@article{BerntRangrezEdenetal.2016, author = {Bernt, Alexander and Rangrez, Ashraf Y. and Eden, Matthias and Jungmann, Andreas and Katz, Sylvia and Rohr, Claudia and M{\"u}ller, Oliver J. and Katus, Hugo A. and Sossalla, Samuel T. and Williams, Tatjana and Ritter, Oliver and Frank, Derk and Frey, Norbert}, title = {Sumoylation-independent activation of Calcineurin-NFAT-signaling via SUMO2 mediates cardiomyocyte hypertrophy}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {35758}, doi = {10.1038/srep35758}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167525}, year = {2016}, abstract = {The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10\(^{7}\) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype. Prohypertrophic effects were also observed in mice expressing SUMO2 in the heart using AAV9 (Adeno-associated virus), complementing the in vitro findings. In addition, increased SUMO2-mediated sumoylation in human cardiomyopathy patients and in mouse models of cardiomyopathy were observed. To decipher the underlying mechanism, we generated a sumoylation-deficient SUMO2 mutant (ΔGG). Surprisingly, ΔGG replicated Cn-NFAT-activation and the prohypertrophic effects of native SUMO2, both in vitro and in vivo, suggesting a sumoylation-independent mechanism. Finally, we discerned a direct interaction between SUMO2 and CnA, which promotes CnA nuclear localization. In conclusion, we identified SUMO2 as a novel activator of Cn-NFAT signaling in cardiomyocytes. In broader terms, these findings reveal an unexpected role for SUMO2 in cardiac hypertrophy and cardiomyopathy, which may open the possibility for therapeutic manipulation of this pathway.}, language = {en} } @article{WilliamsMachannKuehleretal.2011, author = {Williams, Tatjana and Machann, Wolfram and K{\"u}hler, Leif and Hamm, Henning and M{\"u}ller-H{\"o}cker, Josef and Zimmer, Michael and Ertl, Georg and Ritter, Oliver and Beer, Meinrad and Sch{\"o}nberger, Jost}, title = {Novel desmoplakin mutation: juvenile biventricular cardiomyopathy with left ventricular non-compaction and acantholytic palmoplantar keratoderma}, series = {Clinical Research in Cardiology}, volume = {100}, journal = {Clinical Research in Cardiology}, number = {12}, doi = {10.1007/s00392-011-0345-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-141198}, pages = {1087-1093}, year = {2011}, abstract = {Two sons of a consanguineous marriage developed biventricular cardiomyopathy. One boy died of severe heart failure at the age of 6 years, the other was transplanted because of severe heart failure at the age of 10 years. In addition, focal palmoplantar keratoderma and woolly hair were apparent in both boys. As similar phenotypes have been described in Naxos disease and Carvajal syndrome, respectively, the genes for plakoglobin (JUP) and desmoplakin (DSP) were screened for mutations using direct genomic sequencing. A novel homozygous 2 bp deletion was identified in an alternatively spliced region of DSP. The deletion 5208_5209delAG led to a frameshift downstream of amino acid 1,736 with a premature truncation of the predominant cardiac isoform DSP-1. This novel homozygous truncating mutation in the isoform-1 specific region of the DSP C-terminus caused Carvajal syndrome comprising severe early-onset heart failure with features of non-compaction cardiomyopathy, woolly hair and an acantholytic form of palmoplantar keratoderma in our patient. Congenital hair abnormality and manifestation of the cutaneous phenotype in toddler age can help to identify children at risk for cardiac death.}, language = {en} } @article{AhmadWolberEckardtetal.2012, author = {Ahmad, Ruhel and Wolber, Wanja and Eckardt, Sigrid and Koch, Philipp and Schmitt, Jessica and Semechkin, Ruslan and Geis, Christian and Heckmann, Manfred and Br{\"u}stle, Oliver and McLaughlin, John K. and Sir{\´e}n, Anna-Leena and M{\"u}ller, Albrecht M.}, title = {Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {8}, doi = {10.1371/journal.pone.0042800}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130268}, pages = {e42800}, year = {2012}, abstract = {Parent of origin imprints on the genome have been implicated in the regulation of neural cell type differentiation. The ability of human parthenogenetic (PG) embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific differentiation is undefined. We determined the potential of hpESCs to differentiate into various neural subtypes. Concurrently, we examined DNA methylation and expression status of imprinted genes. Under culture conditions promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave rise to glia and neuron-like cells that expressed subtype-specific markers and generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs revealed that maternal-specific gene expression patterns and imprinting marks were generally maintained in PG cells upon differentiation. Our results demonstrate that despite the lack of a paternal genome, hpESCs generate proliferating NSCs that are capable of differentiation into physiologically functional neuron-like cells and maintain allele-specific expression of imprinted genes. Thus, hpESCs can serve as a model to study the role of maternal and paternal genomes in neural development and to better understand imprinting-associated brain diseases.}, language = {en} } @article{SemmlerSacconiBachetal.2014, author = {Semmler, Anna-Lena and Sacconi, Sabrina and Bach, J. Elisa and Liebe, Claus and B{\"u}rmann, Jan and Kley, Rudolf A. and Ferbert, Andreas and Anderheiden, Roland and Van den Bergh, Peter and Martin, Jean-Jacques and De Jonghe, Peter and Neuen-Jacob, Eva and M{\"u}ller, Oliver and Deschauer, Marcus and Bergmann, Markus and Schr{\"o}der, J. Michael and Vorgerd, Matthias and Schulz, J{\"o}rg B. and Weis, Joachim and Kress, Wolfram and Claeys, Kristl G.}, title = {Unusual multisystemic involvement and a novel BAG3 mutation revealed by NGS screening in a large cohort of myofibrillar myopathies}, series = {Orphanet Journal of Rare Diseases}, volume = {9}, journal = {Orphanet Journal of Rare Diseases}, number = {121}, issn = {1750-1172}, doi = {10.1186/s13023-014-0121-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115623}, year = {2014}, abstract = {Background: Myofibrillar myopathies (MFM) are a group of phenotypically and genetically heterogeneous neuromuscular disorders, which are characterized by protein aggregations in muscle fibres and can be associated with multisystemic involvement. Methods: We screened a large cohort of 38 index patients with MFM for mutations in the nine thus far known causative genes using Sanger and next generation sequencing (NGS). We studied the clinical and histopathological characteristics in 38 index patients and five additional relatives (n = 43) and particularly focused on the associated multisystemic symptoms. Results: We identified 14 heterozygous mutations (diagnostic yield of 37\%), among them the novel p. Pro209Gln mutation in the BAG3 gene, which was associated with onset in adulthood, a mild phenotype and an axonal sensorimotor polyneuropathy, in the absence of giant axons at the nerve biopsy. We revealed several novel clinical phenotypes and unusual multisystemic presentations with previously described mutations: hearing impairment with a FLNC mutation, dysphonia with a mutation in DES and the first patient with a FLNC mutation presenting respiratory insufficiency as the initial symptom. Moreover, we described for the first time respiratory insufficiency occurring in a patient with the p. Gly154Ser mutation in CRYAB. Interestingly, we detected a polyneuropathy in 28\% of the MFM patients, including a BAG3 and a MYOT case, and hearing impairment in 13\%, including one patient with a FLNC mutation and two with mutations in the DES gene. In four index patients with a mutation in one of the MFM genes, typical histological findings were only identified at the ultrastructural level (29\%). Conclusions: We conclude that extraskeletal symptoms frequently occur in MFM, particularly cardiac and respiratory involvement, polyneuropathy and/or deafness. BAG3 mutations should be considered even in cases with a mild phenotype or an adult onset. We identified a genetic defect in one of the known genes in less than half of the MFM patients, indicating that more causative genes are still to be found. Next generation sequencing techniques should be helpful in achieving this aim.}, language = {en} } @article{MortonFliesserDittrichetal.2014, author = {Morton, Charles Oliver and Fliesser, Mirjam and Dittrich, Marcus and M{\"u}ller, Tobias and Bauer, Ruth and Kneitz, Susanne and Hope, William and Rogers, Thomas Richard and Einsele, Hermann and L{\"o}ffler, J{\"u}rgen}, title = {Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface}, doi = {10.1371/journal.pone.0098279}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112893}, year = {2014}, abstract = {The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.}, language = {en} } @article{HebestreitZeidlerSchippersetal.2022, author = {Hebestreit, Helge and Zeidler, Cornelia and Schippers, Christopher and de Zwaan, Martina and Deckert, J{\"u}rgen and Heuschmann, Peter and Krauth, Christian and Bullinger, Monika and Berger, Alexandra and Berneburg, Mark and Brandstetter, Lilly and Deibele, Anna and Dieris-Hirche, Jan and Graessner, Holm and G{\"u}ndel, Harald and Herpertz, Stephan and Heuft, Gereon and Lapstich, Anne-Marie and L{\"u}cke, Thomas and Maisch, Tim and Mundlos, Christine and Petermann-Meyer, Andrea and M{\"u}ller, Susanne and Ott, Stephan and Pfister, Lisa and Quitmann, Julia and Romanos, Marcel and Rutsch, Frank and Schaubert, Kristina and Schubert, Katharina and Schulz, J{\"o}rg B. and Schweiger, Susann and T{\"u}scher, Oliver and Ungeth{\"u}m, Kathrin and Wagner, Thomas O. F. and Haas, Kirsten}, title = {Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study}, series = {Orphanet Journal of Rare Diseases}, volume = {17}, journal = {Orphanet Journal of Rare Diseases}, number = {1}, doi = {10.1186/s13023-022-02176-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300440}, year = {2022}, abstract = {Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD's outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30\% in standard care to 40\% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients' quality of life and evaluation of care; and f) physicians' satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease.}, language = {en} } @article{BartelPeinPopperetal.2019, author = {Bartel, Karin and Pein, Helmut and Popper, Bastian and Schmitt, Sabine and Janaki-Raman, Sudha and Schulze, Almut and Lengauer, Florian and Koeberle, Andreas and Werz, Oliver and Zischka, Hans and M{\"u}ller, Rolf and Vollmar, Angelika M. and Schwarzenberg, Karin von}, title = {Connecting lysosomes and mitochondria - a novel role for lipid metabolism in cancer cell death}, series = {Cell Communication and Signaling}, volume = {17}, journal = {Cell Communication and Signaling}, doi = {10.1186/s12964-019-0399-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221524}, year = {2019}, abstract = {Background The understanding of lysosomes has been expanded in recent research way beyond their view as cellular trash can. Lysosomes are pivotal in regulating metabolism, endocytosis and autophagy and are implicated in cancer. Recently it was discovered that the lysosomal V-ATPase, which is known to induce apoptosis, interferes with lipid metabolism in cancer, yet the interplay between these organelles is poorly understood. Methods LC-MS/MS analysis was performed to investigate lipid distribution in cells. Cell survival and signaling pathways were analyzed by means of cell biological methods (qPCR, Western Blot, flow cytometry, CellTiter-Blue). Mitochondrial structure was analyzed by confocal imaging and electron microscopy, their function was determined by flow cytometry and seahorse measurements. Results Our data reveal that interfering with lysosomal function changes composition and subcellular localization of triacylglycerids accompanied by an upregulation of PGC1α and PPARα expression, master regulators of energy and lipid metabolism. Furthermore, cardiolipin content is reduced driving mitochondria into fission, accompanied by a loss of membrane potential and reduction in oxidative capacity, which leads to a deregulation in cellular ROS and induction of mitochondria-driven apoptosis. Additionally, cells undergo a metabolic shift to glutamine dependency, correlated with the fission phenotype and sensitivity to lysosomal inhibition, most prominent in Ras mutated cells. Conclusion This study sheds mechanistic light on a largely uninvestigated triangle between lysosomes, lipid metabolism and mitochondrial function. Insight into this organelle crosstalk increases our understanding of mitochondria-driven cell death. Our findings furthermore provide a first hint on a connection of Ras pathway mutations and sensitivity towards lysosomal inhibitors.}, language = {en} } @article{WenNowakKrolNagleretal.2019, author = {Wen, Xinbo and Nowak-Kr{\´o}l, Agnieszka and Nagler, Oliver and Kraus, Felix and Zhu, Na and Zheng, Nan and M{\"u}ller, Matthias and Schmidt, David and Xie, Zengqi and W{\"u}rthner, Frank}, title = {Tetrahydroxy-perylene bisimide embedded in zinc oxide thin film as electron transporting layer for high performance non-fullerene organic solar cells}, series = {Angewandte Chemie International Edition}, volume = {58}, journal = {Angewandte Chemie International Edition}, number = {37}, doi = {10.1002/anie.201907467}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204723}, pages = {13051-13055}, year = {2019}, abstract = {By introduction of four hydroxy (HO) groups into the two perylene bisimide (PBI) bay areas, new HO-PBI ligands were obtained which upon deprotonation can complex ZnII ions and photosensitize semiconductive zinc oxide thin films. Such coordination is beneficial for dispersing PBI photosensitizer molecules evenly into metal oxide films to fabricate organic-inorganic hybrid interlayers for organic solar cells. Supported by the photoconductive effect of the ZnO:HO-PBI hybrid interlayers, improved electron collection and transportation is achieved in fullerene and non-fullerene polymer solar cell devices, leading to remarkable power conversion efficiencies of up to 15.95 \% for a non-fullerene based organic solar cell.}, language = {en} } @article{McLaughlinSchmulensonTeplytskaetal.2021, author = {Mc Laughlin, Anna M. and Schmulenson, Eduard and Teplytska, Olga and Zimmermann, Sebastian and Opitz, Patrick and Groenland, Stefanie L. and Huitema, Alwin D. R. and Steeghs, Neeltje and M{\"u}ller, Lothar and Fuxius, Stefan and Illerhaus, Gerald and Joerger, Markus and Mayer, Frank and Fuhr, Uwe and Holdenrieder, Stefan and Hempel, Georg and Scherf-Clavel, Oliver and Jaehde, Ulrich and Kloft, Charlotte}, title = {Developing a nationwide infrastructure for therapeutic drug monitoring of targeted oral anticancer drugs: the ON-TARGET study protocol}, series = {Cancers}, volume = {13}, journal = {Cancers}, number = {24}, issn = {2072-6694}, doi = {10.3390/cancers13246281}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252196}, year = {2021}, abstract = {Exposure-efficacy and/or exposure-toxicity relationships have been identified for up to 80\% of oral anticancer drugs (OADs). Usually, OADs are administered at fixed doses despite their high interindividual pharmacokinetic variability resulting in large differences in drug exposure. Consequently, a substantial proportion of patients receive a suboptimal dose. Therapeutic Drug Monitoring (TDM), i.e., dosing based on measured drug concentrations, may be used to improve treatment outcomes. The prospective, multicenter, non-interventional ON-TARGET study (DRKS00025325) aims to investigate the potential of routine TDM to reduce adverse drug reactions in renal cell carcinoma patients receiving axitinib or cabozantinib. Furthermore, the feasibility of using volumetric absorptive microsampling (VAMS), a minimally invasive and easy to handle blood sampling technique, for sample collection is examined. During routine visits, blood samples are collected and sent to bioanalytical laboratories. Venous and VAMS blood samples are collected in the first study phase to facilitate home-based capillary blood sampling in the second study phase. Within one week, the drug plasma concentrations are measured, interpreted, and reported back to the physician. Patients report their drug intake and toxicity using PRO-CTCAE-based questionnaires in dedicated diaries. Ultimately, the ON-TARGET study aims to develop a nationwide infrastructure for TDM for oral anticancer drugs.}, language = {en} } @article{SchulzRuppertHermsetal.2017, author = {Schulz, Herbert and Ruppert, Ann-Kathrin and Herms, Stefan and Wolf, Christiane and Mirza-Schreiber, Nazanin and Stegle, Oliver and Czamara, Darina and Forstner, Andreas J. and Sivalingam, Sugirthan and Schoch, Susanne and Moebus, Susanne and P{\"u}tz, Benno and Hillmer, Axel and Fricker, Nadine and Vatter, Hartmut and M{\"u}ller-Myhsok, Bertram and N{\"o}then, Markus M. and Becker, Albert J. and Hoffmann, Per and Sander, Thomas and Cichon, Sven}, title = {Genome-wide mapping of genetic determinants influencing DNA methylation and gene expression in human hippocampus}, series = {Nature Communications}, volume = {8}, journal = {Nature Communications}, doi = {10.1038/s41467-017-01818-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173168}, year = {2017}, abstract = {Emerging evidence emphasizes the strong impact of regulatory genomic elements in neurodevelopmental processes and the complex pathways of brain disorders. The present genome-wide quantitative trait loci analyses explore the \(cis\)-regulatory effects of single-nucleotide polymorphisms (SNPs) on DNA methylation (meQTL) and gene expression (eQTL) in 110 human hippocampal biopsies. We identify \(cis\)-meQTLs at 14,118 CpG methylation sites and \(cis\)-eQTLs for 302 3′-mRNA transcripts of 288 genes. Hippocampal \(cis\)-meQTL-CpGs are enriched in flanking regions of active promoters, CpG island shores, binding sites of the transcription factor CTCF and brain eQTLs. \(Cis\)-acting SNPs of hippocampal meQTLs and eQTLs significantly overlap schizophrenia-associated SNPs. Correlations of CpG methylation and RNA expression are found for 34 genes. Our comprehensive maps of \(cis\)-acting hippocampal meQTLs and eQTLs provide a link between disease-associated SNPs and the regulatory genome that will improve the functional interpretation of non-coding genetic variants in the molecular genetic dissection of brain disorders.}, language = {en} } @article{EnglmeiervonHoermannRiekeretal.2022, author = {Englmeier, Jana and von Hoermann, Christian and Rieker, Daniel and Benbow, Marc Eric and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Lackner, Tom{\´a}š and Mitesser, Oliver and Redlich, Sarah and Riebl, Rebekka and Rojas-Botero, Sandra and Rummler, Thomas and Salamon, J{\"o}rg-Alfred and Sommer, David and Steffan-Dewenter, Ingolf and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg}, title = {Dung-visiting beetle diversity is mainly affected by land use, while community specialization is driven by climate}, series = {Ecology and Evolution}, volume = {12}, journal = {Ecology and Evolution}, number = {10}, issn = {2045-7758}, doi = {10.1002/ece3.9386}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-312846}, year = {2022}, abstract = {Dung beetles are important actors in the self-regulation of ecosystems by driving nutrient cycling, bioturbation, and pest suppression. Urbanization and the sprawl of agricultural areas, however, destroy natural habitats and may threaten dung beetle diversity. In addition, climate change may cause shifts in geographical distribution and community composition. We used a space-for-time approach to test the effects of land use and climate on α-diversity, local community specialization (H\(_2\)′) on dung resources, and γ-diversity of dung-visiting beetles. For this, we used pitfall traps baited with four different dung types at 115 study sites, distributed over a spatial extent of 300 km × 300 km and 1000 m in elevation. Study sites were established in four local land-use types: forests, grasslands, arable sites, and settlements, embedded in near-natural, agricultural, or urban landscapes. Our results show that abundance and species density of dung-visiting beetles were negatively affected by agricultural land use at both spatial scales, whereas γ-diversity at the local scale was negatively affected by settlements and on a landscape scale equally by agricultural and urban land use. Increasing precipitation diminished dung-visiting beetle abundance, and higher temperatures reduced community specialization on dung types and γ-diversity. These results indicate that intensive land use and high temperatures may cause a loss in dung-visiting beetle diversity and alter community networks. A decrease in dung-visiting beetle diversity may disturb decomposition processes at both local and landscape scales and alter ecosystem functioning, which may lead to drastic ecological and economic damage.}, language = {en} } @article{HanitschBaumannBoztugetal.2020, author = {Hanitsch, Leif and Baumann, Ulrich and Boztug, Kaan and Burkhard-Meier, Ulrike and Fasshauer, Maria and Habermehl, Pirmin and Hauck, Fabian and Klock, Gerd and Liese, Johannes and Meyer, Oliver and M{\"u}ller, Rainer and Pachlopnik-Schmid, Jana and Pfeiffer-Kascha, Dorothea and Warnatz, Klaus and Wehr, Claudia and Wittke, Kirsten and Niehues, Tim and von Bernuth, Horst}, title = {Treatment and management of primary antibody deficiency: German interdisciplinary evidence-based consensus guideline}, series = {European Journal of Immunology}, volume = {50}, journal = {European Journal of Immunology}, number = {10}, doi = {10.1002/eji.202048713}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-225731}, pages = {1432 -- 1446}, year = {2020}, abstract = {This evidence-based clinical guideline provides consensus-recommendations for the treatment and care of patients with primary antibody deficiencies (PADs). The guideline group comprised 20 clinical and scientific expert associations of the German, Swiss, and Austrian healthcare system and representatives of patients. Recommendations were based on results of a systematic literature search, data extraction, and evaluation of methodology and study quality in combination with the clinical expertise of the respective representatives. Consensus-based recommendations were determined via nominal group technique. PADs are the largest clinically relevant group of primary immunodeficiencies. Most patients with PADs present with increased susceptibility to infections, however immune dysregulation, autoimmunity, and cancer affect a significant number of patients and may precede infections. This guideline therefore covers interdisciplinary clinical and therapeutic aspects of infectious (e.g., antibiotic prophylaxis, management of bronchiectasis) and non-infectious manifestations (e.g., management of granulomatous disease, immune cytopenia). PADs are grouped into disease entities with definitive, probable, possible, or unlikely benefit of IgG-replacement therapy. Summary and consensus-recommendations are provided for treatment indication, dosing, routes of administration, and adverse events of IgG-replacement therapy. Special aspects of concomitant impaired T-cell function are highlighted as well as clinical data on selected monogenetic inborn errors of immunity formerly classified into PADs (APDS, CTLA-4-, and LRBA-deficiency).}, language = {en} } @article{UhlerRedlichZhangetal.2021, author = {Uhler, Johannes and Redlich, Sarah and Zhang, Jie and Hothorn, Torsten and Tobisch, Cynthia and Ewald, J{\"o}rg and Thorn, Simon and Seibold, Sebastian and Mitesser, Oliver and Morin{\`e}re, J{\´e}r{\^o}me and Bozicevic, Vedran and Benjamin, Caryl S. and Englmeier, Jana and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Riebl, Rebekka and Rojas-Botero, Sandra and Rummler, Thomas and Uphus, Lars and Schmidt, Stefan and Steffan-Dewenter, Ingolf and M{\"u}ller, J{\"o}rg}, title = {Relationships of insect biomass and richness with land use along a climate gradient}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-021-26181-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265058}, year = {2021}, abstract = {Recently reported insect declines have raised both political and social concern. Although the declines have been attributed to land use and climate change, supporting evidence suffers from low taxonomic resolution, short time series, a focus on local scales, and the collinearity of the identified drivers. In this study, we conducted a systematic assessment of insect populations in southern Germany, which showed that differences in insect biomass and richness are highly context dependent. We found the largest difference in biomass between semi-natural and urban environments (-42\%), whereas differences in total richness (-29\%) and the richness of threatened species (-56\%) were largest from semi-natural to agricultural environments. These results point to urbanization and agriculture as major drivers of decline. We also found that richness and biomass increase monotonously with increasing temperature, independent of habitat. The contrasting patterns of insect biomass and richness question the use of these indicators as mutual surrogates. Our study provides support for the implementation of more comprehensive measures aimed at habitat restoration in order to halt insect declines.}, language = {en} } @article{BaeMuellerFoersteretal.2022, author = {Bae, Soyeon and M{\"u}ller, J{\"o}rg and F{\"o}rster, Bernhard and Hilmers, Torben and Hochrein, Sophia and Jacobs, Martin and Leroy, Benjamin M. L. and Pretzsch, Hans and Weisser, Wolfgang W. and Mitesser, Oliver}, title = {Tracking the temporal dynamics of insect defoliation by high-resolution radar satellite data}, series = {Methods in Ecology and Evolution}, volume = {13}, journal = {Methods in Ecology and Evolution}, number = {1}, doi = {10.1111/2041-210X.13726}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-258222}, pages = {121-132}, year = {2022}, abstract = {Quantifying tree defoliation by insects over large areas is a major challenge in forest management, but it is essential in ecosystem assessments of disturbance and resistance against herbivory. However, the trajectory from leaf-flush to insect defoliation to refoliation in broadleaf trees is highly variable. Its tracking requires high temporal- and spatial-resolution data, particularly in fragmented forests. In a unique replicated field experiment manipulating gypsy moth Lymantria dispar densities in mixed-oak forests, we examined the utility of publicly accessible satellite-borne radar (Sentinel-1) to track the fine-scale temporal trajectory of defoliation. The ratio of backscatter intensity between two polarizations from radar data of the growing season constituted a canopy development index (CDI) and a normalized CDI (NCDI), which were validated by optical (Sentinel-2) and terrestrial laser scanning (TLS) data as well by intensive caterpillar sampling from canopy fogging. The CDI and NCDI strongly correlated with optical and TLS data (Spearman's ρ = 0.79 and 0.84, respectively). The ΔNCDII\(_{Defoliation(A-C)}\) significantly explained caterpillar abundance (R\(^{2}\) = 0.52). The NCDI at critical timesteps and ΔNCDI related to defoliation and refoliation well discriminated between heavily and lightly defoliated forests. We demonstrate that the high spatial and temporal resolution and the cloud independence of Sentinel-1 radar potentially enable spatially unrestricted measurements of the highly dynamic canopy herbivory. This can help monitor insect pests, improve the prediction of outbreaks and facilitate the monitoring of forest disturbance, one of the high priority Essential Biodiversity Variables, in the near future.}, language = {en} } @article{EnglmeierMitesserBenbowetal.2023, author = {Englmeier, Jana and Mitesser, Oliver and Benbow, M. Eric and Hothorn, Torsten and von Hoermann, Christian and Benjamin, Caryl and Fricke, Ute and Ganuza, Cristina and Haensel, Maria and Redlich, Sarah and Riebl, Rebekka and Rojas Botero, Sandra and Rummler, Thomas and Steffan-Dewenter, Ingolf and Stengel, Elisa and Tobisch, Cynthia and Uhler, Johannes and Uphus, Lars and Zhang, Jie and M{\"u}ller, J{\"o}rg}, title = {Diverse effects of climate, land use, and insects on dung and carrion decomposition}, series = {Ecosystems}, volume = {26}, journal = {Ecosystems}, number = {2}, issn = {1432-9840}, doi = {10.1007/s10021-022-00764-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325064}, pages = {397-411}, year = {2023}, abstract = {Land-use intensification and climate change threaten ecosystem functions. A fundamental, yet often overlooked, function is decomposition of necromass. The direct and indirect anthropogenic effects on decomposition, however, are poorly understood. We measured decomposition of two contrasting types of necromass, rat carrion and bison dung, on 179 study sites in Central Europe across an elevational climate gradient of 168-1122 m a.s.l. and within both local and regional land uses. Local land-use types included forest, grassland, arable fields, and settlements and were embedded in three regional land-use types (near-natural, agricultural, and urban). The effects of insects on decomposition were quantified by experimental exclusion, while controlling for removal by vertebrates. We used generalized additive mixed models to evaluate dung weight loss and carrion decay rate along elevation and across regional and local land-use types. We observed a unimodal relationship of dung decomposition with elevation, where greatest weight loss occurred between 600 and 700 m, but no effects of local temperature, land use, or insects. In contrast to dung, carrion decomposition was continuously faster with both increasing elevation and local temperature. Carrion reached the final decomposition stage six days earlier when insect access was allowed, and this did not depend on land-use effect. Our experiment identified different major drivers of decomposition on each necromass form. The results show that dung and carrion decomposition are rather robust to local and regional land use, but future climate change and decline of insects could alter decomposition processes and the self-regulation of ecosystems.}, language = {en} } @article{MuellerMitesserSchaeferetal.2023, author = {M{\"u}ller, J{\"o}rg and Mitesser, Oliver and Schaefer, H. Martin and Seibold, Sebastian and Busse, Annika and Kriegel, Peter and Rabl, Dominik and Gelis, Rudy and Arteaga, Alejandro and Freile, Juan and Leite, Gabriel Augusto and de Melo, Tomaz Nascimento and LeBien, Jack and Campos-Cerqueira, Marconi and Bl{\"u}thgen, Nico and Tremlett, Constance J. and B{\"o}ttger, Dennis and Feldhaar, Heike and Grella, Nina and Falcon{\´i}-L{\´o}pez, Ana and Donoso, David A. and Moriniere, Jerome and Buřivalov{\´a}, Zuzana}, title = {Soundscapes and deep learning enable tracking biodiversity recovery in tropical forests}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-41693-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358130}, year = {2023}, abstract = {Tropical forest recovery is fundamental to addressing the intertwined climate and biodiversity loss crises. While regenerating trees sequester carbon relatively quickly, the pace of biodiversity recovery remains contentious. Here, we use bioacoustics and metabarcoding to measure forest recovery post-agriculture in a global biodiversity hotspot in Ecuador. We show that the community composition, and not species richness, of vocalizing vertebrates identified by experts reflects the restoration gradient. Two automated measures - an acoustic index model and a bird community composition derived from an independently developed Convolutional Neural Network - correlated well with restoration (adj-R² = 0.62 and 0.69, respectively). Importantly, both measures reflected composition of non-vocalizing nocturnal insects identified via metabarcoding. We show that such automated monitoring tools, based on new technologies, can effectively monitor the success of forest recovery, using robust and reproducible data.}, language = {en} }