67851}, year = {2010}, abstract = {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.}, subject = {Visualisierung}, language = {en} } @article{GerovaWickeChiharaetal.2021, author = {Gerova, Milan and Wicke, Laura and Chihara, Kotaro and Schneider, Cornelius and Lavigne, Rob and Vogel, J{\"o}rg}, title = {A grad-seq view of RNA and protein complexes in Pseudomonas aeruginosa under standard and bacteriophage predation conditions}, series = {mbio}, volume = {12}, journal = {mbio}, number = {1}, doi = {10.1128/mBio.03454-20}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259054}, pages = {e03454-20}, year = {2021}, abstract = {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.}, language = {en} } @article{AdeyemoShapiraTombaccinietal.1991, author = {Adeyemo, O. M. and Shapira, S. and Tombaccini, D. and Pollard, H. and Feuerstein, G. and Sir{\´e}n, Anna-Leena}, title = {A goldfish model for evaluation of the neurotoxicit of \(\omega\)-conotoxin GVIA and screening of monoclonal antibodies}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63087}, year = {1991}, abstract = {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}, subject = {Neurobiologie}, language = {en} } @article{Zillober1993, author = {Zillober, Christian}, title = {A globally convergent version of the method of moving asymptotes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-31984}, year = {1993}, abstract = {No abstract available}, language = {en} } @article{CarradecPelletierDaSilvaetal.2018, author = {Carradec, Quentin and Pelletier, Eric and Da Silva, Corinne and Alberti, Adriana and Seeleuthner, Yoann and Blanc-Mathieu, Romain and Lima-Mendez, Gipsi and Rocha, Fabio and Tirichine, Leila and Labadie, Karine and Kirilovsky, Amos and Bertrand, Alexis and Engelen, Stefan and Madoui, Mohammed-Amin and M{\´e}heust, Rapha{\"e}l and Poulain, Julie and Romac, Sarah and Richter, Daniel J. and Yoshikawa, Genki and Dimier, C{\´e}line and Kandels-Lewis, Stefanie and Picheral, Marc and Searson, Sarah and Jaillon, Olivier and Aury, Jean-Marc and Karsenti, Eric and Sullivan, Matthew B. and Sunagawa, Shinichi and Bork, Peer and Not, Fabrice and Hingamp, Pascal and Raes, Jeroen and Guidi, Lionel and Ogata, Hiroyuki and de Vargas, Colomban and Iudicone, Daniele and Bowler, Chris and Wincker, Patrick}, title = {A global ocean atlas of eukaryotic gene}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, organization = {Tara Oceans Coordinators}, doi = {10.1038/s41467-017-02342-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-222250}, year = {2018}, abstract = {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.}, language = {en} } @article{BarYosefGildorRamirezZavalaetal.2018, author = {Bar-Yosef, Hagit and Gildor, Tsvia and Ram{\´i}rez-Zavala, Bernardo and Schmauch, Christian and Weissman, Ziva and Pinsky, Mariel and Naddaf, Rawi and Morschh{\"a}user, Joachim and Arkowitz, Robert A. and Kornitzer, Daniel}, title = {A global analysis of kinase function in Candida albicans hyphal morphogenesis reveals a role for the endocytosis regulator Akl1}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {8}, journal = {Frontiers in Cellular and Infection Microbiology}, issn = {2235-2988}, doi = {10.3389/fcimb.2018.00017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197204}, year = {2018}, abstract = {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.}, language = {en} } @article{HerrmannKarunakaranFichtner2020, author = {Herrmann, Thomas and Karunakaran, Mohindar Murugesh and Fichtner, Alina Suzann}, title = {A glance over the fence: Using phylogeny and species comparison for a better understanding of antigen recognition by human γδ T-cells}, series = {Immunological Reviews}, volume = {298}, journal = {Immunological Reviews}, number = {1}, doi = {10.1111/imr.12919}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218373}, pages = {218 -- 236}, year = {2020}, abstract = {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.}, language = {en} } @article{HuesteggePieczykolanKoch2023, author = {Huestegge, Lynn and Pieczykolan, Aleks and Koch, Iring}, title = {A Gestalt account of human behavior is supported by evidence from switching between single and dual actions}, series = {Scientific Reports}, volume = {13}, journal = {Scientific Reports}, doi = {10.1038/s41598-023-47788-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357862}, year = {2023}, abstract = {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.}, language = {en} } @article{RaynerColemanPurvesetal.2019, author = {Rayner, Christopher and Coleman, Jonathan R. I. and Purves, Kirstin L. and Hodsoll, John and Goldsmith, Kimberley and Alpers, Georg W. and Andersson, Evelyn and Arolt, Volker and Boberg, Julia and B{\"o}gels, Susan and Creswell, Cathy and Cooper, Peter and Curtis, Charles and Deckert, J{\"u}rgen and Domschke, Katharina and El Alaoui, Samir and Fehm, Lydia and Fydrich, Thomas and Gerlach, Alexander L. and Grocholewski, Anja and Hahlweg, Kurt and Hamm, Alfons and Hedman, Erik and Heiervang, Einar R. and Hudson, Jennifer L. and J{\"o}hren, Peter and Keers, Robert and Kircher, Tilo and Lang, Thomas and Lavebratt, Catharina and Lee, Sang-hyuck and Lester, Kathryn J. and Lindefors, Nils and Margraf, J{\"u}rgen and Nauta, Maaike and Pan{\´e}-Farr{\´e}, Christiane A. and Pauli, Paul and Rapee, Ronald M. and Reif, Andreas and Rief, Winfried and Roberts, Susanna and Schalling, Martin and Schneider, Silvia and Silverman, Wendy K. and Str{\"o}hle, Andreas and Teismann, Tobias and Thastum, Mikael and Wannem{\"u}ller, Andre and Weber, Heike and Wittchen, Hans-Ulrich and Wolf, Christiane and R{\"u}ck, Christian and Breen, Gerome and Eley, Thalia C.}, title = {A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders}, series = {Translational Psychiatry}, volume = {9}, journal = {Translational Psychiatry}, number = {150}, doi = {10.1038/s41398-019-0481-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225048}, pages = {1-13}, year = {2019}, abstract = {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.}, language = {en} } @article{LuisHorrerPhilippetal.2021, author = {Luis, Werner and Horrer, G{\"u}nther and Philipp, Michael and Lubitz, Katharina and Kuntze-Fechner, Maximilian W. and Radius, Udo}, title = {A General Synthetic Route to NHC-Phosphinidenes: NHC-mediated Dehydrogenation of Primary Phosphines}, series = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie}, volume = {647}, journal = {Zeitschrift f{\"u}r anorganische und allgemeine Chemie}, number = {8}, doi = {10.1002/zaac.202000405}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258016}, pages = {881-895}, year = {2021}, abstract = {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.}, language = {en} } @article{BrehmHaasGoebeletal.1992, author = {Brehm, Klaus and Haas, Albert and Goebel, Werner and Kreft, J{\"u}rgen}, title = {A gene encoding a superoxide dismutase of the facultative intracellular bacterium Listeria monocytogenes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-60515}, year = {1992}, abstract = {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.}, subject = {Biologie}, language = {en} } @article{DegenkolbeKoenigZimmeretal.2013, author = {Degenkolbe, Elisa and K{\"o}nig, Jana and Zimmer, Julia and Walther, Maria and Reißner, Carsten and Nickel, Joachim and Pl{\"o}ger, Frank and Raspopovic, Jelena and Sharpe, James and Dathe, Katharina and Hecht, Jacqueline T. and Mundlos, Stefan and Doelken, Sandra C. and Seemann, Petra}, title = {A GDF5 Point Mutation Strikes Twice - Causing BDA1 and SYNS2}, series = {PLOS Genetics}, volume = {9}, journal = {PLOS Genetics}, number = {10}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003846}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-127556}, pages = {e1003846}, year = {2013}, abstract = {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.}, language = {en} } @article{SteuerCostaVanderAuweraGlocketal.2019, author = {Steuer Costa, Wagner and Van der Auwera, Petrus and Glock, Caspar and Liewald, Jana F. and Bach, Maximilian and Sch{\"u}ler, Christina and Wabnig, Sebastian and Oranth, Alexandra and Masurat, Florentin and Bringmann, Henrik and Schoofs, Liliane and Stelzer, Ernst H. K. and Fischer, Sabine C. and Gottschalk, Alexander}, title = {A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics}, series = {Nature Communications}, volume = {10}, journal = {Nature Communications}, doi = {10.1038/s41467-019-12098-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-223273}, year = {2019}, abstract = {Animals must slow or halt locomotion to integrate sensory inputs or to change direction. In Caenorhabditis elegans, the GABAergic and peptidergic neuron RIS mediates developmentally timed quiescence. Here, we show RIS functions additionally as a locomotion stop neuron. RIS optogenetic stimulation caused acute and persistent inhibition of locomotion and pharyngeal pumping, phenotypes requiring FLP-11 neuropeptides and GABA. RIS photoactivation allows the animal to maintain its body posture by sustaining muscle tone, yet inactivating motor neuron oscillatory activity. During locomotion, RIS axonal Ca2+ signals revealed functional compartmentalization: Activity in the nerve ring process correlated with locomotion stop, while activity in a branch correlated with induced reversals. GABA was required to induce, and FLP-11 neuropeptides were required to sustain locomotion stop. RIS attenuates neuronal activity and inhibits movement, possibly enabling sensory integration and decision making, and exemplifies dual use of one cell across development in a compact nervous system.}, language = {en} } @article{HommersRichterYangetal.2018, author = {Hommers, L. G. and Richter, J. and Yang, Y. and Raab, A. and Baumann, C. and Lang, K. and Schiele, M. A. and Weber, H. and Wittmann, A. and Wolf, C. and Alpers, G. W. and Arolt, V. and Domschke, K. and Fehm, L. and Fydrich, T. and Gerlach, A. and Gloster, A. T. and Hamm, A. O. and Helbig-Lang, S. and Kircher, T. and Lang, T. and Pan{\´e}-Farr{\´e}, C. A. and Pauli, P. and Pfleiderer, B. and Reif, A. and Romanos, M. and Straube, B. and Str{\"o}hle, A. and Wittchen, H.-U. and Frantz, S. and Ertl, G. and Lohse, M. J. and Lueken, U. and Deckert, J.}, title = {A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety}, series = {Translational Psychiatry}, volume = {8}, journal = {Translational Psychiatry}, doi = {10.1038/s41398-018-0278-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-322497}, year = {2018}, abstract = {Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.}, language = {en} } @article{PalmisanoKullmannHanafietal.2022, author = {Palmisano, Chiara and Kullmann, Peter and Hanafi, Ibrahem and Verrecchia, Marta and Latoschik, Marc Erich and Canessa, Andrea and Fischbach, Martin and Isaias, Ioannis Ugo}, title = {A fully-immersive virtual reality setup to study gait modulation}, series = {Frontiers in Human Neuroscience}, volume = {16}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2022.783452}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267099}, year = {2022}, abstract = {Objective: Gait adaptation to environmental challenges is fundamental for independent and safe community ambulation. The possibility of precisely studying gait modulation using standardized protocols of gait analysis closely resembling everyday life scenarios is still an unmet need. Methods: We have developed a fully-immersive virtual reality (VR) environment where subjects have to adjust their walking pattern to avoid collision with a virtual agent (VA) crossing their gait trajectory. We collected kinematic data of 12 healthy young subjects walking in real world (RW) and in the VR environment, both with (VR/A+) and without (VR/A-) the VA perturbation. The VR environment closely resembled the RW scenario of the gait laboratory. To ensure standardization of the obstacle presentation the starting time speed and trajectory of the VA were defined using the kinematics of the participant as detected online during each walking trial. Results: We did not observe kinematic differences between walking in RW and VR/A-, suggesting that our VR environment per se might not induce significant changes in the locomotor pattern. When facing the VA all subjects consistently reduced stride length and velocity while increasing stride duration. Trunk inclination and mediolateral trajectory deviation also facilitated avoidance of the obstacle. Conclusions: This proof-of-concept study shows that our VR/A+ paradigm effectively induced a timely gait modulation in a standardized immersive and realistic scenario. This protocol could be a powerful research tool to study gait modulation and its derangements in relation to aging and clinical conditions.}, language = {en} } @article{UereyenBachoferKuenzer2022, author = {Uereyen, Soner and Bachofer, Felix and Kuenzer, Claudia}, title = {A framework for multivariate analysis of land surface dynamics and driving variables — a case study for Indo-Gangetic river basins}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {1}, issn = {2072-4292}, doi = {10.3390/rs14010197}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255295}, year = {2022}, abstract = {The analysis of the Earth system and interactions among its spheres is increasingly important to improve the understanding of global environmental change. In this regard, Earth observation (EO) is a valuable tool for monitoring of long term changes over the land surface and its features. Although investigations commonly study environmental change by means of a single EO-based land surface variable, a joint exploitation of multivariate land surface variables covering several spheres is still rarely performed. In this regard, we present a novel methodological framework for both, the automated processing of multisource time series to generate a unified multivariate feature space, as well as the application of statistical time series analysis techniques to quantify land surface change and driving variables. In particular, we unify multivariate time series over the last two decades including vegetation greenness, surface water area, snow cover area, and climatic, as well as hydrological variables. Furthermore, the statistical time series analyses include quantification of trends, changes in seasonality, and evaluation of drivers using the recently proposed causal discovery algorithm Peter and Clark Momentary Conditional Independence (PCMCI). We demonstrate the functionality of our methodological framework using Indo-Gangetic river basins in South Asia as a case study. The time series analyses reveal increasing trends in vegetation greenness being largely dependent on water availability, decreasing trends in snow cover area being mostly negatively coupled to temperature, and trends of surface water area to be spatially heterogeneous and linked to various driving variables. Overall, the obtained results highlight the value and suitability of this methodological framework with respect to global climate change research, enabling multivariate time series preparation, derivation of detailed information on significant trends and seasonality, as well as detection of causal links with minimal user intervention. This study is the first to use multivariate time series including several EO-based variables to analyze land surface dynamics over the last two decades using the causal discovery algorithm PCMCI.}, language = {en} } @article{HermJanieschHelmetal.2023, author = {Herm, Lukas-Valentin and Janiesch, Christian and Helm, Alexander and Imgrund, Florian and Hofmann, Adrian and Winkelmann, Axel}, title = {A framework for implementing robotic process automation projects}, series = {Information Systems and e-Business Management}, volume = {21}, journal = {Information Systems and e-Business Management}, number = {1}, issn = {1617-9846}, doi = {10.1007/s10257-022-00553-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-323798}, pages = {1-35}, year = {2023}, abstract = {Robotic process automation is a disruptive technology to automate already digital yet manual tasks and subprocesses as well as whole business processes rapidly. In contrast to other process automation technologies, robotic process automation is lightweight and only accesses the presentation layer of IT systems to mimic human behavior. Due to the novelty of robotic process automation and the varying approaches when implementing the technology, there are reports that up to 50\% of robotic process automation projects fail. To tackle this issue, we use a design science research approach to develop a framework for the implementation of robotic process automation projects. We analyzed 35 reports on real-life projects to derive a preliminary sequential model. Then, we performed multiple expert interviews and workshops to validate and refine our model. The result is a framework with variable stages that offers guidelines with enough flexibility to be applicable in complex and heterogeneous corporate environments as well as for small and medium-sized companies. It is structured by the three phases of initialization, implementation, and scaling. They comprise eleven stages relevant during a project and as a continuous cycle spanning individual projects. Together they structure how to manage knowledge and support processes for the execution of robotic process automation implementation projects.}, language = {en} } @article{GroeberEngelhardtLangeetal.2016, author = {Groeber, Florian and Engelhardt, Lisa and Lange, Julia and Kurdyn, Szymon and Schmid, Freia F. and R{\"u}cker, Christoph and Mielke, Stephan and Walles, Heike and Hansmann, Jan}, title = {A First Vascularized Skin Equivalent as an Alternative to Animal Experimentation}, series = {ALTEX - Alternatives to Animal Experimentation}, volume = {33}, journal = {ALTEX - Alternatives to Animal Experimentation}, number = {4}, doi = {10.14573/altex.1604041}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164438}, pages = {415-422}, year = {2016}, abstract = {Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin \& eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.}, language = {en} } @article{ThonfeldGessnerHolzwarthetal.2022, author = {Thonfeld, Frank and Gessner, Ursula and Holzwarth, Stefanie and Kriese, Jennifer and da Ponte, Emmanuel and Huth, Juliane and Kuenzer, Claudia}, title = {A first assessment of canopy cover loss in Germany's forests after the 2018-2020 drought years}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {3}, issn = {2072-4292}, doi = {10.3390/rs14030562}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-255306}, year = {2022}, abstract = {Central Europe was hit by several unusually strong periods of drought and heat between 2018 and 2020. These droughts affected forest ecosystems. Cascading effects with bark beetle infestations in spruce stands were fatal to vast forest areas in Germany. We present the first assessment of canopy cover loss in Germany for the period of January 2018-April 2021. Our approach makes use of dense Sentinel-2 and Landsat-8 time-series data. We computed the disturbance index (DI) from the tasseled cap components brightness, greenness, and wetness. Using quantiles, we generated monthly DI composites and calculated anomalies in a reference period (2017). From the resulting map, we calculated the canopy cover loss statistics for administrative entities. Our results show a canopy cover loss of 501,000 ha for Germany, with large regional differences. The losses were largest in central Germany and reached up to two-thirds of coniferous forest loss in some districts. Our map has high spatial (10 m) and temporal (monthly) resolution and can be updated at any time.}, language = {en} } @article{AdolfiDuKneitzetal.2021, author = {Adolfi, Mateus C. and Du, Kang and Kneitz, Susanne and Cabau, C{\´e}dric and Zahm, Margot and Klopp, Christophe and Feron, Romain and Paix{\~a}o, R{\^o}mulo V. and Varela, Eduardo S. and de Almeida, Fernanda L. and de Oliveira, Marcos A. and N{\´o}brega, Rafael H. and Lopez-Roques, C{\´e}line and Iampietro, Carole and Lluch, J{\´e}r{\^o}me and Kloas, Werner and Wuertz, Sven and Schaefer, Fabian and St{\"o}ck, Matthias and Guiguen, Yann and Schartl, Manfred}, title = {A duplicated copy of id2b is an unusual sex-determining candidate gene on the Y chromosome of arapaima (Arapaima gigas)}, series = {Scientific Reports}, volume = {11}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-021-01066-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265672}, year = {2021}, abstract = {Arapaima gigas is one of the largest freshwater fish species of high ecological and economic importance. Overfishing and habitat destruction are severe threats to the remaining wild populations. By incorporating a chromosomal Hi-C contact map, we improved the arapaima genome assembly to chromosome-level, revealing an unexpected high degree of chromosome rearrangements during evolution of the bonytongues (Osteoglossiformes). Combining this new assembly with pool-sequencing of male and female genomes, we identified id2bbY, a duplicated copy of the inhibitor of DNA binding 2b (id2b) gene on the Y chromosome as candidate male sex-determining gene. A PCR-test for id2bbY was developed, demonstrating that this gene is a reliable male-specific marker for genotyping. Expression analyses showed that this gene is expressed in juvenile male gonads. Its paralog, id2ba, exhibits a male-biased expression in immature gonads. Transcriptome analyses and protein structure predictions confirm id2bbY as a prime candidate for the master sex-determiner. Acting through the TGF beta signaling pathway, id2bbY from arapaima would provide the first evidence for a link of this family of transcriptional regulators to sex determination. Our study broadens our current understanding about the evolution of sex determination genetic networks and provide a tool for improving arapaima aquaculture for commercial and conservation purposes.}, language = {en} } @article{EisenhuthVellmerRauhetal.2021, author = {Eisenhuth, Nicole and Vellmer, Tim and Rauh, Elisa T. and Butter, Falk and Janzen, Christian J.}, title = {A DOT1B/Ribonuclease H2 Protein Complex Is Involved in R-Loop Processing, Genomic Integrity, and Antigenic Variation in Trypanosoma brucei}, series = {mbio}, volume = {12}, journal = {mbio}, number = {6}, doi = {10.1128/mBio.01352-21}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260698}, pages = {e01352-21}, year = {2021}, abstract = {The parasite Trypanosoma brucei periodically changes the expression of protective variant surface glycoproteins (VSGs) to evade its host's immune sys-tem in a process known as antigenic variation. One route to change VSG expres-sion is the transcriptional activation of a previously silent VSG expression site (ES), a subtelomeric region containing the VSG genes. Homologous recombination of a different VSG from a large reservoir into the active ES represents another route. The conserved histone methyltransferase DOT1B is involved in transcriptional silencing of inactive ES and influences ES switching kinetics. The molecular machin-ery that enables DOT1B to execute these regulatory functions remains elusive, however. To better understand DOT1B-mediated regulatory processes, we purified DOT1B-associated proteins using complementary biochemical approaches. We iden-tified several novel DOT1B interactors. One of these was the RNase H2 complex, previously shown to resolve RNA-DNA hybrids, maintain genome integrity, and play a role in antigenic variation. Our study revealed that DOT1B depletion results in an increase in RNA-DNA hybrids, accumulation of DNA damage, and ES switch-ing events. Surprisingly, a similar pattern of VSG deregulation was observed in RNase H2 mutants. We propose that both proteins act together in resolving R-loops to ensure genome integrity and contribute to the tightly regulated process of anti-genic variation.}, language = {en} } @article{ColvillBoothNilletal.2016, author = {Colvill, Emma and Booth, Jeremy and Nill, Simeon and Fast, Martin and Bedford, James and Oelfke, Uwe and Nakamura, Mitsuhiro and Poulsen, Per and Worm, Esben and Hansen, Rune and Ravkilde, Thomas and Rydh{\"o}g, Jonas Scherman and Pommer, Tobias and af Rosenschold, Per Munck and Lang, Stephanie and Guckenberger, Matthias and Groh, Christian and Herrmann, Christian and Verellen, Dirk and Poels, Kenneth and Wang, Lei and Hadsell, Michael and Sothmann, Thilo and Blanck, Oliver and Keall, Paul}, title = {A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: a multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking}, series = {Radiotherapy and Oncology}, volume = {119}, journal = {Radiotherapy and Oncology}, number = {1}, doi = {10.1016/j.radonc.2016.03.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189605}, pages = {159-165}, year = {2016}, abstract = {Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for gamma-tests recorded. Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2\%/2 mm gamma-fail rate of 1.6\% with adaptation and 15.2\% without adaptation (p < 0.001). For all prostate the mean 2\%/2 mm gamma-fail rate was 1.4\% with adaptation and 17.3\% without adaptation (p < 0.001). The difference between the four systems was small with an average 2\%/2 mm gamma-fail rate of <3\% for all systems with adaptation for lung and prostate. Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.}, language = {en} } @article{HollerFischerWeberetal.1987, author = {Holler, E. and Fischer, H. and Weber, C. and Stopper, Helga and Steger, H. and Simek, H.}, title = {A DNA polymerase with unusual properties from the slime mold Physarum polycephalum}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-63501}, year = {1987}, abstract = {Two forms of a DNA polymerase have been purified from microplasmodia of Physarum polycephalum by poly(ethyleneimine) precipitation and chromatography on DEAE-Sephacel, phosphocellulose, heparin Sepharose, hydroxyapatite, DNA-agarose, blue-Sepharose. They were separated from DNA polymerase cx on phosphocellulose and from each other on heparin-Sepharose. Form HS1 enzymewas 30-40\% pure and form HS2 enzyme 60\% with regard toprotein contents of the preparations. Form HS2 enzymewas generated from form HS1 enzyme on prolonged standing of enzyme preparations. The DNA polymerases were obtained as complexes of a 60-kDa protein associated with either a 135-kDa (HS1) or a 110-kDa (HS2) DNA-polymerizing polypeptidein a 1:1 molar stoichiometry. The biochemical function of the 60-kDa protein remained unknown. The complexes tended to dissociate during gradient centrifugation and during partition chromatography as weil as during polyacrylamide gradient gel electrophoresis under nondenaturing conditions at high dilutions of samples. Both forms existed in plasmodia extracts, their proportions depending on several factors including those which promoted proteolysis. The DNA polymerases resembled eucaryotic DNA polymerase ß by several criteria and were functionally indistinguishable from each other. It is suggested that lower eucaryotes contain repair DNA polymerases, which are similar to those of eubacteria on a molecular mass basis.}, subject = {Toxikologie}, language = {en} } @article{KistlerSiwyFranketal.2011, author = {Kistler, Andreas D. and Siwy, Justyna and Frank, Breunig and Jeevaratnam, Praveen and Scherl, Alexander and Mullen, William and Warnock, David G. and Wanner, Christoph and Hughes, Derralynn A. and Mischak, Harald and W{\"u}thrich, Rudolf P. and Serra, Andreas L.}, title = {A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0020534}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133526}, pages = {e20534}, year = {2011}, abstract = {Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naive female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2\% sensitivity and 97.8\% specificity when tested in an independent validation cohort consisting of 17 treatment-naive Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy.}, language = {en} } @article{KarunakaranSubramanianJinetal.2023, author = {Karunakaran, Mohindar M. and Subramanian, Hariharan and Jin, Yiming and Mohammed, Fiyaz and Kimmel, Brigitte and Juraske, Claudia and Starick, Lisa and N{\"o}hren, Anna and L{\"a}nder, Nora and Willcox, Carrie R. and Singh, Rohit and Schamel, Wolfgang W. and Nikolaev, Viacheslav O. and Kunzmann, Volker and Wiemer, Andrew J. and Willcox, Benjamin E. and Herrmann, Thomas}, title = {A distinct topology of BTN3A IgV and B30.2 domains controlled by juxtamembrane regions favors optimal human γδ T cell phosphoantigen sensing}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-41938-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358179}, year = {2023}, abstract = {Butyrophilin (BTN)-3A and BTN2A1 molecules control the activation of human Vγ9Vδ2 T cells during T cell receptor (TCR)-mediated sensing of phosphoantigens (PAg) derived from microbes and tumors. However, the molecular rules governing PAg sensing remain largely unknown. Here, we establish three mechanistic principles of PAg-mediated γδ T cell activation. First, in humans, following PAg binding to the intracellular BTN3A1-B30.2 domain, Vγ9Vδ2 TCR triggering involves the extracellular V-domain of BTN3A2/BTN3A3. Moreover, the localization of both protein domains on different chains of the BTN3A homo-or heteromers is essential for efficient PAg-mediated activation. Second, the formation of BTN3A homo-or heteromers, which differ in intracellular trafficking and conformation, is controlled by molecular interactions between the juxtamembrane regions of the BTN3A chains. Finally, the ability of PAg not simply to bind BTN3A-B30.2, but to promote its subsequent interaction with the BTN2A1-B30.2 domain, is essential for T-cell activation. Defining these determinants of cooperation and the division of labor in BTN proteins improves our understanding of PAg sensing and elucidates a mode of action that may apply to other BTN family members.}, language = {en} } @article{WongPittig2022, author = {Wong, Alex H. K. and Pittig, Andre}, title = {A dimensional measure of safety behavior: A non-dichotomous assessment of costly avoidance in human fear conditioning}, series = {Psychological Research}, volume = {86}, journal = {Psychological Research}, number = {1}, issn = {1430-2772}, doi = {10.1007/s00426-021-01490-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267688}, pages = {312-330}, year = {2022}, abstract = {Safety behavior prevents the occurrence of threat, thus it is typically considered adaptive. However, safety behavior in anxiety-related disorders is often costly, and persists even the situation does not entail realistic threat. Individuals can engage in safety behavior to varying extents, however, these behaviors are typically measured dichotomously (i.e., to execute or not). To better understand the nuances of safety behavior, this study developed a dimensional measure of safety behavior that had a negative linear relationship with the admission of an aversive outcome. In two experiments, a Reward group receiving fixed or individually calibrated incentives competing with safety behavior showed reduced safety behavior than a Control group receiving no incentives. This allowed extinction learning to a previously learnt warning signal in the Reward group (i.e., updating the belief that this stimulus no longer signals threat). Despite the Reward group exhibited extinction learning, both groups showed a similar increase in fear to the warning signal once safety behavior was no longer available. This null group difference was due to some participants in the Reward group not incentivized enough to disengage from safety behavior. Dimensional assessment revealed a dissociation between low fear but substantial safety behavior to a safety signal in the Control group. This suggests that low-cost safety behavior does not accurately reflect the fear-driven processes, but also other non-fear-driven processes, such as cost (i.e., engage in safety behavior merely because it bears little to no cost). Pinpointing both processes is important for furthering the understanding of safety behavior.}, language = {en} } @article{BayerPruckner2023, author = {Bayer, Daniel and Pruckner, Marco}, title = {A digital twin of a local energy system based on real smart meter data}, series = {Energy Informatics}, volume = {6}, journal = {Energy Informatics}, doi = {10.1186/s42162-023-00263-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357456}, year = {2023}, abstract = {The steadily increasing usage of smart meters generates a valuable amount of high-resolution data about the individual energy consumption and production of local energy systems. Private households install more and more photovoltaic systems, battery storage and big consumers like heat pumps. Thus, our vision is to augment these collected smart meter time series of a complete system (e.g., a city, town or complex institutions like airports) with simulatively added previously named components. We, therefore, propose a novel digital twin of such an energy system based solely on a complete set of smart meter data including additional building data. Based on the additional geospatial data, the twin is intended to represent the addition of the abovementioned components as realistically as possible. Outputs of the twin can be used as a decision support for either system operators where to strengthen the system or for individual households where and how to install photovoltaic systems and batteries. Meanwhile, the first local energy system operators had such smart meter data of almost all residential consumers for several years. We acquire those of an exemplary operator and discuss a case study presenting some features of our digital twin and highlighting the value of the combination of smart meter and geospatial data.}, language = {en} } @article{MuellerChandraFuraijatetal.2020, author = {M{\"u}ller, Frank and Chandra, Shivani and Furaijat, Ghefar and Kruse, Stefan and Waligorski, Alexandra and Simmenroth, Anne and Kleinert, Evelyn}, title = {A digital communication assistance tool (DCAT) to obtain medical history from foreign-language patients: development and pilot testing in a primary health care center for refugees}, series = {International Journal of Environmental Research and Public Health}, volume = {17}, journal = {International Journal of Environmental Research and Public Health}, number = {4}, issn = {1660-4601}, doi = {10.3390/ijerph17041368}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200640}, year = {2020}, abstract = {Background: Language barriers play a critical role in the treatment of migrant and refugee patients. In Germany, primary care interpreters are often not available especially in rural areas or if patients demand spontaneous or urgent consultations. Methods: In order to enable patients and their physicians to communicate effectively about the current illness history, we developed a digital communication assistance tool (DCAT) for 19 different languages and dialects. This paper reports the multidisciplinary process of the conceptual design and the iterative development of this cross-cultural user-centered application in an action-oriented approach. Results: We piloted our app with 36 refugee patients prior to a clinical study and used the results for further development. The acceptance and usability of the app by patients was high. Conclusion: Using digital tools for overcoming language barriers can be a feasible approach when providing health care to foreign-language patients.}, language = {en} } @article{SeibelVolmer2021, author = {Seibel, Sebastian and Volmer, Judith}, title = {A Diary Study on Anticipated Leisure Time, Morning Recovery, and Employees' Work Engagement}, series = {International Journal of Environmental Research and Public Health}, volume = {18}, journal = {International Journal of Environmental Research and Public Health}, number = {18}, issn = {1660-4601}, doi = {10.3390/ijerph18189436}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246090}, year = {2021}, abstract = {Recovery during yesterday's leisure time is beneficial for morning recovery, and morning recovery fosters employees' work engagement, a positive, motivational state associated with job performance. We extended existing research by assuming that both, morning recovery (considered a resource) and anticipated leisure time (considered an anticipated resource gain), relate to work engagement. Anticipated leisure time comprises two constructs: general anticipation of leisure time, which refers to employees' cognitive evaluation of their entire upcoming leisure time, and pleasant anticipation of a planned leisure activity, which describes a positive affective reaction because of one specific, upcoming leisure activity. We suggested that employees with high pleasant anticipation generate more thoughts of a planned leisure activity (ToPLA), which may distract them from their work, reducing their work engagement. A diary study over five days showed that morning recovery and general anticipation of leisure time were positively related to work engagement. Furthermore, employees with higher pleasant anticipation of a planned leisure activity reported more ToPLA. In contrast to our expectations, neither pleasant anticipation nor ToPLA was related to work engagement. In sum, this study introduced anticipated leisure time as a novel antecedent of work engagement and demonstrated that anticipated resource gains are important for high work engagement.}, language = {en} } @article{BaeuerleinRiedelBakeretal.2013, author = {B{\"a}uerlein, Carina A. and Riedel, Simone S. and Baker, Jeanette and Brede, Christian and Jord{\´a}n Garrote, Ana-Laura and Chopra, Martin and Ritz, Miriam and Beilhack, Georg F. and Schulz, Stephan and Zeiser, Robert and Schlegel, Paul G. and Einsele, Hermann and Negrin, Robert S. and Beilhack, Andreas}, title = {A diagnostic window for the treatment of acute graft-versus-host disease prior to visible clinical symptoms in a murine model}, series = {BMC Medicine}, journal = {BMC Medicine}, doi = {10.1186/1741-7015-11-134}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-96797}, year = {2013}, abstract = {Background Acute graft-versus-host disease (aGVHD) poses a major limitation for broader therapeutic application of allogeneic hematopoietic cell transplantation (allo-HCT). Early diagnosis of aGVHD remains difficult and is based on clinical symptoms and histopathological evaluation of tissue biopsies. Thus, current aGVHD diagnosis is limited to patients with established disease manifestation. Therefore, for improved disease prevention it is important to develop predictive assays to identify patients at risk of developing aGVHD. Here we address whether insights into the timing of the aGVHD initiation and effector phases could allow for the detection of migrating alloreactive T cells before clinical aGVHD onset to permit for efficient therapeutic intervention. Methods Murine major histocompatibility complex (MHC) mismatched and minor histocompatibility antigen (miHAg) mismatched allo-HCT models were employed to assess the spatiotemporal distribution of donor T cells with flow cytometry and in vivo bioluminescence imaging (BLI). Daily flow cytometry analysis of peripheral blood mononuclear cells allowed us to identify migrating alloreactive T cells based on homing receptor expression profiles. Results We identified a time period of 2 weeks of massive alloreactive donor T cell migration in the blood after miHAg mismatch allo-HCT before clinical aGVHD symptoms appeared. Alloreactive T cells upregulated α4β7 integrin and P-selectin ligand during this migration phase. Consequently, targeted preemptive treatment with rapamycin, starting at the earliest detection time of alloreactive donor T cells in the peripheral blood, prevented lethal aGVHD. Conclusions Based on this data we propose a critical time frame prior to the onset of aGVHD symptoms to identify alloreactive T cells in the peripheral blood for timely and effective therapeutic intervention.}, language = {en} } @article{Schamel2017, author = {Schamel, Johannes}, title = {A demographic perspective on the spatial behaviour of hikers in mountain areas: the example of Berchtesgaden National Park}, series = {eco.mont - Journal on Protected Mountain Areas Research and Management}, volume = {9}, journal = {eco.mont - Journal on Protected Mountain Areas Research and Management}, number = {Special issue}, issn = {2073-1558}, doi = {10.1553/eco.mont-9-sis66}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172128}, pages = {66-74}, year = {2017}, abstract = {In Germany, as in many Western societies, demographic change will lead to a higher number of senior visitors to natural recreational areas and national parks. Given the high physiological requirements of many outdoor recreation activities, especially in mountain areas, it seems likely that demographic change will affect the spatial behaviour of national park visitors, which may pose a challenge to the management of these areas. With the help of GPS tracking and a standardized questionnaire (n=481), this study empirically investigates the spatial behaviour of demographic age brackets in Berchtesgaden National Park (NP) and the potential effects of demographic change on the use of the area. Cluster analysis revealed four activity types in the study area. More than half of the groups with visitors aged 60 and older belong to the activity type of Walker.}, language = {en} } @article{GesslerThomasCouillinetal.1989, author = {Gessler, Manfred and Thomas, G. H. and Couillin, P. and Junien, C. and McGillivray, B. C. and Hayden, M. and Jaschek, G. and Bruns, G. A.}, title = {A deletion map of the WAGR region on chromosome II}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-59255}, year = {1989}, abstract = {The WAGR (Wilms tumor, aniridia, genitourinary anomalies, and mental retardation) region has been assigned to chromosome 11p13 on the basis of overlapping constitutional deletions found in affected individuals. We have utilized 31 DNA probes which map to the WAGR deletion region, together with six reference loci and 13 WAGR-related deletions, to subdivide this area into 16 intervals. Specific intervals have been correlated with phenotypic features, leading to the identification of individual subregions for the aniridia and Wilms tumor loci. Delineation, by specific probes, of multiple intervals above and below the critical region and of five intervals within the overlap area provides a framework map for molecular characterization of WAGR gene loci and of deletion boundary regions.}, subject = {Biochemie}, language = {en} } @article{GrollBurdickChoetal.2019, author = {Groll, J and Burdick, J A and Cho, D-W and Derby, B and Gelinsky, M and Heilshorn, S C and J{\"u}ngst, T and Malda, J and Mironov, V A and Nakayama, K and Ovsianikov, A and Sun, W and Takeuchi, S and Yoo, J J and Woodfield, T B F}, title = {A definition of bioinks and their distinction from biomaterial inks}, series = {Biofabrication}, volume = {11}, journal = {Biofabrication}, number = {1}, doi = {10.1088/1758-5090/aaec52}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-253993}, year = {2019}, abstract = {Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384-402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.}, language = {en} } @article{SivarajanOberwinklerRolletal.2022, author = {Sivarajan, Rinu and Oberwinkler, Heike and Roll, Valeria and K{\"o}nig, Eva-Maria and Steinke, Maria and Bodem, Jochen}, title = {A defined anthocyanin mixture sourced from bilberry and black currant inhibits Measles virus and various herpesviruses}, series = {BMC Complementary Medicine and Therapies}, volume = {22}, journal = {BMC Complementary Medicine and Therapies}, doi = {10.1186/s12906-022-03661-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301423}, year = {2022}, abstract = {Background Anthocyanin-containing plant extracts and carotenoids, such as astaxanthin, have been well-known for their antiviral and anti-inflammatory activity, respectively. We hypothesised that a mixture of Ribes nigrum L. (Grossulariaceae) (common name black currant (BC)) and Vaccinium myrtillus L. (Ericaceae) (common name bilberry (BL)) extracts (BC/BL) with standardised anthocyanin content as well as single plant extracts interfered with the replication of Measles virus and Herpesviruses in vitro. Methods We treated cell cultures with BC/BL or defined single plant extracts, purified anthocyanins and astaxanthin in different concentrations and subsequently infected the cultures with the Measles virus (wild-type or vaccine strain Edmonston), Herpesvirus 1 or 8, or murine Cytomegalovirus. Then, we analysed the number of infected cells and viral infectivity and compared the data to non-treated controls. Results The BC/BL extract inhibited wild-type Measles virus replication, syncytia formation and cell-to-cell spread. This suppression was dependent on the wild-type virus-receptor-interaction since the Measles vaccine strain was unaffected by BC/BL treatment. Furthermore, the evidence was provided that the delphinidin-3-rutinoside chloride, a component of BC/BL, and purified astaxanthin, were effective anti-Measles virus compounds. Human Herpesvirus 1 and murine Cytomegalovirus replication was inhibited by BC/BL, single bilberry or black currant extracts, and the BC/BL component delphinidin-3-glucoside chloride. Additionally, we observed that BC/BL seemed to act synergistically with aciclovir. Moreover, BC/BL, the single bilberry and black currant extracts, and the BC/BL components delphinidin-3-glucoside chloride, cyanidin-3-glucoside, delphinidin-3-rutinoside chloride, and petunidin-3-galactoside inhibited human Herpesvirus 8 replication. Conclusions Our data indicate that Measles viruses and Herpesviruses are differentially susceptible to a specific BC/BL mixture, single plant extracts, purified anthocyanins and astaxanthin. These compounds might be used in the prevention of viral diseases and in addition to direct-acting antivirals, such as aciclovir.}, language = {en} } @article{WechAnkenbrandBleyetal.2022, author = {Wech, Tobias and Ankenbrand, Markus Johannes and Bley, Thorsten Alexander and Heidenreich, Julius Frederik}, title = {A data-driven semantic segmentation model for direct cardiac functional analysis based on undersampled radial MR cine series}, series = {Magnetic Resonance in Medicine}, volume = {87}, journal = {Magnetic Resonance in Medicine}, number = {2}, doi = {10.1002/mrm.29017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257616}, pages = {972-983}, year = {2022}, abstract = {Purpose Image acquisition and subsequent manual analysis of cardiac cine MRI is time-consuming. The purpose of this study was to train and evaluate a 3D artificial neural network for semantic segmentation of radially undersampled cardiac MRI to accelerate both scan time and postprocessing. Methods A database of Cartesian short-axis MR images of the heart (148,500 images, 484 examinations) was assembled from an openly accessible database and radial undersampling was simulated. A 3D U-Net architecture was pretrained for segmentation of undersampled spatiotemporal cine MRI. Transfer learning was then performed using samples from a second database, comprising 108 non-Cartesian radial cine series of the midventricular myocardium to optimize the performance for authentic data. The performance was evaluated for different levels of undersampling by the Dice similarity coefficient (DSC) with respect to reference labels, as well as by deriving ventricular volumes and myocardial masses. Results Without transfer learning, the pretrained model performed moderately on true radial data [maximum number of projections tested, P = 196; DSC = 0.87 (left ventricle), DSC = 0.76 (myocardium), and DSC =0.64 (right ventricle)]. After transfer learning with authentic data, the predictions achieved human level even for high undersampling rates (P = 33, DSC = 0.95, 0.87, and 0.93) without significant difference compared with segmentations derived from fully sampled data. Conclusion A 3D U-Net architecture can be used for semantic segmentation of radially undersampled cine acquisitions, achieving a performance comparable with human experts in fully sampled data. This approach can jointly accelerate time-consuming cine image acquisition and cumbersome manual image analysis.}, language = {en} } @article{BeerJoschinskiSastreetal.2017, author = {Beer, Katharina and Joschinski, Jens and Sastre, Alazne Arrazola and Krauss, Jochen and Helfrich-F{\"o}rster, Charlotte}, title = {A damping circadian clock drives weak oscillations in metabolism and locomotor activity of aphids (Acyrthosiphon pisum)}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {14906}, doi = {10.1038/s41598-017-15014-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170020}, year = {2017}, abstract = {Timing seasonal events, like reproduction or diapause, is crucial for the survival of many species. Global change causes phenologies worldwide to shift, which requires a mechanistic explanation of seasonal time measurement. Day length (photoperiod) is a reliable indicator of winter arrival, but it remains unclear how exactly species measure day length. A reference for time of day could be provided by a circadian clock, by an hourglass clock, or, as some newer models suggest, by a damped circadian clock. However, damping of clock outputs has so far been rarely observed. To study putative clock outputs of Acyrthosiphon pisum aphids, we raised individual nymphs on coloured artificial diet, and measured rhythms in metabolic activity in light-dark illumination cycles of 16:08 hours (LD) and constant conditions (DD). In addition, we kept individuals in a novel monitoring setup and measured locomotor activity. We found that A. pisum is day-active in LD, potentially with a bimodal distribution. In constant darkness rhythmicity of locomotor behaviour persisted in some individuals, but patterns were mostly complex with several predominant periods. Metabolic activity, on the other hand, damped quickly. A damped circadian clock, potentially driven by multiple oscillator populations, is the most likely explanation of our results.}, language = {en} } @article{ReussKieselKundeetal.2012, author = {Reuss, Heiko and Kiesel, Andrea and Kunde, Wilfried and W{\"u}hr, Peter}, title = {A cue from the unconscious - masked symbols prompt spatial anticipation}, series = {Frontiers in Psychology}, volume = {3}, journal = {Frontiers in Psychology}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123971}, pages = {397}, year = {2012}, abstract = {Anticipating where an event will occur enables us to instantaneously respond to events that occur at the expected location. Here we investigated if such spatial anticipations can be triggered by symbolic information that participants cannot consciously see. In two experiments involving a Posner cueing task and a visual search task, a central cue informed participants about the likely location of the next target stimulus. In half of the trials, this cue was rendered invisible by pattern masking. In both experiments, visible cues led to cueing effects, that is, faster responses after valid compared to invalid cues. Importantly, even masked cues caused cueing effects, though to a lesser extent. Additionally, we analyzed effects on attention that persist from one trial to the subsequent trial. We found that spatial anticipations are able to interfere with newly formed spatial anticipations and influence orienting of attention in the subsequent trial. When the preceding cue was visible, the corresponding spatial anticipation persisted to an extent that prevented a noticeable effect of masked cues. The effects of visible cues were likewise modulated by previous spatial anticipations, but were strong enough to also exert an impact on attention themselves. Altogether, the results suggest that spatial anticipations can be formed on the basis of unconscious stimuli, but that interfering influences like still active spatial anticipations can suppress this effect.}, language = {en} } @article{ReymusStawarczykWinkleretal.2020, author = {Reymus, M. and Stawarczyk, B. and Winkler, A. and Ludwig, J. and Kess, S. and Krastl, G. and Krug, R.}, title = {A critical evaluation of the material properties and clinical suitability of in-house printed and commercial tooth replicas for endodontic training}, series = {International Endodontic Journal}, volume = {53}, journal = {International Endodontic Journal}, number = {10}, doi = {10.1111/iej.13361}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218085}, pages = {1446 -- 1454}, year = {2020}, abstract = {Aim To assess the suitability of several 3D-printed resins for the manufacturing of tooth replicas for endodontic training in comparison with commercially available replicas by analysing the properties of the materials and comparing them with real teeth during endodontic training. Methodology Tooth replicas were 3D-printed using four resins (NextDent Model, NextDent C\&B, V-Print ee and Vero White Plus) and compared with two commercially available products (VDW and Smile Factory) as well as extracted human teeth. Martens hardness, indentation modulus and radiopacity were investigated on these tooth replicas. Experienced dentists evaluated the suitability of the replicas for endodontic training by comparing them with real teeth in terms of appearance, anatomy, radiopacity, similarity to dentine during access opening, canal gauging and canal instrumentation. Data were analysed using the Kolmogorov-Smirnov and Mann-Whitney U-test. Results The greatest hardness values were recorded for human dentine (P < 0.001), followed by V-Print ee and the commercial tooth replica of Smile Factory. The greatest radiopacity was associated with VOC and dentine (P < 0.001) in comparison with the other materials tested. The appearance of the in-house printed tooth replicas was subjectively evaluated by the dentists as being more realistic than the commercially available products. No differences between the replicas was detected during mechanical instrumentation of root canals. Conclusion None of the tooth replicas were able to simulate human dentine from the perspectives evaluated. V-Print ee had radiopacity comparable with dentine, but its hardness was not comparable with dentine.}, language = {en} } @article{StaigerCadotKooteretal.2012, author = {Staiger, Christine and Cadot, Sidney and Kooter, Raul and Dittrich, Marcus and M{\"u}ller, Tobias and Klau, Gunnar W. and Wessels, Lodewyk F. A.}, title = {A Critical Evaluation of Network and Pathway-Based Classifiers for Outcome Prediction in Breast Cancer}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {4}, doi = {10.1371/journal.pone.0034796}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131323}, pages = {e34796}, year = {2012}, abstract = {Recently, several classifiers that combine primary tumor data, like gene expression data, and secondary data sources, such as protein-protein interaction networks, have been proposed for predicting outcome in breast cancer. In these approaches, new composite features are typically constructed by aggregating the expression levels of several genes. The secondary data sources are employed to guide this aggregation. Although many studies claim that these approaches improve classification performance over single genes classifiers, the gain in performance is difficult to assess. This stems mainly from the fact that different breast cancer data sets and validation procedures are employed to assess the performance. Here we address these issues by employing a large cohort of six breast cancer data sets as benchmark set and by performing an unbiased evaluation of the classification accuracies of the different approaches. Contrary to previous claims, we find that composite feature classifiers do not outperform simple single genes classifiers. We investigate the effect of (1) the number of selected features; (2) the specific gene set from which features are selected; (3) the size of the training set and (4) the heterogeneity of the data set on the performance of composite feature and single genes classifiers. Strikingly, we find that randomization of secondary data sources, which destroys all biological information in these sources, does not result in a deterioration in performance of composite feature classifiers. Finally, we show that when a proper correction for gene set size is performed, the stability of single genes sets is similar to the stability of composite feature sets. Based on these results there is currently no reason to prefer prognostic classifiers based on composite features over single genes classifiers for predicting outcome in breast cancer.}, language = {en} } @article{KarakStepanenkoAddicoatetal.2022, author = {Karak, Suvendu and Stepanenko, Vladimir and Addicoat, Matthew A. and Keßler, Philipp and Moser, Simon and Beuerle, Florian and W{\"u}rthner, Frank}, title = {A Covalent Organic Framework for Cooperative Water Oxidation}, series = {Journal of the American Chemical Society}, volume = {144}, journal = {Journal of the American Chemical Society}, number = {38}, issn = {0002-7863}, doi = {10.1021/jacs.2c07282}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-287591}, pages = {17661-17670}, year = {2022}, abstract = {The future of water-derived hydrogen as the "sustainable energy source" straightaway bets on the success of the sluggish oxygen-generating half-reaction. The endeavor to emulate the natural photosystem II for efficient water oxidation has been extended across the spectrum of organic and inorganic combinations. However, the achievement has so far been restricted to homogeneous catalysts rather than their pristine heterogeneous forms. The poor structural understanding and control over the mechanistic pathway often impede the overall development. Herein, we have synthesized a highly crystalline covalent organic framework (COF) for chemical and photochemical water oxidation. The interpenetrated structure assures the catalyst stability, as the catalyst's performance remains unaltered after several cycles. This COF exhibits the highest ever accomplished catalytic activity for such an organometallic crystalline solid-state material where the rate of oxygen evolution is as high as ∼26,000 μmol L\(^{-1}\) s\(^{-1}\) (second-order rate constant k ≈ 1650 μmol L s\(^{-1}\) g\(^{-2}\)). The catalyst also proves its exceptional activity (k ≈ 1600 μmol L s\(^{-1}\) g\(^{-2}\)) during light-driven water oxidation under very dilute conditions. The cooperative interaction between metal centers in the crystalline network offers 20-30-fold superior activity during chemical as well as photocatalytic water oxidation as compared to its amorphous polymeric counterpart.}, language = {en} } @article{JainVelezAcostaetal.2012, author = {Jain, M. and V{\´e}lez, J. I. and Acosta, M. T. and Palacio, L. G. and Balog, J. and Roessler, E. and Pineda, D. and Londo{\~n}o, A. C. and Palacio, J. D. and Arbelaez, A. and Lopera, F. and Elia, J. and Hakonarson, H. and Seitz, C. and Freitag, C. M. and Palmason, H. and Meyer, J. and Romanos, M. and Walitza, S. and Hemminger, U. and Warnke, A. and Romanos, J. and Renner, T. and Jacob, C. and Lesch, K.-P. and Swanson, J. and Castellanos, F. X. and Bailey-Wilson, J. E. and Arcos-Burgos, M. and Muenke, M.}, title = {A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD}, series = {Molecular Psychiatry}, volume = {17}, journal = {Molecular Psychiatry}, doi = {10.1038/mp.2011.59}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125128}, pages = {741-747}, year = {2012}, abstract = {In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10-8) and 11q and 17p (P<1 × 10-6). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.}, language = {en} } @article{FakhriLatifi2021, author = {Fakhri, Seyed Arvin and Latifi, Hooman}, title = {A consumer grade UAV-based framework to estimate structural attributes of coppice and high oak forest stands in semi-arid regions}, series = {Remote Sensing}, volume = {13}, journal = {Remote Sensing}, number = {21}, issn = {2072-4292}, doi = {10.3390/rs13214367}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248469}, year = {2021}, abstract = {Semi-arid tree covers, in both high and coppice growth forms, play an essential role in protecting water and soil resources and provides multiple ecosystem services across fragile ecosystems. Thus, they require continuous inventories. Quantification of forest structure in these tree covers provides important measures for their management and biodiversity conservation. We present a framework, based on consumer-grade UAV photogrammetry, to separately estimate primary variables of tree height (H) and crown area (A) across diverse coppice and high stands dominated by Quercus brantii Lindl. along the latitudinal gradient of Zagros mountains of western Iran. Then, multivariate linear regressions were parametrized with H and A to estimate the diameter at breast height (DBH) of high trees because of its importance to accelerate the existing practical DBH inventories across Zagros Forests. The estimated variables were finally applied to a model tree aboveground biomass (AGB) for both vegetative growth forms by local allometric equations and Random Forest models. In each step, the estimated variables were evaluated against the field reference values, indicating practically high accuracies reaching root mean square error (RMSE) of 0.68 m and 4.74 cm for H and DBH, as well as relative RMSE < 10\% for AGB estimates. The results generally suggest an effective framework for single tree-based attribute estimation over mountainous, semi-arid coppice, and high stands.}, language = {en} } @article{HirschKraussOpferkuchetal.2016, author = {Hirsch, Martin and Krauss, Manuel E. and Opferkuch, Toby and Porod, Werner and Staub, Florian}, title = {A constrained supersymmetric left-right model}, series = {JOURNAL OF HIGH ENERGY PHYSICS}, volume = {03}, journal = {JOURNAL OF HIGH ENERGY PHYSICS}, number = {009}, doi = {10.1007/JHEP03(2016)009}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168016}, year = {2016}, abstract = {We present a supersymmetric left-right model which predicts gauge coupling unification close to the string scale and extra vector bosons at the TeV scale. The subtleties in constructing a model which is in agreement with the measured quark masses and mixing for such a low left-right breaking scale are discussed. It is shown that in the constrained version of this model radiative breaking of the gauge symmetries is possible and a SM-like Higgs is obtained. Additional CP-even scalars of a similar mass or even much lighter are possible. The expected mass hierarchies for the supersymmetric states differ clearly from those of the constrained MSSM. In particular, the lightest down-type squark, which is a mixture of the sbottom and extra vector-like states, is always lighter than the stop. We also comment on the model's capability to explain current anomalies observed at the LHC.}, language = {en} } @article{HaackHauckKlingenbergetal.2021, author = {Haack, J. and Hauck, C. and Klingenberg, C. and Pirner, M. and Warnecke, S.}, title = {A Consistent BGK Model with Velocity-Dependent Collision Frequency for Gas Mixtures}, series = {Journal of Statistical Physics}, volume = {184}, journal = {Journal of Statistical Physics}, number = {3}, issn = {1572-9613}, doi = {10.1007/s10955-021-02821-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-269146}, pages = {31}, year = {2021}, abstract = {We derive a multi-species BGK model with velocity-dependent collision frequency for a non-reactive, multi-component gas mixture. The model is derived by minimizing a weighted entropy under the constraint that the number of particles of each species, total momentum, and total energy are conserved. We prove that this minimization problem admits a unique solution for very general collision frequencies. Moreover, we prove that the model satisfies an H-Theorem and characterize the form of equilibrium.}, language = {en} } @article{LibreSeisslerGuerreroetal.2021, author = {Libre, Camille and Seissler, Tanja and Guerrero, Santiago and Batisse, Julien and Verriez, C{\´e}dric and Stupfler, Benjamin and Gilmer, Orian and Cabrera-Rodriguez, Romina and Weber, Melanie M. and Valenzuela-Fernandez, Agustin and Cimarelli, Andrea and Etienne, Lucie and Marquet, Roland and Paillart, Jean-Christophe}, title = {A conserved uORF regulates APOBEC3G translation and is targeted by HIV-1 Vif protein to repress the antiviral factor}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {1}, issn = {2227-9059}, doi = {10.3390/biomedicines10010013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252147}, year = {2021}, abstract = {The HIV-1 Vif protein is essential for viral fitness and pathogenicity. Vif decreases expression of cellular restriction factors APOBEC3G (A3G), A3F, A3D and A3H, which inhibit HIV-1 replication by inducing hypermutation during reverse transcription. Vif counteracts A3G at several levels (transcription, translation, and protein degradation) that altogether reduce the levels of A3G in cells and prevent its incorporation into viral particles. How Vif affects A3G translation remains unclear. Here, we uncovered the importance of a short conserved uORF (upstream ORF) located within two critical stem-loop structures of the 5′ untranslated region (5′-UTR) of A3G mRNA for this process. A3G translation occurs through a combination of leaky scanning and translation re-initiation and the presence of an intact uORF decreases the extent of global A3G translation under normal conditions. Interestingly, the uORF is also absolutely required for Vif-mediated translation inhibition and redirection of A3G mRNA into stress granules. Overall, we discovered that A3G translation is regulated by a small uORF conserved in the human population and that Vif uses this specific feature to repress its translation.}, language = {en} } @article{FroehlichPapenfortBergeretal.2012, author = {Fr{\"o}hlich, Kathrin S. and Papenfort, Kai and Berger, Allison A. and Vogel, J{\"o}rg}, title = {A conserved RpoS-dependent small RNA controls the synthesis of major porin OmpD}, series = {Nucleic Acids Research}, volume = {40}, journal = {Nucleic Acids Research}, number = {8}, doi = {10.1093/nar/gkr1156}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-134230}, pages = {3623-3640}, year = {2012}, abstract = {A remarkable feature of many small non-coding RNAs (sRNAs) of Escherichia coli and Salmonella is their accumulation in the stationary phase of bacterial growth. Several stress response regulators and sigma factors have been reported to direct the transcription of stationary phase-specific sRNAs, but a widely conserved sRNA gene that is controlled by the major stationary phase and stress sigma factor, Sigma(S) (RpoS), has remained elusive. We have studied in Salmonella the conserved SdsR sRNA, previously known as RyeB, one of the most abundant stationary phase-specific sRNAs in E. coli. Alignments of the sdsR promoter region and genetic analysis strongly suggest that this sRNA gene is selectively transcribed by Sigma(S). We show that SdsR down-regulates the synthesis of the major Salmonella porin OmpD by Hfq-dependent base pairing; SdsR thus represents the fourth sRNA to regulate this major outer membrane porin. Similar to the InvR, MicC and RybB sRNAs, SdsR recognizes the ompD mRNA in the coding sequence, suggesting that this mRNA may be primarily targeted downstream of the start codon. The SdsR-binding site in ompD was localized by 3'-RACE, an experimental approach that promises to be of use in predicting other sRNA-target interactions in bacteria.}, language = {en} } @article{SanderXuEilersetal.2017, author = {Sander, Bodo and Xu, Wenshan and Eilers, Martin and Popov, Nikita and Lorenz, Sonja}, title = {A conformational switch regulates the ubiquitin ligase HUWE1}, series = {eLife}, volume = {6}, journal = {eLife}, doi = {10.7554/eLife.21036}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171862}, year = {2017}, abstract = {The human ubiquitin ligase HUWE1 has key roles in tumorigenesis, yet it is unkown how its activity is regulated. We present the crystal structure of a C-terminal part of HUWE1, including the catalytic domain, and reveal an asymmetric auto-inhibited dimer. We show that HUWE1 dimerizes in solution and self-associates in cells, and that both occurs through the crystallographic dimer interface. We demonstrate that HUWE1 is inhibited in cells and that it can be activated by disruption of the dimer interface. We identify a conserved segment in HUWE1 that counteracts dimer formation by associating with the dimerization region intramolecularly. Our studies reveal, intriguingly, that the tumor suppressor p14ARF binds to this segment and may thus shift the conformational equilibrium of HUWE1 toward the inactive state. We propose a model, in which the activity of HUWE1 underlies conformational control in response to physiological cues—a mechanism that may be exploited for cancer therapy.}, language = {en} } @article{PetersFohmannRudeletal.2021, author = {Peters, Simon and Fohmann, Ingo and Rudel, Thomas and Schubert-Unkmeir, Alexandra}, title = {A Comprehensive Review on the Interplay between Neisseria spp. and Host Sphingolipid Metabolites}, series = {Cells}, volume = {10}, journal = {Cells}, number = {11}, issn = {2073-4409}, doi = {10.3390/cells10113201}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250203}, year = {2021}, abstract = {Sphingolipids represent a class of structural related lipids involved in membrane biology and various cellular processes including cell growth, apoptosis, inflammation and migration. Over the past decade, sphingolipids have become the focus of intensive studies regarding their involvement in infectious diseases. Pathogens can manipulate the sphingolipid metabolism resulting in cell membrane reorganization and receptor recruitment to facilitate their entry. They may recruit specific host sphingolipid metabolites to establish a favorable niche for intracellular survival and proliferation. In contrast, some sphingolipid metabolites can also act as a first line defense against bacteria based on their antimicrobial activity. In this review, we will focus on the strategies employed by pathogenic Neisseria spp. to modulate the sphingolipid metabolism and hijack the sphingolipid balance in the host to promote cellular colonization, invasion and intracellular survival. Novel techniques and innovative approaches will be highlighted that allow imaging of sphingolipid derivatives in the host cell as well as in the pathogen.}, language = {en} } @article{PaulsBlechschmidtFrantzmannetal.2018, author = {Pauls, Dennis and Blechschmidt, Christine and Frantzmann, Felix and el Jundi, Basil and Selcho, Mareike}, title = {A comprehensive anatomical map of the peripheral octopaminergic/tyraminergic system of Drosophila melanogaster}, series = {Scientific Reports}, volume = {8}, journal = {Scientific Reports}, number = {15314}, doi = {10.1038/s41598-018-33686-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177412}, year = {2018}, abstract = {The modulation of an animal's behavior through external sensory stimuli, previous experience and its internal state is crucial to survive in a constantly changing environment. In most insects, octopamine (OA) and its precursor tyramine (TA) modulate a variety of physiological processes and behaviors by shifting the organism from a relaxed or dormant condition to a responsive, excited and alerted state. Even though OA/TA neurons of the central brain are described on single cell level in Drosophila melanogaster, the periphery was largely omitted from anatomical studies. Given that OA/TA is involved in behaviors like feeding, flying and locomotion, which highly depend on a variety of peripheral organs, it is necessary to study the peripheral connections of these neurons to get a complete picture of the OA/TA circuitry. We here describe the anatomy of this aminergic system in relation to peripheral tissues of the entire fly. OA/TA neurons arborize onto skeletal muscles all over the body and innervate reproductive organs, the heart, the corpora allata, and sensory organs in the antennae, legs, wings and halteres underlining their relevance in modulating complex behaviors.}, language = {en} }