TY - JOUR A1 - Böhm, Jennifer A1 - Scherzer, Sönke A1 - Krol, Elzbieta A1 - Kreuzer, Ines A1 - von Meyer, Katharina A1 - Lorey, Christian A1 - Mueller, Thomas D. A1 - Shabala, Lana A1 - Monte, Isabel A1 - Salano, Roberto A1 - Al-Rasheid, Khaled A. S. A1 - Rennenberg, Heinz A1 - Shabala, Sergey A1 - Neher, Erwin A1 - Hedrich, Rainer T1 - The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake JF - Current Biology N2 - Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant. KW - Venusfliegenfalle KW - Dionaea muscipula Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128054 VL - 26 IS - 3 ER - TY - JOUR A1 - Böhm, J. A1 - Scherzer, S. A1 - Shabala, S. A1 - Krol, E. A1 - Neher, E. A1 - Mueller, T. D. A1 - Hedrich, R. T1 - Venus flytrap HKT1-type channel provides for prey sodium uptake into carnivorous plant without conflicting with electrical excitability JF - Molecular Plant N2 - The animal diet of the carnivorous Venus flytrap, Dionaea muscipula, contains a sodium load that enters the capture organ via an HKT1-type sodium channel, expressed in special epithelia cells on the inner trap lobe surface. DmHKT1 expression and sodium uptake activity is induced upon prey contact. Here, we analyzed the HKT1 properties required for prey sodium osmolyte management of carnivorous Dionaea. Analyses were based on homology modeling, generation of model-derived point mutants, and their functional testing in Xenopus oocytes. We showed that the wild-type HKT1 and its Na\(^+\)- and K\(^+\)-permeable mutants function as ion channels rather than K\(^+\) transporters driven by proton or sodium gradients. These structural and biophysical features of a high-capacity, Na\(^+\)-selective ion channel enable Dionaea glands to manage prey-derived sodium loads without confounding the action potential-based information management of the flytrap. KW - sodium channel KW - HKT1 KW - Dionaea muscipula KW - action potential KW - glands KW - sodium uptake Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189803 VL - 9 IS - 3 ER - TY - JOUR A1 - Buttmann, Mathias A1 - Seuffert, Linda A1 - Mäder, Uwe A1 - Toyka, Klaus V. T1 - Malignancies after mitoxantrone for multiple sclerosis: a retrospective cohort study JF - Neurology N2 - Objective: To assess the therapy-related risk of malignancies in mitoxantrone-treated patients with multiple sclerosis. Methods: This retrospective observational cohort study included all mitoxantrone-treated patients with multiple sclerosis seen at our department between 1994 and 2007. We collected follow-up information on medically confirmed malignancies, life status, and cause of death, as of 2010. Malignancy rates were compared to the German national cancer registry matched for sex, age, and year of occurrence. Results: Follow-up was completed in 676 of 677 identified patients. Median follow-up time was 8.7 years (interquartile range 6.8-11.2), corresponding to 6,220 person-years. Median cumulative mitoxantrone dose was 79.0 mg/m(2) (interquartile range 50.8-102.4). Thirty-seven patients (5.5%) were diagnosed with a malignancy after mitoxantrone initiation, revealing a standardized incidence ratio of 1.50 (95% confidence interval CI] 1.05-2.08). Entities included breast cancer (n = 9), colorectal cancer (n = 7), acute myeloid leukemia (n = 4, 0.6%), and others (each entity n = 1 or 2). The standardized incidence ratio of colorectal cancer was 2.98 (95% CI 1.20-6.14) and of acute myeloid leukemia 10.44 (95% CI 3.39-24.36). It was not increased for other entities including breast cancer. Multivariate Cox regression identified higher age at treatment initiation but neither cumulative mitoxantrone dose (>75 vs 75 mg/m(2)) nor treatment with other immunosuppressive drugs or sex as a risk factor. Fifty-five patients had died, among them 12 of a malignancy and 43 reportedly of other causes. Conclusions: While the overall incidence of malignancies was only mildly increased, the risk of leukemia and colorectal cancer was heightened. If confirmed, posttherapy colonoscopy could become advisable. KW - multiple sclerosis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188300 VL - 86 ER - TY - JOUR A1 - Busch, Martin A1 - Nadal, Jennifer A1 - Schmid, Matthias A1 - Paul, Katharina A1 - Titze, Stephanie A1 - Hübner, Silvia A1 - Köttgen, Anna A1 - Schultheiss, Ulla T. A1 - Baid-Agrawal, Seema A1 - Lorenzen, Johan A1 - Schlieper, Georg A1 - Sommerer, Claudia A1 - Krane, Vera A1 - Hilge, Robert A1 - Kielstein, Jan T. A1 - Kronenberg, Florian A1 - Wanner, Christoph A1 - Eckardt, Kai-Uwe A1 - Wolf, Gunter T1 - Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort JF - BMC Nephrology N2 - Background Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. Methods The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18–74 years with an estimated glomerular filtration rate (eGFR) between 30–60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. Results At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25th–75th percentile: 6.8–7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 % CI 1.02–1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04–1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26–7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77–6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Conclusions Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels. KW - Chronic kidney disease KW - Glycaemic control KW - Hemoglobin A1C KW - Insulin therapy KW - Oral antidiabetic drugs KW - Diabetes mellitus Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164687 VL - 17 IS - 59 ER - TY - JOUR A1 - Busch, Albert A1 - Hoffjan, Sabine A1 - Bergmann, Frauke A1 - Hartung, Birgit A1 - Jung, Helena A1 - Hanel, Daniela A1 - Tzschach, Andeas A1 - Kadar, Janos A1 - von Kodolitsch, Yskert A1 - Germer, Christoph-Thomas A1 - Trobisch, Heiner A1 - Strasser, Erwin A1 - Wildenauer, René T1 - Vascular type Ehlers-Danlos syndrome is associated with platelet dysfunction and low vitamin D serum concentration JF - Orphanet Journal of Rare Diseases N2 - Background The vascular type represents a very rare, yet the clinically most fatal entity of Ehlers-Danlos syndrome (EDS). Patients are often admitted due to arterial bleedings and the friable tissue and the altered coagulation contribute to the challenge in treatment strategies. Until now there is little information about clotting characteristics that might influence hemostasis decisively and eventually worsen emergency situations. Results 22 vascular type EDS patients were studied for hemoglobin, platelet volume and count, Quick and activated partial thromboplastin time, fibrinogen, factor XIII, von Willebrand disease, vitamin D and platelet aggregation by modern standard laboratory methods. Results show a high prevalence of over 50 % for platelet aggregation disorders in vascular type EDS patients, especially for collagen and epinephrine induced tests, whereas the plasmatic cascade did not show any alterations. Additionally, more than half of the tested subjects showed low vitamin D serum levels, which might additionally affect vascular wall integrity. Conclusion The presented data underline the importance of detailed laboratory screening methods in vascular type EDS patients in order to allow for targeted application of platelet-interacting substances that might be of decisive benefit in the emergency setting. KW - vascular type KW - vitamin D KW - Ehlers-Danlos syndrome KW - EDS KW - platelet dysfunction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147757 VL - 11 IS - 111 ER - TY - JOUR A1 - Busch, Albert A1 - Busch, Martin A1 - Scholz, Claus-Jürgen A1 - Kellersmann, Richard A1 - Otto, Christoph A1 - Chernogubova, Ekaterina A1 - Maegdefessel, Lars A1 - Zernecke, Alma A1 - Lorenz, Udo T1 - Aneurysm miRNA Signature Differs, Depending on Disease Localization and Morphology JF - International Journal of Molecular Science N2 - Limited comprehension of aneurysm pathology has led to inconclusive results from clinical trials. miRNAs are key regulators of post-translational gene modification and are useful tools in elucidating key features of aneurysm pathogenesis in distinct entities of abdominal and popliteal aneurysms. Here, surgically harvested specimens from 19 abdominal aortic aneurysm (AAA) and 8 popliteal artery aneurysm (PAA) patients were analyzed for miRNA expression and histologically classified regarding extracellular matrix (ECM) remodeling and inflammation. DIANA-based computational target prediction and pathway enrichment analysis verified our results, as well as previous ones. miRNA-362, -19b-1, -194, -769, -21 and -550 were significantly down-regulated in AAA samples depending on degree of inflammation. Similar or inverse regulation was found for miR-769, 19b-1 and miR-550, -21, whereas miR-194 and -362 were unaltered in PAA. In situ hybridization verified higher expression of miR-550 and -21 in PAA compared to AAA and computational analysis for target genes and pathway enrichment affirmed signal transduction, cell-cell-interaction and cell degradation pathways, in line with previous results. Despite the vague role of miRNAs for potential diagnostic and treatment purposes, the number of candidates from tissue signature studies is increasing. Tissue morphology influences subsequent research, yet comparison of distinct entities of aneurysm disease can unravel core pathways. KW - AAA KW - miRNA expression KW - pathway analysis KW - histologic diversity KW - popliteal aneurysm Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146422 SN - International Journal of Molecular Science VL - 17 IS - 1 ER - TY - JOUR A1 - Burns, Alan J. A1 - Goldstein, Allan M. A1 - Newgreen, Donald F. A1 - Stamp, Lincon A1 - Schäfer, Karl-Herbert A1 - Metzger, Marco A1 - Hotta, Ryo A1 - Young, Heather M. A1 - Andrews, Peter W. A1 - Thapar, Nikhil A1 - Belkind-Gerson, Jaime A1 - Bondurand, Nadege A1 - Bornstein, Joel C. A1 - Chan, Wood Yee A1 - Cheah, Kathryn A1 - Gershon, Michael D. A1 - Heuckeroth, Robert O. A1 - Hofstra, Robert M.W. A1 - Just, Lothar A1 - Kapur, Raj P. A1 - King, Sebastian K. A1 - McCann, Conor J. A1 - Nagy, Nandor A1 - Ngan, Elly A1 - Obermayr, Florian A1 - Pachnis, Vassilis A1 - Pasricha, Pankaj J. A1 - Sham, Mai Har A1 - Tam, Paul A1 - Vanden Berghe, Pieter T1 - White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies JF - Developmental Biology N2 - Over the last 20 years, there has been increasing focus on the development of novel stem cell based therapies for the treatment of disorders and diseases affecting the enteric nervous system (ENS) of the gastrointestinal tract (so-called enteric neuropathies). Here, the idea is that ENS progenitor/stem cells could be transplanted into the gut wall to replace the damaged or absent neurons and glia of the ENS. This White Paper sets out experts' views on the commonly used methods and approaches to identify, isolate, purify, expand and optimize ENS stem cells, transplant them into the bowel, and assess transplant success, including restoration of gut function. We also highlight obstacles that must be overcome in order to progress from successful preclinical studies in animal models to ENS stem cell therapies in the clinic. KW - Neural crest cells KW - Rat mynteric plexus KW - Intestinal pseudoobstruction KW - Hypertrophic pyloric-stenosis KW - Hirschsprung disease liability KW - Slow-transit constipation KW - Oxide synthase gene KW - Term follow-up KW - Nitric-oxide KW - In-vivo KW - Enteric nervous system KW - Enteric neuropathies KW - Stem cells KW - Cell replacement therapy KW - Hirschsprung disease Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187415 VL - 417 IS - 2 ER - TY - JOUR A1 - Buck, Andreas A1 - Decristoforo, Clemens T1 - Highlights lecture EANM 2015: the search for nuclear medicine's superheroes JF - European Journal of Nuclear Medicine and Molecular Imaging N2 - The EANM 2015 Annual Congress, held from October 10th to 14th in Hamburg, Germany, was outstanding in many respects. With 5550 participants, this was by far the largest European congress concerning nuclear medicine. More than 1750 scientific presentations were submitted, with more than 250 abstracts from young scientists, indicating that the future success of our discipline is fuelled by a high number of young individuals becoming involved in a multitude of scientific activities. Significant improvements have been made in molecular imaging of cancer, particularly in prostate cancer. PSMA-directed PET/CT appears to become a new gold standard for staging and restaging purposes. Novel tumour specific compounds have shown their potential for target identification also in other solid neoplasms and further our understanding of tumour biology and heterogeneity. In addition, a variety of nuclear imaging techniques guiding surgical interventions have been introduced. A particular focus of the congress was put on targeted, radionuclide based therapies. Novel theranostic concepts addressing also tumour entities with high incidence rates such as prostate cancer, melanoma, and lymphoma, have shown effective anti-tumour activity. Strategies have been presented to improve further already established therapeutic regimens such as somatostatin receptor based radio receptor therapy for treating advanced neuroendocrine tumours. Significant contributions were presented also in the neurosciences track. An increasing number of target structures of high interest in neurology and psychiatry are now available for PET and SPECT imaging, facilitating specific imaging of different subtypes of dementia and movement disorders as well as neuroinflammation. Major contributions in the cardiovascular track focused on further optimization of cardiac perfusion imaging by reducing radiation exposure, reducing scanning time, and improving motion correction. Besides coronary artery disease, many contributions focused on cardiac inflammation, cardiac sarcoidosis, and specific imaging of large vessel vasculitis. The physics and instrumentation track included many highlights such as novel, high resolution scanners. The most noteworthy news and developments of this meeting were summarized in the highlights lecture. Only 55 scientific contributions were mentioned, and hence they represent only a brief summary, which is outlined in this article. For a more detailed view, all presentations can be accessed by the online version of the European Journal of Nuclear Medicine and Molecular Imaging (Volume 42, Supplement 1). KW - Conjugate arc therapy KW - Phase-II KW - 18F-FDG PET/CT KW - Highlights Lecture KW - Molecular Imaging KW - Prostate-cancer KW - Radionuclide therapy KW - Myocardial perfusion KW - Preclinical evaluation KW - Targeted therapy KW - Thyroid cancer KW - SPECT KW - 2015 KW - EANM KW - Hamburg KW - Physics and instrumentation KW - Radiopharmacy KW - Oncology KW - Radionuclide Therapy KW - Cardiology KW - Neurosciences Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187613 VL - 43 IS - 10 ER - TY - JOUR A1 - Buch, Marina-Rafaela T1 - Madame Chrysanthème (1887) et Japoneries d’automne (1889) de Pierre Loti entre japonisme et exotisme désenchanté JF - promptus - Würzburger Beiträge zur Romanistik N2 - The novel Madame Chrysanthème (1887) and the essays collected in Japoneries d’automne (1889) written by French travel author Pierre Loti offer a paradoxical view of Japan during the Meiji period. In both travel writings, the author is torn between aesthetic japonism – which spread all over Europe at the end of the 19th century – and exotic expectations, i.e. the picturesque fascination of the Other. The latter, however, remains unsatisfied throughout his stay. In both writings, Pierre Loti provides an insight into Japan that entirely reflects the spirit of his time. Thereby, he contributes to an image of Japan, which will long remain vivid in the Occident. Contemporaries perceive Loti’s representation of Japan as a realistic testimony, tinged with both sensory impressions and his highly ambiguous feelings towards the distant country, which in the end remained incomprehensible to him. KW - Madame Chrysanthème KW - Japoneries d’automne KW - Pierre Loti KW - Loti, Pierre KW - Japan KW - Meiji-Periode Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161603 SN - 2510-2613 VL - 2 ER - TY - JOUR A1 - Brüning, Christoph A1 - Wehner, Johannes A1 - Hausner, Julian A1 - Wenzel, Michael A1 - Engel, Volker T1 - Exciton dynamics in perturbed vibronic molecular aggregates JF - Structural Dynamics N2 - A site specific perturbation of a photo-excited molecular aggregate can lead to a localization of excitonic energy. We investigate this localization dynamics for laser-prepared excited states. Changing the parameters of the electric field significantly influences the exciton localization which offers the possibility for a selective control of this process. This is demonstrated for aggregates possessing a single vibrational degree of freedom per monomer unit. It is shown that the effects identified for the molecular dimer can be generalized to larger aggregates with a high density of vibronic states. KW - absorption spectra KW - excited states KW - polymers KW - excitons KW - wave functions Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126085 VL - 3 ER - TY - JOUR A1 - Brunke, Dirk T1 - Der nationalepische Pionier Esteban Echeverría. Ein Beitrag zur Entstehungsgeschichte des romantischen epischen Gedichts in Hispanoamerika JF - promptus - Würzburger Beiträge zur Romanistik N2 - This article concentrates on the Argentine author Esteban Echeverría who is known as the founding father of Romanticism in the River Plate region. The author of this article intends to show that the importance of Echeverría for the development of Argentine national literature goes beyond the spreading of Romanticist aesthetics. Especially his poem La cautiva (1837) has been regarded as the national epic poem of Argentina because it represents national landscape and the early days of national history. However, as the classification of this narrative poem as the national epic poem already indicates, Echeverría also contributed to the presence of this prestigious genre at the River Plate region. By investigating Echeverría‘s less known verse texts – namely the texts which were read by all Romantics but which have been neglected by literary studies so far – this article illustrates that Echeverría gave decisive impulses for the presence of the epic poem at the River Plate. KW - episches Gedicht KW - romantisches Gedicht KW - Hispanoamerika KW - Entstehungsgeschichte KW - Echeverría, Esteban KW - Hispanoamerika KW - Literatur KW - Gedicht Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161592 SN - 2510-2613 VL - 2 ER - TY - JOUR A1 - Brunet, Frédéric G. A1 - Volff, Jean-Nicolas A1 - Schartl, Manfred T1 - Whole Genome Duplications Shaped the Receptor Tyrosine Kinase Repertoire of Jawed Vertebrates JF - Genome Biology Evolution N2 - The receptor tyrosine kinase (RTK) gene family, involved primarily in cell growth and differentiation, comprises proteins with a common enzymatic tyrosine kinase intracellular domain adjacent to a transmembrane region. The amino-terminal portion of RTKs is extracellular and made of different domains, the combination of which characterizes each of the 20 RTK subfamilies among mammals. We analyzed a total of 7,376 RTK sequences among 143 vertebrate species to provide here the first comprehensive census of the jawed vertebrate repertoire. We ascertained the 58 genes previously described in the human and mouse genomes and established their phylogenetic relationships. We also identified five additional RTKs amounting to a total of 63 genes in jawed vertebrates. We found that the vertebrate RTK gene family has been shaped by the two successive rounds of whole genome duplications (WGD) called 1R and 2R (1R/2R) that occurred at the base of the vertebrates. In addition, the Vegfr and Ephrin receptor subfamilies were expanded by single gene duplications. In teleost fish, 23 additional RTK genes have been retained after another expansion through the fish-specific third round (3R) of WGD. Several lineage-specific gene losses were observed. For instance, birds have lost three RTKs, and different genes are missing in several fish sublineages. The RTK gene family presents an unusual high gene retention rate from the vertebrate WGDs (58.75% after 1R/2R, 64.4% after 3R), resulting in an expansion that might be correlated with the evolution of complexity of vertebrate cellular communication and intracellular signaling. KW - receptor tyrosine kinase KW - vertebrates KW - deuterostomes KW - whole genome duplications Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146988 VL - 8 IS - 15 ER - TY - JOUR A1 - Brevik, Erlend J A1 - van Donkelaar, Marjolein M. J. A1 - Weber, Heike A1 - Sánchez-Mora, Cristina A1 - Jacob, Christian A1 - Rivero, Olga A1 - Kittel-Schneider, Sarah A1 - Garcia-martinez, Iris A1 - Aebi, Marcel A1 - van Hulzen, Kimm A1 - Cormand, Bru A1 - Ramos-Quiroga, Josep A A1 - Lesch, Klaus-Peter A1 - Reif, Andreas A1 - Ribases, Marta A1 - Franke, Barbara A1 - Posserud, Maj-Britt A1 - Johansson, Stefan A1 - Lundervold, Astri J. A1 - Haavik, Jan A1 - Zayats, Tetyana T1 - Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder JF - American Journal of Medical Genetics Part B-Neuropsychiatric Genetics N2 - Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P<5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders. KW - Large multicenter ADHD KW - Antisocial behavior KW - Diagnostic approach KW - Rating scale KW - Gene KW - Deficit/hyperactivity disorder KW - Susceptibility loci KW - Conduct disorder KW - Association KW - Adult KW - ADHD KW - Aggression KW - GWAS Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188116 VL - 171B IS - 5 ER - TY - JOUR A1 - Brendtke, Rico A1 - Wiehl, Michael A1 - Groeber, Florian A1 - Schwarz, Thomas A1 - Walles, Heike A1 - Hansmann, Jan T1 - Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models JF - PLoS ONE N2 - Tissue dehydration results in three major types of exsiccosis—hyper-, hypo-, or isonatraemia. All three types entail alterations of salt concentrations leading to impaired biochemical processes, and can finally cause severe morbidity. The aim of our study was to demonstrate the feasibility of a microwave-based sensor technology for the non-invasive measurement of the hydration status. Electromagnetic waves at high frequencies interact with molecules, especially water. Hence, if a sample contains free water molecules, this can be detected in a reflected microwave signal. To develop the sensor system, human three-dimensional skin equivalents were instituted as a standardized test platform mimicking reproducible exsiccosis scenarios. Therefore, skin equivalents with a specific hydration and density of matrix components were generated and microwave measurements were performed. Hydration-specific spectra allowed deriving the hydration state of the skin models. A further advantage of the skin equivalents was the characterization of the impact of distinct skin components on the measured signals to investigate mechanisms of signal generation. The results demonstrate the feasibility of a non-invasive microwave-based hydration sensor technology. The sensor bears potential to be integrated in a wearable medical device for personal health monitoring. KW - gels KW - microwave radiation KW - collagens KW - skin physiology KW - reflection KW - skin anatomy KW - epidermis KW - antennas Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179934 VL - 11 IS - 4 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Krummenacher, Ivo A1 - Mailänder, Lisa A1 - Pentecost, Leanne A1 - Vargas, Alfredo T1 - Formation of a stable radical by oxidation of a tetraorganoborate JF - Chemical Communications N2 - Herein, we describe the selective formation of a stable neutral spiroborate radical by one-electron oxidation of the corresponding tetraorganoborate salt Li[B(C\(_4\)Ph\(_4\))\(_2\)], formally containing a tetrahedral borate centre and a s-cis-butadiene radical cation as the spin-bearing site. Spectroscopic and computational methods have been used to determine the spin distribution and the chromism observed in the solid state. KW - tetraorganoborate salt KW - spiroborates KW - one-electron oxidation KW - spin distribution KW - chromism Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191321 VL - 52 IS - 43 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Ewing, William C. A1 - Ghosh, Sundargopal A1 - Kramer, Thomas A1 - Mattock, James D. A1 - Östreicher, Sebastian A1 - Vargas, Alfredo A1 - Werner, Christine T1 - Trimetallaborides as starting points for the syntheses of large metal-rich molecular borides and clusters JF - Chemical Science N2 - Treatment of an anionic dimanganaborylene complex ([{Cp(CO)\(_2\)Mn}\(_2\)B]\(^-\)) with coinage metal cations stabilized by a very weakly coordinating Lewis base (SMe\(_2\)) led to the coordination of the incoming metal and subsequent displacement of dimethylsulfide in the formation of hexametalladiborides featuring planar four-membered M\(_2\)B\(_2\) cores (M = Cu, Au) comparable to transition metal clusters constructed around four-membered rings composed solely of coinage metals. The analogies between compounds consisting of B\(_2\)M\(_2\) units and M\(_4\) (M = Cu, Au) units speak to the often overlooked metalloid nature of boron. Treatment of one of these compounds (M = Cu) with a Lewis-basic metal fragment (Pt(PCy\(_3\))\(_2\)) led to the formation of a tetrametallaboride featuring two manganese, one copper and one platinum atom, all bound to boron in a geometry not yet seen for this kind of compound. Computational examination suggests that this geometry is the result of d\(^{10}\)-d\(^{10}\) dispersion interactions between the copper and platinum fragments. KW - anionic dimetalloborylene complexes KW - trimetallaborides KW - tetrametallaborides KW - Boron KW - metallaboranes KW - crystal structure KW - metal borylene complexes Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191511 VL - 7 IS - 1 ER - TY - JOUR A1 - Braunschweig, Holger A1 - Constantinidis, Philipp A1 - Dellermann, Theresa A1 - Ewing, William A1 - Fischer, Ingo A1 - Hess, Merlin A1 - Knight, Fergus A1 - Rempel, Anna A1 - Schneider, Christoph A1 - Ullrich, Stefan A1 - Vargas, Alfredo A1 - Woolins, Derek T1 - Highly Strained Heterocycles Constructed from Boron–Boron Multiple Bonds and Heavy Chalcogens JF - Angewandte Chemie, International Edition N2 - The reactions of a diborene with elemental selenium or tellurium are shown to afford a diboraselenirane or diboratellurirane, respectively. These reactions are reminiscent of the sequestration of subvalent oxygen and nitrogen in the formation of oxiranes and aziridines; however, such reactivity is not known between alkenes and the heavy chalcogens. Although carbon is too electronegative to affect the reduction of elements with lower relative electronegativity, the highly reducing nature of the B B double bond enables reactions with Se0 and Te0. The capacity of multiple bonds between boron atoms to donate electron density is highlighted in reactions where diborynes behave as nucleophiles, attacking one of the two Te atoms of diaryltellurides, forming salts consisting of diboratellurenium cations and aryltelluride anions. KW - Boron KW - Heterocycles KW - Multiple bonds KW - Selenium KW - Tellurium KW - Bor KW - Heterocyclische Verbindungen KW - Selen KW - Tellur Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-138237 N1 - This is the peer reviewed version of the following article: Angew. Chem. Int. Ed. 2016, 55, 5606–5609, which has been published in final form at 10.1002/anie.201601691. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving. N1 - Accepted Version VL - 55 IS - 18 SP - 5606 EP - 5609 ER - TY - JOUR A1 - Bratengeier, Klaus A1 - Holubyev, Kostyantyn T1 - Anisotropy of dose contributions-an instrument to upgrade real time IMRT and VMAT adaptation? JF - Medical Physics N2 - Purpose: To suggest a definition of dose deposition anisotropy for the purpose of ad hoc adaptation of intensity modulated arc therapy (IMRT) and volumetric arc therapy (VMAT), particularly in the vicinity of important organs at risk (OAR), also for large deformations. Methods: Beam's-eye-view (BEV) based fluence warping is a standard adaptation method with disadvantages for strongly varying OAR shapes. 2-Step-adaptation overcomes these difficulties by a deeper analysis of the 3D properties of adaptation processes, but requires separate arcs for every OAR to spare, which makes it impractical for cases with multiple OARs. The authors aim to extend the 2-Step method to arbitrary intensity modulated plan by analyzing the anisotropy of dose contributions. Anisotropy was defined as a second term of Fourier transformation of gantry angle dependent dose contributions. For a cylindrical planning target volume (PTV) surrounding an OAR of varying diameter, the anisotropy and the dose-normalized anisotropy were analyzed for several scenarios of optimized fluence distributions. 2-Step adaptation to decreasing and increasing OAR diameter was performed, and compared to a usual fluence based adaptation method. For two clinical cases, prostate and neck, the VMAT was generated and the behavior of anisotropy was qualitatively explored for deformed organs at risk. # Results: Dose contribution anisotropy in the PTV peaks around nearby OARs. The thickness of the "anisotropy wall" around OAR increases for increasing OAR radius, as also does the width of 2-Step dose saturating fluence peak adjacent to the OAR K. Bratengeier et al., "A comparison between 2-Step IMRT and conventional IMRT planning," Radiother. Oncol. 84, 298-306 (2007)]. Different optimized beam fluence profiles resulted in comparable radial dependence of normalized anisotropy. As predicted, even for patient cases, anisotropy was inflated even more than increasing diameters of OAR. Conclusions: For cylindrically symmetric cases, the dose distribution anisotropy defined in the present work implicitly contains adaptation-relevant information about 3D relationships between PTV and OAR and degree of OAR sparing. For more complex realistic cases, it shows the predicted behavior qualitatively. The authors claim to have found a first component for advancing a 2-Step adaptation to a universal adaptation algorithm based on the BEV projection of the dose anisotropy. Further planning studies to explore the potential of anisotropy for adaptation algorithms using phantoms and clinical cases of differing complexity will follow. KW - modulated arc therapy KW - 2-step IMRT KW - radiation-therapy KW - online adaption KW - prostate-cancer KW - plans KW - IMAT KW - tracking KW - radiotherapy KW - adaption KW - IMRT KW - VMAT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186833 VL - 43 IS - 11 ER - TY - JOUR A1 - Bousquet, J. A1 - Farrell, J. A1 - Crooks, G. A1 - Hellings, P. A1 - Bel, E. H. A1 - Bewick, M. A1 - Chavannes, N. H. A1 - Correia de Sousa, J. A1 - Cruz, A. A. A1 - Haahtela, T. A1 - Joos, G. A1 - Khaltaev, N. A1 - Malva, J. A1 - Muraro, A. A1 - Nogues, M. A1 - Palkonen, S. A1 - Pedersen, S. A1 - Robalo-Cordeiro, C. A1 - Samolinski, B. A1 - Strandberg, T. A1 - Valiulis, A. A1 - Yorgancioglu, A. A1 - Zuberbier, T. A1 - Bedbrook, A. A1 - Aberer, W. A1 - Adachi, M. A1 - Agusti, A. A1 - Akdis, C. A. A1 - Akdis, M. A1 - Ankri, J. A1 - Alonso, A. A1 - Annesi-Maesano, I. A1 - Ansotegui, I. J. A1 - Anto, J. M. A1 - Arnavielhe, S. A1 - Arshad, H. A1 - Bai, C. A1 - Baiardini, I. A1 - Bachert, C. A1 - Baigenzhin, A. K. A1 - Barbara, C. A1 - Bateman, E. D. A1 - Beghé, B. A1 - Ben Kheder, A. A1 - Bennoor, K. S. A1 - Benson, M. A1 - Bergmann, K. C. A1 - Bieber, T. A1 - Bindslev-Jensen, C. A1 - Bjermer, L. A1 - Blain, H. A1 - Blasi, F. A1 - Boner, A. L. A1 - Bonini, M. A1 - Bonini, S. A1 - Bosnic-Anticevitch, S. A1 - Boulet, L. P. A1 - Bourret, R. A1 - Bousquet, P. J. A1 - Braido, F. A1 - Briggs, A. H. A1 - Brightling, C. E. A1 - Brozek, J. A1 - Buhl, R. A1 - Burney, P. G. A1 - Bush, A. A1 - Caballero-Fonseca, F. A1 - Caimmi, D. A1 - Calderon, M. A. A1 - Calverley, P. M. A1 - Camargos, P. A. M. A1 - Canonica, G. W. A1 - Camuzat, T. A1 - Carlsen, K. H. A1 - Carr, W. A1 - Carriazo, A. A1 - Casale, T. A1 - Cepeda Sarabia, A. M. A1 - Chatzi, L. A1 - Chen, Y. Z. A1 - Chiron, R. A1 - Chkhartishvili, E. A1 - Chuchalin, A. G. A1 - Chung, K. F. A1 - Ciprandi, G. A1 - Cirule, I. A1 - Cox, L. A1 - Costa, D. J. A1 - Custovic, A. A1 - Dahl, R. A1 - Dahlen, S. E. A1 - Darsow, U. A1 - De Carlo, G. A1 - De Blay, F. A1 - Dedeu, T. A1 - Deleanu, D. A1 - De Manuel Keenoy, E. A1 - Demoly, P. A1 - Denburg, J. A. A1 - Devillier, P. A1 - Didier, A. A1 - Dinh-Xuan, A. T. A1 - Djukanovic, R. A1 - Dokic, D. A1 - Douagui, H. A1 - Dray, G. A1 - Dubakiene, R. A1 - Durham, S. R. A1 - Dykewicz, M. S. A1 - El-Gamal, Y. A1 - Emuzyte, R. A1 - Fabbri, L. M. A1 - Fletcher, M. A1 - Fiocchi, A. A1 - Fink Wagner, A. A1 - Fonseca, J. A1 - Fokkens, W. J. A1 - Forastiere, F. A1 - Frith, P. A1 - Gaga, M. A1 - Gamkrelidze, A. A1 - Garces, J. A1 - Garcia-Aymerich, J. A1 - Gemicioğlu, B. A1 - Gereda, J. E. A1 - González Diaz, S. A1 - Gotua, M. A1 - Grisle, I. A1 - Grouse, L. A1 - Gutter, Z. A1 - Guzmán, M. A. A1 - Heaney, L. G. A1 - Hellquist-Dahl, B. A1 - Henderson, D. A1 - Hendry, A. A1 - Heinrich, J. A1 - Heve, D. A1 - Horak, F. A1 - Hourihane, J. O’. B. A1 - Howarth, P. A1 - Humbert, M. A1 - Hyland, M. E. A1 - Illario, M. A1 - Ivancevich, J. C. A1 - Jardim, J. R. A1 - Jares, E. J. A1 - Jeandel, C. A1 - Jenkins, C. A1 - Johnston, S. L. A1 - Jonquet, O. A1 - Julge, K. A1 - Jung, K. S. A1 - Just, J. A1 - Kaidashev, I. A1 - Kaitov, M. R. A1 - Kalayci, O. A1 - Kalyoncu, A. F. A1 - Keil, T. A1 - Keith, P. K. A1 - Klimek, L. A1 - Koffi N’Goran, B. A1 - Kolek, V. A1 - Koppelman, G. H. A1 - Kowalski, M. L. A1 - Kull, I. A1 - Kuna, P. A1 - Kvedariene, V. A1 - Lambrecht, B. A1 - Lau, S. A1 - Larenas‑Linnemann, D. A1 - Laune, D. A1 - Le, L. T. T. A1 - Lieberman, P. A1 - Lipworth, B. A1 - Li, J. A1 - Lodrup Carlsen, K. A1 - Louis, R. A1 - MacNee, W. A1 - Magard, Y. A1 - Magnan, A. A1 - Mahboub, B. A1 - Mair, A. A1 - Majer, I. A1 - Makela, M. J. A1 - Manning, P. A1 - Mara, S. A1 - Marshall, G. D. A1 - Masjedi, M. R. A1 - Matignon, P. A1 - Maurer, M. A1 - Mavale‑Manuel, S. A1 - Melén, E. A1 - Melo‑Gomes, E. A1 - Meltzer, E. O. A1 - Menzies‑Gow, A. A1 - Merk, H. A1 - Michel, J. P. A1 - Miculinic, N. A1 - Mihaltan, F. A1 - Milenkovic, B. A1 - Mohammad, G. M. Y. A1 - Molimard, M. A1 - Momas, I. A1 - Montilla‑Santana, A. A1 - Morais‑Almeida, M. A1 - Morgan, M. A1 - Mösges, R. A1 - Mullol, J. A1 - Nafti, S. A1 - Namazova‑Baranova, L. A1 - Naclerio, R. A1 - Neou, A. A1 - Neffen, H. A1 - Nekam, K. A1 - Niggemann, B. A1 - Ninot, G. A1 - Nyembue, T. D. A1 - O’Hehir, R. E. A1 - Ohta, K. A1 - Okamoto, Y. A1 - Okubo, K. A1 - Ouedraogo, S. A1 - Paggiaro, P. A1 - Pali‑Schöll, I. A1 - Panzner, P. A1 - Papadopoulos, N. A1 - Papi, A. A1 - Park, H. S. A1 - Passalacqua, G. A1 - Pavord, I. A1 - Pawankar, R. A1 - Pengelly, R. A1 - Pfaar, O. A1 - Picard, R. A1 - Pigearias, B. A1 - Pin, I. A1 - Plavec, D. A1 - Poethig, D. A1 - Pohl, W. A1 - Popov, T. A. A1 - Portejoie, F. A1 - Potter, P. A1 - Postma, D. A1 - Price, D. A1 - Rabe, K. F. A1 - Raciborski, F. A1 - Radier Pontal, F. A1 - Repka‑Ramirez, S. A1 - Reitamo, S. A1 - Rennard, S. A1 - Rodenas, F. A1 - Roberts, J. A1 - Roca, J. A1 - Rodriguez Mañas, L. A1 - et al, T1 - Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5) JF - Clinical and Translational Allergy N2 - Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing. KW - EIP on AHA KW - European Innovation Partnership on Active and Healthy Ageing KW - AIRWAYS ICPs KW - MACVIA KW - Scaling up KW - Chronic respiratory diseases KW - ARIA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166874 VL - 6 IS - 29 ER - TY - JOUR A1 - Bousquet, J. A1 - Anto, J. M. A1 - Akdis, M. A1 - Auffray, C. A1 - Keil, T. A1 - Momas, I. A1 - Postma, D. S. A1 - Valenta, R. A1 - Wickman, M. A1 - Cambon-Thomsen, A. A1 - Haahtela, T. A1 - Lambrecht, B. N. A1 - Lodrup Carlsen, K. C. A1 - Koppelman, G. H. A1 - Sunyer, J. A1 - Zuberbier, T. A1 - Annesi-Maesano, I. A1 - Arno, A. A1 - Bindslev-Jensen, C. A1 - De Carlo, G. A1 - Forastiere, F. A1 - Heinrich, J. A1 - Kowalski, M. L. A1 - Maier, D. A1 - Melen, E. A1 - Palkonen, S. A1 - Smit, H. A. A1 - Standl, M. A1 - Wright, J. A1 - Asarnoj, A. A1 - Benet, M. A1 - Ballardini, N. A1 - Garcia-Aymerich, J. A1 - Gehring, U. A1 - Guerra, S. A1 - Hohman, C. A1 - Kull, I. A1 - Lupinek, C. A1 - Pinart, M. A1 - Skrindo, I. A1 - Westman, M. A1 - Smagghe, D. A1 - Akdis, C. A1 - Albang, R. A1 - Anastasova, V. A1 - Anderson, N. A1 - Bachert, C. A1 - Ballereau, S. A1 - Ballester, F. A1 - Basagana, X. A1 - Bedbrook, A. A1 - Bergstrom, A. A1 - von Berg, A. A1 - Brunekreef, B. A1 - Burte, E. A1 - Carlsen, K.H. A1 - Chatzi, L. A1 - Coquet, J.M. A1 - Curin, M. A1 - Demoly, P. A1 - Eller, E. A1 - Fantini, M.P. A1 - Gerhard, B. A1 - Hammad, H. A1 - von Hertzen, L. A1 - Hovland, V. A1 - Jacquemin, B. A1 - Just, J. A1 - Keller, T. A1 - Kerkhof, M. A1 - Kiss, R. A1 - Kogevinas, M. A1 - Koletzko, S. A1 - Lau, S. A1 - Lehmann, I. A1 - Lemonnier, N. A1 - McEachan, R. A1 - Makela, M. A1 - Mestres, J. A1 - Minina, E. A1 - Mowinckel, P. A1 - Nadif, R. A1 - Nawijn, M. A1 - Oddie, S. A1 - Pellet, J. A1 - Pin, I. A1 - Porta, D. A1 - Rancière, F. A1 - Rial-Sebbag, A. A1 - Schuijs, M.J. A1 - Siroux, V. A1 - Tischer, C.G. A1 - Torrent, M. A1 - Varraso, R. A1 - De Vocht, J. A1 - Wenger, K. A1 - Wieser, S. A1 - Xu, C. T1 - Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015 JF - Allergy N2 - MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda. KW - asthma KW - birth cohort KW - atopic-dermatitis KW - immune-responses KW - IgE KW - multimorbidity KW - polysensitization KW - rhinitis KW - chronic respiratory-diseases KW - childhood asthma KW - immunological reactivity KW - IgE sensitazion KW - immunoglobulin-e KW - integraed care Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186858 VL - 71 IS - 11 ER - TY - JOUR A1 - Bossert, Nelli A1 - de Bruin, Donny A1 - Götz, Maria A1 - Bouwmeester, Dirk A1 - Heinrich, Doris T1 - Fluorescence-tunable Ag-DNA biosensor with tailored cytotoxicity for live-cell applications JF - Scientific Reports N2 - DNA-stabilized silver clusters (Ag-DNA) show excellent promise as a multi-functional nanoagent for molecular investigations in living cells. The unique properties of these fluorescent nanomaterials allow for intracellular optical sensors with tunable cytotoxicity based on simple modifications of the DNA sequences. Three Ag-DNA nanoagent designs are investigated, exhibiting optical responses to the intracellular environments and sensing-capability of ions, functional inside living cells. Their sequence-dependent fluorescence responses inside living cells include (1) a strong splitting of the fluorescence peak for a DNA hairpin construct, (2) an excitation and emission shift of up to 120 nm for a single-stranded DNA construct, and (3) a sequence robust in fluorescence properties. Additionally, the cytotoxicity of these Ag-DNA constructs is tunable, ranging from highly cytotoxic to biocompatible Ag-DNA, independent of their optical sensing capability. Thus, Ag-DNA represents a versatile live-cell nanoagent addressable towards anti-cancer, patient-specific and anti-bacterial applications. KW - Ag-DNA KW - DNA-encapsulated silver nanoclusters KW - nanoagent KW - fluorescence Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167482 VL - 6 IS - 37897 ER - TY - JOUR A1 - Boschert, V. A1 - Frisch, C. A1 - Back, J. W. A1 - van Pee,, K. A1 - Weidauer, S. E. A1 - Muth, E.-M. A1 - Schmieder, P. A1 - Beerbaum, M. A1 - Knappik, A. A1 - Timmerman, P. A1 - Mueller, T. D. T1 - The sclerostin-neutralizing antibody AbD09097 recognizes an epitope adjacent to sclerostin's binding site for the Wnt co-receptor LRP6 JF - Open Biology N2 - The glycoprotein sclerostin has been identified as a negative regulator of bone growth. It exerts its function by interacting with the Wnt co-receptor LRP5/6, blocks the binding of Wnt factors and thereby inhibits Wnt signalling. Neutralizing anti-sclerostin antibodies are able to restore Wnt activity and enhance bone growth thereby presenting a new osteoanabolic therapy approach for diseases such as osteoporosis. We have generated various Fab antibodies against human and murine sclerostin using a phage display set-up. Biochemical analyses have identified one Fab developed against murine sclerostin, AbD09097 that efficiently neutralizes sclerostin's Wnt inhibitory activity. In vitro interaction analysis using sclerostin variants revealed that this neutralizing Fab binds to sclerostin's flexible second loop, which has been shown to harbour the LRP5/6 binding motif. Affinity maturation was then applied to AbD09097, providing a set of improved neutralizing Fab antibodies which particularly bind human sclerostin with enhanced affinity. Determining the crystal structure of AbD09097 provides first insights into how this antibody might recognize and neutralize sclerostin. Together with the structure–function relationship derived from affinity maturation these new data will foster the rational design of new and highly efficient anti-sclerostin antibodies for the therapy of bone loss diseases such as osteoporosis. KW - phage display KW - Wnt signalling KW - sclerostin KW - neutralizing antibody KW - osteoporosis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177925 VL - 6 ER - TY - JOUR A1 - Bornstein, Stefan R. A1 - Allolio, Bruno A1 - Arlt, Wiebke A1 - Barthel, Andreas A1 - Don-Wauchope, Andrew A1 - Hammer, Gary D. A1 - Husebye, Eystein S. A1 - Merke, Deborah P. A1 - Murad, M. Hassan A1 - Stratakis, Constantine A. A1 - Torpy, David J. T1 - Diagnosis and treatment of primary adrenal insufficiency: an Endocrine Society Clinical Practice Guideline JF - Journal of Clinical Endocrinology & Metabolism N2 - Objective: This clinical practice guideline addresses the diagnosis and treatment of primary adrenal insufficiency. Participants: The Task Force included a chair, selected by The Clinical Guidelines Subcommittee of the Endocrine Society, eight additional clinicians experienced with the disease, a methodologist, and a medical writer. The co-sponsoring associations (European Society of Endocrinology and the American Association for Clinical Chemistry) had participating members. The Task Force received no corporate funding or remuneration in connection with this review. Evidence: This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to determine the strength of recommendations and the quality of evidence. Consensus Process: The evidence used to formulate recommendations was derived from two commissioned systematic reviews as well as other published systematic reviews and studies identified by the Task Force. The guideline was reviewed and approved sequentially by the Endocrine Society's Clinical Guidelines Subcommittee and Clinical Affairs Core Committee, members responding to a web posting, and the Endocrine Society Council. At each stage, the Task Force incorporated changes in response to written comments. Conclusions: We recommend diagnostic tests for the exclusion of primary adrenal insufficiency in all patients with indicative clinical symptoms or signs. In particular, we suggest a low diagnostic (and therapeutic) threshold in acutely ill patients, as well as in patients with predisposing factors. This is also recommended for pregnant women with unexplained persistent nausea, fatigue, and hypotension. We recommend a short corticotropin test (250 mu g) as the "gold standard" diagnostic tool to establish the diagnosis. If a short corticotropin test is not possible in the first instance, we recommend an initial screening procedure comprising the measurement of morning plasma ACTH and cortisol levels. Diagnosis of the underlying cause should include a validated assay of autoantibodies against 21-hydroxylase. In autoantibody-negative individuals, other causes should be sought. We recommend once-daily fludrocortisone (median, 0.1 mg) and hydrocortisone (15-25 mg/d) or cortisone acetate replacement (20-35 mg/d) applied in two to three daily doses in adults. In children, hydrocortisone (similar to 8 mg/m\(^2\)/d) is recommended. Patients should be educated about stress dosing and equipped with a steroid card and glucocorticoid preparation for parenteral emergency administration. Follow-up should aim at monitoring appropriate dosing of corticosteroids and associated autoimmune diseases, particularly autoimmune thyroid disease. KW - glucocorticoid replacement therapy KW - Addison's disease KW - short Synacthen test KW - insulin tolerance test Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190893 VL - 101 IS - 2 ER - TY - JOUR A1 - Born, Dennis-Peter A1 - Zinner, Christoph A1 - Düking, Peter A1 - Sperlich, Billy T1 - Multi-Directional Sprint Training Improves Change-Of-Direction Speed and Reactive Agility in Young Highly Trained Soccer Players JF - Journal of Sports Science and Medicine N2 - The aim of this study was to evaluate the effect of a repeated sprint training with multi-directional change-of-direction (COD) movements (RSmulti) compared to repeated shuttle sprints (RSS) on variables related to COD speed and reactive agility. Nineteen highly-trained male U15 soccer players were assigned into two groups performing either RSmulti or RSS. For both groups, each training session involved 20 repeated 15 s sprints interspersed with 30 s recovery. With RSmulti the COD movements were randomized and performed in response to a visual stimulus, while the RSS involved predefined 180° COD movements. Before and following the six training sessions, performance in the Illinois agility test (IAT), COD speed in response to a visual stimulus, 20 m linear sprint time and vertical jumping height were assessed. Both groups improved their performance in the IAT (p < 0.01, ES = 1.13; p = 0.01, ES = 0.55). The COD speed in response to a visual stimulus improved with the RSmulti (p < 0.01, ES = 1.03), but not the RSS (p = 0.46, ES = 0.28). No differences were found for 20 m sprint time (P=0.73, ES = 0.07; p = 0.14, ES = 0.28) or vertical jumping height (p = 0.46, ES = 0.11; p = 0.29, ES = 0.12) for the RSmulti and RSS, respectively. In conclusion, performance in the IAT improved with the RSmulti as well as RSS. With the RSmulti however, the COD movements are performed in response to a visual stimulus, which may result in specific adaptations that improve COD speed and reactive agility in young highly trained soccer players. KW - team sport KW - COD movements KW - repeated shuttle sprints KW - speed KW - Speedcourt Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146866 UR - http://www.jssm.org/researchjssm-15-314.xml.xml VL - 15 ER - TY - JOUR A1 - Borkert, Franziska T1 - BibScout – der mobile Auskunftsdienst an der UB Würzburg JF - BuB. Forum Bibliothek und Information N2 - Seit dem Wintersemester 2014/15 setzt die Universitätsbibliothek (UB) Würzburg in der Zentralbibliothek sogenannte BibScouts ein. Das sind studentische Hilfskräfte, die die Nutzerinnen und Nutzer der Bibliothek – hauptsächlich Studierende – beim Kopieren, Drucken, Scannen und beim Auffinden von Büchern unterstützen. Die BibScouts haben keinen festen Standort, sondern helfen direkt vor Ort, an den Kopierern, Computern, Scan-Stationen und in den Lesesälen. Erkennbar sind sie an blauen Westen mit dem Logo der UB Würzburg sowie dem Hinweis »Fragen? Ich helfe weiter!« auf dem Rücken. Die BibScouts, die nur während der Vorlesungszeit eingesetzt werden, entlasten durch ihre Anwesenheit das bibliothekarische Personal an der Informationstheke. KW - mobiler Auskunftsdienst KW - peer-to-peer Auskunftsdienst KW - roving reference KW - roaming reference KW - Auskunftsdienst KW - Universitätsbibliothek Würzburg Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148145 UR - http://b-u-b.de/archiv/ VL - 68 IS - 12 ER - TY - JOUR A1 - Boll, Sabine A1 - Bartholomaeus, Marie A1 - Peter, Ulrike A1 - Lupke, Ulrike A1 - Gamer, Matthias T1 - Attentional mechanisms of social perception are biased in social phobia JF - Journal of Anxiety Disorders N2 - Previous studies of social phobia have reported an increased vigilance to social threat cues but also an avoidance of socially relevant stimuli such as eye gaze. The primary aim of this study was to examine attentional mechanisms relevant for perceiving social cues by means of abnormalities in scanning of facial features in patients with social phobia. In two novel experimental paradigms, patients with social phobia and healthy controls matched on age, gender and education were compared regarding their gazing behavior towards facial cues. The first experiment was an emotion classification paradigm which allowed for differentiating reflexive attentional shifts from sustained attention towards diagnostically relevant facial features. In the second experiment, attentional orienting by gaze direction was assessed in a gaze-cueing paradigm in which non-predictive gaze cues shifted attention towards or away from subsequently presented targets. We found that patients as compared to controls reflexively oriented their attention more frequently towards the eyes of emotional faces in the emotion classification paradigm. This initial hypervigilance for the eye region was observed at very early attentional stages when faces were presented for 150 ms, and persisted when facial stimuli were shown for 3 s. Moreover, a delayed attentional orienting into the direction of eye gaze was observed in individuals with social phobia suggesting a differential time course of eye gaze processing in patients and controls. Our findings suggest that basic mechanisms of early attentional exploration of social cues are biased in social phobia and might contribute to the development and maintenance of the disorder. KW - Social anxiety KW - Eye gaze KW - Vigilance KW - Amygdala KW - Emotional expression KW - Gaze perception Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189046 VL - 40 ER - TY - JOUR A1 - Blättner, Sebastian A1 - Das, Sudip A1 - Paprotka, Kerstin A1 - Eilers, Ursula A1 - Krischke, Markus A1 - Kretschmer, Dorothee A1 - Remmele, Christian W. A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Schuelein-Voelk, Christina A1 - Hertlein, Tobias A1 - Mueller, Martin J. A1 - Huettel, Bruno A1 - Reinhardt, Richard A1 - Ohlsen, Knut A1 - Rudel, Thomas A1 - Fraunholz, Martin J. T1 - Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes JF - PLoS Pathogens N2 - Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection. KW - cell death KW - cytotoxicity KW - Staphylococcus aureus KW - host cells KW - neutrophils KW - macrophages KW - transposable elements KW - epithelial cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180380 VL - 12 IS - 9 ER - TY - JOUR A1 - Bluemel, Christina A1 - Linke, Fraenze A1 - Herrmann, Ken A1 - Simunovic, Iva A1 - Eiber, Matthias A1 - Kestler, Christian A1 - Buck, Andreas K. A1 - Schirbel, Andreas A1 - Bley, Thorsten A. A1 - Wester, Hans-Juergen A1 - Vergho, Daniel A1 - Becker, Axel T1 - Impact of \(^{68}\)Ga-PSMA PET/CT on salvage radiotherapy planning in patients with prostate cancer and persisting PSA values or biochemical relapse after prostatectomy JF - EJNMMI Research N2 - Background Salvage radiotherapy (SRT) is clinically established in prostate cancer (PC) patients with PSA persistence or biochemical relapse (BCR) after prior radical surgery. PET/CT imaging prior to SRT may be performed to localize disease recurrence. The recently introduced \(^{68}\)Ga-PSMA outperforms other PET tracers for detection of recurrence and is therefore expected also to impact radiation planning. Forty-five patients with PSA persistence (16 pts) or BCR (29 pts) after prior prostatectomy, scheduled to undergo SRT of the prostate bed, underwent \(^{68}\)Ga-PSMA PET/CT. The median PSA level was 0.67 ng/ml. The impact of \(^{68}\)Ga-PSMA PET/CT on the treatment decision was assessed. Patients with oligometastatic (≤5 lesions) PC underwent radiotherapy (RT), with the extent of the RT area and dose escalation being based on PET positivity. Results Suspicious lesions were detected in 24/45 (53.3 %) patients. In 62.5 % of patients, lesions were only detected by 68Ga-PSMA PET. Treatment was changed in 19/45 (42.2 %) patients, e.g., extending SRT to metastases (9/19), administering dose escalation in patients with morphological local recurrence (6/19), or replacing SRT by systemic therapy (2/19). 38/45 (84.4 %) followed the treatment recommendation, with data on clinical follow-up being available in 21 patients treated with SRT. All but one showed biochemical response (mean PSA decline 78 ± 19 %) within a mean follow-up of 8.12 ± 5.23 months. Conclusions \(^{68}\)Ga-PSMA PET/CT impacts treatment planning in more than 40 % of patients scheduled to undergo SRT. Future prospective studies are needed to confirm this significant therapeutic impact on patients prior to SRT. KW - prostate cancer KW - salvage radiotherapy KW - PSMA KW - PET/CT KW - recurrence Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147798 VL - 6 IS - 78 ER - TY - JOUR A1 - Biscotti, Maria Assunta A1 - Gerdol, Marco A1 - Canapa, Adriana A1 - Forconi, Mariko A1 - Olmo, Ettore A1 - Pallavicini, Alberto A1 - Barucca, Marco A1 - Schartl, Manfred T1 - The Lungfish Transcriptome: A Glimpse into Molecular Evolution Events at the Transition from Water to Land JF - Scientific Reports N2 - Lungfish and coelacanths are the only living sarcopterygian fish. The phylogenetic relationship of lungfish to the last common ancestor of tetrapods and their close morphological similarity to their fossil ancestors make this species uniquely interesting. However their genome size, the largest among vertebrates, is hampering the generation of a whole genome sequence. To provide a partial solution to the problem, a high-coverage lungfish reference transcriptome was generated and assembled. The present findings indicate that lungfish, not coelacanths, are the closest relatives to land-adapted vertebrates. Whereas protein-coding genes evolve at a very slow rate, possibly reflecting a “living fossil” status, transposable elements appear to be active and show high diversity, suggesting a role for them in the remarkable expansion of the lungfish genome. Analyses of single genes and gene families documented changes connected to the water to land transition and demonstrated the value of the lungfish reference transcriptome for comparative studies of vertebrate evolution. KW - lungfish KW - transcriptome KW - genome KW - sarcopterygian fish Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167753 VL - 6 IS - 21571 ER - TY - JOUR A1 - Biehl, Stefanie C. A1 - Merz, Christian J. A1 - Dresler, Thomas A1 - Heupel, Julia A1 - Reichert, Susanne A1 - Jacob, Christian P. A1 - Deckert, Jürgen A1 - Herrmann, Martin J. T1 - Increase or Decrease of fMRI Activity in Adult Attention Deficit/ Hyperactivity Disorder: Does It Depend on Task Difficulty? JF - International Journal of Neuropsychopharmacology N2 - Background: Attention deficit/hyperactivity disorder has been shown to affect working memory, and fMRI studies in children and adolescents with attention deficit/hyperactivity disorder report hypoactivation in task-related attentional networks. However, studies with adult attention deficit/hyperactivity disorder patients addressing this issue as well as the effects of clinically valid methylphenidate treatment are scarce. This study contributes to closing this gap. Methods: Thirty-five adult patients were randomized to 6 weeks of double-blind placebo or methylphenidate treatment. Patients completed an fMRI n-back working memory task both before and after the assigned treatment, and matched healthy controls were tested and compared to the untreated patients. Results: There were no whole-brain differences between any of the groups. However, when specified regions of interest were investigated, the patient group showed enhanced BOLD responses in dorsal and ventral areas before treatment. This increase was correlated with performance across all participants and with attention deficit/hyperactivity disorder symptoms in the patient group. Furthermore, we found an effect of treatment in the right superior frontal gyrus, with methylphenidate-treated patients exhibiting increased activation, which was absent in the placebo-treated patients. Conclusions: Our results indicate distinct activation differences between untreated adult attention deficit/hyperactivity disorder patients and matched healthy controls during a working memory task. These differences might reflect compensatory efforts by the patients, who are performing at the same level as the healthy controls. We furthermore found a positive effect of methylphenidate on the activation of a frontal region of interest. These observations contribute to a more thorough understanding of adult attention deficit/hyperactivity disorder and provide impulses for the evaluation of therapy-related changes. KW - working memory KW - clinical trial KW - child memory KW - short-term methylphenidate brain KW - methylphenidate KW - adult attention deficit/hyperactivity disorder KW - fMRI KW - functional magnetic resonance imaging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147551 VL - 19 IS - 10 ER - TY - JOUR A1 - Biedermann, B. A1 - Billoni, M. A1 - Denner, A. A1 - Dittmaier, S. A1 - Hofer, L. A1 - Jäger, B. A1 - Salfelder, L. T1 - Next-to-leading-order electroweak corrections to pp -> W\(^{+}\)W\(^{-}\) -> 4 leptons at the LHC JF - JOURNAL OF HIGH ENERGY PHYSICS N2 - We present results of the first calculation of next-to-leading-order electroweak corrections to W-boson pair production at the LHC that fully takes into account leptonic W-boson decays and off-shell effects. Employing realistic event selections, we discuss the corrections in situations that are typical for the study of W-boson pairs as a signal process or of Higgs-boson decays H → WW∗, to which W-boson pair production represents an irreducible background. In particular, we compare the full off-shell results, obtained treating the W-boson resonances in the complex-mass scheme, to previous results in the so-called double-pole approximation, which is based on an expansion of the loop amplitudes about the W resonance poles. At small and intermediate scales, i.e. in particular in angular and rapidity distributions, the two approaches show the expected agreement at the level of fractions of a percent, but larger differences appear in the TeV range. For transverse-momentum distributions, the differences can even exceed the 10% level in the TeV range where “background diagrams” with one instead of two resonant W bosons gain in importance because of recoil effects. KW - NLO Computations KW - W-boson KW - LHC Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167790 VL - 06 IS - 065 ER - TY - JOUR A1 - Bialas, David A1 - Zitzler-Kunkel, André A1 - Kirchner, Eva A1 - Schmidt, David A1 - Würthner, Frank T1 - Structural and quantum chemical analysis of exciton coupling in homo- and heteroaggregate stacks of merocyanines JF - Nature Communications N2 - Exciton coupling is of fundamental importance and determines functional properties of organic dyes in (opto-)electronic and photovoltaic devices. Here we show that strong exciton coupling is not limited to the situation of equal chromophores as often assumed. Quadruple dye stacks were obtained from two bis(merocyanine) dyes with same or different chromophores, respectively, which dimerize in less-polar solvents resulting in the respective homo- and heteroaggregates. The structures of the quadruple dye stacks were assigned by NMR techniques and unambiguously confirmed by single-crystal X-ray analysis. The heteroaggregate stack formed from the bis(merocyanine) bearing two different chromophores exhibits remarkably different ultraviolet/vis absorption bands compared with those of the homoaggregate of the bis(merocyanine) comprising two identical chromophores. Quantum chemical analysis based on an extension of Kasha’s exciton theory appropriately describes the absorption properties of both types of stacks revealing strong exciton coupling also between different chromophores within the heteroaggregate. KW - exciton coupling KW - merocyanines KW - quantum chemical analysis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170200 VL - 7 ER - TY - JOUR A1 - Bhavsar, Shefalee K. A1 - Singh, Yogesh A1 - Sharma, Piyush A1 - Khairnar, Vishal A1 - Hosseinzadeh, Zohreh A1 - Zhang, Shaqiu A1 - Palmada, Monica A1 - Sabolic, Ivan A1 - Koepsell, Hermann A1 - Lang, Karl S. A1 - Lang, Philipp A. A1 - Lang, Florian T1 - Expression of JAK3 Sensitive Na\(^+\) Coupled Glucose Carrier SGLT1 in Activated Cytotoxic T Lymphocytes JF - Cellular Physiology and Biochemistry N2 - Background: Similar to tumor cells, activated T-lymphocytes generate ATP mainly by glycolytic degradation of glucose. Lymphocyte glucose uptake involves non-concentrative glucose carriers of the GLUT family. In contrast to GLUT isoforms, Na+-coupled glucose-carrier SGLT1 accumulates glucose against glucose gradients and is effective at low extracellular glucose concentrations. The present study explored expression and regulation of SGLT1 in activated murine splenic cytotoxic T cells (CTLs) and human Jurkat T cells. Methods: FACS analysis, immunofluorescence, confocal microscopy, chemiluminescence and Western blotting were employed to estimate SGLT1 expression, function and regulation in lymphocytes, as well as dual electrode voltage clamp in SGLT1 ± JAK3 expressing Xenopus oocytes to quantify the effect of janus kinase3 (JAK3) on SGLT1 function. Results: SGLT1 is expressed in murine CTLs and also in human Jurkat T cells. 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake was significantly decreased by SGLT1-blocker phloridzin (0.2 mM) and by pharmacological inhibition of JAK3 with WHI-P131 (156 µM), WHI-P154 (11.2 µM) and JAK3 inhibitor VI (0.5 µM). Electrogenic glucose transport (Iglucose) in Xenopus oocytes expressing human SGLT1 was increased by additional expression of human wild type JAK3, active A568VJAK3 but not inactive K851AJAK3. Coexpression of JAK3 enhanced the maximal transport rate without significantly modifying affinity of the carrier. Iglucose in SGLT1+JAK3 expressing oocytes was significantly decreased by WHI-P154 (11.2 µM). JAK3 increased the SGLT1 protein abundance in the cell membrane. Inhibition of carrier insertion by brefeldin A (5 µM) in SGLT1+JAK3 expressing oocytes resulted in a decline of Iglucose, which was similar in presence and absence of JAK3. Conclusions: SGLT1 is expressed in murine cytotoxic T cells and human Jurkat T cells and significantly contributes to glucose uptake in those cells post activation. JAK3 up-regulates SGLT1 activity by increasing the carrier protein abundance in the cell membrane, an effect enforcing cellular glucose uptake into activated lymphocytes and thus contributing to the immune response. KW - tumor cell KW - Cytotoxic T lymphocytes KW - Glucose uptake KW - Jurkat T cells KW - Energy depletion KW - Janus kinase Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164900 VL - 39 IS - 3 ER - TY - JOUR A1 - Beykan, Seval A1 - Dam, Jan S. A1 - Eberlein, Uta A1 - Kaufmann, Jens A1 - Kjærgaard, Benedict A1 - Jødal, Lars A1 - Bouterfa, Hakim A1 - Bejot, Romain A1 - Lassmann, Michael A1 - Jensen, Svend Borup T1 - \(^{177}\)Lu-OPS201 targeting somatostatin receptors: in vivo biodistribution and dosimetry in a pig model JF - EJNMMI Research N2 - Background \(^{177}\)Lu is used in peptide receptor radionuclide therapies for the treatment of neuroendocrine tumors. Based on the recent literature, SST2 antagonists are superior to agonists in tumor uptake. The compound OPS201 is the novel somatostatin antagonist showing the highest SST2 affinity. The aim of this study was to measure the in vivo biodistribution and dosimetry of \(^{177}\)Lu-OPS201 in five anesthetized Danish Landrace pigs as an appropriate substitute for humans to quantitatively assess the absorbed doses for future clinical applications. Results \(^{177}\)Lu-OPS201 was obtained with a specific activity ranging from 10 to 17 MBq/μg. Prior to administration, the radiochemical purity was measured as s > 99.7 % in all cases. After injection, fast clearance of the compound from the blood stream was observed. Less than 5 % of the injected activity was presented in blood 10 min after injection. A series of SPECT/CT and whole-body scans conducted until 10 days after intravenous injection showed uptake mostly in the liver, spine, and kidneys. There was no visible uptake in the spleen. Blood samples were taken to determine the time-activity curve in the blood. Time-activity curves and time-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq \(^{177}\)Lu-OPS201, the highest predicted absorbed doses are obtained for the kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of 177Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels. Conclusions The \(^{177}\)Lu-OPS201 was well tolerated and caused no abnormal physiological or behavioral signs. In vivo distributions and absorbed doses of pigs are comparable to those observed in other publications. According to the biodistribution data in pigs, presented in this work, the expected radiation exposure in humans will be within the acceptable range. KW - lutetium-177 KW - JR11 KW - antagonist KW - dosimetry KW - neuroendocrine tumor (NET) KW - OPS201 KW - pig model KW - PRRT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146888 VL - 6 IS - 50 ER - TY - JOUR A1 - Bert, Bettina A1 - Chmielewska, Justyna A1 - Bergmann, Sven A1 - Busch, Maximilian A1 - Driever, Wolfgang A1 - Finger-Baier, Karin A1 - Hößler, Johanna A1 - Köhler, Almut A1 - Leich, Nora A1 - Misgeld, Thomas A1 - Nöldner, Torsten A1 - Reiher, Annegret A1 - Schartl, Manfred A1 - Seebach-Sproedt, Anja A1 - Thumberger, Thomas A1 - Schönfelder, Gilbert A1 - Grune, Barbara T1 - Considerations for a European animal welfare standard to evaluate adverse phenotypes in teleost fish JF - The EMBO Journal N2 - No abstract available. KW - Danio-rerio KW - Zebrafish KW - Pain Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188783 VL - 35 IS - 11 ER - TY - JOUR A1 - Bernt, Alexander A1 - Rangrez, Ashraf Y. A1 - Eden, Matthias A1 - Jungmann, Andreas A1 - Katz, Sylvia A1 - Rohr, Claudia A1 - Müller, Oliver J. A1 - Katus, Hugo A. A1 - Sossalla, Samuel T. A1 - Williams, Tatjana A1 - Ritter, Oliver A1 - Frank, Derk A1 - Frey, Norbert T1 - Sumoylation-independent activation of Calcineurin-NFAT-signaling via SUMO2 mediates cardiomyocyte hypertrophy JF - Scientific Reports N2 - The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10\(^{7}\) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype. Prohypertrophic effects were also observed in mice expressing SUMO2 in the heart using AAV9 (Adeno-associated virus), complementing the in vitro findings. In addition, increased SUMO2-mediated sumoylation in human cardiomyopathy patients and in mouse models of cardiomyopathy were observed. To decipher the underlying mechanism, we generated a sumoylation-deficient SUMO2 mutant (ΔGG). Surprisingly, ΔGG replicated Cn-NFAT-activation and the prohypertrophic effects of native SUMO2, both in vitro and in vivo, suggesting a sumoylation-independent mechanism. Finally, we discerned a direct interaction between SUMO2 and CnA, which promotes CnA nuclear localization. In conclusion, we identified SUMO2 as a novel activator of Cn-NFAT signaling in cardiomyocytes. In broader terms, these findings reveal an unexpected role for SUMO2 in cardiac hypertrophy and cardiomyopathy, which may open the possibility for therapeutic manipulation of this pathway. KW - Calcineurin-NFATsignaling KW - activation KW - SUMO2 KW - cardiac hypertrophy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167525 VL - 6 IS - 35758 ER - TY - JOUR A1 - Berges, Carsten A1 - Kerkau, Thomas A1 - Werner, Sandra A1 - Wolf, Nelli A1 - Winter, Nadine A1 - Hünig, Thomas A1 - Einsele, Hermann A1 - Topp, Max S. A1 - Beyersdorf, Niklas T1 - Hsp90 inhibition ameliorates CD4\(^{+}\) T cell-mediated acute Graft versus Host disease in mice JF - Immunity, Inflammation and Disease N2 - Introduction: For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co‐transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)—a potentially life‐threatening complication. Methods: Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD. Results: Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4\(^{+}\) T cell transplantation with the Hsp90 inhibitor 17‐(dimethylaminoethylamino)‐17‐demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. DMAG treatment was, however, insufficient to prolong overall survival of leukemia‐bearing mice after transplantation of allogeneic CD4\(^{+}\) and CD8\(^{+}\) T cells. Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4\(^{+}\) T cells with a relative resistance of CD4\(^{+}\) regulatory and CD8\(^{+}\) T cells toward Hsp90 inhibition. Conclusions: Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect. KW - Hsp90 KW - leukemia KW - acute Graft versus Host Disease KW - Graft versus Tumor Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168318 VL - 4 IS - 4 ER - TY - JOUR A1 - Benoit, Joshua B. A1 - Adelman, Zach N. A1 - Reinhardt, Klaus A1 - Dolan, Amanda A1 - Poelchau, Monica A1 - Jennings, Emily C. A1 - Szuter, Elise M. A1 - Hagan, Richard W. A1 - Gujar, Hemant A1 - Shukla, Jayendra Nath A1 - Zhu, Fang A1 - Mohan, M. A1 - Nelson, David R. A1 - Rosendale, Andrew J. A1 - Derst, Christian A1 - Resnik, Valentina A1 - Wernig, Sebastian A1 - Menegazzi, Pamela A1 - Wegener, Christian A1 - Peschel, Nicolai A1 - Hendershot, Jacob M. A1 - Blenau, Wolfgang A1 - Predel, Reinhard A1 - Johnston, Paul R. A1 - Ioannidis, Panagiotis A1 - Waterhouse, Robert M. A1 - Nauen, Ralf A1 - Schorn, Corinna A1 - Ott, Mark-Christoph A1 - Maiwald, Frank A1 - Johnston, J. Spencer A1 - Gondhalekar, Ameya D. A1 - Scharf, Michael E. A1 - Raje, Kapil R. A1 - Hottel, Benjamin A. A1 - Armisén, David A1 - Crumière, Antonin Jean Johan A1 - Refki, Peter Nagui A1 - Santos, Maria Emilia A1 - Sghaier, Essia A1 - Viala, Sèverine A1 - Khila, Abderrahman A1 - Ahn, Seung-Joon A1 - Childers, Christopher A1 - Lee, Chien-Yueh A1 - Lin, Han A1 - Hughes, Daniel S.T. A1 - Duncan, Elizabeth J. A1 - Murali, Shwetha C. A1 - Qu, Jiaxin A1 - Dugan, Shannon A1 - Lee, Sandra L. A1 - Chao, Hsu A1 - Dinh, Huyen A1 - Han, Yi A1 - Doddapaneni, Harshavardhan A1 - Worley, Kim C. A1 - Muzny, Donna M. A1 - Wheeler, David A1 - Panfilio, Kristen A. A1 - Jentzsch, Iris M. Vargas A1 - Jentzsch, IMV A1 - Vargo, Edward L. A1 - Booth, Warren A1 - Friedrich, Markus A1 - Weirauch, Matthew T. A1 - Anderson, Michelle A.E. A1 - Jones, Jeffery W. A1 - Mittapalli, Omprakash A1 - Zhao, Chaoyang A1 - Zhou, Jing-Jiang A1 - Evans, Jay D. A1 - Attardo, Geoffrey M. A1 - Robertson, Hugh M. A1 - Zdobnov, Evgeny M. A1 - Ribeiro, Jose M.C. A1 - Gibbs, Richard A. A1 - Werren, John H. A1 - Palli, Subba R. A1 - Schal, Coby A1 - Richards, Stephen T1 - Unique features of a global human ectoparasite identified through sequencing of the bed bug genome JF - Nature Communications N2 - The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host–symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human–bed bug and symbiont–bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite. KW - human ectoparasite KW - bed bug KW - Cimex lectularius KW - genome Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166221 VL - 7 IS - 10165 ER - TY - JOUR A1 - Bening, C. A1 - Hamouda, K. A1 - Leyh, R. T1 - Sex differences in volume overload in skinned fibers JF - BMC Cardiovascular Disorders N2 - Background The impact of sex on cardiac morphology and function in chronic volume overload has been described in detail. However, the relation between sex and contractile properties at the actin-myosin level has not been well defined. Therefore, we evaluated the influence of sex on the contractile capacities of patients with chronic volume overload. Methods In 36 patients (18 males, 65 ± 9 years; 18 females, 65 ± 13 years) scheduled for elective mitral valve surgery due to severe mitral regurgitation (MR) with preserved left ventricular function, right auricle samples were obtained prior to extracorporal circulation. The fibers were prepared and skinned and exposed to a gradual increase in the calcium concentration (from pCa of 6.5–4.0) for calcium-induced force-developing measurements. Calcium sensitivity was also measured and recorded. Results The pCa-force relationship of the fibers obtained from males and females was significantly different, with the force values of the female fibers greater than those of male fibers at maximum calcium concentrations (pCa of 4.0: 3.6 ± 0.3 mN versus 3.2 ± 0.4 mN, p 0.02) and pCa of 4.5 2.6 ± 0.6 versus 2.0 ± 0.5, p 0.002). In contrast, the force values of female fibers were lower at mean calcium concentrations compared to those of male fibers (at 5.5 and pCa of 6.0: 1.0 ± 0.3 mN versus 1.2 ± 0.5 mN, p 0.04; 0.61 ± 0.05 versus 0.88 ± 0.09, p 0.04). Calcium sensitivity was observed at pCa of 5.0 in females and pCa of 4.5 in males. Conclusion This study demonstrated that female fibers from patients exposed to chronic volume overload developed higher force values at a given calcium concentration compared to fibers from male patients. We assume that female patients might tap the full force potential, which is required when exposed to the highest calcium concentrations in our experimental cycle. The calcium sensitivity among genders was significantly different, with the results suggesting that males have higher calcium sensitivity and might compensate for lower force values at maximal calcium concentrations by a higher affinity for calcium. Hence, female patients with MR seem to work more “energy efficient”. KW - calcium sensitivity KW - pCa KW - force relationship KW - skinned fibers Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147896 VL - 16 IS - 197 ER - TY - JOUR A1 - Ben Ami, Tal A1 - Tong, Yuehong A1 - Bhuiyan, Alauddin A1 - Huisingh, Carrie A1 - Ablonczy, Zsolt A1 - Ach, Thomas A1 - Curcio, Christine A. A1 - Smith, R. Theodore T1 - Spatial and Spectral Characterization of Human Retinal Pigment Epithelium Fluorophore Families by Ex Vivo Hyperspectral Autofluorescence Imaging JF - Translational Vision Science & Technology N2 - Purpose: Discovery of candidate spectra for abundant fluorophore families in human retinal pigment epithelium (RPE) by ex vivo hyperspectral imaging. Methods: Hyperspectral autofluorescence emission images were captured between 420 and 720 nm (10-nm intervals), at two excitation bands (436–460, 480–510 nm), from three locations (fovea, perifovea, near-periphery) in 20 normal RPE/Bruch's membrane (BrM) flatmounts. Mathematical factorization extracted a BrM spectrum (S0) and abundant lipofuscin/melanolipofuscin (LF/ML) spectra of RPE origin (S1, S2, S3) from each tissue. Results: Smooth spectra S1 to S3, with perinuclear localization consistent with LF/ML at all three retinal locations and both excitations in 14 eyes (84 datasets), were included in the analysis. The mean peak emissions of S0, S1, and S2 at λ\(_{ex}\) 436 nm were, respectively, 495 ± 14, 535 ± 17, and 576 ± 20 nm. S3 was generally trimodal, with peaks at either 580, 620, or 650 nm (peak mode, 650 nm). At λ\(_{ex}\) 480 nm, S0, S1, and S2 were red-shifted to 526 ± 9, 553 ± 10, and 588 ± 23 nm, and S3 was again trimodal (peak mode, 620 nm). S1 often split into two spectra, S1A and S1B. S3 strongly colocalized with melanin. There were no significant differences across age, sex, or retinal location. Conclusions: There appear to be at least three families of abundant RPE fluorophores that are ubiquitous across age, retinal location, and sex in this sample of healthy eyes. Further molecular characterization by imaging mass spectrometry and localization via super-resolution microscopy should elucidate normal and abnormal RPE physiology involving fluorophores. Translational Relevance: Our results help establish hyperspectral autofluorescence imaging of the human retinal pigment epithelium as a useful tool for investigating retinal health and disease. KW - spectral characterization KW - human retinal pigment epithelium KW - fluorophores KW - hyperspectral autofluorescence imaging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168328 VL - 5 IS - 3 ER - TY - JOUR A1 - Bemm, Felix A1 - Becker, Dirk A1 - Larisch, Christina A1 - Kreuzer, Ines A1 - Escalante-Perez, Maria A1 - Schulze, Waltraud X. A1 - Ankenbrand, Markus A1 - Van de Weyer, Anna-Lena A1 - Krol, Elzbieta A1 - Al-Rasheid, Khaled A. A1 - Mithöfer, Axel A1 - Weber, Andreas P. A1 - Schultz, Jörg A1 - Hedrich, Rainer T1 - Venus flytrap carnivorous lifestyle builds on herbivore defense strategies JF - Genome Research N2 - Although the concept of botanical carnivory has been known since Darwin's time, the molecular mechanisms that allow animal feeding remain unknown, primarily due to a complete lack of genomic information. Here, we show that the transcriptomic landscape of the Dionaea trap is dramatically shifted toward signal transduction and nutrient transport upon insect feeding, with touch hormone signaling and protein secretion prevailing. At the same time, a massive induction of general defense responses is accompanied by the repression of cell death-related genes/processes. We hypothesize that the carnivory syndrome of Dionaea evolved by exaptation of ancient defense pathways, replacing cell death with nutrient acquisition. KW - Dionaea-muscipula ellis KW - Plant utricularia-gibba KW - Programmed cell-death KW - Genomics data sets KW - RNA-SEQ data KW - Arabidopsis-thaliana KW - Jasmonate perception KW - Action potentials KW - Stress responses KW - Wonderful plants Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188799 VL - 26 IS - 6 ER - TY - JOUR A1 - Bekes, Inga A1 - Friedl, Thomas W. P. A1 - Köhler, Tanja A1 - Möbus, Volker A1 - Janni, Wolfgang A1 - Wöckel, Achim A1 - Wulff, Christine T1 - Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer? JF - Molecular Cancer N2 - Background Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types. Methods Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition. Results VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5. Conclusions Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition. KW - ovarian cancer KW - vascular permeability KW - ascites KW - VEGF KW - claudin 5 KW - VE-cadherin Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169298 VL - 15 IS - 13 ER - TY - JOUR A1 - Beer, Katharina A1 - Steffan-Dewenter, Ingolf A1 - Härtel, Stephan A1 - Helfrich-Förster, Charlotte T1 - A new device for monitoring individual activity rhythms of honey bees reveals critical effects of the social environment on behavior JF - Journal of Comparative Physiology A N2 - Chronobiological studies of individual activity rhythms in social insects can be constrained by the artificial isolation of individuals from their social context. We present a new experimental set-up that simultaneously measures the temperature rhythm in a queen-less but brood raising mini colony and the walking activity rhythms of singly kept honey bees that have indirect social contact with it. Our approach enables monitoring of individual bees in the social context of a mini colony under controlled laboratory conditions. In a pilot experiment, we show that social contact with the mini colony improves the survival of monitored young individuals and affects locomotor activity patterns of young and old bees. When exposed to conflicting Zeitgebers consisting of a light-dark (LD) cycle that is phase-delayed with respect to the mini colony rhythm, rhythms of young and old bees are socially synchronized with the mini colony rhythm, whereas isolated bees synchronize to the LD cycle. We conclude that the social environment is a stronger Zeitgeber than the LD cycle and that our new experimental set-up is well suited for studying the mechanisms of social entrainment in honey bees. KW - Social entrainment KW - Foragers KW - Nurses KW - Locomotor activity KW - Temperature rhythms Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188030 VL - 202 IS - 8 ER - TY - JOUR A1 - Becker, Nils A1 - Kucharski, Robert A1 - Rössler, Wolfgang A1 - Maleszka, Ryszard T1 - Age‐dependent transcriptional and epigenomic responses to light exposure in the honey bee brain JF - FEBS Open Bio N2 - Light is a powerful environmental stimulus of special importance in social honey bees that undergo a behavioral transition from in-hive to outdoor foraging duties. Our previous work has shown that light exposure induces structural neuronal plasticity in the mushroom bodies (MBs), a brain center implicated in processing inputs from sensory modalities. Here, we extended these analyses to the molecular level to unravel light-induced transcriptomic and epigenomic changes in the honey bee brain. We have compared gene expression in brain compartments of 1- and 7-day-old light-exposed honey bees with age-matched dark-kept individuals. We have found a number of differentially expressed genes (DEGs), both novel and conserved, including several genes with reported roles in neuronal plasticity. Most of the DEGs show age-related changes in the amplitude of light-induced expression and are likely to be both developmentally and environmentally regulated. Some of the DEGs are either known to be methylated or are implicated in epigenetic processes suggesting that responses to light exposure are at least partly regulated at the epigenome level. Consistent with this idea light alters the DNA methylation pattern of bgm, one of the DEGs affected by light exposure, and the expression of microRNA miR-932. This confirms the usefulness of our approach to identify candidate genes for neuronal plasticity and provides evidence for the role of epigenetic processes in driving the molecular responses to visual stimulation. KW - DNA methylation KW - insect brain KW - light-induced gene expression KW - microRNA KW - neuronal plasticity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147080 VL - 6 IS - 7 ER - TY - JOUR A1 - Beck, Lukas T1 - Zur Funktionsweise der Prokura als handelsrechtliche Vollmacht JF - JURA - Juristische Ausbildung N2 - Kein Abstract verfügbar. KW - Prokura Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195109 SN - 1612-7021 SN - 0170-1452 N1 - Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich. VL - 38 IS - 9 PB - De Gruyter ER - TY - JOUR A1 - Bechtle, Philip A1 - Camargo-Molina, José Eliel A1 - Desch, Klaus A1 - Dreiner, Herbert K. A1 - Hamer, Matthias A1 - Krämer, Michael A1 - O'Leary, Ben A1 - Porod, Werner A1 - Sarrazin, Björn A1 - Stefaniak, Tim A1 - Uhlenbrock, Mathias A1 - Wienemann, Peter T1 - Killing the cMSSM softly JF - The European Physical Journal C N2 - We investigate the constrained Minimal Supersymmetric Standard Model (cMSSM) in the light of constraining experimental and observational data from precision measurements, astrophysics, direct supersymmetry searches at the LHC and measurements of the properties of the Higgs boson, by means of a global fit using the program Fittino. As in previous studies, we find rather poor agreement of the best fit point with the global data. We also investigate the stability of the electro-weak vacuum in the preferred region of parameter space around the best fit point. We find that the vacuum is metastable, with a lifetime significantly longer than the age of the Universe. For the first time in a global fit of supersymmetry, we employ a consistent methodology to evaluate the goodness-of-fit of the cMSSM in a frequentist approach by deriving p values from large sets of toy experiments. We analyse analytically and quantitatively the impact of the choice of the observable set on the p value, and in particular its dilution when confronting the model with a large number of barely constraining measurements. Finally, for the preferred sets of observables, we obtain p values for the cMSSM below 10 %, i.e. we exclude the cMSSM as a model at the 90 % confidence level. KW - Dark Matter KW - Higgs Boson KW - Higgs Mass KW - Supersymmetry Breaking KW - Light Supersymmetric Particle Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165045 VL - 76 IS - 96 ER - TY - JOUR A1 - Baur, Johannes A1 - Ritter, Christian O. A1 - Germer, Christoph-Thomas A1 - Klein, Ingo A1 - Kickuth, Ralph A1 - Steger, Ulrich T1 - Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma JF - Hepatic Medicine N2 - Purpose: In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE). Patients and methods: In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. Results: No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. Conclusion: No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE. KW - transarterial chemoembolization KW - hepatocellular carcinoma KW - drug-eluting beads Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146553 VL - 2016 IS - 8 ER - TY - JOUR A1 - Baumeister, Joachim A1 - Striffler, Albrecht A1 - Brandt, Marc A1 - Neumann, Michael T1 - Collaborative Decision Support and Documentation in Chemical Safety with KnowSEC JF - Journal of Cheminformatics N2 - To protect the health of human and environment, the European Union implemented the REACH regulation for chemical substances. REACH is an acronym for Registration, Evaluation, Authorization, and Restriction of Chemicals. Under REACH, the authorities have the task of assessing chemical substances, especially those that might pose a risk to human health or environment. The work under REACH is scientifically, technically and procedurally a complex and knowledge-intensive task that is jointly performed by the European Chemicals Agency and member state authorities in Europe. The assessment of substances under REACH conducted in the German Environment Agency is supported by the knowledge-based system KnowSEC, which is used for the screening, documentation, and decision support when working on chemical substances. The software KnowSEC integrates advanced semantic technologies and strong problem solving methods. It allows for the collaborative work on substances in the context of the European REACH regulation. We discuss the applied methods and process models and we report on experiences with the implementation and use of the system. KW - decision support KW - knowledge-based systems KW - ontologies KW - expert systems KW - semantic technologies Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146575 VL - 8 IS - 21 ER - TY - JOUR A1 - Batsching, Sophie A1 - Wolf, Reinhard A1 - Heisenberg, Martin T1 - Inescapable Stress Changes Walking Behavior in Flies - Learned Helplessness Revisited JF - PLoS ONE N2 - Like other animals flies develop a state of learned helplessness in response to unescapable aversive events. To show this, two flies, one 'master', one 'yoked', are each confined to a dark, small chamber and exposed to the same sequence of mild electric shocks. Both receive these shocks when the master fly stops walking for more than a second. Behavior in the two animals is differently affected by the shocks. Yoked flies are transiently impaired in place learning and take longer than master flies to exit from the chamber towards light. After the treatment they walk more slowly and take fewer and shorter walking bouts. The low activity is attributed to the fly's experience that its escape response, an innate behavior to terminate the electric shocks, does not help anymore. Earlier studies using heat pulses instead of electric shocks had shown similar effects. This parallel supports the interpretation that it is the uncontrollability that induces the state. KW - learning KW - locomotion KW - animal behavior KW - behavioral conditioning KW - walking KW - vibration KW - light pulses KW - conditioned response Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-178640 VL - 11 IS - 11 ER - TY - JOUR A1 - Bartelheim, Kerstin A1 - Nemes, Karolina A1 - Seeringer, Angela A1 - Kerl, Kornelius A1 - Buechner, Jochen A1 - Boos, Joachim A1 - Graf, Norbert A1 - Dürken, Matthias A1 - Gerss, Joachim A1 - Hasselblatt, Martin A1 - Kortmann, Rolf-Dieter A1 - Teichert von Luettichau, Irene A1 - Nagel, Inga A1 - Nygaard, Randi A1 - Oyen, Florian A1 - Quiroga, Eduardo A1 - Schlegel, Paul-Gerhardt A1 - Schmid, Irene A1 - Schneppenheim, Reinhard A1 - Siebert, Reiner A1 - Solano-Paez, Palma A1 - Timmermann, Beate A1 - Warmuth-Metz, Monika A1 - Frühwald, Michael Christoph T1 - Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007 JF - Cancer Medicine N2 - Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU‐RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high‐dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64% (genetic analyses, FISH, MLPA, sequencing) up to 97% (neuropathology, INI1 stain). Germ‐line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6‐year overall and event‐free survival rates were 46% (±0.10) and 45% (±0.09), respectively. Serious adverse events and one treatment‐related death due to insufficiency of a ventriculo peritoneal shunt (VP‐shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU‐RHAB provides the best available basis for phase I/II clinical trials. KW - AT/RT KW - EU‐RHAB Registry KW - pediatric brain tumor KW - Rhabdoid 2007 Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164799 VL - 5 IS - 8 ER -