@article{GerlichAndreicaKueffneretal.2020, author = {Gerlich, C. and Andreica, I. and K{\"u}ffner, R. and Krause, D. and Lakomek, H. J. and Reusch, A. and Braun, J.}, title = {Evaluation einer Basisschulung f{\"u}r Patienten mit rheumatoider Arthritis}, series = {Zeitschrift f{\"u}r Rheumatologie}, volume = {79}, journal = {Zeitschrift f{\"u}r Rheumatologie}, doi = {10.1007/s00393-020-00769-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280359}, pages = {737-748}, year = {2020}, abstract = {Hintergrund Ein neues Rahmenkonzept hat die flexible Ableitung und Nutzung von rheumatologischen Schulungsprogrammen f{\"u}r unterschiedliche Versorgungsbereiche erm{\"o}glicht. Auf dieser Grundlage wurde eine 5‑st{\"u}ndige Basisschulung f{\"u}r Patienten mit rheumatoider Arthritis (RA) entwickelt, es wurden rheumatologische Fach{\"a}rzte und Psychologen trainiert, und dann wurde die Wirksamkeit nach dem Wirkmodell der Patientenschulung evaluiert. Methoden Mit dem Studiendesign einer extern randomisierten Wartekontrollgruppenstudie mit 3 Messzeitpunkten wurde gepr{\"u}ft, wie sich die 5‑st{\"u}ndige Basisschulung auf das Erkrankungs- und Behandlungswissen sowie auf die Gesundheitskompetenz von RA-Patienten (n = 249) auswirkt. Weitere Fragen betrafen Einstellungsparameter, Kommunikationskompetenz, Erkrankungsauswirkungen und die Zufriedenheit mit der Schulung. Die Auswertungen erfolgten auf Intention-to-treat-Basis mit Kovarianzanalysen f{\"u}r die Hauptzielgr{\"o}ßen unter Ber{\"u}cksichtigung des Ausgangswertes. Ergebnisse Die Analysen zeigen, dass die Basisschulung RA wirksam ist. Noch 3 Monate nach der Schulung verf{\"u}gten die Schulungsteilnehmer {\"u}ber mehr Wissen und Gesundheitskompetenz als die Wartekontrollgruppe mit kleinem bis mittelgroßem Effekt (d = 0,37 bzw. 0,38). In den Nebenzielgr{\"o}ßen zeigten sich mit Ausnahme der Krankheitskommunikation keine weiteren Schulungseffekte. Diskussion Die Basisschulung bietet eine gute Grundlage, auf der weitere Interventionen zur Verbesserung von Einstellungs- und Erkrankungsparametern aufbauen k{\"o}nnen. Sie eignet sich damit als zentraler Baustein f{\"u}r die rheumatologische Versorgung auf verschiedenen Ebenen.}, language = {de} } @article{KosmalaGruschwitzVeldhoenetal.2020, author = {Kosmala, Aleksander and Gruschwitz, Philipp and Veldhoen, Simon and Weng, Andreas Max and Krauss, Bernhard and Bley, Thorsten Alexander and Petritsch, Bernhard}, title = {Dual-energy CT angiography in suspected pulmonary embolism: influence of injection protocols on image quality and perfused blood volume}, series = {The International Journal of Cardiovascular Imaging}, volume = {36}, journal = {The International Journal of Cardiovascular Imaging}, number = {10}, issn = {1569-5794}, doi = {10.1007/s10554-020-01911-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314739}, pages = {2051-2059}, year = {2020}, abstract = {Abstract To compare intravenous contrast material (CM) injection protocols for dual-energy CT pulmonary angiography (CTPA) in patients with suspected acute pulmonary embolism with regard to image quality and pulmonary perfused blood volume (PBV) values. A total of 198 studies performed with four CM injection protocols varying in CM volume and iodine delivery rates (IDR) were retrospectively included: (A) 60 ml at 5 ml/s (IDR = 1.75gI/s), (B) 50 ml at 5 ml/s (IDR = 1.75gI/s), (C) 50 ml at 4 ml/s (IDR = 1.40gI/s), (D) 40 ml at 3 ml/s (IDR = 1.05gI/s). Image quality and PBV values at different resolution settings were compared. Pulmonary arterial tract attenuation was highest for protocol A (397 ± 110 HU; p vs. B = 0.13; vs. C = 0.02; vs. D < 0.001). CTPA image quality of protocol A was rated superior compared to protocols B and D by reader 1 (p = 0.01; < 0.001), and superior to protocols B, C and D by reader 2 (p < 0.001; 0.02; < 0.001). Otherwise, there were no significant differences in CTPA quality ratings. Subjective iodine map ratings did not vary significantly between protocols A, B, and C. Both readers rated protocol D inferior to all other protocols (p < 0.05). PBV values did not vary significantly between protocols A and B at resolution settings of 1, 4 and 10 (p = 0.10; 0.10; 0.09), while otherwise PBV values displayed a decreasing trend from protocol A to D (p < 0.05). Higher CM volume and IDR are associated with superior CTPA and iodine map quality and higher absolute PBV values.}, language = {en} } @article{HaufNiedingSeger2020, author = {Hauf, Juliane E. K. and Nieding, Gerhild and Seger, Benedikt T.}, title = {The development of dynamic perceptual simulations during sentence comprehension}, series = {Cognitive Processing}, volume = {21}, journal = {Cognitive Processing}, number = {2}, doi = {10.1007/s10339-020-00959-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283665}, pages = {197-208}, year = {2020}, abstract = {Based on an embodied account of language comprehension, this study investigated the dynamic characteristics of children and adults' perceptual simulations during sentence comprehension, using a novel paradigm to assess the perceptual simulation of objects moving up and down a vertical axis. The participants comprised adults (N = 40) and 6-, 8-, and 10-year-old children (N = 116). After listening in experimental trials to sentences implying that objects moved upward or downward, the participants were shown pictures and had to decide as quickly as possible whether the objects depicted had been mentioned in the sentences. The target pictures moved either up or down and then stopped in the middle of the screen. All age groups' reaction times were found to be shorter when the objects moved in the directions that the sentences implied. Age exerted no developmental effect on reaction times. The findings suggest that dynamic perceptual simulations are fundamental to language comprehension in text recipients aged 6 and older.}, language = {en} } @article{AdolfBraunFussetal.2020, author = {Adolf, Christian and Braun, Leah T. and Fuss, Carmina T. and Hahner, Stefanie and K{\"u}nzel, Heike and Handgriff, Laura and Sturm, Lisa and Heinrich, Daniel A. and Schneider, Holger and Bidlingmaier, Martin and Reincke, Martin}, title = {Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism}, series = {Endocrine}, volume = {69}, journal = {Endocrine}, number = {3}, issn = {1355-008X}, doi = {10.1007/s12020-020-02348-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315966}, pages = {625-633}, year = {2020}, abstract = {Context Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis. Patients and methods We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment. Study design Observational longitudinal cohort study. Setting Tertiary care hospital. Results Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers. Conclusion This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.}, language = {en} } @article{ElhfnawyElsalamawyAbdelraoufetal.2020, author = {Elhfnawy, Ahmed Mohamed and Elsalamawy, Doaa and Abdelraouf, Mervat and Schliesser, Mira and Volkmann, Jens and Fluri, Felix}, title = {Red flags for a concomitant giant cell arteritis in patients with vertebrobasilar stroke: a cross-sectional study and systematic review}, series = {Acta Neurologica Belgica}, volume = {120}, journal = {Acta Neurologica Belgica}, number = {6}, issn = {0300-9009}, doi = {10.1007/s13760-020-01344-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-315610}, pages = {1389-1398}, year = {2020}, abstract = {Giant cell arteritis (GCA) may affect the brain-supplying arteries, resulting in ischemic stroke, whereby the vertebrobasilar territory is most often involved. Since etiology is unknown in 25\% of stroke patients and GCA is hardly considered as a cause, we examined in a pilot study, whether screening for GCA after vertebrobasilar stroke might unmask an otherwise missed disease. Consecutive patients with vertebrobasilar stroke were prospectively screened for GCA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin, and halo sign of the temporal and vertebral artery on ultrasound. Furthermore, we conducted a systematic literature review for relevant studies. Sixty-five patients were included, and two patients (3.1\%) were diagnosed with GCA. Patients with GCA were older in age (median 85 versus 69 years, p = 0.02). ESR and CRP were significantly increased and hemoglobin was significantly lower in GCA patients compared to non-GCA patients (median, 75 versus 11 mm in 1 h, p = 0.001; 3.84 versus 0.25 mg/dl, p = 0.01, 10.4 versus 14.6 mg/dl, p = 0.003, respectively). Multiple stenoses/occlusions in the vertebrobasilar territory affected our two GCA patients (100\%), but only five (7.9\%) non-GCA patients (p = 0.01). Our literature review identified 13 articles with 136 stroke patients with concomitant GCA. Those were old in age. Headache, increased inflammatory markers, and anemia were frequently reported. Multiple stenoses/occlusions in the vertebrobasilar territory affected around 70\% of stroke patients with GCA. Increased inflammatory markers, older age, anemia, and multiple stenoses/occlusions in the vertebrobasilar territory may be regarded as red flags for GCA among patients with vertebrobasilar stroke.}, language = {en} } @article{RiedererterMeulen2020, author = {Riederer, Peter and ter Meulen, Volker}, title = {Coronaviruses: a challenge of today and a call for extended human postmortem brain analyses}, series = {Journal of Neural Transmission}, volume = {127}, journal = {Journal of Neural Transmission}, number = {9}, issn = {0300-9564}, doi = {10.1007/s00702-020-02230-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-314637}, pages = {1217-1228}, year = {2020}, abstract = {While there is abounding literature on virus-induced pathology in general and coronavirus in particular, recent evidence accumulates showing distinct and deleterious brain affection. As the respiratory tract connects to the brain without protection of the blood-brain barrier, SARS-CoV-2 might in the early invasive phase attack the cardiorespiratory centres located in the medulla/pons areas, giving rise to disturbances of respiration and cardiac problems. Furthermore, brainstem regions are at risk to lose their functional integrity. Therefore, long-term neurological as well as psychiatric symptomatology and eventual respective disorders cannot be excluded as evidenced from influenza-A triggered post-encephalitic Parkinsonism and HIV-1 triggered AIDS-dementia complex. From the available evidences for coronavirus-induced brain pathology, this review concludes a number of unmet needs for further research strategies like human postmortem brain analyses. SARS-CoV-2 mirroring experimental animal brain studies, characterization of time-dependent and region-dependent spreading behaviours of coronaviruses, enlightening of pathological mechanisms after coronavirus infection using long-term animal models and clinical observations of patients having had COVID-19 infection are calling to develop both protective strategies and drug discoveries to avoid early and late coronavirus-induced functional brain disturbances, symptoms and eventually disorders. To fight SARS-CoV-2, it is an urgent need to enforce clinical, molecular biological, neurochemical and genetic research including brain-related studies on a worldwide harmonized basis.}, language = {en} } @article{DashkovskiyKapustyanSchmid2020, author = {Dashkovskiy, Sergey and Kapustyan, Oleksiy and Schmid, Jochen}, title = {A local input-to-state stability result w.r.t. attractors of nonlinear reaction-diffusion equations}, series = {Mathematics of Control, Signals, and Systems}, volume = {32}, journal = {Mathematics of Control, Signals, and Systems}, number = {3}, doi = {10.1007/s00498-020-00256-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281099}, pages = {309-326}, year = {2020}, abstract = {We establish the local input-to-state stability of a large class of disturbed nonlinear reaction-diffusion equations w.r.t. the global attractor of the respective undisturbed system.}, language = {en} } @article{Geiger2020, author = {Geiger, Dietmar}, title = {Plant glucose transporter structure and function}, series = {Pfl{\"u}gers Archiv - European Journal of Physiology}, volume = {472}, journal = {Pfl{\"u}gers Archiv - European Journal of Physiology}, number = {9}, doi = {10.1007/s00424-020-02449-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-280643}, pages = {1111-1128}, year = {2020}, abstract = {The carbohydrate D-glucose is the main source of energy in living organisms. In contrast to animals, as well as most fungi, bacteria, and archaea, plants are capable to synthesize a surplus of sugars characterizing them as autothrophic organisms. Thus, plants are de facto the source of all food on earth, either directly or indirectly via feed to livestock. Glucose is stored as polymeric glucan, in animals as glycogen and in plants as starch. Despite serving a general source for metabolic energy and energy storage, glucose is the main building block for cellulose synthesis and represents the metabolic starting point of carboxylate- and amino acid synthesis. Finally yet importantly, glucose functions as signalling molecule conveying the plant metabolic status for adjustment of growth, development, and survival. Therefore, cell-to-cell and long-distance transport of photoassimilates/sugars throughout the plant body require the fine-tuned activity of sugar transporters facilitating the transport across membranes. The functional plant counterparts of the animal sodium/glucose transporters (SGLTs) are represented by the proton-coupled sugar transport proteins (STPs) of the plant monosaccharide transporter(-like) family (MST). In the framework of this special issue on "Glucose Transporters in Health and Disease," this review gives an overview of the function and structure of plant STPs in comparison to the respective knowledge obtained with the animal Na+-coupled glucose transporters (SGLTs).}, language = {en} } @book{Reuter2020, author = {Reuter, Oliver M.}, title = {Erfahrungsverankerte Rezeption : Eine Methode zur Verzahnung von Produktion und Rezeption}, edition = {1. Auflage}, publisher = {kopaed}, isbn = {978-3-86736-580-2}, doi = {10.25972/OPUS-34528}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-346008}, publisher = {Universit{\"a}t W{\"u}rzburg}, pages = {210}, year = {2020}, abstract = {Eine Rezeption auf den von Kindern und Jugendlichen selbst gemachten Erfahrungen aufzubauen, ist das zentrale Anliegen der ausgef{\"u}hrten Methode zur Verschr{\"a}nkung von produktiven und rezeptiven Anteilen im Kunstunterricht. Indem vor der Rezeption eine bildnerische Praxis stattfindet, k{\"o}nnen Ideen und Vorstellungen selbst{\"a}ndig und individuell entwickelt und in Bilder {\"u}bersetzt werden. Bei der erfahrungsverankerten Vermittlung basiert die Rezeption auf einer Schnittmenge zwischen eigenen Handlungen im bildnerischen oder darstellenden Prozess und zentralen Aspekten des Werks. Solche Referenzpunkte zwischen der Produktion und der Rezeption k{\"o}nnen im Material, im Thema, in der Gattung, im bildnerischen Verfahren oder in einer k{\"u}nstlerischen Strategie ausfindig gemacht werden. Sie dienen dazu, Einsichten, Einstellungen, Kenntnisse und Wissen aus der Produktion in die Rezeption mitzunehmen. Somit ist die Methode der erfahrungsverankerten Rezeption gleichermaßen geeignet f{\"u}r die Vermittlung historischer wie f{\"u}r zeitgen{\"o}ssischer Kunst. Nach der Darlegung und Konturierung der Konzeption zeigt die Publikation Wege auf, die erfahrungsverankerte Rezeption in Unterricht zu {\"u}berf{\"u}hren. Exemplarische Unterrichtsskizzen illustrieren die Umsetzung im Kunstunterricht.}, subject = {Erfahrung}, language = {de} } @article{OPUS4-27753, title = {Search for squarks and gluinos in final states with same-sign leptons and jets using 139 fb\(^{-1}\) of data collected with the ATLAS detector}, series = {Journal of High Energy Physics}, journal = {Journal of High Energy Physics}, number = {6}, organization = {The ATLAS Collaboration}, doi = {10.1007/JHEP06(2020)046}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-277538}, pages = {46}, year = {2020}, abstract = {A search for supersymmetric partners of gluons and quarks is presented, involving signatures with jets and either two isolated leptons (electrons or muons) with the same electric charge, or at least three isolated leptons. A data sample of proton-proton collisions at root s = 13 TeV recorded with the ATLAS detector at the Large Hadron Collider between 2015 and 2018, corresponding to a total integrated luminosity of 139 fb(-1), is used for the search. No significant excess over the Standard Model expectation is observed. The results are interpreted in simplified supersymmetric models featuring both R-parity conservation and R-parity violation, raising the exclusion limits beyond those of previous ATLAS searches to 1600 GeV for gluino masses and 750 GeV for bottom and top squark masses in these scenarios.}, language = {en} } @article{FofanovProkopovKuhletal.2020, author = {Fofanov, Mikhail V. and Prokopov, Dmitry Yu. and Kuhl, Heiner and Schartl, Manfred and Trifonov, Vladimir A.}, title = {Evolution of microRNA biogenesis genes in the sterlet (Acipenser ruthenus) and other polyploid vertebrates}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {24}, issn = {1422-0067}, doi = {10.3390/ijms21249562}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285230}, year = {2020}, abstract = {MicroRNAs play a crucial role in eukaryotic gene regulation. For a long time, only little was known about microRNA-based gene regulatory mechanisms in polyploid animal genomes due to difficulties of polyploid genome assembly. However, in recent years, several polyploid genomes of fish, amphibian, and even invertebrate species have been sequenced and assembled. Here we investigated several key microRNA-associated genes in the recently sequenced sterlet (Acipenser ruthenus) genome, whose lineage has undergone a whole genome duplication around 180 MYA. We show that two paralogs of drosha, dgcr8, xpo1, and xpo5 as well as most ago genes have been retained after the acipenserid-specific whole genome duplication, while ago1 and ago3 genes have lost one paralog. While most diploid vertebrates possess only a single copy of dicer1, we strikingly found four paralogs of this gene in the sterlet genome, derived from a tandem segmental duplication that occurred prior to the last whole genome duplication. ago1,3,4 and exportins1,5 look to be prone to additional segment duplications producing up to four-five paralog copies in ray-finned fishes. We demonstrate for the first time exon microsatellite amplification in the acipenserid drosha2 gene, resulting in a highly variable protein product, which may indicate sub- or neofunctionalization. Paralogous copies of most microRNA metabolism genes exhibit different expression profiles in various tissues and remain functional despite the rediploidization process. Subfunctionalization of microRNA processing gene paralogs may be beneficial for different pathways of microRNA metabolism. Genetic variability of microRNA processing genes may represent a substrate for natural selection, and, by increasing genetic plasticity, could facilitate adaptations to changing environments.}, language = {en} } @article{LiedertNemitzHaffnerLuntzeretal.2020, author = {Liedert, Astrid and Nemitz, Claudia and Haffner-Luntzer, Melanie and Schick, Fabian and Jakob, Franz and Ignatius, Anita}, title = {Effects of estrogen receptor and Wnt signaling activation on mechanically induced bone formation in a mouse model of postmenopausal bone loss}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {21}, issn = {1422-0067}, doi = {10.3390/ijms21218301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285487}, year = {2020}, abstract = {In the adult skeleton, bone remodeling is required to replace damaged bone and functionally adapt bone mass and structure according to the mechanical requirements. It is regulated by multiple endocrine and paracrine factors, including hormones and growth factors, which interact in a coordinated manner. Because the response of bone to mechanical signals is dependent on functional estrogen receptor (ER) and Wnt/β-catenin signaling and is impaired in postmenopausal osteoporosis by estrogen deficiency, it is of paramount importance to elucidate the underlying mechanisms as a basis for the development of new strategies in the treatment of osteoporosis. The present study aimed to investigate the effectiveness of the activation of the ligand-dependent ER and the Wnt/β-catenin signal transduction pathways on mechanically induced bone formation using ovariectomized mice as a model of postmenopausal bone loss. We demonstrated that both pathways interact in the regulation of bone mass adaption in response to mechanical loading and that the activation of Wnt/β-catenin signaling considerably increased mechanically induced bone formation, whereas the effects of estrogen treatment strictly depended on the estrogen status in the mice.}, language = {en} } @article{HohenesterKanitzSchiergensetal.2020, author = {Hohenester, Simon and Kanitz, Veronika and Schiergens, Tobias and Einer, Claudia and Nagel, Jutta and Wimmer, Ralf and Reiter, Florian P. and Gerbes, Alexander L. and De Toni, Enrico N. and Bauer, Christian and Holdt, Lesca and Mayr, Doris and Rust, Christian and Schnurr, Max and Zischka, Hans and Geier, Andreas and Denk, Gerald}, title = {IL-18 but not IL-1 signaling is pivotal for the initiation of liver injury in murine non-alcoholic fatty liver disease}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {22}, issn = {1422-0067}, doi = {10.3390/ijms21228602}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285221}, year = {2020}, abstract = {Non-alcoholic fatty liver disease (NAFLD) is rising in prevalence, and a better pathophysiologic understanding of the transition to its inflammatory phenotype (NASH) is key to the development of effective therapies. To evaluate the contribution of the NLRP3 inflammasome and its downstream effectors IL-1 and IL-18 in this process, we applied the true-to-life "American lifestyle-induced obesity syndrome" (ALiOS) diet mouse model. Development of obesity, fatty liver and liver damage was investigated in mice fed for 24 weeks according to the ALiOS protocol. Lipidomic changes in mouse livers were compared to human NAFLD samples. Receptor knockout mice for IL-1 and IL-18 were used to dissect the impact of downstream signals of inflammasome activity on the development of NAFLD. The ALiOS diet induced obesity and liver steatosis. The lipidomic changes closely mimicked changes in human NAFLD. A pro-inflammatory gene expression pattern in liver tissue and increased serum liver transaminases indicated early liver damage in the absence of histological evidence of NASH. Mechanistically, Il-18r\(^{-/-}\)- but not Il-1r\(^{-/-}\) mice were protected from early liver damage, possibly due to silencing of the pro-inflammatory gene expression pattern. Our study identified NLRP3 activation and IL-18R-dependent signaling as potential modulators of early liver damage in NAFLD, preceding development of histologic NASH.}, language = {en} } @article{NaseemOsmanoğluKaltdorfetal.2020, author = {Naseem, Muhammad and Osmanoğlu, {\"O}zge and Kaltdorf, Martin and Alblooshi, Afnan Ali M. A. and Iqbal, Jibran and Howari, Fares M. and Srivastava, Mugdha and Dandekar, Thomas}, title = {Integrated framework of the immune-defense transcriptional signatures in the Arabidopsis shoot apical meristem}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {16}, issn = {1422-0067}, doi = {10.3390/ijms21165745}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285730}, year = {2020}, abstract = {The growing tips of plants grow sterile; therefore, disease-free plants can be generated from them. How plants safeguard growing apices from pathogen infection is still a mystery. The shoot apical meristem (SAM) is one of the three stem cells niches that give rise to the above ground plant organs. This is very well explored; however, how signaling networks orchestrate immune responses against pathogen infections in the SAM remains unclear. To reconstruct a transcriptional framework of the differentially expressed genes (DEGs) pertaining to various SAM cellular populations, we acquired large-scale transcriptome datasets from the public repository Gene Expression Omnibus (GEO). We identify here distinct sets of genes for various SAM cellular populations that are enriched in immune functions, such as immune defense, pathogen infection, biotic stress, and response to salicylic acid and jasmonic acid and their biosynthetic pathways in the SAM. We further linked those immune genes to their respective proteins and identify interactions among them by mapping a transcriptome-guided SAM-interactome. Furthermore, we compared stem-cells regulated transcriptome with innate immune responses in plants showing transcriptional separation among their DEGs in Arabidopsis. Besides unleashing a repertoire of immune-related genes in the SAM, our analysis provides a SAM-interactome that will help the community in designing functional experiments to study the specific defense dynamics of the SAM-cellular populations. Moreover, our study promotes the essence of large-scale omics data re-analysis, allowing a fresh look at the SAM-cellular transcriptome repurposing data-sets for new questions.}, language = {en} } @article{WinkelbeinerWandtEbertetal.2020, author = {Winkelbeiner, Nicola and Wandt, Viktoria K. and Ebert, Franziska and Lossow, Kristina and Bankoglu, Ezgi E. and Martin, Maximilian and Mangerich, Aswin and Stopper, Helga and Bornhorst, Julia and Kipp, Anna P. and Schwerdtle, Tanja}, title = {A multi-endpoint approach to base excision repair incision activity augmented by PARylation and DNA damage levels in mice: impact of sex and age}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {18}, issn = {1422-0067}, doi = {10.3390/ijms21186600}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285706}, year = {2020}, abstract = {Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2'-deoxyguanosine (8-oxodG), 5-hydroxy-2'-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.}, language = {en} } @article{vanderVeenVlietstravanDussenetal.2020, author = {van der Veen, Sanne J. and Vlietstra, Wytze J. and van Dussen, Laura and van Kuilenburg, Andr{\´e} B.P. and Dijkgraaf, Marcel G. W. and Lenders, Malte and Brand, Eva and Wanner, Christoph and Hughes, Derralynn and Elliott, Perry M. and Hollak, Carla E. M. and Langeveld, Mirjam}, title = {Predicting the development of anti-drug antibodies against recombinant alpha-galactosidase A in male patients with classical Fabry disease}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {16}, issn = {1422-0067}, doi = {10.3390/ijms21165784}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285687}, year = {2020}, abstract = {Fabry Disease (FD) is a rare, X-linked, lysosomal storage disease that mainly causes renal, cardiac and cerebral complications. Enzyme replacement therapy (ERT) with recombinant alpha-galactosidase A is available, but approximately 50\% of male patients with classical FD develop inhibiting anti-drug antibodies (iADAs) that lead to reduced biochemical responses and an accelerated loss of renal function. Once immunization has occurred, iADAs tend to persist and tolerization is hard to achieve. Here we developed a pre-treatment prediction model for iADA development in FD using existing data from 120 classical male FD patients from three European centers, treated with ERT. We found that nonsense and frameshift mutations in the α-galactosidase A gene (p = 0.05), higher plasma lysoGb3 at baseline (p < 0.001) and agalsidase beta as first treatment (p = 0.006) were significantly associated with iADA development. Prediction performance of a Random Forest model, using multiple variables (AUC-ROC: 0.77) was compared to a logistic regression (LR) model using the three significantly associated variables (AUC-ROC: 0.77). The LR model can be used to determine iADA risk in individual FD patients prior to treatment initiation. This helps to determine in which patients adjusted treatment and/or immunomodulatory regimes may be considered to minimize iADA development risk.}, language = {en} } @article{RasouliKianiPouyaLietal.2020, author = {Rasouli, Fatemeh and Kiani-Pouya, Ali and Li, Leiting and Zhang, Heng and Chen, Zhonghua and Hedrich, Rainer and Wilson, Richard and Shabala, Sergey}, title = {Sugar beet (Beta vulgaris) guard cells responses to salinity stress: a proteomic analysis}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {7}, issn = {1422-0067}, doi = {10.3390/ijms21072331}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285765}, year = {2020}, abstract = {Soil salinity is a major environmental constraint affecting crop growth and threatening global food security. Plants adapt to salinity by optimizing the performance of stomata. Stomata are formed by two guard cells (GCs) that are morphologically and functionally distinct from the other leaf cells. These microscopic sphincters inserted into the wax-covered epidermis of the shoot balance CO\(_2\) intake for photosynthetic carbon gain and concomitant water loss. In order to better understand the molecular mechanisms underlying stomatal function under saline conditions, we used proteomics approach to study isolated GCs from the salt-tolerant sugar beet species. Of the 2088 proteins identified in sugar beet GCs, 82 were differentially regulated by salt treatment. According to bioinformatics analysis (GO enrichment analysis and protein classification), these proteins were involved in lipid metabolism, cell wall modification, ATP biosynthesis, and signaling. Among the significant differentially abundant proteins, several proteins classified as "stress proteins" were upregulated, including non-specific lipid transfer protein, chaperone proteins, heat shock proteins, inorganic pyrophosphatase 2, responsible for energized vacuole membrane for ion transportation. Moreover, several antioxidant enzymes (peroxide, superoxidase dismutase) were highly upregulated. Furthermore, cell wall proteins detected in GCs provided some evidence that GC walls were more flexible in response to salt stress. Proteins such as L-ascorbate oxidase that were constitutively high under both control and high salinity conditions may contribute to the ability of sugar beet GCs to adapt to salinity by mitigating salinity-induced oxidative stress.}, language = {en} } @article{SamperAgreloSchiraHeinenBeyeretal.2020, author = {Samper Agrelo, Iria and Schira-Heinen, Jessica and Beyer, Felix and Groh, Janos and B{\"u}termann, Christine and Estrada, Veronica and Poschmann, Gereon and Bribian, Ana and Jadasz, Janusz J. and Lopez-Mascaraque, Laura and Kremer, David and Martini, Rudolf and M{\"u}ller, Hans Werner and Hartung, Hans Peter and Adjaye, James and St{\"u}hler, Kai and K{\"u}ry, Patrick}, title = {Secretome analysis of mesenchymal stem cell factors fostering oligodendroglial differentiation of neural stem cells in vivo}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {12}, issn = {1422-0067}, doi = {10.3390/ijms21124350}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285465}, year = {2020}, abstract = {Mesenchymal stem cell (MSC)-secreted factors have been shown to significantly promote oligodendrogenesis from cultured primary adult neural stem cells (aNSCs) and oligodendroglial precursor cells (OPCs). Revealing underlying mechanisms of how aNSCs can be fostered to differentiate into a specific cell lineage could provide important insights for the establishment of novel neuroregenerative treatment approaches aiming at myelin repair. However, the nature of MSC-derived differentiation and maturation factors acting on the oligodendroglial lineage has not been identified thus far. In addition to missing information on active ingredients, the degree to which MSC-dependent lineage instruction is functional in vivo also remains to be established. We here demonstrate that MSC-derived factors can indeed stimulate oligodendrogenesis and myelin sheath generation of aNSCs transplanted into different rodent central nervous system (CNS) regions, and furthermore, we provide insights into the underlying mechanism on the basis of a comparative mass spectrometry secretome analysis. We identified a number of secreted proteins known to act on oligodendroglia lineage differentiation. Among them, the tissue inhibitor of metalloproteinase type 1 (TIMP-1) was revealed to be an active component of the MSC-conditioned medium, thus validating our chosen secretome approach.}, language = {en} } @article{QuastGescheidtSpichty2020, author = {Quast, Helmut and Gescheidt, Georg and Spichty, Martin}, title = {Topological dynamics of a radical ion pair: Experimental and computational assessment at the relevant nanosecond timescale}, series = {Chemistry}, volume = {2}, journal = {Chemistry}, number = {2}, issn = {2624-8549}, doi = {10.3390/chemistry2020014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285195}, pages = {219 -- 230}, year = {2020}, abstract = {Chemical processes mostly happen in fluid environments where reaction partners encounter via diffusion. The bimolecular encounters take place at a nanosecond time scale. The chemical environment (e.g., solvent molecules, (counter)ions) has a decisive influence on the reactivity as it determines the contact time between two molecules and affects the energetics. For understanding reactivity at an atomic level and at the appropriate dynamic time scale, it is crucial to combine matching experimental and theoretical data. Here, we have utilized all-atom molecular-dynamics simulations for accessing the key time scale (nanoseconds) using a QM/MM-Hamiltonian. Ion pairs consisting of a radical ion and its counterion are ideal systems to assess the theoretical predictions because they reflect dynamics at an appropriate time scale when studied by temperature-dependent EPR spectroscopy. We have investigated a diketone radical anion with its tetra-ethylammonium counterion. We have established a funnel-like transition path connecting two (equivalent) complexation sites. The agreement between the molecular-dynamics simulation and the experimental data presents a new paradigm for ion-ion interactions. This study exemplarily demonstrates the impact of the molecular environment on the topological states of reaction intermediates and how these states can be consistently elucidated through the combination of theory and experiment. We anticipate that our findings will contribute to the prediction of bimolecular transformations in the condensed phase with relevance to chemical synthesis, polymers, and biological activity.}, language = {en} } @article{StojanovićFuchsFiedleretal.2020, author = {Stojanović, Stevan D. and Fuchs, Maximilian and Fiedler, Jan and Xiao, Ke and Meinecke, Anna and Just, Annette and Pich, Andreas and Thum, Thomas and Kunz, Meik}, title = {Comprehensive bioinformatics identifies key microRNA players in ATG7-deficient lung fibroblasts}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {11}, issn = {1422-0067}, doi = {10.3390/ijms21114126}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285181}, year = {2020}, abstract = {Background: Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. Method: We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. Results: The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a-5p related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. Conclusions: We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research.}, language = {en} } @article{KauffmannHoehneAssafetal.2020, author = {Kauffmann, Frederic and H{\"o}hne, Christian and Assaf, Alexandre Thomas and Vollkommer, Tobias and Semmusch, Jan and Reitmeier, Aline and Stein, Jamal Michel and Heiland, Max and Smeets, Ralf and Rutkowski, Rico}, title = {The influence of local pamidronate application on alveolar dimensional preservation after tooth extraction — an animal experimental study}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {10}, issn = {1422-0067}, doi = {10.3390/ijms21103616}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285173}, year = {2020}, abstract = {The aim of this randomized, controlled animal exploratory trial was to investigate the influence of local application of aminobisphosphonate pamidronate during the socket preservation procedure. Mandibular premolars were extracted in five G{\"o}ttingen minipigs. Two animals underwent socket preservation using BEGO OSS (n = 8 sockets) and three animals using BEGO OSS + Pamifos (15 mg) (n = 12 sockets). After jaw impression, cast models (baseline, eight weeks postoperative) were digitized using an inLab X5 scanner (Dentsply Sirona) and the generated STL data were superimposed and analyzed with GOM Inspect 2018 (GOM, Braunschweig). After 16 weeks, the lower jaws were prepared and examined using standard histological methods. In the test group (BEGO OSS + pamidronate), buccooral dimensional loss was significantly lower, both vestibulary (-0.80 ± 0.57 mm vs. -1.92 ± 0.63 mm; p = 0.00298) and lingually (-1.36 ± 0.58 mm vs. -2.56 ± 0.65 mm; p = 0.00104) compared with the control group (BEGO OSS). The test group showed a significant difference between vestibular and lingual dimensional loss (p = 0.04036). Histology showed cortical and cancellous bone in the alveolar sockets without signs of local inflammation. Adjuvant application of pamidronate during socket preservation reduces alveolar dimensional loss significantly. Further investigations with regard to dose-response relationships, volume effects, side effects, and a verification of the suitability in combination with other bone substitute materials (BSMs) are necessary.}, language = {en} } @article{PaisdziorDimitriouSchoepeetal.2020, author = {Paisdzior, Sarah and Dimitriou, Ioanna Maria and Sch{\"o}pe, Paul Curtis and Annibale, Paolo and Scheerer, Patrick and Krude, Heiko and Lohse, Martin J. and Biebermann, Heike and K{\"u}hnen, Peter}, title = {Differential signaling profiles of MC4R mutations with three different ligands}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {4}, issn = {1422-0067}, doi = {10.3390/ijms21041224}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285108}, year = {2020}, abstract = {The melanocortin 4 receptor (MC4R) is a key player in hypothalamic weight regulation and energy expenditure as part of the leptin-melanocortin pathway. Mutations in this G protein coupled receptor (GPCR) are the most common cause for monogenetic obesity, which appears to be mediated by changes in the anorectic action of MC4R via G\(_S\)-dependent cyclic adenosine-monophosphate (cAMP) signaling as well as other signaling pathways. To study potential bias in the effects of MC4R mutations between the different signaling pathways, we investigated three major MC4R mutations: a G\(_S\) loss-of-function (S127L) and a G\(_S\) gain-of-function mutant (H158R), as well as the most common European single nucleotide polymorphism (V103I). We tested signaling of all four major G protein families plus extracellular regulated kinase (ERK) phosphorylation and β-arrestin2 recruitment, using the two endogenous agonists, α- and β-melanocyte stimulating hormone (MSH), along with a synthetic peptide agonist (NDP-α-MSH). The S127L mutation led to a full loss-of-function in all investigated pathways, whereas V103I and H158R were clearly biased towards the G\(_{q/11}\) pathway when challenged with the endogenous ligands. These results show that MC4R mutations can cause vastly different changes in the various MC4R signaling pathways and highlight the importance of a comprehensive characterization of receptor mutations.}, language = {en} } @article{AmeriSchiattarellaCrottietal.2020, author = {Ameri, Pietro and Schiattarella, Gabriele Giacomo and Crotti, Lia and Torchio, Margherita and Bertero, Edoardo and Rodolico, Daniele and Forte, Maurizio and Di Mauro, Vittoria and Paolillo, Roberta and Chimenti, Cristina and Torella, Daniele and Catalucci, Daniele and Sciarretta, Sebastiano and Basso, Cristina and Indolfi, Ciro and Perrino, Cinzia}, title = {Novel basic science insights to improve the management of heart failure: Review of the working group on cellular and molecular biology of the heart of the Italian Society of Cardiology}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {4}, issn = {1422-0067}, doi = {10.3390/ijms21041192}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285085}, year = {2020}, abstract = {Despite important advances in diagnosis and treatment, heart failure (HF) remains a syndrome with substantial morbidity and dismal prognosis. Although implementation and optimization of existing technologies and drugs may lead to better management of HF, new or alternative strategies are desirable. In this regard, basic science is expected to give fundamental inputs, by expanding the knowledge of the pathways underlying HF development and progression, identifying approaches that may improve HF detection and prognostic stratification, and finding novel treatments. Here, we discuss recent basic science insights that encompass major areas of translational research in HF and have high potential clinical impact.}, language = {en} } @article{DollKolbSchnappetal.2020, author = {Doll, Julia and Kolb, Susanne and Schnapp, Linda and Rad, Aboulfazl and R{\"u}schendorf, Franz and Khan, Imran and Adli, Abolfazl and Hasanzadeh, Atefeh and Liedtke, Daniel and Knaup, Sabine and Hofrichter, Michaela AH and M{\"u}ller, Tobias and Dittrich, Marcus and Kong, Il-Keun and Kim, Hyung-Goo and Haaf, Thomas and Vona, Barbara}, title = {Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients}, series = {International Journal of Molecular Sciences}, volume = {21}, journal = {International Journal of Molecular Sciences}, number = {1}, issn = {1422-0067}, doi = {10.3390/ijms21010311}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285142}, year = {2020}, abstract = {CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss.}, language = {en} } @article{ZhouDierksKertelsetal.2020, author = {Zhou, Xiang and Dierks, Alexander and Kertels, Olivia and Kircher, Malte and Schirbel, Andreas and Samnick, Samuel and Buck, Andreas K. and Knorz, Sebastian and B{\"o}ckle, David and Scheller, Lukas and Messerschmidt, Janin and Barakat, Mohammad and Kort{\"u}m, K. Martin and Rasche, Leo and Einsele, Hermann and Lapa, Constantin}, title = {18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in patients with smoldering multiple myeloma: imaging pattern and clinical features}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {8}, issn = {2072-6694}, doi = {10.3390/cancers12082333}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211240}, year = {2020}, abstract = {This study aimed to explore the correlation between imaging patterns and clinical features in patients with smoldering multiple myeloma (SMM) who simultaneously underwent 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor positron emission tomography/computed tomography (PET/CT). We retrieved and analyzed clinical characteristics and PET imaging data of 10 patients with SMM. We found a significant correlation between bone marrow (BM) plasma cell (PC) infiltration and mean standardized uptake values (SUV\(_{mean}\)) of lumbar vertebrae L2-L4 on 11C-Methionine PET/CT scans (r = 0.676, p = 0.031) and 68Ga-Pentixafor PET/CT scans (r = 0.839, p = 0.002). However, there was no significant correlation between BM involvement and SUV\(_{mean}\) of lumbar vertebrae L2-L4 on 18F-FDG PET/CT scans (r = 0.558, p = 0.093). Similarly, mean target-to-background ratios (TBR\(_{mean}\)) of lumbar vertebrae L2-L4 also correlated with bone marrow plasma cell (BMPC) infiltration in 11C-Methionine PET/CT (r = 0.789, p = 0.007) and 68Ga-Pentixafor PET/CT (r = 0.724, p = 0.018) PET/CT. In contrast, we did not observe a significant correlation between BMPC infiltration rate and TBR\(_{mean}\) in 18F-FDG PET/CT (r = 0.355, p = 0.313). Additionally, on 11C-Methionine PET/CT scans, we found a significant correlation between BMPC infiltration and TBR\(_{max}\) of lumbar vertebrae L2-L4 (r = 0.642, p = 0.045). In conclusion, 11C-Methionine and 68Ga-Pentixafor PET/CT demonstrate higher sensitivity than 18F-FDG PET/CT in detecting BM involvement in SMM.}, language = {en} } @article{SubramaniyanSridharanHowardetal.2020, author = {Subramaniyan, Boopathi and Sridharan, Sangita and Howard, Cory M. and Tilley, Augustus M.C. and Basuroy, Tupa and Serna, Ivana de la and Butt, Elke and Raman, Dayanidhi}, title = {Role of the CXCR4-LASP1 axis in the stabilization of Snail1 in triple-negative breast cancer}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {9}, issn = {2072-6694}, doi = {10.3390/cancers12092372}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211217}, year = {2020}, abstract = {The CXCL12-CXCR4 axis plays a vital role in many steps of breast cancer metastasis, but the molecular mechanisms have not been fully elucidated. We previously reported that activation of CXCR4 by CXCL12 promotes the nuclear localization of LASP1 (LIM and SH3 protein 1). The nuclear LASP1 then interacts with Snail1 in triple-negative breast cancer (TNBC) cell lines. In this study, we report that the nuclear accumulation and retention of Snail1 was dependent on an increase in nuclear LASP1 levels driven by active CXCR4. The CXCR4-LASP1 axis may directly regulate the stabilization of nuclear Snail1, by upregulating nuclear levels of pS473-Akt, pS9-GSK-3β, A20, and LSD1. Furthermore, the activation of CXCR4 induced association of LASP1 with Snail1, A20, GSK-3β, and LSD1 endogenously. Thus, nuclear LASP1 may also regulate protein-protein interactions that facilitate the stability of Snail1. Genetic ablation of LASP1 resulted in the mislocalization of nuclear Snail1, loss of the ability of TNBC cells to invade Matrigel and a dysregulated expression of both epithelial and mesenchymal markers, including an increased expression of ALDH1A1, a marker for epithelial breast cancer stem-like cells. Our findings reveal a novel role for the CXCR4-LASP1 axis in facilitating the stability of nuclear localized Snail1.}, language = {en} } @article{KosnopfelSinnbergSaueretal.2020, author = {Kosnopfel, Corinna and Sinnberg, Tobias and Sauer, Birgit and Niessner, Heike and Muenchow, Alina and Fehrenbacher, Birgit and Schaller, Martin and Mertens, Peter R. and Garbe, Claus and Thakur, Basant Kumar and Schittek, Birgit}, title = {Tumour progression stage-dependent secretion of YB-1 stimulates melanoma cell migration and invasion}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {8}, issn = {2072-6694}, doi = {10.3390/cancers12082328}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211206}, year = {2020}, abstract = {Secreted factors play an important role in intercellular communication. Therefore, they are not only indispensable for the regulation of various physiological processes but can also decisively advance the development and progression of tumours. In the context of inflammatory disease, Y-box binding protein 1 (YB-1) is actively secreted and the extracellular protein promotes cell proliferation and migration. In malignant melanoma, intracellular YB-1 expression increases during melanoma progression and represents an unfavourable prognostic marker. Here, we show active secretion of YB-1 from melanoma cells as opposed to benign cells of the skin. Intriguingly, YB-1 secretion correlates with the stage of melanoma progression and depends on a calcium- and ATP-dependent non-classical secretory pathway leading to the occurrence of YB-1 in the extracellular space as a free protein. Along with an elevated YB-1 secretion of melanoma cells in the metastatic growth phase, extracellular YB-1 exerts a stimulating effect on melanoma cell migration, invasion, and tumourigenicity. Collectively, these data suggest that secreted YB-1 plays a functional role in melanoma cell biology, stimulating metastasis, and may serve as a novel biomarker in malignant melanoma that reflects tumour aggressiveness.}, language = {en} } @article{SchmidSchmidtHazuretal.2020, author = {Schmid, Rafael and Schmidt, Sonja K. and Hazur, Jonas and Detsch, Rainer and Maurer, Evelyn and Boccaccini, Aldo R. and Hauptstein, Julia and Teßmar, J{\"o}rg and Blunk, Torsten and Schr{\"u}fer, Stefan and Schubert, Dirk W. and Horch, Raymund E. and Bosserhoff, Anja K. and Arkudas, Andreas and Kengelbach-Weigand, Annika}, title = {Comparison of hydrogels for the development of well-defined 3D cancer models of breast cancer and melanoma}, series = {Cancers}, volume = {12}, journal = {Cancers}, number = {8}, issn = {2072-6694}, doi = {10.3390/cancers12082320}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211195}, year = {2020}, abstract = {Bioprinting offers the opportunity to fabricate precise 3D tumor models to study tumor pathophysiology and progression. However, the choice of the bioink used is important. In this study, cell behavior was studied in three mechanically and biologically different hydrogels (alginate, alginate dialdehyde crosslinked with gelatin (ADA-GEL), and thiol-modified hyaluronan (HA-SH crosslinked with PEGDA)) with cells from breast cancer (MDA-MB-231 and MCF-7) and melanoma (Mel Im and MV3), by analyzing survival, growth, and the amount of metabolically active, living cells via WST-8 labeling. Material characteristics were analyzed by dynamic mechanical analysis. Cell lines revealed significantly increased cell numbers in low-percentage alginate and HA-SH from day 1 to 14, while only Mel Im also revealed an increase in ADA-GEL. MCF-7 showed a preference for 1\% alginate. Melanoma cells tended to proliferate better in ADA-GEL and HA-SH than mammary carcinoma cells. In 1\% alginate, breast cancer cells showed equally good proliferation compared to melanoma cell lines. A smaller area was colonized in high-percentage alginate-based hydrogels. Moreover, 3\% alginate was the stiffest material, and 2.5\% ADA-GEL was the softest material. The other hydrogels were in the same range in between. Therefore, cellular responses were not only stiffness-dependent. With 1\% alginate and HA-SH, we identified matrices that enable proliferation of all tested tumor cell lines while maintaining expected tumor heterogeneity. By adapting hydrogels, differences could be accentuated. This opens up the possibility of understanding and analyzing tumor heterogeneity by biofabrication.}, language = {en} } @article{IsaacsMikasiObasaetal.2020, author = {Isaacs, Darren and Mikasi, Sello Given and Obasa, Adetayo Emmanuel and Ikomey, George Mondinde and Shityakov, Sergey and Cloete, Ruben and Jacobs, Graeme Brendon}, title = {Structural comparison of diverse HIV-1 subtypes using molecular modelling and docking analyses of integrase inhibitors}, series = {Viruses}, volume = {12}, journal = {Viruses}, number = {9}, issn = {1999-4915}, doi = {10.3390/v12090936}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211170}, year = {2020}, abstract = {The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-na{\"i}ve populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.}, language = {en} } @article{UlbrichtNickelWeidenbachetal.2020, author = {Ulbricht, Andrea and Nickel, Lisa and Weidenbach, Katrin and Vargas Gebauer, Herman and Kießling, Claudia and F{\"o}rstner, Konrad U. and Schmitz, Ruth A.}, title = {The CARF protein MM_0565 affects transcription of the casposon-encoded cas1-solo gene in Methanosarcina mazei G{\"o}1}, series = {Biomolecules}, volume = {10}, journal = {Biomolecules}, number = {8}, issn = {2218-273X}, doi = {10.3390/biom10081161}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211097}, year = {2020}, abstract = {Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) loci are found in bacterial and archaeal genomes where they provide the molecular machinery for acquisition of immunity against foreign DNA. In addition to the cas genes fundamentally required for CRISPR activity, a second class of genes is associated with the CRISPR loci, of which many have no reported function in CRISPR-mediated immunity. Here, we characterize MM_0565 associated to the type I-B CRISPR-locus of Methanosarcina mazei G{\"o}1. We show that purified MM_0565 composed of a CRISPR-Cas Associated Rossmann Fold (CARF) and a winged helix-turn-helix domain forms a dimer in solution; in vivo, the dimeric MM_0565 is strongly stabilized under high salt stress. While direct effects on CRISPR-Cas transcription were not detected by genetic approaches, specific binding of MM_0565 to the leader region of both CRISPR-Cas systems was observed by microscale thermophoresis and electromobility shift assays. Moreover, overexpression of MM_0565 strongly induced transcription of the cas1-solo gene located in the recently reported casposon, the gene product of which shows high similarity to classical Cas1 proteins. Based on our findings, and taking the absence of the expressed CRISPR locus-encoded Cas1 protein into account, we hypothesize that MM_0565 might modulate the activity of the CRISPR systems on different levels.}, language = {en} } @article{Weinreich2020, author = {Weinreich, Oliver}, title = {Psalterien in W{\"u}rzburger Brevieren zwischen 1479 und 1575}, series = {W{\"u}rzburger Di{\"o}zesangeschichtsbl{\"a}tter}, volume = {83}, journal = {W{\"u}rzburger Di{\"o}zesangeschichtsbl{\"a}tter}, issn = {0342-3093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-303750}, pages = {73-86}, year = {2020}, abstract = {Es werden Psalterien aus Brevieren vorgestellt, die zwischen 1479 und 1575 in W{\"u}rzburg oder im Auftrag des F{\"u}rstbischofs von W{\"u}rzburg gedruckt worden sind.}, subject = {W{\"u}rzburg}, language = {de} } @article{MenekseRennerMahlmeisteretal.2020, author = {Menekse, Kaan and Renner, Rebecca and Mahlmeister, Bernhard and Stolte, Matthias and W{\"u}rthner, Frank}, title = {Bowl-shaped naphthalimide-annulated corannulene as nonfullerene acceptor in organic solar cells}, series = {Organic Materials}, volume = {2}, journal = {Organic Materials}, number = {3}, issn = {2625-1825}, doi = {10.1055/s-0040-1714283}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299095}, pages = {229-234}, year = {2020}, abstract = {An electron-poor bowl-shaped naphthalimide-annulated corannulene with branched alkyl residues in the imide position was synthesized by a palladium-catalyzed cross-coupling annulation sequence. This dipolar compound exhibits strong absorption in the visible range along with a low-lying LUMO level at -3.85 eV, enabling n-type charge transport in organic thin-film transistors. Furthermore, we processed inverted bulk-heterojunction solar cells in combination with the two donor polymers PCE-10 and PM6 to achieve open-circuit voltages up to 1.04 V. By using a blend of the self-assembled naphthalimide-annulated corannulene and PCE-10, we were able to obtain a power conversion efficiency of up to 2.1\%, which is to the best of our knowledge the highest reported value for a corannulene-based organic solar cell to date.}, language = {en} } @misc{GottschlichDunkelDrenckhahnetal.2020, author = {Gottschlich, G{\"u}nter and Dunkel, Franz G. and Drenckhahn, Detlev and Weber, Heinrich E. and Gallo, Lorenzo}, title = {Forum Geobotanicum Vol. 9 (2020)}, volume = {9(2020)}, editor = {Meierott, Lenz and Drenckhahn, Detlev and Dunkel, Franz G. and Ewald, J{\"o}rg and Fleischmann, Andreas}, issn = {1867-9315}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-298919}, year = {2020}, abstract = {Forum Geobotanicum is an electronic journal devoted to disseminate information concerning geographical distribution, ecology, morphology, taxonomy and conservation of vascular plants in the European Union with a main focus on middle Europe. It covers from molecular biology to environmental aspects. The focus is to publish original papers, reviews and announcements for the educated generalist as well as the specialist in this broad field. Forum Geobotanicum does not aim to supplant existing paper journals, but will be much more flexible in format, publication time and world-wide distribution than paper journals. Many important studies are being currently published in local journals and booklets and some of them are published privately. Hence, these studies will become aware to only a limited readership. Forum Geobotanicum will encourage authors of such papers to submit them as special issues of the journal. Moreover, the journal is planning to build up an E-mail-address section to support communication between geobotanists in Europe. The editors are optimistic that this electronic journal will develop to a widely used communication forum that will help to stimulate activities in the entire field of geobotany in middle Europe. To overcome problems of long term archivation and effective taxonomic publication of articles published electronically in Forum Geobotanicum, print versions of each volume of the journal and appropriate digital storage devices will be delivered freely to selected university libraries and state libraries in middle Europe.}, subject = {Geobotanik}, language = {de} } @article{LeonhardtLihoreauSpaethe2020, author = {Leonhardt, Sara D. and Lihoreau, Mathieu and Spaethe, Johannes}, title = {Mechanisms of nutritional resource exploitation by insects}, series = {Insects}, volume = {11}, journal = {Insects}, number = {9}, issn = {2075-4450}, doi = {10.3390/insects11090570}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211161}, year = {2020}, abstract = {Insects have evolved an extraordinary range of nutritional adaptations to exploit other animals, plants, bacteria, fungi and soils as resources in terrestrial and aquatic environments. This special issue provides some new insights into the mechanisms underlying these adaptations. Contributions comprise lab and field studies investigating the chemical, physiological, cognitive and behavioral mechanisms that enable resource exploitation and nutrient intake regulation in insects. The collection of papers highlights the need for more studies on the comparative sensory ecology, underlying nutritional quality assessment, cue perception and decision making to fully understand how insects adjust resource selection and exploitation in response to environmental heterogeneity and variability.}, language = {en} } @article{WinterPryssProbstetal.2020, author = {Winter, Michael and Pryss, R{\"u}diger and Probst, Thomas and Reichert, Manfred}, title = {Towards the applicability of measuring the electrodermal activity in the context of process model comprehension: feasibility study}, series = {Sensors}, volume = {20}, journal = {Sensors}, number = {16}, issn = {1424-8220}, doi = {10.3390/s20164561}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211276}, year = {2020}, abstract = {Process model comprehension is essential in order to understand the five Ws (i.e., who, what, where, when, and why) pertaining to the processes of organizations. However, research in this context showed that a proper comprehension of process models often poses a challenge in practice. For this reason, a vast body of research exists studying the factors having an influence on process model comprehension. In order to point research towards a neuro-centric perspective in this context, the paper at hand evaluates the appropriateness of measuring the electrodermal activity (EDA) during the comprehension of process models. Therefore, a preliminary test run and a feasibility study were conducted relying on an EDA and physical activity sensor to record the EDA during process model comprehension. The insights obtained from the feasibility study demonstrated that process model comprehension leads to an increased activity in the EDA. Furthermore, EDA-related results indicated significantly that participants were confronted with a higher cognitive load during the comprehension of complex process models. In addition, the experiences and limitations we learned in measuring the EDA during the comprehension of process models are discussed in this paper. In conclusion, the feasibility study demonstrated that the measurement of the EDA could be an appropriate method to obtain new insights into process model comprehension.}, language = {en} } @article{KemmlerKohlJakobetal.2020, author = {Kemmler, Wolfgang and Kohl, Matthias and Jakob, Franz and Engelke, Klaus and Stengel, Simon von}, title = {Effects of high intensity dynamic resistance exercise and whey protein supplements on osteosarcopenia in older men with low bone and muscle mass. Final results of the randomized controlled FrOST study}, series = {Nutrients}, volume = {12}, journal = {Nutrients}, number = {8}, issn = {2072-6643}, doi = {10.3390/nu12082341}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211108}, year = {2020}, abstract = {The present study aimed to evaluate the effect of high intensity dynamic resistance exercise (HIT-DRT) and whey protein supplementation (WPS) on bone mineral density (BMD) and sarcopenia parameters in osteosarcopenic men. Men ≥ 72 years with osteosarcopenia (n = 43) were randomly assigned to a HIT-RT (HIT-RT: n = 21) or a non-training control group (n = 22). Supervised HIT-RT twice/week was applied for 18 months, while the control group maintained their habitual lifestyle. Supplying WPS, total protein intake amounted to 1.5-1.6 (HIT-RT) and 1.2 g/kg/body mass/d (control). Both groups were supplied with calcium and vitamin D. Primary study outcomes were BMD and the sarcopenia Z-score. After adjusting for multiplicity, we observed significant positive effects for sarcopenia Z-score (standardized mean difference (SMD): 1.40), BMD at lumbar spine (SMD: 0.72) and total hip (SMD: 0.72). In detail, effect sizes for skeletal muscle mass changes were very pronounced (1.97, p < 0.001), while effects for functional sarcopenia parameters were moderate (0.87, p = 0.008; handgrip strength) or low (0.39, p = 0.209; gait velocity). Apart from one man who reported short periods of temporary worsening of existing joint pain, no HIT-RT/WPS-related adverse effects or injuries were reported. We consider HIT-RT supported by whey protein supplementation as a feasible, attractive, safe and highly effective option to fight osteosarcopenia in older men.}, language = {en} } @article{SognoTraidlHoffmannKuenzer2020, author = {Sogno, Patrick and Traidl-Hoffmann, Claudia and Kuenzer, Claudia}, title = {Earth Observation data supporting non-communicable disease research: a review}, series = {Remote Sensing}, volume = {12}, journal = {Remote Sensing}, number = {16}, issn = {2072-4292}, doi = {10.3390/rs12162541}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211113}, year = {2020}, abstract = {A disease is non-communicable when it is not transferred from one person to another. Typical examples include all types of cancer, diabetes, stroke, or allergies, as well as mental diseases. Non-communicable diseases have at least two things in common — environmental impact and chronicity. These diseases are often associated with reduced quality of life, a higher rate of premature deaths, and negative impacts on a countries' economy due to healthcare costs and missing work force. Additionally, they affect the individual's immune system, which increases susceptibility toward communicable diseases, such as the flu or other viral and bacterial infections. Thus, mitigating the effects of non-communicable diseases is one of the most pressing issues of modern medicine, healthcare, and governments in general. Apart from the predisposition toward such diseases (the genome), their occurrence is associated with environmental parameters that people are exposed to (the exposome). Exposure to stressors such as bad air or water quality, noise, extreme heat, or an overall unnatural surrounding all impact the susceptibility to non-communicable diseases. In the identification of such environmental parameters, geoinformation products derived from Earth Observation data acquired by satellites play an increasingly important role. In this paper, we present a review on the joint use of Earth Observation data and public health data for research on non-communicable diseases. We analyzed 146 articles from peer-reviewed journals (Impact Factor ≥ 2) from all over the world that included Earth Observation data and public health data for their assessments. Our results show that this field of synergistic geohealth analyses is still relatively young, with most studies published within the last five years and within national boundaries. While the contribution of Earth Observation, and especially remote sensing-derived geoinformation products on land surface dynamics is on the rise, there is still a huge potential for transdisciplinary integration into studies. We see the necessity for future research and advocate for the increased incorporation of thematically profound remote sensing products with high spatial and temporal resolution into the mapping of exposomes and thus the vulnerability and resilience assessment of a population regarding non-communicable diseases.}, language = {en} } @article{KannBruennertHansenetal.2020, author = {Kann, Simone and Bruennert, Daniela and Hansen, Jessica and Concha Mendoza, Gustavo Andr{\´e}s and Crespo Gonzalez, Jos{\´e} Jos{\´e} and Armenta Quintero, Cielo Leonor and Hanke, Miriam and Hagen, Ralf Matthias and Backhaus, Joy and Frickmann, Hagen}, title = {High prevalence of intestinal pathogens in Indigenous in Colombia}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {9}, issn = {2077-0383}, doi = {10.3390/jcm9092786}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211289}, year = {2020}, abstract = {Background: Intestinal infections remain a major public health burden in developing countries. Due to social, ecological, environmental, and cultural conditions, Indigenous peoples in Colombia are at particularly high risk. Materials: 137 stool samples were analyzed by microscopy and real-time-Polymerase Chain Reaction (RT-PCR), targeting protozoan parasites (Giardia intestinalis, Entamoeba histolytica, Cryptosporidium spp., and Cyclospora cayetanensis), bacteria (Campylobacter jejuni, Salmonella spp., Shigella ssp./enteroinvasive E. coli (EIEC), Yersinia spp., enterohemorrhagic E. coli (EHEC), enteropathogenic E. coli (EPEC), enterotoxin-producing E. coli (ETEC), enteroaggregative E. coli (EAEC), and Tropheryma whipplei), and helminths (Necator americanus, Strongyloides stercoralis, Ascaris lumbricoides, Ancylostoma spp., Trichuris. trichiura, Taenia spp., Hymenolepis nana, Enterobius vermicularis, and Schistosoma spp.). Microscopy found additional cases of helminth infections. Results: At least one pathogen was detected in 93\% of the samples. The overall results revealed protozoa in 79\%, helminths in 69\%, and bacteria in 41\%. G. intestinalis (48\%), Necator/hookworm (27\%), and EAEC (68\%) were the most common in each group. Noteworthy, T. whipplei was positive in 7\% and T. trichirua in 23\% of the samples. A significant association of one infection promoting the other was determined for G. intestinalis and C. jejuni, helminth infections, and EIEC. Conclusions: The results illustrate the high burden of gastrointestinal pathogens among Indigenous peoples compared to other developing countries. Countermeasures are urgently required.}, language = {en} } @article{KristDornquastReinholdetal.2020, author = {Krist, Lilian and Dornquast, Christina and Reinhold, Thomas and Becher, Heiko and Icke, Katja and Danquah, Ina and Willich, Stefan N. and Keil, Thomas}, title = {Physical activity trajectories among persons of Turkish descent living in Germany — a cohort study}, series = {International Journal of Environmental Research and Public Health}, volume = {17}, journal = {International Journal of Environmental Research and Public Health}, number = {17}, issn = {1660-4601}, doi = {10.3390/ijerph17176349}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-211221}, year = {2020}, abstract = {Physical activity (PA) behavior is increasingly described as trajectories taking changes over a longer period into account. Little is known, however, about predictors of those trajectories among migrant populations. Therefore, the aim of the present cohort study was to describe changes of PA over six years and to explore migration-related and other predictors for different PA trajectories in adults of Turkish descent living in Berlin. At baseline (2011/2012) and after six years, sociodemographics, health behavior, and medical information were assessed. Four PA trajectories were defined using data of weekly PA from baseline and follow-up: "inactive", "decreasing", "increasing", and "stable active". Multivariable regression analyses were performed in order to determine predictors for the "stable active" trajectory, and results were presented as adjusted odds ratios (aOR) with 95\% confidence intervals (95\%CI). In this analysis, 197 people (60.9\% women, mean age ± standard deviation 49.9 ± 12.8 years) were included. A total of 77.7\% were first-generation migrants, and 50.5\% had Turkish citizenship. The four PA trajectories differed regarding citizenship, preferred questionnaire language, and marital status. "Stable active" trajectory membership was predicted by educational level (high vs. low: aOR 4.20, 95\%CI [1.10; 16.00]), citizenship (German or dual vs. Turkish only: 3.60 [1.20; 10.86]), preferred questionnaire language (German vs. Turkish: 3.35 [1.05; 10.66]), and BMI (overweight vs. normal weight: 0.28 [0.08; 0.99]). In our study, migration-related factors only partially predicted trajectory membership, however, persons with citizenship of their country of origin and/or with poor language skills should be particularly considered when planning PA prevention programs.}, language = {en} } @article{PalladinoChiocchettiFranketal.2020, author = {Palladino, Viola Stella and Chiocchetti, Andreas G. and Frank, Lukas and Haslinger, Denise and McNeill, Rhiannon and Radtke, Franziska and Till, Andreas and Haupt, Simone and Br{\"u}stle, Oliver and G{\"u}nther, Katharina and Edenhofer, Frank and Hoffmann, Per and Reif, Andreas and Kittel-Schneider, Sarah}, title = {Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD}, series = {Journal of Clinical Medicine}, volume = {9}, journal = {Journal of Clinical Medicine}, number = {12}, issn = {2077-0383}, doi = {10.3390/jcm9124092}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220074}, year = {2020}, abstract = {The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.}, language = {en} } @article{BiltuevaProkopovRomanenkoetal.2020, author = {Biltueva, Larisa S. and Prokopov, Dmitry Yu. and Romanenko, Svetlana A. and Interesova, Elena A. and Schartl, Manfred and Trifonov, Vladimir A.}, title = {Chromosome distribution of highly conserved tandemly arranged repetitive DNAs in the Siberian sturgeon (Acipenser baerii)}, series = {Genes}, volume = {11}, journal = {Genes}, number = {11}, issn = {2073-4425}, doi = {10.3390/genes11111375}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219371}, year = {2020}, abstract = {Polyploid genomes present a challenge for cytogenetic and genomic studies, due to the high number of similar size chromosomes and the simultaneous presence of hardly distinguishable paralogous elements. The karyotype of the Siberian sturgeon (Acipenser baerii) contains around 250 chromosomes and is remarkable for the presence of paralogs from two rounds of whole-genome duplications (WGD). In this study, we applied the sterlet-derived acipenserid satDNA-based whole chromosome-specific probes to analyze the Siberian sturgeon karyotype. We demonstrate that the last genome duplication event in the Siberian sturgeon was accompanied by the simultaneous expansion of several repetitive DNA families. Some of the repetitive probes serve as good cytogenetic markers distinguishing paralogous chromosomes and detecting ancestral syntenic regions, which underwent fusions and fissions. The tendency of minisatellite specificity for chromosome size groups previously observed in the sterlet genome is also visible in the Siberian sturgeon. We provide an initial physical chromosome map of the Siberian sturgeon genome supported by molecular markers. The application of these data will facilitate genomic studies in other recent polyploid sturgeon species.}, language = {en} } @article{UsmanMahmoodConradetal.2020, author = {Usman, Muhammad and Mahmood, Talha and Conrad, Christopher and Bodla, Habib Ullah}, title = {Remote Sensing and modelling based framework for valuing irrigation system efficiency and steering indicators of consumptive water use in an irrigated region}, series = {Sustainability}, volume = {12}, journal = {Sustainability}, number = {22}, issn = {2071-1050}, doi = {10.3390/su12229535}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219358}, year = {2020}, abstract = {Water crises are becoming severe in recent times, further fueled by population increase and climate change. They result in complex and unsustainable water management. Spatial estimation of consumptive water use is vital for performance assessment of the irrigation system using Remote Sensing (RS). For this study, its estimation is done using the Soil Energy Balance Algorithm for Land (SEBAL) approach. Performance indicators including equity, adequacy, and reliability were worked out at various spatiotemporal scales. Moreover, optimization and sustainable use of water resources are not possible without knowing the factors mainly influencing consumptive water use of major crops. For that purpose, random forest regression modelling was employed using various sets of factors for site-specific, proximity, and cropping system. The results show that the system is underperforming both for Kharif (i.e., summer) and Rabi (i.e., winter) seasons. Performance indicators highlight poor water distribution in the system, a shortage of water supply, and unreliability. The results are relatively good for Rabi as compared to Kharif, with an overall poor situation for both seasons. Factors importance varies for different crops. Overall, distance from canal, road density, canal density, and farm approachability are the most important factors for explaining consumptive water use. Auditing of consumptive water use shows the potential for resource optimization through on-farm water management by the targeted approach. The results are based on the present situation without considering future changes in canal water supply and consumptive water use under climate change.}, language = {en} } @article{Kraft2020, author = {Kraft, Stephan}, title = {"Gipp ammall BILD." Zur Initialz{\"u}ndung der Doppelhandlung in Arno Schmidts "Kaff auch Mare Crisium"}, series = {Bargfelder Bote}, journal = {Bargfelder Bote}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-282509}, year = {2020}, abstract = {Kein Abstract verf{\"u}gbar.}, language = {de} } @article{RiethToberLimbachetal.2020, author = {Rieth, Thorsten and Tober, Natalie and Limbach, Daniel and Haspel, Tobias and Sperner, Marcel and Schupp, Niklas and Wicker, Philipp and Glang, Stefan and Lehmann, Matthias and Detert, Heiner}, title = {Impact of substitution pattern and chain length on the thermotropic properties of alkoxy-substituted triphenyl-tristriazolotriazines}, series = {Molecules}, volume = {25}, journal = {Molecules}, number = {23}, issn = {1420-3049}, doi = {10.3390/molecules25235761}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220019}, year = {2020}, abstract = {Tristriazolotriazines (TTTs) with a threefold alkoxyphenyl substitution were prepared and studied by DSC, polarized optical microscopy (POM) and X-ray scattering. Six pentyloxy chains are sufficient to induce liquid-crystalline behavior in these star-shaped compounds. Thermotropic properties of TTTs with varying substitution patterns and a periphery of linear chains of different lengths, branching in the chain and swallow-tails, are compared. Generally, these disks display broad and stable thermotropic mesophases, with the tangential TTT being superior to the radial isomer. The structure-property relationships of the number of alkyl chains, their position, length and structure were studied.}, language = {en} } @article{ThurowKrischkeMuelleretal.2020, author = {Thurow, Corinna and Krischke, Markus and Mueller, Martin J. and Gatz, Christiane}, title = {Induction of jasmonoyl-isoleucine (JA-Ile)-dependent JASMONATE ZIM-DOMAIN (JAZ) genes in NaCl-treated Arabidopsis thaliana roots can occur at very low JA-Ile levels and in the absence of the JA/JA-Ile transporter JAT1/AtABCG16}, series = {Plants}, volume = {9}, journal = {Plants}, number = {12}, issn = {2223-7747}, doi = {10.3390/plants9121635}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219382}, year = {2020}, abstract = {The plant hormone jasmonoyl-isoleucine (JA-Ile) is an important regulator of plant growth and defense in response to various biotic and abiotic stress cues. Under our experimental conditions, JA-Ile levels increased approximately seven-fold in NaCl-treated Arabidopsis thaliana roots. Although these levels were around 1000-fold lower than in wounded leaves, genes of the JA-Ile signaling pathway were induced by a factor of 100 or more. Induction was severely compromised in plants lacking the JA-Ile receptor CORONATINE INSENSITIVE 1 or enzymes required for JA-Ile biosynthesis. To explain efficient gene expression at very low JA-Ile levels, we hypothesized that salt-induced expression of the JA/JA-Ile transporter JAT1/AtABCG16 would lead to increased nuclear levels of JA-Ile. However, mutant plants with different jat1 alleles were similar to wild-type ones with respect to salt-induced gene expression. The mechanism that allows COI1-dependent gene expression at very low JA-Ile levels remains to be elucidated.}, language = {en} } @article{SteinCoulibalyBalimaetal.2020, author = {Stein, Katharina and Coulibaly, Drissa and Balima, Larba Hubert and Goetze, Dethardt and Linsenmair, Karl Eduard and Porembski, Stefan and Stenchly, Kathrin and Theodorou, Panagiotis}, title = {Plant-pollinator networks in savannas of Burkina Faso, West Africa}, series = {Diversity}, volume = {13}, journal = {Diversity}, number = {1}, issn = {1424-2818}, doi = {10.3390/d13010001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220157}, year = {2020}, abstract = {West African savannas are severely threatened with intensified land use and increasing degradation. Bees are important for terrestrial biodiversity as they provide native plant species with pollination services. However, little information is available regarding their mutualistic interactions with woody plant species. In the first network study from sub-Saharan West Africa, we investigated the effects of land-use intensity and climatic seasonality on plant-bee communities and their interaction networks. In total, we recorded 5686 interactions between 53 flowering woody plant species and 100 bee species. Bee-species richness and the number of interactions were higher in the low compared to medium and high land-use intensity sites. Bee- and plant-species richness and the number of interactions were higher in the dry compared to the rainy season. Plant-bee visitation networks were not strongly affected by land-use intensity; however, climatic seasonality had a strong effect on network architecture. Null-model corrected connectance and nestedness were higher in the dry compared to the rainy season. In addition, network specialization and null-model corrected modularity were lower in the dry compared to the rainy season. Our results suggest that in our study region, seasonal effects on mutualistic network architecture are more pronounced compared to land-use change effects. Nonetheless, the decrease in bee-species richness and the number of plant-bee interactions with an increase in land-use intensity highlights the importance of savanna conservation for maintaining bee diversity and the concomitant provision of ecosystem services.}, language = {en} } @article{PlumEggersHellingetal.2020, author = {Plum, Sarah and Eggers, Britta and Helling, Stefan and Stepath, Markus and Theiss, Carsten and Leite, Renata E. P. and Molina, Mariana and Grinberg, Lea T. and Riederer, Peter and Gerlach, Manfred and May, Caroline and Marcus, Katrin}, title = {Proteomic characterization of synaptosomes from human substantia nigra indicates altered mitochondrial translation in Parkinson's disease}, series = {Cells}, volume = {9}, journal = {Cells}, number = {12}, issn = {2073-4409}, doi = {10.3390/cells9122580}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-219978}, year = {2020}, abstract = {The pathological hallmark of Parkinson's disease (PD) is the loss of neuromelanin-containing dopaminergic neurons within the substantia nigra pars compacta (SNpc). Additionally, numerous studies indicate an altered synaptic function during disease progression. To gain new insights into the molecular processes underlying the alteration of synaptic function in PD, a proteomic study was performed. Therefore, synaptosomes were isolated by density gradient centrifugation from SNpc tissue of individuals at advanced PD stages (N = 5) as well as control subjects free of pathology (N = 5) followed by mass spectrometry-based analysis. In total, 362 proteins were identified and assigned to the synaptosomal core proteome. This core proteome comprised all proteins expressed within the synapses without regard to data analysis software, gender, age, or disease. The differential analysis between control subjects and PD cases revealed that CD9 antigen was overrepresented and fourteen proteins, among them Thymidine kinase 2 (TK2), mitochondrial, 39S ribosomal protein L37, neurolysin, and Methionine-tRNA ligase (MARS2) were underrepresented in PD suggesting an alteration in mitochondrial translation within synaptosomes.}, language = {en} } @article{SchaeferZernecke2020, author = {Sch{\"a}fer, Sarah and Zernecke, Alma}, title = {CD8\(^+\) T cells in atherosclerosis}, series = {Cells}, volume = {10}, journal = {Cells}, number = {1}, issn = {2073-4409}, doi = {10.3390/cells10010037}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220170}, year = {2020}, abstract = {Atherosclerotic lesions are populated by cells of the innate and adaptive immune system, including CD8\(^+\) T cells. The CD8\(^+\) T cell infiltrate has recently been characterized in mouse and human atherosclerosis and revealed activated, cytotoxic, and possibly dysfunctional and exhausted cell phenotypes. In mouse models of atherosclerosis, antibody-mediated depletion of CD8\(^+\) T cells ameliorates atherosclerosis. CD8\(^+\) T cells control monopoiesis and macrophage accumulation in early atherosclerosis. In addition, CD8\(^+\) T cells exert cytotoxic functions in atherosclerotic plaques and contribute to macrophage cell death and necrotic core formation. CD8\(^+\) T cell activation may be antigen-specific, and epitopes of atherosclerosis-relevant antigens may be targets of CD8\(^+\) T cells and their cytotoxic activity. CD8\(^+\) T cell functions are tightly controlled by costimulatory and coinhibitory immune checkpoints. Subsets of regulatory CD25\(^+\)CD8\(^+\) T cells with immunosuppressive functions can inhibit atherosclerosis. Importantly, local cytotoxic CD8\(^+\) T cell responses may trigger endothelial damage and plaque erosion in acute coronary syndromes. Understanding the complex role of CD8\(^+\) T cells in atherosclerosis may pave the way for defining novel treatment approaches in atherosclerosis. In this review article, we discuss these aspects, highlighting the emerging and critical role of CD8\(^+\) T cells in atherosclerosis.}, language = {en} } @article{PellegrinoDelBufaloDeAngelisetal.2020, author = {Pellegrino, Marsha and Del Bufalo, Francesca and De Angelis, Biagio and Quintarelli, Concetta and Caruana, Ignazio and de Billy, Emmanuel}, title = {Manipulating the metabolism to improve the efficacy of CAR T-cell immunotherapy}, series = {Cells}, volume = {10}, journal = {Cells}, number = {1}, issn = {2073-4409}, doi = {10.3390/cells10010014}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220140}, year = {2020}, abstract = {The adoptive transfer of the chimeric antigen receptor (CAR) expressing T-cells has produced unprecedented successful results in the treatment of B-cell malignancies. However, the use of this technology in other malignancies remains less effective. In the setting of solid neoplasms, CAR T-cell metabolic fitness needs to be optimal to reach the tumor and execute their cytolytic function in an environment often hostile. It is now well established that both tumor and T cell metabolisms play critical roles in controlling the immune response by conditioning the tumor microenvironment and the fate and activity of the T cells. In this review, after a brief description of the tumoral and T cell metabolic reprogramming, we summarize the latest advances and new strategies that have been developed to improve the metabolic fitness and efficacy of CAR T-cell products.}, language = {en} } @article{AltieriDiDatoModicaetal.2020, author = {Altieri, Barbara and Di Dato, Carla and Modica, Roberta and Bottiglieri, Filomena and Di Sarno, Antonella and Pittaway, James F.H. and Martini, Chiara and Faggiano, Antongiulio and Colao, Annamaria}, title = {Bone metabolism and vitamin D implication in gastroenteropancreatic neuroendocrine tumors}, series = {Nutrients}, volume = {12}, journal = {Nutrients}, number = {4}, issn = {2072-6643}, doi = {10.3390/nu12041021}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203823}, year = {2020}, abstract = {Patients affected by gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) have an increased risk of developing osteopenia and osteoporosis, as several factors impact on bone metabolism in these patients. In fact, besides the direct effect of bone metastasis, bone health can be affected by hormone hypersecretion (including serotonin, cortisol, and parathyroid hormone-related protein), specific microRNAs, nutritional status (which in turn could be affected by medical and surgical treatments), and vitamin D deficiency. In patients with multiple endocrine neoplasia type 1 (MEN1), a hereditary syndrome associated with NET occurrence, bone damage may carry other consequences. Osteoporosis may negatively impact on the quality of life of these patients and can increment the cost of medical care since these patients usually live with their disease for a long time. However, recommendations suggesting screening to assess bone health in GEP-NET patients are missing. The aim of this review is to critically analyze evidence on the mechanisms that could have a potential impact on bone health in patients affected by GEP-NET, focusing on vitamin D and its role in GEP-NET, as well as on factors associated with MEN1 that could have an impact on bone homeostasis.}, language = {en} }