@article{RadchukRajivPotokinaetal.2019, author = {Radchuk, Volodymyr and Rajiv, Sharma and Potokina, Elena and Radchuk, Ruslana and Weier, Diana and Munz, Eberhard and Schreiber, Miriam and Mascher, Martin and Stein, Nils and Wicker, Thomas and Kilian, Benjamin and Borisjuk, Ljudmilla}, title = {The highly divergent \(Jekyll\) genes, required for sexual reproduction, are lineage specific for the related grass tribes Triticeae and Bromeae}, series = {Plant Journal}, volume = {98}, journal = {Plant Journal}, number = {6}, doi = {10.1111/tpj.14363}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224769}, pages = {961-974}, year = {2019}, abstract = {Phylogenetically related groups of species contain lineage-specific genes that exhibit no sequence similarity to any genes outside the lineage. We describe here that the Jekyll gene, required for sexual reproduction, exists in two much diverged allelic variants, Jek1 and Jek3. Despite low similarity, the Jek1 and Jek3 proteins share identical signal peptides, conserved cysteine positions and direct repeats. The Jek1/Jek3 sequences are located at the same chromosomal locus and inherited in a monogenic Mendelian fashion. Jek3 has a similar expression as Jek1 and complements the Jek1 function in Jek1-deficient plants. Jek1 and Jek3 allelic variants were almost equally distributed in a collection of 485 wild and domesticated barley accessions. All domesticated barleys harboring the Jek1 allele belong to single haplotype J1-H1 indicating a genetic bottleneck during domestication. Domesticated barleys harboring the Jek3 allele consisted of three haplotypes. Jekyll-like sequences were found only in species of the closely related tribes Bromeae and Triticeae but not in other Poaceae. Non-invasive magnetic resonance imaging revealed intrinsic grain structure in Triticeae and Bromeae, associated with the Jekyll function. The emergence of Jekyll suggests its role in the separation of the Bromeae and Triticeae lineages within the Poaceae and identifies the Jekyll genes as lineage-specific.}, language = {en} } @article{ReinermannGessnerAsametal.2019, author = {Reinermann, Sophie and Gessner, Ursula and Asam, Sarah and Kuenzer, Claudia and Dech, Stefan}, title = {The Effect of Droughts on Vegetation Condition in Germany: An Analysis Based on Two Decades of Satellite Earth Observation Time Series and Crop Yield Statistics}, series = {Remote Sensing}, volume = {11}, journal = {Remote Sensing}, number = {15}, doi = {10.3390/rs11151783}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225165}, pages = {1783, 1-21}, year = {2019}, abstract = {Central Europe experienced several droughts in the recent past, such as in the year 2018, which was characterized by extremely low rainfall rates and high temperatures, resulting in substantial agricultural yield losses. Time series of satellite earth observation data enable the characterization of past drought events over large temporal and spatial scales. Within this study, Moderate Resolution Spectroradiometer (MODIS) Enhanced Vegetation Index (EVI) (MOD13Q1) 250 m time series were investigated for the vegetation periods of 2000 to 2018. The spatial and temporal development of vegetation in 2018 was compared to other dry and hot years in Europe, like the drought year 2003. Temporal and spatial inter- and intra-annual patterns of EVI anomalies were analyzed for all of Germany and for its cropland, forest, and grassland areas individually. While vegetation development in spring 2018 was above average, the summer months of 2018 showed negative anomalies in a similar magnitude as in 2003, which was particularly apparent within grassland and cropland areas in Germany. In contrast, the year 2003 showed negative anomalies during the entire growing season. The spatial pattern of vegetation status in 2018 showed high regional variation, with north-eastern Germany mainly affected in June, north-western parts in July, and western Germany in August. The temporal pattern of satellite-derived EVI deviances within the study period 2000-2018 were in good agreement with crop yield statistics for Germany. The study shows that the EVI deviation of the summer months of 2018 were among the most extreme in the study period compared to other years. The spatial pattern and temporal development of vegetation condition between the drought years differ.}, language = {en} } @article{SchlottmannSchickeKruegeretal.2019, author = {Schlottmann, Elisabeth and Schicke, David and Kr{\"u}ger, Felix and Lingnau, Benjamin and Schneider, Christian and H{\"o}fling, Sven and L{\"u}dge, Kathy and Porte, Xavier and Reitzenstein, Stephan}, title = {Stochastic polarization switching induced by optical injection in bimodal quantum-dot micropillar lasers}, series = {Optics Express}, volume = {27}, journal = {Optics Express}, number = {20}, doi = {10.1364/OE.27.028816}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228603}, pages = {28816-28831}, year = {2019}, abstract = {Mutual coupling and injection locking of semiconductor lasers is of great interest in non-linear dynamics and its applications for instance in secure data communication and photonic reservoir computing. Despite its importance, it has hardly been studied in microlasers operating at mu W light levels. In this context, vertically emitting quantum dot micropillar lasers are of high interest. Usually, their light emission is bimodal, and the gain competition of the associated linearly polarized fundamental emission modes results in complex switching dynamics. We report on selective optical injection into either one of the two fundamental mode components of a bimodal micropillar laser. Both modes can lock to the master laser and influence the non-injected mode by reducing the available gain. We demonstrate that the switching dynamics can be tailored externally via optical injection in very good agreement with our theory based on semi-classical rate equations. (C) 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement}, language = {en} } @article{RadevaWalterStachetal.2019, author = {Radeva, Mariya Y. and Walter, Elias and Stach, Ramona Alexandra and Yazdi, Amir S. and Schlegel, Nicolas and Sarig, Ofer and Sprecher, Eli and Waschke, Jens}, title = {ST18 Enhances PV-IgG-Induced Loss of Keratinocyte Cohesion in Parallel to Increased ERK Activation}, series = {Frontiers in Immunology}, volume = {10}, journal = {Frontiers in Immunology}, doi = {10.3389/fimmu.2019.00770}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224910}, pages = {770, 1-11}, year = {2019}, abstract = {Pemphigus is an autoimmune blistering disease targeting the desmosomal proteins desmoglein (Dsg) 1 and Dsg3. Recently, a genetic variant of the Suppression of tumorigenicity 18 (ST18) promoter was reported to cause ST18 up-regulation, associated with pemphigus vulgaris (PV)-IgG-mediated increase in cytokine secretion and more prominent loss of keratinocyte cohesion. Here we tested the effects of PV-IgG and the pathogenic pemphigus mouse anti-Dsg3 antibody AK23 on cytokine secretion and ERK activity in human keratinocytes dependent on ST18 expression. Without ST18 overexpression, both PV-IgG and AK23 induced loss of keratinocyte cohesion which was accompanied by prominent fragmentation of Dsg3 immunostaining along cell borders. In contrast, release of pro-inflammatory cytokines such as IL-1 alpha, IL-6, TNF alpha, and IFN-gamma was not altered significantly in both HaCaT and primary NHEK cells. These experiments indicate that cytokine expression is not strictly required for loss of keratinocyte cohesion. Upon ST18 overexpression, fragmentation of cell monolayers increased significantly in response to autoantibody incubation. Furthermore, production of IL-1 alpha and IL-6 was enhanced in some experiments but not in others whereas release of TNF-alpha dropped significantly upon PV-IgG application in both EV- and ST18-transfected HaCaT cells. Additionally, in NHEK, application of PV-IgG but not of AK23 significantly increased ERK activity. In contrast, ST18 overexpression in HaCaT cells augmented ERK activation in response to both c-IgG and AK23 but not PV-IgG. Because inhibition of ERK by U0126 abolished PV-IgG- and AK23-induced loss of cell cohesion in ST18-expressing cells, we conclude that autoantibody-induced ERK activation was relevant in this scenario. In summary, similar to the situation in PV patients carrying ST18 polymorphism, overexpression of ST18 enhanced keratinocyte susceptibility to autoantibody-induced loss of cell adhesion, which may be caused in part by enhanced ERK signaling.}, language = {en} } @article{ThoelkenThammErbacheretal.2019, author = {Th{\"o}lken, Clemens and Thamm, Markus and Erbacher, Christoph and Lechner, Marcus}, title = {Sequence and structural properties of circular RNAs in the brain of nurse and forager honeybees (Apis mellifera)}, series = {BMC Genomics}, volume = {20}, journal = {BMC Genomics}, doi = {10.1186/s12864-018-5402-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-241302}, year = {2019}, abstract = {Background The honeybee (Apis mellifera) represents a model organism for social insects displaying behavioral plasticity. This is reflected by an age-dependent task allocation. The most protruding tasks are performed by young nurse bees and older forager bees that take care of the brood inside the hive and collect food from outside the hive, respectively. The molecular mechanism leading to the transition from nurse bees to foragers is currently under intense research. Circular RNAs, however, were not considered in this context so far. As of today, this group of non-coding RNAs was only known to exist in two other insects, Drosophila melanogaster and Bombyx mori. Here we complement the state of circular RNA research with the first characterization in a social insect. Results We identified numerous circular RNAs in the brain of A. mellifera nurse bees and forager bees using RNA-Seq with exonuclease enrichment. Presence and circularity were verified for the most abundant representatives. Back-splicing in honeybee occurs further towards the end of transcripts and in transcripts with a high number of exons. The occurrence of circularized exons is correlated with length and CpG-content of their flanking introns. The latter coincides with increased DNA-methylation in the respective loci. For two prominent circular RNAs the abundance in worker bee brains was quantified in TaqMan assays. In line with previous findings of circular RNAs in Drosophila, circAmrsmep2 accumulates with increasing age of the insect. In contrast, the levels of circAmrad appear age-independent and correlate with the bee's task. Its parental gene is related to amnesia-resistant memory. Conclusions We provide the first characterization of circRNAs in a social insect. Many of the RNAs identified here show homologies to circular RNAs found in Drosophila and Bombyx, indicating that circular RNAs are a common feature among insects. We find that exon circularization is correlated to DNA-methylation at the flanking introns. The levels of circAmrad suggest a task-dependent abundance that is decoupled from age. Moreover, a GO term analysis shows an enrichment of task-related functions. We conclude that circular RNAs could be relevant for task allocation in honeybee and should be investigated further in this context.}, language = {en} } @article{GrebinykPrylutskaGrebinyketal.2019, author = {Grebinyk, Anna and Prylutska, Svitlana and Grebinyk, Sergii and Prylutskyy, Yuriy and Ritter, Uwe and Matyshevska, Olga and Dandekar, Thomas and Frohme, Marcus}, title = {Complexation with C\(_{60}\) fullerene increases doxorubicin efficiency against leukemic cells in vitro}, series = {Nanoscale Research Letters}, volume = {14}, journal = {Nanoscale Research Letters}, number = {61}, doi = {10.1186/s11671-019-2894-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228257}, year = {2019}, abstract = {Conventional anticancer chemotherapy is limited because of severe side effects as well as a quickly evolving multidrug resistance of the tumor cells. To address this problem, we have explored a C\(_{60}\) fullerene-based nanosized system as a carrier for anticancer drugs for an optimized drug delivery to leukemic cells.Here, we studied the physicochemical properties and anticancer activity of C\(_{60}\) fullerene noncovalent complexes with the commonly used anticancer drug doxorubicin. C\(_{60}\)-Doxorubicin complexes in a ratio 1:1 and 2:1 were characterized with UV/Vis spectrometry, dynamic light scattering, and high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The obtained analytical data indicated that the 140-nm complexes were stable and could be used for biological applications. In leukemic cell lines (CCRF-CEM, Jurkat, THP1 and Molt-16), the nanocomplexes revealed 3.5 higher cytotoxic potential in comparison with the free drug in a range of nanomolar concentrations. Also, the intracellular drug's level evidenced C\(_{60}\) fullerene considerable nanocarrier function.The results of this study indicated that C\(_{60}\) fullerene-based delivery nanocomplexes had a potential value for optimization of doxorubicin efficiency against leukemic cells.}, language = {en} } @article{RichterHuettmannRekowskietal.2019, author = {Richter, Julia and H{\"u}ttmann, Andreas and Rekowski, Jan and Schmitz, Christine and G{\"a}rtner, Selina and Rosenwald, Andreas and Hansmann, Martin-Leo and Hartmann, Sylvia and M{\"o}ller, Peter and Wacker, Hans-Heinrich and Feller, Alfred and Thorns, Christoph and M{\"u}ller, Stefan and D{\"u}hrsen, Ulrich and Klapper, Wolfram}, title = {Molecular characteristics of diffuse large B-cell lymphoma in the Positron Emission Tomography-Guided Therapy of Aggressive Non-Hodgkin lymphomas (PETAL) trial: correlation with interim PET and outcome}, series = {Blood Cancer Journal}, volume = {9}, journal = {Blood Cancer Journal}, doi = {10.1038/s41408-019-0230-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226185}, pages = {67}, year = {2019}, abstract = {No abstract available}, language = {en} } @article{AkshatAaboudAadetal.2019, author = {Akshat, Puri and Aaboud, M. and Aad, G. and Abbott, B. and Abdinov, O. and Abeloos, B. and Abhayasinghe, D. K. and Abidi, S. H. and Abou Zeid, O. S. and Abraham, N. L. and Abramowicz, H. and Abreu, H. and Abulaiti, Y. and Acharya, B. S. and Adachi, S. and Adam, L. and Adamczyk, L. and Adelman, J. and Adersberger, M. and Adiguzel, A. and Adye, T. and Affolder, A. A. and Afik, Y. and Agheorghiesei, C. and Aguilar-Saavedra, J. A. and Ahmadov, F. and Aiellil, G. and Akatsuka, S. and Akesson, T. P. A. and Akilli, E. and Akimov, A. V. and Alberghi, G. L. and Albert, J. and Albicocco, P. and Alconada Verzini, M. J. and Alderweireld, S. and Aleksa, M. and Aleksandrov, I. N. and Alexa, C. and Alexopoulos, T. and Alhroob, M. and Ali, B. and Alimonti, G. and Alison, J. and Andre, S. P. and Allaire, C. and Allbrooke, B. M. M. and Allen, B. W. and Allport, P. P. and Aloisio, A. and Alonso, A. and Alonso, F. and Alpigiani, C. and Alshehri, A. A. and Alstaty, M. I. and Alvarez, Gonzalez B. and Alvarez Piqueras, D. and Alviggi, M. G. and Amadio, B. T. and Amaral, Coutinho, Y. and Ambler, A. and Ambroz, L. and Amelung, C. and Amidei, D. and Amor Dos Santos, S. P. and Amoroso, S. and Amrouche, C. S. and Anastopoulos, C. and Ancu, L. S. and Andari, N. and Andeen, T. and Anders, C. F. and Anders, J. K. and Anderson, K. J. and Andreazza, A. and Andrei, V. and et al,}, title = {Measurement of angular and momentum distributions of charged particles within and around jets in Pb plus Pb and pp collisions at root s(NN)=5.02 TeV with ATLAS at the LHC : XXVIIth International Conference on Ultrarelativistic Nucleus-Nucleus Collisions (Quark Matter 2018)}, series = {Nuclear Physics A}, volume = {982}, journal = {Nuclear Physics A}, number = {2}, doi = {10.1016/j.nuclphysa.2018.09.021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224703}, pages = {177-179}, year = {2019}, abstract = {Studies of the fragmentation of jets into charged particles in heavy-ion collisions can help in understanding the mechanism of jet quenching by the hot and dense QCD matter created in such collisions, the quark-gluon plasma. These proceedings present a measurement of the angular distribution of charged particles around the jet axis in root s(NN) = 5.02 TeV Pb+Pb and pp collisions, done using the ATLAS detector at the LHC. The measurement is performed inside jets reconstructed with the anti-k(t) algorithm with radius parameter R = 0.4, and is extended to regions outside the jet cone. Results are presented as a function of Pb+Pb collision centrality, and both jet and charged-particle transverse momenta.}, language = {en} } @article{RademakerSchuberthDijkstra2019, author = {Rademaker, Manuel E. and Schuberth, Florian and Dijkstra, Theo K.}, title = {Measurement error correlation within blocks of indicators in consistent partial least squares : Issues and remedies}, series = {Internet Research}, volume = {29}, journal = {Internet Research}, number = {3}, doi = {10.1108/IntR-12-2017-0525}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224901}, pages = {448-463}, year = {2019}, abstract = {Purpose The purpose of this paper is to enhance consistent partial least squares (PLSc) to yield consistent parameter estimates for population models whose indicator blocks contain a subset of correlated measurement errors. Design/methodology/approach Correction for attenuation as originally applied by PLSc is modified to include a priori assumptions on the structure of the measurement error correlations within blocks of indicators. To assess the efficacy of the modification, a Monte Carlo simulation is conducted. Findings In the presence of population measurement error correlation, estimated parameter bias is generally small for original and modified PLSc, with the latter outperforming the former for large sample sizes. In terms of the root mean squared error, the results are virtually identical for both original and modified PLSc. Only for relatively large sample sizes, high population measurement error correlation, and low population composite reliability are the increased standard errors associated with the modification outweighed by a smaller bias. These findings are regarded as initial evidence that original PLSc is comparatively robust with respect to misspecification of the structure of measurement error correlations within blocks of indicators. Originality/value Introducing and investigating a new approach to address measurement error correlation within blocks of indicators in PLSc, this paper contributes to the ongoing development and assessment of recent advancements in partial least squares path modeling.}, language = {en} } @article{RuizDiefenbacherNelsonetal.2019, author = {Ruiz, E. Josue and Diefenbacher, Markus E. and Nelson, Jessica K. and Sancho, Rocio and Pucci, Fabio and Chakraborty, Atanu and Moreno, Paula and Annibaldi, Alessandro and Liccardi, Gianmaria and Encheva, Vesela and Mitter, Richard and Rosenfeldt, Mathias and Snijders, Ambrosius P. and Meier, Pascal and Calzado, Marco A. and Behrens, Axel}, title = {LUBAC determines chemotherapy resistance in squamous cell lung cancer}, series = {Journal of Experimental Medicine}, volume = {216}, journal = {Journal of Experimental Medicine}, number = {2}, doi = {10.1084/jem.20180742}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227146}, pages = {450-465}, year = {2019}, abstract = {Lung squamous cell carcinoma (LSCC) and adenocarcinoma (LADC) are the most common lung cancer subtypes. Molecular targeted treatments have improved LADC patient survival but are largely ineffective in LSCC. The tumor suppressor FBW7 is commonly mutated or down-regulated in human LSCC, and oncogenic KRasG12D activation combined with Fbxw7 inactivation in mice (KF model) caused both LSCC and LADC. Lineage-tracing experiments showed that CC10(+), but not basal, cells are the cells of origin of LSCC in KF mice. KF LSCC tumors recapitulated human LSCC resistance to cisplatin-based chemotherapy, and we identified LUBAC-mediated NF-kappa B signaling as a determinant of chemotherapy resistance in human and mouse. Inhibition of NF-kappa B activation using TAK1 or LUBAC inhibitors resensitized LSCC tumors to cisplatin, suggesting a future avenue for LSCC patient treatment.}, language = {en} } @article{RobindeWreedeWolschkeetal.2019, author = {Robin, Marie and de Wreede, Liesbeth C. and Wolschke, Christine and Schetelig, Johannes and Eikema, Diderik-Jan and Van Lint, Maria Teresa and Knelange, Nina Simone and Beelen, Dietrich and Brecht, Arne and Niederwieser, Dietger and Vitek, Antonin and Bethge, Wolfgang and Arnold, Renate and Finke, J{\"u}rgen and Volin, Liisa and Yakoub-Agha, Ibrahim and Nagler, Arnon and Poir{\´e}, Xavier and Einsele, Hermann and Chevallier, Patrice and Holler, Ernst and Ljungman, Per and Robinson, Stephen and Radujkovic, Alekxandar and McLornan, Donal and Chalandon, Yves and Kr{\"o}ger, Nicolaus}, title = {Long-term outcome after allogeneic hematopoietic cell transplantation for myelofibrosis}, series = {Haematologica}, volume = {104}, journal = {Haematologica}, number = {9}, doi = {10.3324/haematol.2018.205211}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226386}, pages = {1782-1788}, year = {2019}, abstract = {Allogeneic hematopoietic stem cell transplant remains the only curative treatment for myelofibrosis. Most post-transplantation events Aoccur during the first two years and hence we aimed to analyze the outcome of 2-year disease-free survivors. A total of 1055 patients with myelofibrosis transplanted between 1995 and 2014 and registered in the registry of the European Society for Blood and Marrow Transplantation were included. Survival was compared to the matched general population to determine excess mortality and the risk factors that are associated. In the 2-year survivors, disease-free survival was 64\% (60-68\%) and overall survival was 74\% (71-78\%) at ten years; results were better in younger individuals and in women. Excess mortality was 14\% (8-21\%) in patients aged <45 years and 33\% (13-53\%) in patients aged >= 65 years. The main cause of death was relapse of the primary disease. Graft-versus-host disease (GvHD) before two years decreased the risk of relapse. Multivariable analysis of excess mortality showed that age, male sex recipient, secondary myelofibrosis and no GvHD disease prior to the 2-year landmark increased the risk of excess mortality. This is the largest study to date analyzing long-term outcome in patients with myelofibrosis undergoing transplant. Overall it shows a good survival in patients alive and in remission at two years. However, the occurrence of late complications, including late relapses, infectious complications and secondary malignancies, highlights the importance of screening and monitoring of long-term survivors.}, subject = {Midollo-Osseo}, language = {en} } @article{RadeloffRadeloffTiradoetal.2019, author = {Radeloff, Katrin and Radeloff, Andreas and Tirado, Mario Ramos and Scherzad, Agmal and Hagen, Rudolf and Kleinsasser, Norbert H. and Hackenberg, Stephan}, title = {Long-Term Impact of Zinc Oxide Nanoparticles on Differentiation and Cytokine Secretion of Human Adipose-Derived Stromal Cells}, series = {Materials}, volume = {12}, journal = {Materials}, number = {1823}, doi = {10.3390/ma12111823}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224779}, pages = {1-14}, year = {2019}, abstract = {Zinc oxide nanoparticles (ZnO-NPs) are widely utilized, for example in manufacturing paints and in the cosmetic industry. In addition, there is raising interest in the application of NPs in stem cell research. However, cytotoxic, genotoxic and pro-inflammatory effects were shown for NPs. The aim of this study was to evaluate the impact of ZnO-NPs on cytokine secretion and differentiation properties of human adipose tissue-derived stromal cells (ASCs). Human ASCs were exposed to the subtoxic concentration of 0.2 mu g/mL ZnO-NPs for 24 h. After four weeks of cultivation, adipogenic and osteogenic differentiation procedures were performed. The multi-differentiation potential was confirmed histologically and using polymerase chain reaction (PCR). In addition, the gene expression of IL-6, IL-8, vascular endothelial growth factor (VEGF) and caspase 3 was analyzed. Over the course of four weeks after ZnO-NPs exposure, no significant differences were detected in the gene expression of IL-6, IL-8, VEGF and caspase 3 compared to non-exposed cells. The differentiation was also not affected by the ZnO-NPs. These findings underline the fact, that functionality of ASCs is likely to be unaffected by ZnO-NPs, despite a long-term disposition of NPs in the cells, supposing that the starting concentration was safely in the non-toxic range. This might provide important information for single-use nanomedical applications of ZnO-NPs.}, language = {en} } @article{RudeliusRosenfeldtLeichetal.2019, author = {Rudelius, Martina and Rosenfeldt, Mathias Tillmann and Leich, Ellen and Rauert-Wunderlich, Hilka and Solimando, Antonio Giovanni and Ott, German and Rosenwald, Andreas and Beilhack, Andreas}, title = {Inhibition of focal adhesion kinase overcomes resistance of mantle cell lymphoma to ibrutinib in the bone marrow microenvironment}, series = {Haematologica}, volume = {103}, journal = {Haematologica}, number = {1}, doi = {10.3324/haematol.2017.177162}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227117}, pages = {116-125}, year = {2019}, abstract = {Mantle cell lymphoma and other lymphoma subtypes often spread to the bone marrow, and stromal interactions mediated by focal adhesion kinase frequently enhance survival and drug resistance of the lymphoma cells. To study the role of focal adhesion kinase in mantle cell lymphoma, immunohistochemistry of primary cases and functional analysis of mantle cell lymphoma cell lines and primary mantle cell lymphoma cells co-cultured with bone marrow stromal cells (BMSC) using small molecule inhibitors and RNAi-based focal adhesion kinase silencing was performed. We showed that focal adhesion kinase is highly expressed in bone marrow infiltrates of mantle cell lymphoma and in mantle cell lymphoma cell lines. Stroma-mediated activation of focal adhesion kinase led to activation of multiple kinases (AKT, p42/44 and NF-kappa B), that are important for prosurvival and proliferation signaling. Interestingly, RNAi-based focal adhesion kinase silencing or inhibition with small molecule inhibitors (FAKi) resulted in blockage of targeted cell invasion and induced apoptosis by inactivation of multiple signaling cascades, including the classic and alternative NF-kappa B pathway. In addition, the combined treatment of ibrutinib and FAKi was highly synergistic, and ibrutinib resistance of mantle cell lymphoma could be overcome. These data demonstrate that focal adhesion kinase is important for stroma-mediated survival and drug resistance in mantle cell lymphoma, providing indications for a targeted therapeutic strategy.}, subject = {Multiple}, language = {en} } @article{StuckensenLamoEspinosaMuinosLopezetal.2019, author = {Stuckensen, Kai and Lamo-Espinosa, Jos{\´e} M. and Mui{\~n}os-L{\´o}pez, Emma and Ripalda-Cembor{\´a}in, Purificaci{\´o}n and L{\´o}pez-Mart{\´i}nez, Tania and Iglesias, Elena and Abizanda, Gloria and Andreu, Ion and Flandes-Iparraguirre, Mar{\´i}a and Pons-Villanueva, Juan and Elizalde, Reyes and Nickel, Joachim and Ewald, Andrea and Gbureck, Uwe and Pr{\´o}sper, Felipe and Groll, J{\"u}rgen and Granero-Molt{\´o}, Froil{\´a}n}, title = {Anisotropic cryostructured collagen scaffolds for efficient delivery of RhBMP-2 and enhanced bone regeneration}, series = {Materials}, volume = {12}, journal = {Materials}, number = {19}, issn = {1996-1944}, doi = {10.3390/ma12193105}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195966}, year = {2019}, abstract = {In the treatment of bone non-unions, an alternative to bone autografts is the use of bone morphogenetic proteins (BMPs), e.g., BMP-2, BMP-7, with powerful osteoinductive and osteogenic properties. In clinical settings, these osteogenic factors are applied using absorbable collagen sponges for local controlled delivery. Major side effects of this strategy are derived from the supraphysiological doses of BMPs needed, which may induce ectopic bone formation, chronic inflammation, and excessive bone resorption. In order to increase the efficiency of the delivered BMPs, we designed cryostructured collagen scaffolds functionalized with hydroxyapatite, mimicking the structure of cortical bone (aligned porosity, anisotropic) or trabecular bone (random distributed porosity, isotropic). We hypothesize that an anisotropic structure would enhance the osteoconductive properties of the scaffolds by increasing the regenerative performance of the provided rhBMP-2. In vitro, both scaffolds presented similar mechanical properties, rhBMP-2 retention and delivery capacity, as well as scaffold degradation time. In vivo, anisotropic scaffolds demonstrated better bone regeneration capabilities in a rat femoral critical-size defect model by increasing the defect bridging. In conclusion, anisotropic cryostructured collagen scaffolds improve bone regeneration by increasing the efficiency of rhBMP-2 mediated bone healing.}, language = {en} } @article{NaeschenDiekkruegerEversetal.2019, author = {N{\"a}schen, Kristian and Diekkr{\"u}ger, Bernd and Evers, Mariele and H{\"o}llermann, Britta and Steinbach, Stefanie and Thonfeld, Frank}, title = {The impact of land use/land cover change (LULCC) on water resources in a tropical catchment in Tanzania under different climate change scenarios}, series = {Sustainability}, volume = {11}, journal = {Sustainability}, number = {24}, issn = {2071-1050}, doi = {10.3390/su11247083}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193825}, year = {2019}, abstract = {Many parts of sub-Saharan Africa (SSA) are prone to land use and land cover change (LULCC). In many cases, natural systems are converted into agricultural land to feed the growing population. However, despite climate change being a major focus nowadays, the impacts of these conversions on water resources, which are essential for agricultural production, is still often neglected, jeopardizing the sustainability of the socio-ecological system. This study investigates historic land use/land cover (LULC) patterns as well as potential future LULCC and its effect on water quantities in a complex tropical catchment in Tanzania. It then compares the results using two climate change scenarios. The Land Change Modeler (LCM) is used to analyze and to project LULC patterns until 2030 and the Soil and Water Assessment Tool (SWAT) is utilized to simulate the water balance under various LULC conditions. Results show decreasing low flows by 6-8\% for the LULC scenarios, whereas high flows increase by up to 84\% for the combined LULC and climate change scenarios. The effect of climate change is stronger compared to the effect of LULCC, but also contains higher uncertainties. The effects of LULCC are more distinct, although crop specific effects show diverging effects on water balance components. This study develops a methodology for quantifying the impact of land use and climate change and therefore contributes to the sustainable management of the investigated catchment, as it shows the impact of environmental change on hydrological extremes (low flow and floods) and determines hot spots, which are critical for environmental development.}, language = {en} } @article{VillalobosWieseImhoffetal.2019, author = {Villalobos, Alvaro S. and Wiese, Jutta and Imhoff, Johannes F. and Dorador, Cristina and Keller, Alexander and Hentschel, Ute}, title = {Systematic affiliation and genome analysis of Subtercola vilae DB165T with particular emphasis on cold adaptation of an isolate from a high-altitude cold volcano lake}, series = {Microorganisms}, volume = {7}, journal = {Microorganisms}, number = {4}, issn = {2076-2607}, doi = {10.3390/microorganisms7040107}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197394}, year = {2019}, abstract = {Among the Microbacteriaceae the species of Subtercola and Agreia form closely associated clusters. Phylogenetic analysis demonstrated three major phylogenetic branches of these species. One of these branches contains the two psychrophilic species Subtercola frigoramans and Subtercola vilae, together with a larger number of isolates from various cold environments. Genomic evidence supports the separation of Agreia and Subtercola species. In order to gain insight into the ability of S. vilae to adapt to life in this extreme environment, we analyzed the genome with a particular focus on properties related to possible adaptation to a cold environment. General properties of the genome are presented, including carbon and energy metabolism, as well as secondary metabolite production. The repertoire of genes in the genome of S. vilae DB165\(^T\) linked to adaptations to the harsh conditions found in Llullaillaco Volcano Lake includes several mechanisms to transcribe proteins under low temperatures, such as a high number of tRNAs and cold shock proteins. In addition, S. vilae DB165\(^T\) is capable of producing a number of proteins to cope with oxidative stress, which is of particular relevance at low temperature environments, in which reactive oxygen species are more abundant. Most important, it obtains capacities to produce cryo-protectants, and to combat against ice crystal formation, it produces ice-binding proteins. Two new ice-binding proteins were identified which are unique to S. vilae DB165\(^T\). These results indicate that S. vilae has the capacity to employ different mechanisms to live under the extreme and cold conditions prevalent in Llullaillaco Volcano Lake.}, language = {en} } @article{GonzalezDornerBretzetal.2019, author = {Gonz{\´a}lez, Mar{\´i}a Magdalena and Dorner, Daniela and Bretz, Thomas and Garc{\´i}a-Gonz{\´a}lez, Jos{\´e} Andr{\´e}s}, title = {Unbiased long-term monitoring at TeV energies}, series = {Galaxies}, volume = {7}, journal = {Galaxies}, number = {2}, issn = {2075-4434}, doi = {10.3390/galaxies7020051}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197389}, year = {2019}, abstract = {For the understanding of the variable, transient and non-thermal universe, unbiased long-term monitoring is crucial. To constrain the emission mechanisms at the highest energies, it is important to characterize the very high energy emission and its correlation with observations at other wavelengths. At very high energies, only a limited number of instruments is available. This article reviews the current status of monitoring of the extra-galactic sky at TeV energies.}, language = {en} } @article{WickHarteltPuppe2019, author = {Wick, Christoph and Hartelt, Alexander and Puppe, Frank}, title = {Staff, symbol and melody detection of Medieval manuscripts written in square notation using deep Fully Convolutional Networks}, series = {Applied Sciences}, volume = {9}, journal = {Applied Sciences}, number = {13}, issn = {2076-3417}, doi = {10.3390/app9132646}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-197248}, year = {2019}, abstract = {Even today, the automatic digitisation of scanned documents in general, but especially the automatic optical music recognition (OMR) of historical manuscripts, still remains an enormous challenge, since both handwritten musical symbols and text have to be identified. This paper focuses on the Medieval so-called square notation developed in the 11th-12th century, which is already composed of staff lines, staves, clefs, accidentals, and neumes that are roughly spoken connected single notes. The aim is to develop an algorithm that captures both the neumes, and in particular its melody, which can be used to reconstruct the original writing. Our pipeline is similar to the standard OMR approach and comprises a novel staff line and symbol detection algorithm based on deep Fully Convolutional Networks (FCN), which perform pixel-based predictions for either staff lines or symbols and their respective types. Then, the staff line detection combines the extracted lines to staves and yields an F\(_1\) -score of over 99\% for both detecting lines and complete staves. For the music symbol detection, we choose a novel approach that skips the step to identify neumes and instead directly predicts note components (NCs) and their respective affiliation to a neume. Furthermore, the algorithm detects clefs and accidentals. Our algorithm predicts the symbol sequence of a staff with a diplomatic symbol accuracy rate (dSAR) of about 87\%, which includes symbol type and location. If only the NCs without their respective connection to a neume, all clefs and accidentals are of interest, the algorithm reaches an harmonic symbol accuracy rate (hSAR) of approximately 90\%. In general, the algorithm recognises a symbol in the manuscript with an F\(_1\) -score of over 96\%.}, language = {en} } @article{MayrKuenzerGessneretal.2019, author = {Mayr, Stefan and Kuenzer, Claudia and Gessner, Ursula and Klein, Igor and Rutzinger, Martin}, title = {Validation of earth observation time-series: a review for large-area and temporally dense land surface products}, series = {Remote Sensing}, volume = {11}, journal = {Remote Sensing}, number = {22}, issn = {2072-4292}, doi = {10.3390/rs11222616}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193202}, year = {2019}, abstract = {Large-area remote sensing time-series offer unique features for the extensive investigation of our environment. Since various error sources in the acquisition chain of datasets exist, only properly validated results can be of value for research and downstream decision processes. This review presents an overview of validation approaches concerning temporally dense time-series of land surface geo-information products that cover the continental to global scale. Categorization according to utilized validation data revealed that product intercomparisons and comparison to reference data are the conventional validation methods. The reviewed studies are mainly based on optical sensors and orientated towards global coverage, with vegetation-related variables as the focus. Trends indicate an increase in remote sensing-based studies that feature long-term datasets of land surface variables. The hereby corresponding validation efforts show only minor methodological diversification in the past two decades. To sustain comprehensive and standardized validation efforts, the provision of spatiotemporally dense validation data in order to estimate actual differences between measurement and the true state has to be maintained. The promotion of novel approaches can, on the other hand, prove beneficial for various downstream applications, although typically only theoretical uncertainties are provided.}, language = {en} } @article{WaltherWagnerKurzai2019, author = {Walther, Grit and Wagner, Lysett and Kurzai, Oliver}, title = {Updates on the taxonomy of Mucorales with an emphasis on clinically important taxa}, series = {Journal of Fungi}, volume = {5}, journal = {Journal of Fungi}, number = {4}, issn = {2309-608X}, doi = {10.3390/jof5040106}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193081}, year = {2019}, abstract = {Fungi of the order Mucorales colonize all kinds of wet, organic materials and represent a permanent part of the human environment. They are economically important as fermenting agents of soybean products and producers of enzymes, but also as plant parasites and spoilage organisms. Several taxa cause life-threatening infections, predominantly in patients with impaired immunity. The order Mucorales has now been assigned to the phylum Mucoromycota and is comprised of 261 species in 55 genera. Of these accepted species, 38 have been reported to cause infections in humans, as a clinical entity known as mucormycosis. Due to molecular phylogenetic studies, the taxonomy of the order has changed widely during the last years. Characteristics such as homothallism, the shape of the suspensors, or the formation of sporangiola are shown to be not taxonomically relevant. Several genera including Absidia, Backusella, Circinella, Mucor, and Rhizomucor have been amended and their revisions are summarized in this review. Medically important species that have been affected by recent changes include Lichtheimia corymbifera, Mucor circinelloides, and Rhizopus microsporus. The species concept of Rhizopus arrhizus (syn. R. oryzae) is still a matter of debate. Currently, species identification of the Mucorales is best performed by sequencing of the internal transcribed spacer (ITS) region. Ecologically, the Mucorales represent a diverse group but for the majority of taxa, the ecological role and the geographic distribution remain unknown. Understanding the biology of these opportunistic fungal pathogens is a prerequisite for the prevention of infections, and, consequently, studies on the ecology of the Mucorales are urgently needed.}, language = {en} }