@article{DuezelvanPraagSendtner2016, author = {D{\"u}zel, Emrah and van Praag, Henriette and Sendtner, Michael}, title = {Can physical exercise in old age improve memory and hippocampal function?}, series = {Brain}, volume = {139}, journal = {Brain}, number = {3}, doi = {10.1093/brain/awv407}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190721}, pages = {662-673}, year = {2016}, abstract = {Physical exercise can convey a protective effect against cognitive decline in ageing and Alzheimer's disease. While the long-term health-promoting and protective effects of exercise are encouraging, it's potential to induce neuronal and vascular plasticity in the ageing brain is still poorly understood. It remains unclear whether exercise slows the trajectory of normal ageing by modifying vascular and metabolic risk factors and/or consistently boosts brain function by inducing structural and neurochemical changes in the hippocampus and related medial temporal lobe circuitry—brain areas that are important for learning and memory. Hence, it remains to be established to what extent exercise interventions in old age can improve brain plasticity above and beyond preservation of function. Existing data suggest that exercise trials aiming for improvement and preservation may require different outcome measures and that the balance between the two may depend on exercise intensity and duration, the presence of preclinical Alzheimer's disease pathology, vascular and metabolic risk factors and genetic variability.}, language = {en} } @article{WernerKojonazarovGassneretal.2016, author = {Werner, Franziska and Kojonazarov, Baktybek and Gaßner, Birgit and Abeßer, Marco and Schuh, Kai and V{\"o}lker, Katharina and Baba, Hideo A. and Dahal, Bhola K. and Schermuly, Ralph T. and Kuhn, Michaela}, title = {Endothelial actions of atrial natriuretic peptide prevent pulmonary hypertension in mice}, series = {Basic Research in Cardiology}, volume = {111}, journal = {Basic Research in Cardiology}, number = {2}, doi = {10.1007/s00395-016-0541-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190664}, pages = {16}, year = {2016}, abstract = {The cardiac hormone atrial natriuretic peptide (ANP) regulates systemic and pulmonary arterial blood pressure by activation of its cyclic GMP-producing guanylyl cyclase-A (GC-A) receptor. In the lung, these hypotensive effects were mainly attributed to smooth muscle-mediated vasodilatation. It is unknown whether pulmonary endothelial cells participate in the homeostatic actions of ANP. Therefore, we analyzed GC-A/cGMP signalling in lung endothelial cells and the cause and functional impact of lung endothelial GC-A dysfunction. Western blot and cGMP determinations showed that cultured human and murine pulmonary endothelial cells exhibit prominent GC-A expression and activity which were markedly blunted by hypoxia, a condition known to trigger pulmonary hypertension (PH). To elucidate the consequences of impaired endothelial ANP signalling, we studied mice with genetic endothelial cell-restricted ablation of the GC-A receptor (EC GC-A KO). Notably, EC GC-A KO mice exhibit PH already under resting, normoxic conditions, with enhanced muscularization of small arteries and perivascular infiltration of inflammatory cells. These alterations were aggravated on exposure of mice to chronic hypoxia. Lung endothelial GC-A dysfunction was associated with enhanced expression of angiotensin converting enzyme (ACE) and increased pulmonary levels of Angiotensin II. Angiotensin II/AT(1)-blockade with losartan reversed pulmonary vascular remodelling and perivascular inflammation of EC GC-A KO mice, and prevented their increment by chronic hypoxia. This experimental study indicates that endothelial effects of ANP are critical to prevent pulmonary vascular remodelling and PH. Chronic endothelial ANP/GC-A dysfunction, e.g. provoked by hypoxia, is associated with activation of the ACE-angiotensin pathway in the lung and PH.}, language = {en} } @article{BoehmScherzerShabalaetal.2016, author = {B{\"o}hm, J. and Scherzer, S. and Shabala, S. and Krol, E. and Neher, E. and Mueller, T. D. and Hedrich, R.}, title = {Venus flytrap HKT1-type channel provides for prey sodium uptake into carnivorous plant without conflicting with electrical excitability}, series = {Molecular Plant}, volume = {9}, journal = {Molecular Plant}, number = {3}, doi = {10.1016/j.molp.2015.09.017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189803}, pages = {428-436}, year = {2016}, abstract = {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.}, language = {en} } @article{MotykaDyksikRyczkoetal.2016, author = {Motyka, M. and Dyksik, M. and Ryczko, K. and Weih, R. and Dallner, M. and H{\"o}fling, S. and Kamp, M. and Sęk, G. and Misiewicz, J.}, title = {Type-II quantum wells with tensile-strained GaAsSb layers for interband cascade lasers with tailored valence band mixing}, series = {Applied Physics Letters}, volume = {108}, journal = {Applied Physics Letters}, number = {10}, doi = {10.1063/1.4943193}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189795}, year = {2016}, abstract = {Optical properties of modified type II W-shaped quantum wells have been investigated with the aim to be utilized in interband cascade lasers. The results show that introducing a tensely strained GaAsSb layer, instead of a commonly used compressively strained GaInSb, allows employing the active transition involving valence band states with a significant admixture of the light holes. Theoretical predictions of multiband k.p theory have been experimentally verified by using photoluminescence and polarization dependent photoreflectance measurements. These results open a pathway for practical realization of mid-infrared lasing devices with uncommon polarization properties including, for instance, polarization-independent midinfrared light emitters.}, language = {en} } @article{CateGajendraAlsburyetal.2016, author = {Cate, Marie-Sophie and Gajendra, Sangeetha and Alsbury, Samantha and Raabe, Thomas and Tear, Guy and Mitchell, Kevin J.}, title = {Mushroom body defect is required in parallel to Netrin for midline axon guidance in Drosophila}, series = {Development}, volume = {143}, journal = {Development}, number = {6}, doi = {10.1242/dev.129684}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189770}, pages = {972-977}, year = {2016}, abstract = {The outgrowth of many neurons within the central nervous system is initially directed towards or away from the cells lying at the midline. Recent genetic evidence suggests that a simple model of differential sensitivity to the conserved Netrin attractants and Slit repellents is insufficient to explain the guidance of all axons at the midline. In the Drosophila embryonic ventral nerve cord, many axons still cross the midline in the absence of the Netrin genes (NetA and NetB) or their receptor frazzled. Here we show that mutation of mushroom body defect (mud) dramatically enhances the phenotype of Netrin or frazzled mutants, resulting in many more axons failing to cross the midline, although mutations in mud alone have little effect. This suggests that mud, which encodes a microtubule-binding coiled-coil protein homologous to NuMA and LIN-5, is an essential component of a Netrin-independent pathway that acts in parallel to promote midline crossing. We demonstrate that this novel role of Mud in axon guidance is independent of its previously described role in neural precursor development. These studies identify a parallel pathway controlling midline guidance in Drosophila and highlight a novel role for Mud potentially acting downstream of Frizzled to aid axon guidance.}, language = {en} } @article{SulimanSunPedersenetal.2016, author = {Suliman, Salwa and Sun, Yang and Pedersen, Torbjorn O. and Xue, Ying and Nickel, Joachim and Waag, Thilo and Finne-Wistrand, Anna and Steinm{\"u}ller-Nethl, Doris and Krueger, Anke and Costea, Daniela E. and Mustafa, Kamal}, title = {In vivo host response and degradation of copolymer scaffolds functionalized with nanodiamonds and bone morphogenetic protein 2}, series = {Advanced Healthcare Materials}, volume = {5}, journal = {Advanced Healthcare Materials}, number = {6}, doi = {10.1002/adhm.201500723}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189764}, pages = {730-742}, year = {2016}, abstract = {The aim is to evaluate the effect of modifying poly[(L-lactide)-co-(epsilon-caprolactone)] scaffolds (PLCL) with nanodiamonds (nDP) or with nDP+physisorbed BMP-2 (nDP+BMP-2) on in vivo host tissue response and degradation. The scaffolds are implanted subcutaneously in Balb/c mice and retrieved after 1, 8, and 27 weeks. Molecular weight analysis shows that modified scaffolds degrade faster than the unmodified. Gene analysis at week 1 shows highest expression of proinflammatory markers around nDP scaffolds; although the presence of inflammatory cells and foreign body giant cells is more prominent around the PLCL. Tissue regeneration markers are highly expressed in the nDP+BMP-2 scaffolds at week 8. A fibrous capsule is detectable by week 8, thinnest around nDP scaffolds and at week 27 thickest around PLCL scaffolds. mRNA levels of ALP, COL1 alpha 2, and ANGPT1 are signifi cantly upregulating in the nDP+BMP-2 scaffolds at week 1 with ectopic bone seen at week 8. Even when almost 90\% of the scaffold is degraded at week 27, nDP are observable at implantation areas without adverse effects. In conclusion, modifying PLCL scaffolds with nDP does not aggravate the host response and physisorbed BMP-2 delivery attenuates infl ammation while lowering the dose of BMP-2 to a relatively safe and economical level.}, language = {en} } @article{MartiniWillison2016, author = {Martini, Rudolf and Willison, Hugh}, title = {Neuroinflammation in the peripheral nerve: cause, modulator, or bystander in peripheral neuropathies?}, series = {GLIA}, volume = {64}, journal = {GLIA}, number = {4}, doi = {10.1002/glia.22899}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189696}, pages = {475-486}, year = {2016}, abstract = {The role of innate and adaptive inflammation as a primary driver or modifier of neuropathy in premorbidly normal nerves, and as a critical player in amplifying neuropathies of other known causes (e.g., genetic, metabolic) is incompletely understood and under-researched, despite unmet clinical need. Also, cellular and humoral components of the adaptive and innate immune system are substantial disease modifying agents in the context of neuropathies and, at least in some neuropathies, there is an identified tight interrelationship between both compartments of the immune system. Additionally, the quadruple relationship between Schwann cell, axon, macrophage, and endoneurial fibroblast, with their diverse membrane bound and soluble signalling systems, forms a distinct focus for investigation in nerve diseases with inflammation secondary to Schwann cell mutations and possibly others. Identification of key immunological effector pathways that amplify neuropathic features and associated clinical symptomatology including pain should lead to realistic and timely possibilities for translatable therapeutic interventions using existing immunomodulators, alongside the development of novel therapeutic targets.}, language = {en} } @article{ColvillBoothNilletal.2016, author = {Colvill, Emma and Booth, Jeremy and Nill, Simeon and Fast, Martin and Bedford, James and Oelfke, Uwe and Nakamura, Mitsuhiro and Poulsen, Per and Worm, Esben and Hansen, Rune and Ravkilde, Thomas and Rydh{\"o}g, Jonas Scherman and Pommer, Tobias and af Rosenschold, Per Munck and Lang, Stephanie and Guckenberger, Matthias and Groh, Christian and Herrmann, Christian and Verellen, Dirk and Poels, Kenneth and Wang, Lei and Hadsell, Michael and Sothmann, Thilo and Blanck, Oliver and Keall, Paul}, title = {A dosimetric comparison of real-time adaptive and non-adaptive radiotherapy: a multi-institutional study encompassing robotic, gimbaled, multileaf collimator and couch tracking}, series = {Radiotherapy and Oncology}, volume = {119}, journal = {Radiotherapy and Oncology}, number = {1}, doi = {10.1016/j.radonc.2016.03.006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189605}, pages = {159-165}, year = {2016}, abstract = {Purpose: A study of real-time adaptive radiotherapy systems was performed to test the hypothesis that, across delivery systems and institutions, the dosimetric accuracy is improved with adaptive treatments over non-adaptive radiotherapy in the presence of patient-measured tumor motion. Methods and materials: Ten institutions with robotic(2), gimbaled(2), MLC(4) or couch tracking(2) used common materials including CT and structure sets, motion traces and planning protocols to create a lung and a prostate plan. For each motion trace, the plan was delivered twice to a moving dosimeter; with and without real-time adaptation. Each measurement was compared to a static measurement and the percentage of failed points for gamma-tests recorded. Results: For all lung traces all measurement sets show improved dose accuracy with a mean 2\%/2 mm gamma-fail rate of 1.6\% with adaptation and 15.2\% without adaptation (p < 0.001). For all prostate the mean 2\%/2 mm gamma-fail rate was 1.4\% with adaptation and 17.3\% without adaptation (p < 0.001). The difference between the four systems was small with an average 2\%/2 mm gamma-fail rate of <3\% for all systems with adaptation for lung and prostate. Conclusions: The investigated systems all accounted for realistic tumor motion accurately and performed to a similar high standard, with real-time adaptation significantly outperforming non-adaptive delivery methods.}, language = {en} } @article{KuhnScharfenortSchuemannetal.2016, author = {Kuhn, Manuel and Scharfenort, Robert and Sch{\"u}mann, Dirk and Schiele, Miriam A. and M{\"u}nsterk{\"o}tter, Anna L. and Deckert, J{\"u}rgen and Domschke, Katharina and Haaker, Jan and Kalisch, Raffael and Pauli, Paul and Reif, Andreas and Romanos, Marcel and Zwanzger, Peter and Lonsdorf, Tina B.}, title = {Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament}, series = {Social Cognitive and Affective Neuroscience}, volume = {11}, journal = {Social Cognitive and Affective Neuroscience}, number = {4}, doi = {10.1093/scan/nsv137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189645}, pages = {537-547}, year = {2016}, abstract = {Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences.}, language = {en} } @article{ChioreanVonHoffRenietal.2016, author = {Chiorean, E. G. and Von Hoff, D. D. and Reni, M. and Arena, F. P. and Infante, J. R. and Bathini, V. G. and Wood, T. E. and Mainwaring, P. N. and Muldoon, R. T. and Clingan, P. R. and Kunzmann, V. and Ramanathan, R. K. and Tabernero, J. and Goldstein, D. and McGovern, D. and Lu, B. and Ko, A.}, title = {CA19-9 decrease at 8 weeks as a predictor of overall survival in a randomized phase III trial (MPACT) of weekly nab-paclitaxel plus gemcitabine versus gemcitabine alone in patients with metastatic pancreatic cancer}, series = {Annals of Oncology}, volume = {27}, journal = {Annals of Oncology}, number = {4}, doi = {10.1093/annonc/mdw006}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189659}, pages = {654-660}, year = {2016}, abstract = {Background A phase I/II study and subsequent phase III study (MPACT) reported significant correlations between CA19-9 decreases and prolonged overall survival (OS) with nab-paclitaxel plus gemcitabine (nab-P + Gem) treatment for metastatic pancreatic cancer (MPC). CA19-9 changes at week 8 and potential associations with efficacy were investigated as part of an exploratory analysis in the MPACT trial. Patients and methods Untreated patients with MPC (N = 861) received nab-P + Gem or Gem alone. CA19-9 was evaluated at baseline and every 8 weeks. Results Patients with baseline and week-8 CA19-9 measurements were analyzed (nab-P + Gem: 252; Gem: 202). In an analysis pooling the treatments, patients with any CA19-9 decline (80\%) versus those without (20\%) had improved OS (median 11.1 versus 8.0 months; P = 0.005). In the nab-P + Gem arm, patients with (n = 206) versus without (n = 46) any CA19-9 decrease at week 8 had a confirmed overall response rate (ORR) of 40\% versus 13\%, and a median OS of 13.2 versus 8.3 months (P = 0.001), respectively. In the Gem-alone arm, patients with (n = 159) versus without (n = 43) CA19-9 decrease at week 8 had a confirmed ORR of 15\% versus 5\%, and a median OS of 9.4 versus 7.1 months (P = 0.404), respectively. In the nab-P + Gem and Gem-alone arms, by week 8, 16\% (40/252) and 6\% (13/202) of patients, respectively, had an unconfirmed radiologic response (median OS 13.7 and 14.7 months, respectively), and 79\% and 84\% of patients, respectively, had stable disease (SD) (median OS 11.1 and 9 months, respectively). Patients with SD and any CA19-9 decrease (158/199 and 133/170) had a median OS of 13.2 and 9.4 months, respectively. Conclusion This analysis demonstrated that, in patients with MPC, any CA19-9 decrease at week 8 can be an early marker for chemotherapy efficacy, including in those patients with SD. CA19-9 decrease identified more patients with survival benefit than radiologic response by week 8.}, language = {en} } @article{WhiteWiederholdLoeffleretal.2016, author = {White, P. Lewis and Wiederhold, Nathan P. and Loeffler, Juergen and Najvar, Laura K. and Melchers, Willem and Herrera, Monica and Bretagne, Stephane and Wickes, Brian and Kirkpatrick, William R. and Barnes, Rosemary A. and Donnelly, J. Peter and Patterson, Thomas F.}, title = {Comparison of nonculture blood-based tests for diagnosing invasive aspergillosis in an animal model}, series = {Journal of Clinical Microbiology}, volume = {54}, journal = {Journal of Clinical Microbiology}, number = {4}, doi = {10.1128/JCM.03233-15}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189674}, pages = {960-966}, year = {2016}, abstract = {The European Aspergillus PCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and beta-D-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and beta-D-glucan were 73\%, 65\%, 68\%, and 46\%, respectively. The corresponding specificities were 92\%, 79\%, 80\%, and 100\%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and beta-D-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and beta-D-glucan proved optimal (area under the curve AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests.}, language = {en} } @article{BarquistMayhoCumminsetal.2016, author = {Barquist, Lars and Mayho, Matthew and Cummins, Carla and Cain, Amy K. and Boinett, Christine J. and Page, Andrew J. and Langridge, Gemma C. and Quail, Michael A. and Keane, Jacqueline A. and Parkhill, Julian}, title = {The TraDIS toolkit: sequencing and analysis for dense transposon mutant libraries}, series = {Bioinformatics}, volume = {32}, journal = {Bioinformatics}, number = {7}, doi = {10.1093/bioinformatics/btw022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189667}, pages = {1109-1111}, year = {2016}, abstract = {Transposon insertion sequencing is a high-throughput technique for assaying large libraries of otherwise isogenic transposon mutants providing insight into gene essentiality, gene function and genetic interactions. We previously developed the Transposon Directed Insertion Sequencing (TraDIS) protocol for this purpose, which utilizes shearing of genomic DNA followed by specific PCR amplification of transposon-containing fragments and Illumina sequencing. Here we describe an optimized high-yield library preparation and sequencing protocol for TraDIS experiments and a novel software pipeline for analysis of the resulting data. The Bio-Tradis analysis pipeline is implemented as an extensible Perl library which can either be used as is, or as a basis for the development of more advanced analysis tools. This article can serve as a general reference for the application of the TraDIS methodology.}, language = {en} } @article{ThomasZengRiviereetal.2016, author = {Thomas, Anna C. and Zeng, Zhiqiang and Rivi{\`e}re, Jean-Baptiste and O'Shaughnessy, Ryan and Al-Olabi, Lara and St.-Onge, Judith and Atherton, David J. and Aubert, H{\´e}l{\`e}ne and Bagazgoitia, Lorea and Barbarot, S{\´e}bastien and Bourrat, Emmanuelle and Chiaverini, Christine and Chong, W. Kling and Duffourd, Yannis and Glover, Mary and Groesser, Leopold and Hadj-Rabia, Smail and Hamm, Henning and Happle, Rudolf and Mushtaq, Imran and Lacour, Jean-Philippe and Waelchli, Regula and Wobser, Marion and Vabres, Pierre and Patton, E. Elizabeth and Kinsler, Veronica A.}, title = {Mosaic activating mutations in GNA11 and GNAQ are associated with phakomatosis pigmentovascularis and extensive dermal melanocytosis}, series = {Journal of Investigative Dermatology}, volume = {136}, journal = {Journal of Investigative Dermatology}, number = {4}, doi = {10.1016/j.jid.2015.11.027}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189689}, pages = {770-778}, year = {2016}, abstract = {Common birthmarks can be an indicator of underlying genetic disease but are often overlooked. Mongolian blue spots (dermal melanocytosis) are usually localized and transient, but they can be extensive, permanent, and associated with extracutaneous abnormalities. Co-occurrence with vascular birthmarks defines a subtype of phakomatosis pigmentovascularis, a group of syndromes associated with neurovascular, ophthalmological, overgrowth, and malignant complications. Here, we discover that extensive dermal melanocytosis and phakomatosis pigmentovascularis are associated with activating mutations in GNA11 and GNAQ, genes that encode Ga subunits of heterotrimeric G proteins. The mutations were detected at very low levels in affected tissues but were undetectable in the blood, indicating that these conditions are postzygotic mosaic disorders. In vitro expression of mutant GNA11\(^R183C\) and GNA11\(^Q209L\) in human cell lines demonstrated activation of the downstream p38 MAPK signaling pathway and the p38, JNK, and ERK pathways, respectively. Transgenic mosaic zebrafish models expressing mutant GNA11\(^R183C\) under promoter mitfa developed extensive dermal melanocytosis recapitulating the human phenotype. Phakomatosis pigmentovascularis and extensive dermal melanocytosis are therefore diagnoses in the group of mosaic heterotrimeric G-protein disorders, joining McCune-Albright and Sturge-Weber syndromes. These findings will allow accurate clinical and molecular diagnosis of this subset of common birthmarks, thereby identifying infants at risk for serious complications, and provide novel therapeutic opportunities.}, language = {en} } @article{BędkowskiMajekMajeketal.2016, author = {Będkowski, Janusz and Majek, Karol and Majek, Piotr and Musialik, Paweł and Pełka, Michał and N{\"u}chter, Andreas}, title = {Intelligent mobile system for improving spatial design support and security inside buildings}, series = {Mobile Networks and Applications}, volume = {21}, journal = {Mobile Networks and Applications}, number = {2}, doi = {10.1007/s11036-015-0654-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189597}, pages = {313-326}, year = {2016}, abstract = {This paper concerns the an intelligent mobile application for spatial design support and security domain. Mobility has two aspects in our research: The first one is the usage of mobile robots for 3D mapping of urban areas and for performing some specific tasks. The second mobility aspect is related with a novel Software as a Service system that allows access to robotic functionalities and data over the Ethernet, thus we demonstrate the use of the novel NVIDIA GRID technology allowing to virtualize the graphic processing unit. We introduce Complex Shape Histogram, a core component of our artificial intelligence engine, used for classifying 3D point clouds with a Support Vector Machine. We use Complex Shape Histograms also for loop closing detection in the simultaneous localization and mapping algorithm. Our intelligent mobile system is built on top of the Qualitative Spatio-Temporal Representation and Reasoning framework. This framework defines an ontology and a semantic model, which are used for building the intelligent mobile user interfaces. We show experiments demonstrating advantages of our approach. In addition, we test our prototypes in the field after the end-user case studies demonstrating a relevant contribution for future intelligent mobile systems that merge mobile robots with novel data centers.}, language = {en} } @article{ClaussYanKuenzer2016, author = {Clauss, Kersten and Yan, Huimin and Kuenzer, Claudia}, title = {Mapping Paddy Rice in China in 2002, 2005, 2010 and 2014 with MODIS Time Series}, series = {Remote Sensing}, volume = {8}, journal = {Remote Sensing}, number = {5}, doi = {10.3390/rs8050434}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180557}, year = {2016}, abstract = {Rice is an important food crop and a large producer of green-house relevant methane. Accurate and timely maps of paddy fields are most important in the context of food security and greenhouse gas emission modelling. During their life-cycle, rice plants undergo a phenological development that influences their interaction with waves in the visible light and infrared spectrum. Rice growth has a distinctive signature in time series of remotely-sensed data. We used time series of MODIS (Moderate Resolution Imaging Spectroradiometer) products MOD13Q1 and MYD13Q1 and a one-class support vector machine to detect these signatures and classify paddy rice areas in continental China. Based on these classifications, we present a novel product for continental China that shows rice areas for the years 2002, 2005, 2010 and 2014 at 250-m resolution. Our classification has an overall accuracy of 0.90 and a kappa coefficient of 0.77 compared to our own reference dataset for 2014 and correlates highly with rice area statistics from China's Statistical Yearbooks (R2 of 0.92 for 2010, 0.92 for 2005 and 0.90 for 2002). Moderate resolution time series analysis allows accurate and timely mapping of rice paddies over large areas with diverse cropping schemes.}, language = {en} } @article{BlaettnerDasPaprotkaetal.2016, author = {Bl{\"a}ttner, Sebastian and Das, Sudip and Paprotka, Kerstin and Eilers, Ursula and Krischke, Markus and Kretschmer, Dorothee and Remmele, Christian W. and Dittrich, Marcus and M{\"u}ller, Tobias and Schuelein-Voelk, Christina and Hertlein, Tobias and Mueller, Martin J. and Huettel, Bruno and Reinhardt, Richard and Ohlsen, Knut and Rudel, Thomas and Fraunholz, Martin J.}, title = {Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes}, series = {PLoS Pathogens}, volume = {12}, journal = {PLoS Pathogens}, number = {9}, doi = {10.1371/journal.ppat.1005857}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180380}, year = {2016}, abstract = {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.}, language = {en} } @article{FischerHelfrichFoersterPeschel2016, author = {Fischer, Robin and Helfrich-F{\"o}rster, Charlotte and Peschel, Nicolai}, title = {GSK-3 Beta Does Not Stabilize Cryptochrome in the Circadian Clock of Drosophila}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0146571}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180370}, year = {2016}, abstract = {Cryptochrome (CRY) is the primary photoreceptor of Drosophila's circadian clock. It resets the circadian clock by promoting light-induced degradation of the clock protein Timeless (TIM) in the proteasome. Under constant light, the clock stops because TIM is absent, and the flies become arrhythmic. In addition to TIM degradation, light also induces CRY degradation. This depends on the interaction of CRY with several proteins such as the E3 ubiquitin ligases Jetlag (JET) and Ramshackle (BRWD3). However, CRY can seemingly also be stabilized by interaction with the kinase Shaggy (SGG), the GSK-3 beta fly orthologue. Consequently, flies with SGG overexpression in certain dorsal clock neurons are reported to remain rhythmic under constant light. We were interested in the interaction between CRY, Ramshackle and SGG and started to perform protein interaction studies in S2 cells. To our surprise, we were not able to replicate the results, that SGG overexpression does stabilize CRY, neither in S2 cells nor in the relevant clock neurons. SGG rather does the contrary. Furthermore, flies with SGG overexpression in the dorsal clock neurons became arrhythmic as did wild-type flies. Nevertheless, we could reproduce the published interaction of SGG with TIM, since flies with SGG overexpression in the lateral clock neurons shortened their free-running period. We conclude that SGG does not directly interact with CRY but rather with TIM. Furthermore we could demonstrate, that an unspecific antibody explains the observed stabilization effects on CRY.}, language = {en} } @article{GlaserFehrholzCurstedtetal.2016, author = {Glaser, Kirsten and Fehrholz, Markus and Curstedt, Tore and Kunzmann, Steffen and Speer, Christian P.}, title = {Effects of the New Generation Synthetic Reconstituted Surfactant CHF5633 on Pro- and Anti-Inflammatory Cytokine Expression in Native and LPS-Stimulated Adult CD14\(^{+}\) Monocytes}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {1}, doi = {10.1371/journal.pone.0146898}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180195}, year = {2016}, abstract = {Background Surfactant replacement therapy is the standard of care for the prevention and treatment of neonatal respiratory distress syndrome. New generation synthetic surfactants represent a promising alternative to animal-derived surfactants. CHF5633, a new generation reconstituted synthetic surfactant containing SP-B and SP-C analogs and two synthetic phospholipids has demonstrated biophysical effectiveness in vitro and in vivo. While several surfactant preparations have previously been ascribed immunomodulatory capacities, in vitro data on immunomodulation by CHF5633 are limited, so far. Our study aimed to investigate pro- and anti-inflammatory effects of CHF5633 on native and LPS-stimulated human adult monocytes. Methods Highly purified adult CD14\(^{+}\) cells, either native or simultaneously stimulated with LPS, were exposed to CHF5633, its components, or poractant alfa (Curosurf\(^{®}\)). Subsequent expression of TNF-α, IL-1β, IL-8 and IL-10 mRNA was quantified by real-time quantitative PCR, corresponding intracellular cytokine synthesis was analyzed by flow cytometry. Potential effects on TLR2 and TLR4 mRNA and protein expression were monitored by qPCR and flow cytometry. Results Neither CHF5633 nor any of its components induced inflammation or apoptosis in native adult CD14\(^{+}\) monocytes. Moreover, LPS-induced pro-inflammatory responses were not aggravated by simultaneous exposure of monocytes to CHF5633 or its components. In LPS-stimulated monocytes, exposure to CHF5633 led to a significant decrease in TNF-α mRNA (0.57 ± 0.23-fold, p = 0.043 at 4h; 0.56 ± 0.27-fold, p = 0.042 at 14h). Reduction of LPS-induced IL-1β mRNA expression was not significant (0.73 ± 0.16, p = 0.17 at 4h). LPS-induced IL-8 and IL-10 mRNA and protein expression were unaffected by CHF5633. For all cytokines, the observed CHF5633 effects paralleled a Curosurf®-induced modulation of cytokine response. TLR2 and TLR4 mRNA and protein expression were not affected by CHF5633 and Curosurf®, neither in native nor in LPS-stimulated adult monocytes. Conclusion The new generation reconstituted synthetic surfactant CHF5633 was tested for potential immunomodulation on native and LPS-activated adult human monocytes. Our data confirm that CHF5633 does not exert unintended pro-inflammatory effects in both settings. On the contrary, CHF5633 significantly suppressed TNF-α mRNA expression in LPS-stimulated adult monocytes, indicating potential anti-inflammatory effects.}, language = {en} } @article{KoenigWolfHeisenberg2016, author = {Koenig, Sebastian and Wolf, Reinhard and Heisenberg, Martin}, title = {Vision in Flies: Measuring the Attention Span}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0148208}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179947}, year = {2016}, abstract = {A visual stimulus at a particular location of the visual field may elicit a behavior while at the same time equally salient stimuli in other parts do not. This property of visual systems is known as selective visual attention (SVA). The animal is said to have a focus of attention (FoA) which it has shifted to a particular location. Visual attention normally involves an attention span at the location to which the FoA has been shifted. Here the attention span is measured in Drosophila. The fly is tethered and hence has its eyes fixed in space. It can shift its FoA internally. This shift is revealed using two simultaneous test stimuli with characteristic responses at their particular locations. In tethered flight a wild type fly keeps its FoA at a certain location for up to 4s. Flies with a mutation in the radish gene, that has been suggested to be involved in attention-like mechanisms, display a reduced attention span of only 1s.}, language = {en} } @article{BrendtkeWiehlGroeberetal.2016, author = {Brendtke, Rico and Wiehl, Michael and Groeber, Florian and Schwarz, Thomas and Walles, Heike and Hansmann, Jan}, title = {Feasibility Study on a Microwave-Based Sensor for Measuring Hydration Level Using Human Skin Models}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0153145}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179934}, year = {2016}, abstract = {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.}, language = {en} } @article{TahaClausLappannetal.2016, author = {Taha, Muhamed-Kheir and Claus, Heike and Lappann, Martin and Veyrier, Fr{\´e}d{\´e}ric J. and Otto, Andreas and Becher, D{\"o}rte and Deghmane, Ala-Eddine and Frosch, Matthias and Hellenbrand, Wiebke and Hong, Eva and du Ch{\^a}telet, Isabelle Parent and Prior, Karola and Harmsen, Dag and Vogel, Ulrich}, title = {Evolutionary Events Associated with an Outbreak of Meningococcal Disease in Men Who Have Sex with Men}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0154047}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179870}, year = {2016}, abstract = {Meningococci spread via respiratory droplets, whereas the closely related gonococci are transmitted sexually. Several outbreaks of invasive meningococcal disease have been reported in Europe and the United States among men who have sex with men (MSM). We recently identified an outbreak of serogroup C meningococcal disease among MSM in Germany and France. In this study, genomic and proteomic techniques were used to analyze the outbreak isolates. In addition, genetically identical urethritis isolates were recovered from France and Germany and included in the analysis. Genome sequencing revealed that the isolates from the outbreak among MSM and from urethritis cases belonged to a clade within clonal complex 11. Proteome analysis showed they expressed nitrite reductase, enabling anaerobic growth as previously described for gonococci. Invasive isolates from MSM, but not urethritis isolates, further expressed functional human factor H binding protein associated with enhanced survival in a newly developed transgenic mouse model expressing human factor H, a complement regulatory protein. In conclusion, our data suggest that urethritis and outbreak isolates followed a joint adaptation route including adaption to the urogenital tract.}, language = {en} } @article{OrtizSotoSeibel2016, author = {Ortiz-Soto, Maria Elena and Seibel, J{\"u}rgen}, title = {Expression of Functional Human Sialyltransferases ST3Gal1 and ST6Gal1 in Escherichia coli}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0155410}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179807}, year = {2016}, abstract = {Sialyltransferases (STs) are disulfide-containing, type II transmembrane glycoproteins that catalyze the transfer of sialic acid to proteins and lipids and participate in the synthesis of the core structure oligosaccharides of human milk. Sialic acids are found at the outermost position of glycostructures, playing a key role in health and disease. Sialylation is also essential for the production of recombinant therapeutic proteins (RTPs). Despite their importance, availability of sialyltransferases is limited due to the low levels of stable, soluble and active protein produced in bacterial expression systems, which hampers biochemical and structural studies on these enzymes and restricts biotechnological applications. We report the successful expression of active human sialyltransferases ST3Gal1 and ST6Gal1 in commercial Escherichia coli strains designed for production of disulfide-containing proteins. Fusion of hST3Gal1 with different solubility enhancers and substitution of exposed hydrophobic amino acids by negatively charged residues (supercharging-like approach) were performed to promote solubility and folding. Co-expression of sialyltransferases with the chaperon/foldases sulfhydryl oxidase, protein disulfide isomerase and disulfide isomerase C was explored to improve the formation of native disulfide bonds. Active sialyltransferases fused with maltose binding protein (MBP) were obtained in sufficient amounts for biochemical and structural studies when expressed under oxidative conditions and co-expression of folding factors increased the yields of active and properly folded sialyltransferases by 20\%. Mutation of exposed hydrophobic amino acids increased recovery of active enzyme by 2.5-fold, yielding about 7 mg of purified protein per liter culture. Functionality of recombinant enzymes was evaluated in the synthesis of sialosides from the β-d-galactoside substrates lactose, N-acetyllactosamine and benzyl 2-acetamido-2-deoxy-3-O-(β-d-galactopyranosyl)-α-d-galactopyranoside.}, language = {en} } @article{SimsekyilmazLiehnWeinandyetal.2016, author = {Simsekyilmaz, Sakine and Liehn, Elisa A. and Weinandy, Stefan and Schreiber, Fabian and Megens, Remco T. A. and Theelen, Wendy and Smeets, Ralf and Jockenh{\"o}vel, Stefan and Gries, Thomas and M{\"o}ller, Martin and Klee, Doris and Weber, Christian and Zernecke, Alma}, title = {Targeting In-Stent-Stenosis with RGD- and CXCL1-Coated Mini-Stents in Mice}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0155829}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179745}, year = {2016}, abstract = {Atherosclerotic lesions that critically narrow the artery can necessitate an angioplasty and stent implantation. Long-term therapeutic effects, however, are limited by excessive arterial remodeling. We here employed a miniaturized nitinol-stent coated with star-shaped polyethylenglycole (star-PEG), and evaluated its bio-functionalization with RGD and CXCL1 for improving in-stent stenosis after implantation into carotid arteries of mice. Nitinol foils or stents (bare metal) were coated with star-PEG, and bio-functionalized with RGD, or RGD/CXCL1. Cell adhesion to star-PEG-coated nitinol foils was unaltered or reduced, whereas bio-functionalization with RGD but foremost RGD/CXCL1 increased adhesion of early angiogenic outgrowth cells (EOCs) and endothelial cells but not smooth muscle cells when compared with bare metal foils. Stimulation of cells with RGD/CXCL1 furthermore increased the proliferation of EOCs. In vivo, bio-functionalization with RGD/CXCL1 significantly reduced neointima formation and thrombus formation, and increased re-endothelialization in apoE\(^{-/-}\) carotid arteries compared with bare-metal nitinol stents, star-PEG-coated stents, and stents bio-functionalized with RGD only. Bio-functionalization of star-PEG-coated nitinol-stents with RGD/CXCL1 reduced in-stent neointima formation. By supporting the adhesion and proliferation of endothelial progenitor cells, RGD/CXCL1 coating of stents may help to accelerate endothelial repair after stent implantation, and thus may harbor the potential to limit the complication of in-stent restenosis in clinical approaches.}, language = {en} } @article{MorisVandenBroeckToscoetal.2016, author = {Moris, Lisa and Van den Broeck, Thomas and Tosco, Lorenzo and Van Baelen, Anthony and Gontero, Paolo and Karnes, Robert Jeffrey and Everaerts, Wouter and Albersen, Maarten and Bastian, Patrick J. and Chlosta, Piotr and Claessens, Frank and Chun, Felix K. and Graefen, Markus and Gratzke, Christian and Kneitz, Burkhard and Marchioro, Giansilvio and Salas, Rafael Sanchez and Tombal, Bertrand and Van Der Poel, Henk and Walz, Jochen Christoph and De Meerleer, Gert and Bossi, Alberto and Haustermans, Karin and Montorsi, Francesco and Van Poppel, Hendrik and Spahn, Martin and Briganti, Alberto and Joniau, Steven}, title = {Impact of lymph node burden on survival of high-risk prostate cancer patients following radical prostatectomy and pelvic lymph node dissection}, series = {Frontiers in Surgery}, volume = {3}, journal = {Frontiers in Surgery}, organization = {European Multicenter Prostate Cancer Clinical and Translational Research Group (EMPaCT)}, issn = {2296-875X}, doi = {10.3389/fsurg.2016.00065}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-195721}, year = {2016}, abstract = {Aim To determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP). Material and methods In this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan-Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD. Results Mean age was 65 years (median: 66, IQR 60-70). Positive surgical margins were present in 53.7\% (n = 671). Final Gleason score (GS) was 2-6 in 12.7\% (n = 158), 7 in 52\% (n = 649), and 8-10 in 35.4\% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12-17). Of all patients, 1,128 (90.3\%) had 0-3 positive LNs, while 126 (9.7\%) had ≥4 positive LNs. Patients with 0-3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50\%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37\% (p < 0.0001) survival at 10 years for patients with 0-3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8-10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS. Conclusion Four or more positive LNs, pathological stage pT4, and final GS of 8-10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.}, language = {en} } @article{DipaolaPavanCattaneoetal.2016, author = {Dipaola, Mariangela and Pavan, Esteban E. and Cattaneo, Andrea and Frazzitta, Giuseppe and Pezzoli, Gianni and Cavallari, Paolo and Frigo, Carlo A. and Isaias, Ioannis U.}, title = {Mechanical Energy Recovery during Walking in Patients with Parkinson Disease}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0156420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179739}, year = {2016}, abstract = {The mechanisms of mechanical energy recovery during gait have been thoroughly investigated in healthy subjects, but never described in patients with Parkinson disease (PD). The aim of this study was to investigate whether such mechanisms are preserved in PD patients despite an altered pattern of locomotion. We consecutively enrolled 23 PD patients (mean age 64±9 years) with bilateral symptoms (H\&Y ≥II) if able to walk unassisted in medication-off condition (overnight suspension of all dopaminergic drugs). Ten healthy subjects (mean age 62±3 years) walked both at their 'preferred' and 'slow' speeds, to match the whole range of PD velocities. Kinematic data were recorded by means of an optoelectronic motion analyzer. For each stride we computed spatio-temporal parameters, time-course and range of motion (ROM) of hip, knee and ankle joint angles. We also measured kinetic (Wk), potential (W\(_{p}\)), total (W\(_{totCM}\)) energy variations and the energy recovery index (ER). Along with PD progression, we found a significant correlation of W\(_{totCM}\) and W\(_{p}\) with knee ROM and in particular with knee extension in terminal stance phase. W\(_{k}\) and ER were instead mainly related to gait velocity. In PD subjects, the reduction of knee ROM significantly diminished both W\(_{p}\) and W\(_{totCM}\). Rehabilitation treatments should possibly integrate passive and active mobilization of knee to prevent a reduction of gait-related energetic components.}, language = {en} } @article{VieraElMerahbiNieswandtetal.2016, author = {Viera, Jonathan Trujillo and El-Merahbi, Rabih and Nieswandt, Bernhard and Stegner, David and Sumara, Grzegorz}, title = {Phospholipases D1 and D2 Suppress Appetite and Protect against Overweight}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0157607}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179729}, year = {2016}, abstract = {Obesity is a major risk factor predisposing to the development of peripheral insulin resistance and type 2 diabetes (T2D). Elevated food intake and/or decreased energy expenditure promotes body weight gain and acquisition of adipose tissue. Number of studies implicated phospholipase D (PLD) enzymes and their product, phosphatidic acid (PA), in regulation of signaling cascades controlling energy intake, energy dissipation and metabolic homeostasis. However, the impact of PLD enzymes on regulation of metabolism has not been directly determined so far. In this study we utilized mice deficient for two major PLD isoforms, PLD1 and PLD2, to assess the impact of these enzymes on regulation of metabolic homeostasis. We showed that mice lacking PLD1 or PLD2 consume more food than corresponding control animals. Moreover, mice deficient for PLD2, but not PLD1, present reduced energy expenditure. In addition, deletion of either of the PLD enzymes resulted in development of elevated body weight and increased adipose tissue content in aged animals. Consistent with the fact that elevated content of adipose tissue predisposes to the development of hyperlipidemia and insulin resistance, characteristic for the pre-diabetic state, we observed that Pld1\(^{-/-}\) and Pld2\(^{-/-}\) mice present elevated free fatty acids (FFA) levels and are insulin as well as glucose intolerant. In conclusion, our data suggest that deficiency of PLD1 or PLD2 activity promotes development of overweight and diabetes.}, language = {en} } @article{PrelogHilligardtSchmidtetal.2016, author = {Prelog, Martina and Hilligardt, Deborah and Schmidt, Christian A. and Przybylski, Grzegorz K. and Leierer, Johannes and Almanzar, Giovanni and El Hajj, Nady and Lesch, Klaus-Peter and Arolt, Volker and Zwanzger, Peter and Haaf, Thomas and Domschke, Katharina}, title = {Hypermethylation of FOXP3 Promoter and Premature Aging of the Immune System in Female Patients with Panic Disorder?}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {6}, doi = {10.1371/journal.pone.0157930}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179684}, year = {2016}, abstract = {Immunological abnormalities associated with pathological conditions, such as higher infection rates, inflammatory diseases, cancer or cardiovascular events are common in patients with panic disorder. In the present study, T cell receptor excision circles (TRECs), Forkhead-Box-Protein P3 gene (FOXP3) methylation of regulatory T cells (Tregs) and relative telomere lengths (RTLs) were investigated in a total and subsamples of 131 patients with panic disorder as compared to 131 age- and sex-matched healthy controls in order to test for a potential dysfunction and premature aging of the immune system in anxiety disorders. Significantly lower TRECs (p = 0.004) as well as significant hypermethylation of the FOXP3 promoter region (p = 0.005) were observed in female (but not in male) patients with panic disorder as compared to healthy controls. No difference in relative telomere length was discerned between patients and controls, but significantly shorter telomeres in females, smokers and older persons within the patient group. The presently observed reduced TRECs in panic disorder patients and FOXP3 hypermethylation in female patients with panic disorder potentially reflect impaired thymus and immunosuppressive Treg function, which might partly account for the known increased morbidity and mortality of anxiety disorders conferred by e.g. cancer and cardiovascular disorders.}, language = {en} } @article{KoenigWolfHeisenberg2016, author = {Koenig, Sebastian and Wolf, Reinhard and Heisenberg, Martin}, title = {Visual Attention in Flies-Dopamine in the Mushroom Bodies Mediates the After-Effect of Cueing}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {8}, doi = {10.1371/journal.pone.0161412}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-179564}, year = {2016}, abstract = {Visual environments may simultaneously comprise stimuli of different significance. Often such stimuli require incompatible responses. Selective visual attention allows an animal to respond exclusively to the stimuli at a certain location in the visual field. In the process of establishing its focus of attention the animal can be influenced by external cues. Here we characterize the behavioral properties and neural mechanism of cueing in the fly Drosophila melanogaster. A cue can be attractive, repulsive or ineffective depending upon (e.g.) its visual properties and location in the visual field. Dopamine signaling in the brain is required to maintain the effect of cueing once the cue has disappeared. Raising or lowering dopamine at the synapse abolishes this after-effect. Specifically, dopamine is necessary and sufficient in the αβ-lobes of the mushroom bodies. Evidence is provided for an involvement of the αβ\(_{posterior}\) Kenyon cells.}, language = {en} } @article{UeceylerSchroeterKafkeetal.2016, author = {{\"U}{\c{c}}eyler, Nurcan and Schr{\"o}ter, Nils and Kafke, Waldemar and Kramer, Daniela and Wanner, Christoph and Weidemann, Frank and Sommer, Claudia}, title = {Skin Globotriaosylceramide 3 Load Is Increased in Men with Advanced Fabry Disease}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0166484}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178856}, year = {2016}, abstract = {Background The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity. Methods At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data. Results We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy. Conclusions Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients.}, language = {en} } @article{BatschingWolfHeisenberg2016, author = {Batsching, Sophie and Wolf, Reinhard and Heisenberg, Martin}, title = {Inescapable Stress Changes Walking Behavior in Flies - Learned Helplessness Revisited}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0167066}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178640}, year = {2016}, abstract = {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.}, language = {en} } @article{KirschUllrichKunde2016, author = {Kirsch, Wladimir and Ullrich, Benjamin and Kunde, Wilfried}, title = {Are Effects of Action on Perception Real? Evidence from Transformed Movements}, series = {PLoS ONE}, volume = {11}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0167993}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-178574}, year = {2016}, abstract = {It has been argued that several reported non-visual influences on perception cannot be truly perceptual. If they were, they should affect the perception of target objects and reference objects used to express perceptual judgments, and thus cancel each other out. This reasoning presumes that non-visual manipulations impact target objects and comparison objects equally. In the present study we show that equalizing a body-related manipulation between target objects and reference objects essentially abolishes the impact of that manipulation so as it should do when that manipulation actually altered perception. Moreover, the manipulation has an impact on judgements when applied to only the target object but not to the reference object, and that impact reverses when only applied to the reference object but not to the target object. A perceptual explanation predicts this reversal, whereas explanations in terms of post-perceptual response biases or demand effects do not. Altogether these results suggest that body-related influences on perception cannot as a whole be attributed to extra-perceptual factors.}, language = {en} } @article{RohlederHuangXueetal.2016, author = {Rohleder, Florian and Huang, Jing and Xue, Yutong and Kuper, Jochen and Round, Adam and Seidman, Michael and Wang, Weidong and Kisker, Caroline}, title = {FANCM interacts with PCNA to promote replication traverse of DNA interstrand crosslinks}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {7}, doi = {10.1093/nar/gkw037}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175401}, pages = {3219-3232}, year = {2016}, abstract = {FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.}, language = {en} } @article{FroehlichHanekePapenfortetal.2016, author = {Fr{\"o}hlich, Kathrin S. and Haneke, Katharina and Papenfort, Kai and Vogel, J{\"o}rg}, title = {The target spectrum of SdsR small RNA in Salmonella}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {21}, doi = {10.1093/nar/gkw632}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175365}, pages = {10406-10422}, year = {2016}, abstract = {Model enteric bacteria such as Escherichia coli and Salmonella enterica express hundreds of small non-coding RNAs (sRNAs), targets for most of which are yet unknown. Some sRNAs are remarkably well conserved, indicating that they serve cellular functions that go beyond the necessities of a single species. One of these 'core sRNAs' of largely unknown function is the abundant ∼100-nucleotide SdsR sRNA which is transcribed by the general stress σ-factor, σ\(^{S}\) and accumulates in stationary phase. In Salmonella, SdsR was known to inhibit the synthesis of the species-specific porin, OmpD. However, sdsR genes are present in almost all enterobacterial genomes, suggesting that additional, conserved targets of this sRNA must exist. Here, we have combined SdsR pulse-expression with whole genome transcriptomics to discover 20 previously unknown candidate targets of SdsR which include mRNAs coding for physiologically important regulators such as the carbon utilization regulator, CRP, the nucleoid-associated chaperone, StpA and the antibiotic resistance transporter, TolC. Processing of SdsR by RNase E results in two cellular SdsR variants with distinct target spectra. While the overall physiological role of this orphan core sRNA remains to be fully understood, the new SdsR targets present valuable leads to determine sRNA functions in resting bacteria.}, language = {en} } @article{WiedenmannBocquillonDeaconetal.2016, author = {Wiedenmann, J. and Bocquillon, E. and Deacon, R.S. and Hartinger, S. and Herrmann, O. and Klapwijk, T.M. and Maier, L. and Ames, C. and Br{\"u}ne, C. and Gould, C. and Oiwa, A. and Ishibashi, K. and Tarucha, S. and Buhmann, H. and Molenkamp, L.W.}, title = {4π-periodic Josephson supercurrent in HgTe-based topological Josephson junctions}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms10303}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175353}, year = {2016}, abstract = {The Josephson effect describes the generic appearance of a supercurrent in a weak link between two superconductors. Its exact physical nature deeply influences the properties of the supercurrent. In recent years, considerable efforts have focused on the coupling of superconductors to the surface states of a three-dimensional topological insulator. In such a material, an unconventional induced p-wave superconductivity should occur, with a doublet of topologically protected gapless Andreev bound states, whose energies vary 4π-periodically with the superconducting phase difference across the junction. In this article, we report the observation of an anomalous response to rf irradiation in a Josephson junction made of a HgTe weak link. The response is understood as due to a 4π-periodic contribution to the supercurrent, and its amplitude is compatible with the expected contribution of a gapless Andreev doublet. Our work opens the way to more elaborate experiments to investigate the induced superconductivity in a three-dimensional insulator.}, language = {en} } @article{HsuKuegelKemmeretal.2016, author = {Hsu, Pin-Jui and K{\"u}gel, Jens and Kemmer, Jeannette and Toldin, Francesco Parisen and Mauerer, Tobias and Vogt, Matthias and Assaad, Fakher and Bode, Matthias}, title = {Coexistence of charge and ferromagnetic order in fcc Fe}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms10949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173969}, year = {2016}, abstract = {Phase coexistence phenomena have been intensively studied in strongly correlated materials where several ordered states simultaneously occur or compete. Material properties critically depend on external parameters and boundary conditions, where tiny changes result in qualitatively different ground states. However, up to date, phase coexistence phenomena have exclusively been reported for complex compounds composed of multiple elements. Here we show that charge- and magnetically ordered states coexist in double-layer Fe/Rh(001). Scanning tunnelling microscopy and spectroscopy measurements reveal periodic charge-order stripes below a temperature of 130 K. Close to liquid helium temperature, they are superimposed by ferromagnetic domains as observed by spin-polarized scanning tunnelling microscopy. Temperature-dependent measurements reveal a pronounced cross-talk between charge and spin order at the ferromagnetic ordering temperature about 70 K, which is successfully modelled within an effective Ginzburg-Landau ansatz including sixth-order terms. Our results show that subtle balance between structural modifications can lead to competing ordering phenomena.}, language = {en} } @article{SessiBiswasBathonetal.2016, author = {Sessi, Paolo and Biswas, Rudro R. and Bathon, Thomas and Storz, Oliver and Wilfert, Stefan and Barla, Alessandro and Kokh, Konstantin A. and Tereshchenko, Oleg E. and Fauth, Kai and Bode, Matthias and Balatsky, Alexander V.}, title = {Dual nature of magnetic dopants and competing trends in topological insulators}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms12027}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172704}, year = {2016}, abstract = {Topological insulators interacting with magnetic impurities have been reported to host several unconventional effects. These phenomena are described within the framework of gapping Dirac quasiparticles due to broken time-reversal symmetry. However, the overwhelming majority of studies demonstrate the presence of a finite density of states near the Dirac point even once topological insulators become magnetic. Here, we map the response of topological states to magnetic impurities at the atomic scale. We demonstrate that magnetic order and gapless states can coexist. We show how this is the result of the delicate balance between two opposite trends, that is, gap opening and emergence of a Dirac node impurity band, both induced by the magnetic dopants. Our results evidence a more intricate and rich scenario with respect to the once generally assumed, showing how different electronic and magnetic states may be generated and controlled in this fascinating class of materials.}, language = {en} } @article{HartelGloggerJonesetal.2016, author = {Hartel, Andreas J.W. and Glogger, Marius and Jones, Nicola G. and Abuillan, Wasim and Batram, Christopher and Hermann, Anne and Fenz, Susanne F. and Tanaka, Motomu and Engstler, Markus}, title = {N-glycosylation enables high lateral mobility of GPI-anchored proteins at a molecular crowding threshold}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms12870}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171368}, year = {2016}, abstract = {The protein density in biological membranes can be extraordinarily high, but the impact of molecular crowding on the diffusion of membrane proteins has not been studied systematically in a natural system. The diversity of the membrane proteome of most cells may preclude systematic studies. African trypanosomes, however, feature a uniform surface coat that is dominated by a single type of variant surface glycoprotein (VSG). Here we study the density-dependence of the diffusion of different glycosylphosphatidylinositol-anchored VSG-types on living cells and in artificial membranes. Our results suggest that a specific molecular crowding threshold (MCT) limits diffusion and hence affects protein function. Obstacles in the form of heterologous proteins compromise the diffusion coefficient and the MCT. The trypanosome VSG-coat operates very close to its MCT. Importantly, our experiments show that N-linked glycans act as molecular insulators that reduce retarding intermolecular interactions allowing membrane proteins to function correctly even when densely packed.}, language = {en} } @article{BialasZitzlerKunkelKirchneretal.2016, author = {Bialas, David and Zitzler-Kunkel, Andr{\´e} and Kirchner, Eva and Schmidt, David and W{\"u}rthner, Frank}, title = {Structural and quantum chemical analysis of exciton coupling in homo- and heteroaggregate stacks of merocyanines}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms12949}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-170200}, year = {2016}, abstract = {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.}, language = {en} } @article{LundtKlembtCherotchenkoetal.2016, author = {Lundt, Nils and Klembt, Sebastian and Cherotchenko, Evgeniia and Betzold, Simon and Iff, Oliver and Nalitov, Anton V. and Klaas, Martin and Dietrich, Christof P. and Kavokin, Alexey V. and H{\"o}fling, Sven and Schneider, Christian}, title = {Room-temperature Tamm-plasmon exciton-polaritons with a WSe\(_{2}\) monolayer}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms13328}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169470}, year = {2016}, abstract = {Solid-state cavity quantum electrodynamics is a rapidly advancing field, which explores the frontiers of light-matter coupling. Metal-based approaches are of particular interest in this field, as they carry the potential to squeeze optical modes to spaces significantly below the diffraction limit. Transition metal dichalcogenides are ideally suited as the active material in cavity quantum electrodynamics, as they interact strongly with light at the ultimate monolayer limit. Here, we implement a Tamm-plasmon-polariton structure and study the coupling to a monolayer of WSe\(_{2}\), hosting highly stable excitons. Exciton-polariton formation at room temperature is manifested in the characteristic energy-momentum dispersion relation studied in photoluminescence, featuring an anti-crossing between the exciton and photon modes with a Rabi-splitting of 23.5 meV. Creating polaritonic quasiparticles in monolithic, compact architectures with atomic monolayers under ambient conditions is a crucial step towards the exploration of nonlinearities, macroscopic coherence and advanced spinor physics with novel, low-mass bosons.}, language = {en} } @article{HeIffLundtetal.2016, author = {He, Yu-Ming and Iff, Oliver and Lundt, Nils and Baumann, Vasilij and Davanco, Marcelo and Srinivasan, Kartik and H{\"o}fling, Sven and Schneider, Christian}, title = {Cascaded emission of single photons from the biexciton in monolayered WSe\(_{2}\)}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms13409}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169363}, year = {2016}, abstract = {Monolayers of transition metal dichalcogenide materials emerged as a new material class to study excitonic effects in solid state, as they benefit from enormous Coulomb correlations between electrons and holes. Especially in WSe\(_{2}\), sharp emission features have been observed at cryogenic temperatures, which act as single photon sources. Tight exciton localization has been assumed to induce an anharmonic excitation spectrum; however, the evidence of the hypothesis, namely the demonstration of a localized biexciton, is elusive. Here we unambiguously demonstrate the existence of a localized biexciton in a monolayer of WSe\(_{2}\), which triggers an emission cascade of single photons. The biexciton is identified by its time-resolved photoluminescence, superlinearity and distinct polarization in micro-photoluminescence experiments. We evidence the cascaded nature of the emission process in a cross-correlation experiment, which yields a strong bunching behaviour. Our work paves the way to a new generation of quantum optics experiments with two-dimensional semiconductors.}, language = {en} } @article{PetersHempAppelhansetal.2016, author = {Peters, Marcell K. and Hemp, Andreas and Appelhans, Tim and Behler, Christina and Classen, Alice and Detsch, Florian and Ensslin, Andreas and Ferger, Stefan W. and Frederiksen, Sara B. and Gebert, Frederike and Haas, Michael and Helbig-Bonitz, Maria and Hemp, Claudia and Kindeketa, William J. and Mwangomo, Ephraim and Ngereza, Christine and Otte, Insa and R{\"o}der, Juliane and Rutten, Gemma and Costa, David Schellenberger and Tardanico, Joseph and Zancolli, Giulia and Deckert, J{\"u}rgen and Eardley, Connal D. and Peters, Ralph S. and R{\"o}del, Mark-Oliver and Schleuning, Matthias and Ssymank, Axel and Kakengi, Victor and Zhang, Jie and B{\"o}hning-Gaese, Katrin and Brandl, Roland and Kalko, Elisabeth K.V. and Kleyer, Michael and Nauss, Thomas and Tschapka, Marco and Fischer, Markus and Steffan-Dewenter, Ingolf}, title = {Predictors of elevational biodiversity gradients change from single taxa to the multi-taxa community level}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms13736}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169374}, year = {2016}, abstract = {The factors determining gradients of biodiversity are a fundamental yet unresolved topic in ecology. While diversity gradients have been analysed for numerous single taxa, progress towards general explanatory models has been hampered by limitations in the phylogenetic coverage of past studies. By parallel sampling of 25 major plant and animal taxa along a 3.7 km elevational gradient on Mt. Kilimanjaro, we quantify cross-taxon consensus in diversity gradients and evaluate predictors of diversity from single taxa to a multi-taxa community level. While single taxa show complex distribution patterns and respond to different environmental factors, scaling up diversity to the community level leads to an unambiguous support for temperature as the main predictor of species richness in both plants and animals. Our findings illuminate the influence of taxonomic coverage for models of diversity gradients and point to the importance of temperature for diversification and species coexistence in plant and animal communities.}, language = {en} } @article{BekesFriedlKoehleretal.2016, author = {Bekes, Inga and Friedl, Thomas W. P. and K{\"o}hler, Tanja and M{\"o}bus, Volker and Janni, Wolfgang and W{\"o}ckel, Achim and Wulff, Christine}, title = {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?}, series = {Molecular Cancer}, volume = {15}, journal = {Molecular Cancer}, number = {13}, doi = {10.1186/s12943-016-0497-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169298}, year = {2016}, abstract = {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.}, language = {en} } @article{KilincEhrigPessianetal.2016, author = {Kilinc, Mehmet Okyay and Ehrig, Klaas and Pessian, Maysam and Minev, Boris R. and Szalay, Aladar A.}, title = {Colonization of xenograft tumors by oncolytic vaccinia virus (VACV) results in enhanced tumor killing due to the involvement of myeloid cells}, series = {Journal of Translational Medicine}, volume = {14}, journal = {Journal of Translational Medicine}, number = {340}, doi = {10.1186/s12967-016-1096-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168914}, year = {2016}, abstract = {Background The mechanisms by which vaccinia virus (VACV) interacts with the innate immune components are complex and involve different mechanisms. iNOS-mediated NO production by myeloid cells is one of the central antiviral mechanisms and this study aims to investigate specifically whether iNOS-mediated NO production by myeloid cells, is involved in tumor eradication following the virus treatment. Methods Human colon adenocarcinoma (HCT-116) xenograft tumors were infected by VACV. Infiltration of iNOS\(^{+}\) myeloid cell population into the tumor, and virus titer was monitored following the treatment. Single-cell suspensions were stained for qualitative and quantitative flow analysis. The effect of different myeloid cell subsets on tumor growth and colonization were investigated by depletion studies. Finally, in vitro culture experiments were carried out to study NO production and tumor cell killing. Student's t test was used for comparison between groups in all of the experiments. Results Infection of human colon adenocarcinoma (HCT-116) xenograft tumors by VACV has led to recruitment of many CD11b\(^{+}\) ly6G\(^{+}\) myeloid-derived suppressor cells (MDSCs), with enhanced iNOS expression in the tumors, and to an increased intratumoral virus titer between days 7 and 10 post-VACV therapy. In parallel, both single and multiple rounds of iNOS-producing cell depletions caused very rapid tumor growth within the same period after virus injection, indicating that VACV-induced iNOS\(^{+}\) MDSCs could be an important antitumor effector component. A continuous blockade of iNOS by its specific inhibitor, L-NIL, showed similar tumor growth enhancement 7-10 days post-infection. Finally, spleen-derived iNOS+ MDSCs isolated from virus-injected tumor bearing mice produced higher amounts of NO and effectively killed HCT-116 cells in in vitro transwell experiments. Conclusions We initially hypothesized that NO could be one of the factors that limits active spreading of the virus in the cancerous tissue. In contrast to our initial hypothesis, we observed that PMN-MDSCs were the main producer of NO through iNOS and NO provided a beneficial antitumor effect, The results strongly support an important novel role for VACV infection in the tumor microenvironment. VACV convert tumor-promoting MDSCs into tumor-killing cells by inducing higher NO production.}, language = {en} } @article{PetritschKoestlerGassenmaieretal.2016, author = {Petritsch, Bernhard and K{\"o}stler, Herbert and Gassenmaier, Tobias and Kunz, Andreas S and Bley, Thorsten A and Horn, Michael}, title = {An investigation into potential gender-specific differences in myocardial triglyceride content assessed by \(^{1}\)H-Magnetic Resonance Spectroscopy at 3Tesla}, series = {Journal of International Medical Research}, volume = {44}, journal = {Journal of International Medical Research}, number = {3}, doi = {10.1177/0300060515603884}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168808}, pages = {585-591}, year = {2016}, abstract = {Objective: Over the past decade, myocardial triglyceride content has become an accepted biomarker for chronic metabolic and cardiac disease. The purpose of this study was to use proton (hydrogen 1)-magnetic resonance spectroscopy (\(^{1}\)H-MRS) at 3Tesla (3 T) field strength to assess potential gender-related differences in myocardial triglyceride content in healthy individuals. Methods: Cardiac MR imaging was performed to enable accurate voxel placement and obtain functional and morphological information. Double triggered (i.e., ECG and respiratory motion gating) \(^{1}\)H-MRS was used to quantify myocardial triglyceride levels for each gender. Two-sample t-test and Mann-Whitney U-test were used for statistical analyses. Results: In total, 40 healthy volunteers (22 male, 18 female; aged >18 years and age matched) were included in the study. Median myocardial triglyceride content was 0.28\% (interquartile range [IQR] 0.17-0.42\%) in male and 0.24\% (IQR 0.14-0.45\%) in female participants, and no statistically significant difference was observed between the genders. Furthermore, no gender-specific difference in ejection fraction was observed, although on average, male participants presented with a higher mean ± SD left ventricular mass (136.3 ± 25.2 g) than female participants (103.9 ± 16.1 g). Conclusions: The study showed that \(^{1}\)H-MRS is a capable, noninvasive tool for acquisition of myocardial triglyceride metabolites. Myocardial triglyceride concentration was shown to be unrelated to gender in this group of healthy volunteers.}, language = {en} } @article{JoschinskiBeerHelfrichFoersteretal.2016, author = {Joschinski, Jens and Beer, Katharina and Helfrich-F{\"o}rster, Charlotte and Krauss, Jochen}, title = {Pea Aphids (Hemiptera: Aphididae) Have Diurnal Rhythms When Raised Independently of a Host Plant}, series = {Journal of Insect Science}, volume = {16}, journal = {Journal of Insect Science}, number = {1}, doi = {10.1093/jisesa/iew013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168783}, pages = {31}, year = {2016}, abstract = {Seasonal timing is assumed to involve the circadian clock, an endogenous mechanism to track time and measure day length. Some debate persists, however, and aphids were among the first organisms for which circadian clock involvement was questioned. Inferences about links to phenology are problematic, as the clock itself is little investigated in aphids. For instance, it is unknown whether aphids possess diurnal rhythms at all. Possibly, the close interaction with host plants prevents independent measurements of rhythmicity. We reared the pea aphid Acyrthosiphon pisum (Harris) on an artificial diet, and recorded survival, moulting, and honeydew excretion. Despite their plant-dependent life style, aphids were independently rhythmic under light-dark conditions. This first demonstration of diurnal aphid rhythms shows that aphids do not simply track the host plant's rhythmicity.}, language = {en} } @article{DennerDittmaierHechtetal.2016, author = {Denner, Ansgar and Dittmaier, Stefan and Hecht, Markus and Pasold, Christian}, title = {NLO QCD and electroweak corrections to Z + γ production with leptonic Z-boson decays}, series = {JOURNAL OF HIGH ENERGY PHYSICS}, volume = {02}, journal = {JOURNAL OF HIGH ENERGY PHYSICS}, number = {057}, doi = {10.1007/JHEP02(2016)057}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168766}, year = {2016}, abstract = {The next-to-leading-order electroweak corrections to pp→l\(^{+}\)l\(^{-}\)/ν¯¯¯ν+γ+X production, including all off-shell effects of intermediate Z bosons in the complex-mass scheme, are calculated for LHC energies, revealing the typically expected large corrections of tens of percent in the TeV range. Contributions from quark-photon and photon-photon initial states are taken into account as well, but their impact is found to be moderate or small. Moreover, the known next-to-leading-order QCD corrections are reproduced. In order to separate hard photons from jets, both a quark-to-photon fragmentation function {\´a} la Glover/Morgan and Frixione's cone isolation are employed. The calculation is available in the form of Monte Carlo programs allowing for the evaluation of arbitrary differential cross sections. Predictions for integrated cross sections are presented for the LHC at 7 TeV, 8 TeV, and 14 TeV, and differential distributions are discussed at 14 TeV for bare muons and dressed leptons. Finally, we consider the impact of anomalous ZZγ and Zγγ couplings.}, language = {en} } @article{HirschKraussOpferkuchetal.2016, author = {Hirsch, Martin and Krauss, Manuel E. and Opferkuch, Toby and Porod, Werner and Staub, Florian}, title = {A constrained supersymmetric left-right model}, series = {JOURNAL OF HIGH ENERGY PHYSICS}, volume = {03}, journal = {JOURNAL OF HIGH ENERGY PHYSICS}, number = {009}, doi = {10.1007/JHEP03(2016)009}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168016}, year = {2016}, abstract = {We present a supersymmetric left-right model which predicts gauge coupling unification close to the string scale and extra vector bosons at the TeV scale. The subtleties in constructing a model which is in agreement with the measured quark masses and mixing for such a low left-right breaking scale are discussed. It is shown that in the constrained version of this model radiative breaking of the gauge symmetries is possible and a SM-like Higgs is obtained. Additional CP-even scalars of a similar mass or even much lighter are possible. The expected mass hierarchies for the supersymmetric states differ clearly from those of the constrained MSSM. In particular, the lightest down-type squark, which is a mixture of the sbottom and extra vector-like states, is always lighter than the stop. We also comment on the model's capability to explain current anomalies observed at the LHC.}, language = {en} } @article{BiedermannBilloniDenneretal.2016, author = {Biedermann, B. and Billoni, M. and Denner, A. and Dittmaier, S. and Hofer, L. and J{\"a}ger, B. and Salfelder, L.}, title = {Next-to-leading-order electroweak corrections to pp -> W\(^{+}\)W\(^{-}\) -> 4 leptons at the LHC}, series = {JOURNAL OF HIGH ENERGY PHYSICS}, volume = {06}, journal = {JOURNAL OF HIGH ENERGY PHYSICS}, number = {065}, doi = {10.1007/JHEP06(2016)065}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167790}, year = {2016}, abstract = {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.}, language = {en} } @article{SchieleReinhardReifetal.2016, author = {Schiele, Miriam A. and Reinhard, Julia and Reif, Andreas and Domschke, Katharina and Romanos, Marcel and Deckert, J{\"u}rgen and Pauli, Paul}, title = {Developmental aspects of fear: Comparing the acquisition and generalization of conditioned fear in children and adults}, series = {Developmental Psychobiology}, volume = {58}, journal = {Developmental Psychobiology}, number = {4}, doi = {10.1002/dev.21393}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189488}, pages = {471-481}, year = {2016}, abstract = {Most research on human fear conditioning and its generalization has focused on adults whereas only little is known about these processes in children. Direct comparisons between child and adult populations are needed to determine developmental risk markers of fear and anxiety. We compared 267 children and 285 adults in a differential fear conditioning paradigm and generalization test. Skin conductance responses (SCR) and ratings of valence and arousal were obtained to indicate fear learning. Both groups displayed robust and similar differential conditioning on subjective and physiological levels. However, children showed heightened fear generalization compared to adults as indexed by higher arousal ratings and SCR to the generalization stimuli. Results indicate overgeneralization of conditioned fear as a developmental correlate of fear learning. The developmental change from a shallow to a steeper generalization gradient is likely related to the maturation of brain structures that modulate efficient discrimination between danger and (ambiguous) safety cues.}, language = {en} } @article{NickersonAtalagdeBonoetal.2016, author = {Nickerson, David and Atalag, Koray and de Bono, Bernard and Geiger, J{\"o}rg and Goble, Carole and Hollmann, Susanne and Lonien, Joachim and M{\"u}ller, Wolfgang and Regierer, Babette and Stanford, Natalie J. and Golebiewski, Martin and Hunter, Peter}, title = {The Human Physiome: how standards, software and innovative service infrastructures are providing the building blocks to make it achievable}, series = {Interface Focus}, volume = {6}, journal = {Interface Focus}, number = {2}, doi = {10.1098/rsfs.2015.0103}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189584}, pages = {13 Seiten}, year = {2016}, abstract = {Reconstructing and understanding the Human Physiome virtually is a complex mathematical problem, and a highly demanding computational challenge. Mathematical models spanning from the molecular level through to whole populations of individuals must be integrated, then personalized. This requires interoperability with multiple disparate and geographically separated data sources, and myriad computational software tools. Extracting and producing knowledge from such sources, even when the databases and software are readily available, is a challenging task. Despite the difficulties, researchers must frequently perform these tasks so that available knowledge can be continually integrated into the common framework required to realize the Human Physiome. Software and infrastructures that support the communities that generate these, together with their underlying standards to format, describe and interlink the corresponding data and computer models, are pivotal to the Human Physiome being realized. They provide the foundations for integrating, exchanging and re-using data and models efficiently, and correctly, while also supporting the dissemination of growing knowledge in these forms. In this paper, we explore the standards, software tooling, repositories and infrastructures that support this work, and detail what makes them vital to realizing the Human Physiome.}, language = {en} } @article{StaussBrunnerBerberichSiebeltetal.2016, author = {Stauss, Dennis and Brunner, Cornelia and Berberich-Siebelt, Friederike and H{\"o}pken, Uta E. and Lipp, Martin and M{\"u}ller, Gerd}, title = {The transcriptional coactivator Bob1 promotes the development of follicular T helper cells via Bcl6}, series = {Embo Journal}, volume = {35}, journal = {Embo Journal}, number = {8}, doi = {10.15252/embj.201591459}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189506}, pages = {881-898}, year = {2016}, abstract = {Follicular T helper (Tfh) cells are key regulators of the germinal center reaction and long-term humoral immunity. Tfh cell differentiation requires the sustained expression of the transcriptional repressor Bcl6; however, its regulation in CD4\(^+\) T cells is incompletely understood. Here, we report that the transcriptional coactivator Bob1, encoded by the Pou2af1 gene, promotes Bcl6 expression and Tfh cell development. We found that Bob1 together with the octamer transcription factors Oct1/Oct2 can directly bind to and transactivate the Bcl6 and Btla promoters. Mixed bone marrow chimeras revealed that Bob1 is required for the expression of normal levels of Bcl6 and BTLA, thereby controlling the pool size and composition of the Tfh compartment in a T cell-intrinsic manner. Our data indicate that T cell-expressed Bob1 is directly involved in Tfh cell differentiation and required for mounting normal T cell-dependent B-cell responses.}, language = {en} } @article{HackerEscalonaEspinosaConsalvoetal.2016, author = {Hacker, Ulrich T. and Escalona-Espinosa, Laura and Consalvo, Nicola and Goede, Valentin and Schiffmann, Lars and Scherer, Stefan J. and Hedge, Priti and Van Cutsem, Eric and Coutelle, Oliver and B{\"u}ning, Hildegard}, title = {Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial}, series = {British Journal of Cancer}, volume = {114}, journal = {British Journal of Cancer}, number = {8}, doi = {10.1038/bjc.2016.30}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189578}, pages = {855-862}, year = {2016}, abstract = {Background: In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker. Methods: Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis. Results: Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml\(^-\)\(^1\)) vs non-Asian patients (3193 pg ml\(^-\)\(^1\)), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml\(^-\)\(^1\) increase: 1.19; 95\% CI 1.10-1.29; P<0.0001 (non-Asians) and 1.37; 95\% CI 1.13-1.64; P = 0.0010 (Asians). Conclusions: Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer.}, language = {en} } @article{MaassDuezelBrigadskietal.2016, author = {Maass, Anne and D{\"u}zel, Sandra and Brigadski, Tanja and Goerke, Monique and Becke, Andreas and Sobieray, Uwe and Neumann, Katja and L{\"o}vd{\´e}n, Martin and Lindenberger, Ulman and B{\"a}ckman, Lars and Braun-Dullaeus, R{\"u}diger and Ahrens, D{\"o}rte and Heinze, Hans-Jochen and M{\"u}ller, Notger G. and Lessmann, Volkmar and Sendtner, Michael and D{\"u}zel, Emrah}, title = {Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults}, series = {NeuroImage}, volume = {131}, journal = {NeuroImage}, doi = {10.1016/j.neuroimage.2015.10.084}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189219}, pages = {142-154}, year = {2016}, abstract = {Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77 years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n = 21) or to a control group (indoor progressive-muscle relaxation/stretching, n = 19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here.}, language = {en} } @article{KurzKampfBuschleetal.2016, author = {Kurz, Felix T. and Kampf, Thomas and Buschle, Lukas R. and Schlemmer, Heinz-Peter and Bendszus, Martin and Heiland, Sabine and Ziener, Christian H.}, title = {Generalized moment analysis of magnetic field correlations for accumulations of spherical and cylindrical magnetic perturbers}, series = {Frontiers in Physics}, volume = {4}, journal = {Frontiers in Physics}, issn = {2296-424X}, doi = {10.3389/fphy.2016.00046}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190604}, year = {2016}, abstract = {In biological tissue, an accumulation of similarly shaped objects with a susceptibility difference to the surrounding tissue generates a local distortion of the external magnetic field in magnetic resonance imaging. It induces stochastic field fluctuations that characteristically influence proton spin dephasing in the vicinity of these magnetic perturbers. The magnetic field correlation that is associated with such local magnetic field inhomogeneities can be expressed in the form of a dynamic frequency autocorrelation function that is related to the time evolution of the measured magnetization. Here, an eigenfunction expansion for two simple magnetic perturber shapes, that of spheres and cylinders, is considered for restricted spin diffusion in a simple model geometry. Then, the concept of generalized moment analysis, an approximation technique that is applied in the study of (non-)reactive processes that involve Brownian motion, allows deriving analytical expressions of the correlation function for different exponential decay forms. Results for the biexponential decay for both spherical and cylindrical magnetized objects are derived and compared with the frequently used (less accurate) monoexponential decay forms. They are in asymptotic agreement with the numerically exact value of the correlation function for long and short times.}, language = {en} } @misc{Karremann2016, author = {Karremann, Isabel}, title = {Hans-Peter Wagner. An Introduction to British and Irish Fiction: Renaissance to Romanticism. Trier: Wissenschaftlicher Verlag Trier, 2014, 262 pp., 60 illustr., € 29.50.}, series = {Anglia}, volume = {134}, journal = {Anglia}, number = {4}, issn = {1865-8938}, doi = {10.1515/ang-2016-0078}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194309}, pages = {711-715}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{AdrianMartinezAlbertAndreetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Albert, A. and Andr{\´e}, M. and Anton, G. and Ardid, M. and Aubert, J.-J. and Avgitas, T. and Baret, B. and Barrios-Mart{\´i}, J. and Basa, S. and Bertin, V. and Biagi, S. and Bormuth, R. and Bou-Cabo, M. and Bouwhuis, M.C. and Bruijn, R. and Brunner, J. and Busto, J. and Capone, A. and Caramete, L. and Carr, J. and Celli, S. and Chiarusi, T. and Circella, M. and Coleiro, A. and Coniglione, R. and Costantini, H. and Coyle, P. and Creusot, A. and Deschamps, A. and De Bonis, G. and Distefano, C. and Donzaud, C. and Dornic, D. and Drouhin, D. and Eberl, T. and El Bojaddaini, I. and Els{\"a}sser, D. and Enzenh{\"o}fer, A. and Fehn, K. and Felis, I. and Fusco, L.A. and Galat{\`a}, S. and Gay, P. and Geißels{\"o}der, S. and Geyer, K. and Giordano, V. and Gleixner, A. and Glotin, H. and Gracia-Ruiz, R. and Graf, K. and Hallmann, S. and van Haren, H. and Heijboer, A.J. and Hello, Y. and Hern{\´a}ndez-Rey, J.-J. and H{\"o}ßl, J. and Hofest{\"a}dt, J. and Hugon, C. and Illuminati, G. and James, C.W. and de Jong, M. and Kadler, M. and Kalekin, O. and Katz, U. and Kießling, D. and Kouchner, A. and Kreter, M. and Kreykenbohm, I. and Kulikovskiy, V. and Lachaud, C. and Lahmann, R. and Lef{\`e}vre, D. and Leonora, E. and Loucatos, S. and Marcelin, M. and Margiotta, A. and Marinelli, A. and Mart{\´i}nez-Mora, J.A. and Mathieu, A. and Michael, T. and Migliozzi, P. and Moussa, A. and Mueller, C. and Nezri, E. and Păvălaș, G.E. and Pellegrino, C. and Perrina, C. and Piattelli, P. and Popa, V. and Pradier, T. and Racca, C. and Riccobene, G. and Roensch, K. and Salda{\~n}a, M. and Samtleben, D.F.E. and Sanguineti, M. and Sapienza, P. and Schnabel, J. and Sch{\"u}ssler, F. and Seitz, T. and Sieger, C. and Spurio, M. and Stolarczyk, Th. and S{\´a}nchez-Losa, A. and Taiuti, M. and Trovato, A. and Tselengidou, M. and Turpin, D. and T{\"o}nnis, C. and Vallage, B. and Vall{\´e}e, C. and Van Elewyck, V. and Vivolo, D. and Wagner, S. and Wilms, J. and Zornoza, J.D. and Z{\´u}{\~n}iga, J.}, title = {A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope}, series = {Journal of Cosmology and Astroparticle Physics}, volume = {2016}, journal = {Journal of Cosmology and Astroparticle Physics}, number = {5}, organization = {The ANTARES collaboration}, doi = {10.1088/1475-7516/2016/05/016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189035}, pages = {12}, year = {2016}, abstract = {A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.}, language = {en} } @article{BollBartholomaeusPeteretal.2016, author = {Boll, Sabine and Bartholomaeus, Marie and Peter, Ulrike and Lupke, Ulrike and Gamer, Matthias}, title = {Attentional mechanisms of social perception are biased in social phobia}, series = {Journal of Anxiety Disorders}, volume = {40}, journal = {Journal of Anxiety Disorders}, doi = {10.1016/j.janxdis.2016.04.004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189046}, pages = {83-93}, year = {2016}, abstract = {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.}, language = {en} } @article{BanalesCardinaleCarpinoetal.2016, author = {Banales, Jesus M. and Cardinale, Vincenzo and Carpino, Guido and Marzioni, Marco and Andersen, Jesper B. and Invernizzi, Pietro and Lind, Guro E. and Folseraas, Trine and Forbes, Stuart J. and Fouassier, Laura and Geier, Andreas and Calvisi, Diego F. and Mertens, Joachim C. and Trauner, Michael and Benedetti, Antonio and Maroni, Luca and Vaquero, Javier and Macias, Rocio I. R. and Raggi, Chiara and Perugorria, Maria J. and Gaudio, Eugenio and Boberg, Kirsten M. and Marin, Jose J. G. and Alvaro, Domenico}, title = {Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)}, series = {Nature Reviews Gastroenterology \& Hepatology}, volume = {13}, journal = {Nature Reviews Gastroenterology \& Hepatology}, number = {5}, doi = {10.1038/nrgastro.2016.51}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189077}, pages = {261-280}, year = {2016}, abstract = {Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.}, language = {en} } @article{KlughammerSchreiber2016, author = {Klughammer, Christof and Schreiber, Ulrich}, title = {Deconvolution of ferredoxin, plastocyanin, and P700 transmittance changes in intact leaves with a new type of kinetic LED array spectrophotometer}, series = {Photosynthesis Research}, volume = {128}, journal = {Photosynthesis Research}, number = {2}, doi = {10.1007/s11120-016-0219-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-189050}, pages = {195-214}, year = {2016}, abstract = {A newly developed compact measuring system for assessment of transmittance changes in the near-infrared spectral region is described; it allows deconvolution of redox changes due to ferredoxin (Fd), P700, and plastocyanin (PC) in intact leaves. In addition, it can also simultaneously measure chlorophyll fluorescence. The major opto-electronic components as well as the principles of data acquisition and signal deconvolution are outlined. Four original pulse-modulated dual-wavelength difference signals are measured (785-840 nm, 810-870 nm, 870-970 nm, and 795-970 nm). Deconvolution is based on specific spectral information presented graphically in the form of 'Differential Model Plots' (DMP) of Fd, P700, and PC that are derived empirically from selective changes of these three components under appropriately chosen physiological conditions. Whereas information on maximal changes of Fd is obtained upon illumination after dark-acclimation, maximal changes of P700 and PC can be readily induced by saturating light pulses in the presence of far-red light. Using the information of DMP and maximal changes, the new measuring system enables on-line deconvolution of Fd, P700, and PC. The performance of the new device is demonstrated by some examples of practical applications, including fast measurements of flash relaxation kinetics and of the Fd, P700, and PC changes paralleling the polyphasic fluorescence rise upon application of a 300-ms pulse of saturating light.}, language = {en} } @article{Froehlich2016, author = {Fr{\"o}hlich, Andrea}, title = {Discussion Report: Formation of Companies}, series = {European Company and Financial Law Review}, volume = {13}, journal = {European Company and Financial Law Review}, number = {2}, issn = {1613-2556}, doi = {10.1515/ecfr-2016-0373}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194468}, pages = {373-374}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{Schmidt2016, author = {Schmidt, Lena}, title = {Discussions Report: Reorganization of Companies}, series = {European Company and Financial Law Review}, volume = {13}, journal = {European Company and Financial Law Review}, number = {2}, issn = {1613-2556}, doi = {10.1515/ecfr-2016-0370}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194479}, pages = {370-372}, year = {2016}, abstract = {No abstract available.}, language = {en} } @misc{Nord2016, author = {Nord, Ilona}, title = {Jan Peter Grevel, Mit Gott im Gr{\"u}nen. Eine Praktische Theologie der Naturerfahrung (Research in Contemporary Religion, Vol. 17), G{\"o}ttingen (Vandenhoeck \& Ruprecht) 2015, 357 pp, ISBN 9783525604519, Eur (D) 110.}, series = {International Journal of Practical Theology}, volume = {20}, journal = {International Journal of Practical Theology}, number = {2}, issn = {1612-9768}, doi = {10.1515/ijpt-2016-0039}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194900}, pages = {282-284}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{TinajeroTrejoRanaNageletal.2016, author = {Tinajero-Trejo, Mariana and Rana, Namrata and Nagel, Christoph and Jesse, Helen E. and Smith, Thomas W. and Wareham, Lauren K. and Hippler, Michael and Schatzschneider, Ulrich and Poole, Robert K.}, title = {Antimicrobial Activity of the Manganese Photoactivated Carbon Monoxide-Releasing Molecule [Mn(CO)\(_3\)(tpa-kappa\(^3\)N)]\(^+\) Against a Pathogenic Escherichia coli that Causes Urinary Infections}, series = {Antioxidants \& Redox Signaling}, volume = {24}, journal = {Antioxidants \& Redox Signaling}, number = {14}, doi = {10.1089/ars.2015.6484}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188910}, pages = {765-780}, year = {2016}, abstract = {Aims: We set out to investigate the antibacterial activity of a new Mn-based photoactivated carbon monoxide-releasing molecule (PhotoCORM, [Mn(CO)\(_3\)(tpa-kappa\(^3\)N)]\(^+\)) against an antibiotic-resistant uropathogenic strain (EC958) of Escherichia coli. Results: Activated PhotoCORM inhibits growth and decreases viability of E. coli EC958, but non-illuminated carbon monoxide-releasing molecule (CORM) is without effect. NADH-supported respiration rates are significantly decreased by activated PhotoCORM, mimicking the effect of dissolved CO gas. CO from the PhotoCORM binds to intracellular targets, namely respiratory oxidases in strain EC958 and a bacterial globin heterologously expressed in strain K-12. However, unlike previously characterized CORMs, the PhotoCORM is not significantly accumulated in cells, as deduced from the cellular manganese content. Activated PhotoCORM reacts avidly with hydrogen peroxide producing hydroxyl radicals; the observed peroxide-enhanced toxicity of the PhotoCORM is ameliorated by thiourea. The PhotoCORM also potentiates the effect of the antibiotic, doxycycline. Innovation: The present work investigates for the first time the antimicrobial activity of a light-activated PhotoCORM against an antibiotic-resistant pathogen. A comprehensive study of the effects of the PhotoCORM and its derivative molecules upon illumination is performed and mechanisms of toxicity of the activated PhotoCORM are investigated. Conclusion: The PhotoCORM allows a site-specific and time-controlled release of CO in bacterial cultures and has the potential to provide much needed information on the generality of CORM activities in biology. Understanding the mechanism(s) of activated PhotoCORM toxicity will be key in exploring the potential of this and similar compounds as antimicrobial agents, perhaps in combinatorial therapies with other agents.}, language = {en} } @article{Teichmann2016, author = {Teichmann, Christoph}, title = {Corporate Restructuring under the EMCA}, series = {European Company and Financial Law Review}, volume = {13}, journal = {European Company and Financial Law Review}, number = {2}, issn = {1613-2556}, doi = {10.1515/ecfr-2016-0277}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194488}, pages = {277 -- 300}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{AlbersBernsteinBrachmannetal.2016, author = {Albers, Gregory W. and Bernstein, Richard A. and Brachmann, Johannes and Camm, John and Easton, J. Donald and Fromm, Peter and Goto, Shinya and Granger, Christopher B. and Hohnloser, Stefan H. and Hylek, Elaine and Jaffer, Amir K. and Krieger, Derk W. and Passman, Rod and Pines, Jesse M. and Reed, Shelby D. and Rothwell, Peter M. and Kowey, Peter R.}, title = {Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report}, series = {Journal of the American Heart Association}, volume = {5}, journal = {Journal of the American Heart Association}, number = {e00294}, doi = {10.1161/JAHA.115.002944}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165709}, pages = {1-11}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{FitchettZinmanWanneretal.2016, author = {Fitchett, David and Zinman, Bernard and Wanner, Christoph and Lachin, John M. and Hantel, Stefan and Salsali, Afshin and Johansen, Odd Erik and Woerle, Hans J. and Broedl, Uli C. and Inzucchi, Silvio E.}, title = {Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME (R) trial}, series = {European Heart Journal}, volume = {37}, journal = {European Heart Journal}, number = {19}, doi = {10.1093/eurheartj/ehv728}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188900}, pages = {1526-1534}, year = {2016}, abstract = {Aims We previously reported that in the EMPA-REG OUTCOME(R) trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure. Methods and results Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1\%) had heart failure at baseline. Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin 265/4687 patients (5.7\%)] than with placebo 198/2333 patients (8.5\%)] hazard ratio, HR: 0.66 (95\% confidence interval: 0.55-0.79); P < 0.001], corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years. Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics, including patients with vs. without heart failure, and across categories of medications to treat diabetes and/or heart failure. Empagliflozin improved other heart failure outcomes, including hospitalization for or death from heart failure 2.8 vs. 4.5\%; HR: 0.61 (0.47-0.79); P < 0.001] and was associated with a reduction in all-cause hospitalization 36.8 vs. 39.6\%; HR: 0.89 (0.82-0.96); P = 0.003]. Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups, but were no more common with empagliflozin than with placebo. Conclusion In patients with type 2 diabetes and high cardiovascular risk, empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure.}, language = {en} } @article{AdrianMartinezAgeronAharonianetal.2016, author = {Adri{\´a}n-Mart{\´i}nez, S. and Ageron, M. and Aharonian, F. and Aiello, S. and Albert, A. and Ameli, F. and Annasontzis, E. and Andre, M. and Androulakis, G. and Anghinolfi, M. and Anton, G. and Ardid, M. and Avgitas, T. and Barbarino, G. and Baret, B. and Barrios-Mart{\´i}, J. and Belhorma, B. and Belias, A. and Berbee, A. and van den Berg, A. and Bertin, V. and Beurthey, S. and van Beeveren, V. and Beverini, N. and Biagi, S. and Biagioni, A. and Billault, M. and Bond{\`i}, M. and Bormuth, R. and Bouhadef, B. and Bourlis, G. and Bourret, S. and Boutonnet, C. and Bouwhuis, M. and Bozza, C. and Bruijn, R. and Brunner, J. and Buis, E. and Busto, J. and Cacopardo, G. and Caillat, L. and Calmai, M. and Calvo, D. and Capone, A. and Caramete, L. and Cecchini, S. and Celli, S. and Champion, C. and Cherkaoui El Moursli, R. and Cherubini, S. and Chiarusi, T. and Circella, M. and Classen, L. and Cocimano, R. and Coelho, J. A. B. and Coleiro, A. and Colonges, S. and Coniglione, R. and Cordelli, M. and Cosquer, A. and Coyle, P. and Creusot, A. and Cuttone, G. and D'Amico, A. and De Bonis, G. and De Rosa, G. and De Sio, C. and Di Capua, F. and Di Palma, I. and D{\´i}az Garc{\´i}a, A. F. and Distefano, C. and Donzaud, C. and Dornic, D. and Dorosti-Hasankiadeh, Q. and Drakopoulou, E. and Drouhin, D. and Drury, L. and Durocher, M. and Eberl, T. and Eichie, S. and van Eijk, D. and El Bojaddaini, I. and El Khayati, N. and Elsaesser, D. and Enzenh{\"o}fer, A. and Fassi, F. and Favali, P. and Fermani, P. and Ferrara, G. and Filippidis, C. and Frascadore, G. and Fusco, L. A. and Gal, T. and Galat{\`a}, S. and Garufi, F. and Gay, P. and Gebyehu, M. and Giordano, V. and Gizani, N. and Gracia, R. and Graf, K. and Gr{\´e}goire, T. and Grella, G. and Habel, R. and Hallmann, S. and van Haren, H. and Harissopulos, S. and Heid, T. and Heijboer, A. and Heine, E. and Henry, S. and Hern{\´a}ndez-Rey, J. J. and Hevinga, M. and Hofest{\"a}dt, J. and Hugon, C. M. F. and Illuminati, G. and James, C. W. and Jansweijer, P. and Jongen, M. and de Jong, M. and Kadler, M. and Kalekin, O. and Kappes, A. and Katz, U. F. and Keller, P. and Kieft, G. and Kießling, D. and Koffeman, E. N. and Kooijman, P. and Kouchner, A. and Kulikovskiy, V. and Lahmann, R. and Lamare, P. and Leisos, A. and Leonora, E. and Lindsey Clark, M. and Liolios, A. and Llorenz Alvarez, C. D. and Lo Presti, D. and L{\"o}hner, H. and Lonardo, A. and Lotze, M. and Loucatos, S. and Maccioni, E. and Mannheim, K. and Margiotta, A. and Marinelli, A. and Mari{\c{s}}, O. and Markou, C. and Mart{\´i}nez-Mora, J. A. and Martini, A. and Mele, R. and Melis, K. W. and Michael, T. and Migliozzi, P. and Migneco, E. and Mijakowski, P. and Miraglia, A. and Mollo, C. M. and Mongelli, M. and Morganti, M. and Moussa, A. and Musico, P. and Musumeci, M. and Navas, S. and Nicoleau, C. A. and Olcina, I. and Olivetto, C. and Orlando, A. and Papaikonomou, A. and Papaleo, R. and Păvăla{\c{s}}, G. E. and Peek, H. and Pellegrino, C. and Perrina, C. and Pfutzner, M. and Piattelli, P. and Pikounis, K. and Poma, G. E. and Popa, V. and Pradier, T. and Pratolongo, F. and P{\"u}hlhofer, G. and Pulvirenti, S. and Quinn, L. and Racca, C. and Raffaelli, F. and Randazzo, N. and Rapidis, P. and Razis, P. and Real, D. and Resvanis, L. and Reubelt, J. and Riccobene, G. and Rossi, C. and Rovelli, A. and Salda{\~n}a, M. and Salvadori, I. and Samtleben, D. F. E. and S{\´a}nchez Garc{\´i}a, A. and S{\´a}nchez Losa, A. and Sanguineti, M. and Santangelo, A. and Santonocito, D. and Sapienza, P. and Schimmel, F. and Schmelling, J. and Sciacca, V. and Sedita, M. and Seitz, T. and Sgura, I. and Simeone, F. and Siotis, I. and Sipala, V. and Spisso, B. and Spurio, M. and Stavropoulos, G. and Steijger, J. and Stellacci, S. M. and Stransky, D. and Taiuti, M. and Tayalati, Y. and T{\´e}zier, D. and Theraube, S. and Thompson, L. and Timmer, P. and T{\"o}nnis, C. and Trasatti, L. and Trovato, A. and Tsirigotis, A. and Tzamarias, S. and Tzamariudaki, E. and Vallage, B. and Van Elewyk, V. and Vermeulen, J. and Vicini, P. and Viola, S. and Vivolo, D. and Volkert, M. and Voulgaris, G. and Wiggers, L. and Wilms, J. and de Wolf, E. and Zachariadou, K. and Zornoza, J. D. and Z{\´u}{\~n}iga, J.}, title = {Letter of intent for KM3NeT 2.0}, series = {Journal of Physics G-Nuclear and Particle Physics}, volume = {43}, journal = {Journal of Physics G-Nuclear and Particle Physics}, number = {8}, doi = {10.1088/0954-3899/43/8/084001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188050}, pages = {84001}, year = {2016}, abstract = {The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and}, language = {en} } @article{SchmidtHieberSillingSchalketal.2016, author = {Schmidt-Hieber, M. and Silling, G. and Schalk, E. and Heinz, W. and Panse, J. and Penack, O. and Christopeit, M. and Buchheidt, D. and Meyding-Lamad{\´e}, U. and H{\"a}hnel, S. and Wolf, H. H. and Ruhnke, M. and Schwartz, S. and Maschmeyer, G.}, title = {CNS infections in patients with hematological disorders (including allogeneic stem-cell transplantation)-Guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO)}, series = {Annals of Oncology}, volume = {27}, journal = {Annals of Oncology}, number = {7}, doi = {10.1093/annonc/mdw155}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188210}, pages = {1207-1225}, year = {2016}, abstract = {Infections of the central nervous system (CNS) are infrequently diagnosed in immunocompetent patients, but they do occur in a significant proportion of patients with hematological disorders. In particular, patients undergoing allogeneic hematopoietic stem-cell transplantation carry a high risk for CNS infections of up to 15\%. Fungi and Toxoplasma gondii are the predominant causative agents. The diagnosis of CNS infections is based on neuroimaging, cerebrospinal fluid examination and biopsy of suspicious lesions in selected patients. However, identification of CNS infections in immunocompromised patients could represent a major challenge since metabolic disturbances, side-effects of antineoplastic or immunosuppressive drugs and CNS involvement of the underlying hematological disorder may mimic symptoms of a CNS infection. The prognosis of CNS infections is generally poor in these patients, albeit the introduction of novel substances (e.g. voriconazole) has improved the outcome in distinct patient subgroups. This guideline has been developed by the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Medical Oncology (DGHO) with the contribution of a panel of 14 experts certified in internal medicine, hematology/oncology, infectious diseases, intensive care, neurology and neuroradiology. Grades of recommendation and levels of evidence were categorized by using novel criteria, as recently published by the European Society of Clinical Microbiology and Infectious Diseases.}, language = {en} } @article{MarxSchindlerMoschetal.2016, author = {Marx, Gernot and Schindler, Achim W. and Mosch, Christoph and Albers, Joerg and Bauer, Michael and Gnass, Irmela and Hobohm, Carsten and Janssens, Uwe and Kluge, Stefan and Kranke, Peter and Maurer, Tobias and Merz, Waltraut and Neugebauer, Edmund and Quintel, Michael and Senninger, Norbert and Trampisch, Hans-Joachim and Waydhas, Christian and Wildenauer, Rene and Zacharowski, Kai and Eikermann, Michaela}, title = {Intravascular volume therapy in adults guidelines from the association of the scientific medical societies in Germany}, series = {European Journal of Anaesthesiology}, volume = {33}, journal = {European Journal of Anaesthesiology}, number = {7}, doi = {10.1097/EJA.0000000000000447}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188223}, pages = {488-521}, year = {2016}, abstract = {No abstract available.}, language = {en} } @article{NietzerBaurSieberetal.2016, author = {Nietzer, Sarah and Baur, Florentin and Sieber, Stefan and Hansmann, Jan and Schwarz, Thomas and Stoffer, Carolin and H{\"a}fner, Heide and Gasser, Martin and Waaga-Gasser, Ana Maria and Walles, Heike and Dandekar, Gudrun}, title = {Mimicking metastases including tumor stroma: a new technique to generate a three-dimensional colorectal cancer model based on a biological decellularized intestinal scaffold}, series = {Tissue Engineering Part C-Methods}, volume = {22}, journal = {Tissue Engineering Part C-Methods}, number = {7}, doi = {10.1089/ten.tec.2015.0557}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188202}, pages = {621-635}, year = {2016}, abstract = {Tumor models based on cancer cell lines cultured two-dimensionally (2D) on plastic lack histological complexity and functionality compared to the native microenvironment. Xenogenic mouse tumor models display higher complexity but often do not predict human drug responses accurately due to species-specific differences. We present here a three-dimensional (3D) in vitro colon cancer model based on a biological scaffold derived from decellularized porcine jejunum (small intestine submucosa+mucosa, SISmuc). Two different cell lines were used in monoculture or in coculture with primary fibroblasts. After 14 days of culture, we demonstrated a close contact of human Caco2 colon cancer cells with the preserved basement membrane on an ultrastructural level as well as morphological characteristics of a well-differentiated epithelium. To generate a tissue-engineered tumor model, we chose human SW480 colon cancer cells, a reportedly malignant cell line. Malignant characteristics were confirmed in 2D cell culture: SW480 cells showed higher vimentin and lower E-cadherin expression than Caco2 cells. In contrast to Caco2, SW480 cells displayed cancerous characteristics such as delocalized E-cadherin and nuclear location of beta-catenin in a subset of cells. One central drawback of 2D cultures-especially in consideration of drug testing-is their artificially high proliferation. In our 3D tissue-engineered tumor model, both cell lines showed decreased numbers of proliferating cells, thus correlating more precisely with observations of primary colon cancer in all stages (UICC I-IV). Moreover, vimentin decreased in SW480 colon cancer cells, indicating a mesenchymal to epithelial transition process, attributed to metastasis formation. Only SW480 cells cocultured with fibroblasts induced the formation of tumor-like aggregates surrounded by fibroblasts, whereas in Caco2 cocultures, a separate Caco2 cell layer was formed separated from the fibroblast compartment beneath. To foster tissue generation, a bioreactor was constructed for dynamic culture approaches. This induced a close tissue-like association of cultured tumor cells with fibroblasts reflecting tumor biopsies. Therapy with 5-fluorouracil (5-FU) was effective only in 3D coculture. In conclusion, our 3D tumor model reflects human tissue-related tumor characteristics, including lower tumor cell proliferation. It is now available for drug testing in metastatic context-especially for substances targeting tumor-stroma interactions.}, language = {en} } @article{PoliteiBouhassiraGermainetal.2016, author = {Politei, Juan M. and Bouhassira, Didier and Germain, Dominique P. and Goizet, Cyril and Guerrero-Sola, Antonio and Hilz, Max J. and Hutton, Elspeth J. and Karaa, Amel and Liuori, Rocco and {\"U}ceyler, Nurcan and Zeltzer, Lonnie K. and Burlina, Alessandro}, title = {Pain in fabry disease: practical recommendations for diagnosis and treatment}, series = {CNS Neuroscience \& Therapeutics}, volume = {22}, journal = {CNS Neuroscience \& Therapeutics}, number = {7}, doi = {10.1111/cns.12542}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188127}, pages = {568-576}, year = {2016}, abstract = {Aims: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. Methods: In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Results: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Wurzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. Conclusion: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications.}, language = {en} } @article{BrevikvanDonkelaarWeberetal.2016, author = {Brevik, Erlend J and van Donkelaar, Marjolein M. J. and Weber, Heike and S{\´a}nchez-Mora, Cristina and Jacob, Christian and Rivero, Olga and Kittel-Schneider, Sarah and Garcia-martinez, Iris and Aebi, Marcel and van Hulzen, Kimm and Cormand, Bru and Ramos-Quiroga, Josep A and Lesch, Klaus-Peter and Reif, Andreas and Ribases, Marta and Franke, Barbara and Posserud, Maj-Britt and Johansson, Stefan and Lundervold, Astri J. and Haavik, Jan and Zayats, Tetyana}, title = {Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder}, series = {American Journal of Medical Genetics Part B-Neuropsychiatric Genetics}, volume = {171B}, journal = {American Journal of Medical Genetics Part B-Neuropsychiatric Genetics}, number = {5}, organization = {IMAGE Consortium}, doi = {10.1002/ajmg.b.32434}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188116}, pages = {733-747}, year = {2016}, abstract = {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.}, language = {en} } @article{FlossKloeckerSchroederetal.2016, author = {Floss, Doreen M. and Kl{\"o}cker, Tobias and Schr{\"o}der, Jutta and Lamertz, Larissa and Mrotzek, Simone and Strobl, Birgit and Hermanns, Heike and Scheller, J{\"u}rgen}, title = {Defining the functional binding sites of interleukin 12 receptor beta 1 and interleukin 23 receptor to Janus kinases}, series = {Molecular Biology of the Cell}, volume = {27}, journal = {Molecular Biology of the Cell}, number = {14}, doi = {10.1091/mbc.E14-12-1645}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188104}, pages = {2301-2316}, year = {2016}, abstract = {The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor beta 1 (IL-12R beta 1) as one component of their receptor signaling complexes, with IL-12R beta 2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12R beta 1, whereas Jak2 binds to IL-23R and also to IL-12R beta 2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12R beta 1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12R beta 1 and Jak2 by IL-23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable.}, language = {en} } @article{WeidemannMaierStoerketal.2016, author = {Weidemann, Frank and Maier, Sebastian K. G. and St{\"o}rk, Stefan and Brunner, Thomas and Liu, Dan and Hu, Kai and Seydelmann, Nora and Schneider, Andreas and Becher, Jan and Canan-K{\"u}hl, Sima and Blaschke, Daniela and Bijnens, Bart and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter}, title = {Usefulness of an implantable loop recorder to detect clinically relevant arrhythmias in patients with advanced fabry cardiomyopathy}, series = {The American Journal of Cardiology}, volume = {118}, journal = {The American Journal of Cardiology}, number = {2}, doi = {10.1016/j.amjcard.2016.04.033}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188093}, pages = {264-274}, year = {2016}, abstract = {Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holier electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holier ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 +/- 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses >= 3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holier ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with an implantable loop recorder.}, language = {en} } @article{DinnesBancosdiRuffanoetal.2016, author = {Dinnes, Jacqueline and Bancos, Irina and di Ruffano, Lavinia Ferrante and Chortis, Vasileios and Davenport, Clare and Bayliss, Susan and Sahdev, Anju and Guest, Peter and Fassnacht, Martin and Deeks, Jonathan J and Arlt, Wiebke}, title = {Imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis}, series = {European Journal of Endocrinology}, volume = {175}, journal = {European Journal of Endocrinology}, number = {2}, doi = {10.1530/EJE-16-0461}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188086}, pages = {R51-R64}, year = {2016}, abstract = {Objective: Adrenal masses are incidentally discovered in 5\% of CT scans. In 2013/2014, 81 million CT examinations were undertaken in the USA and 5 million in the UK. However, uncertainty remains around the optimal imaging approach for diagnosing malignancy. We aimed to review the evidence on the accuracy of imaging tests for differentiating malignant from benign adrenal masses. Design: A systematic review and meta-analysis was conducted. Methods: We searched MEDLINE, EMBASE, Cochrane CENTRAL Register of Controlled Trials, Science Citation Index, Conference Proceedings Citation Index, and ZETOC (January 1990 to August 2015). We included studies evaluating the accuracy of CT, MRI, or F-18-fluoro-deoxyglucose (FDG)-PET compared with an adequate histological or imaging-based follow-up reference standard. Results: We identified 37 studies suitable for inclusion, after screening 5469 references and 525 full-text articles. Studies evaluated the accuracy of CT (n = 16), MRI (n = 15), and FDG-PET (n = 9) and were generally small and at high or unclear risk of bias. Only 19 studies were eligible for meta-analysis. Limited data suggest that CT density >10 HU has high sensitivity for detection of adrenal malignancy in participants with no prior indication for adrenal imaging, that is, masses with <= 10 HU are unlikely to be malignant. All other estimates of test performance are based on too small numbers. Conclusions: Despite their widespread use in routine assessment, there is insufficient evidence for the diagnostic value of individual imaging tests in distinguishing benign from malignant adrenal masses. Future research is urgently needed and should include prospective test validation studies for imaging and novel diagnostic approaches alongside detailed health economics analysis.}, language = {en} } @article{MuellerSchmitz2016, author = {M{\"u}ller, Daniel and Schmitz, Patrick W.}, title = {Transaction costs and the property rights approach to the theory of the firm}, series = {European Economic Review}, volume = {87}, journal = {European Economic Review}, doi = {10.1016/j.euroecorev.2016.04.013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188042}, pages = {92-107}, year = {2016}, abstract = {The standard property rights approach is focused on ex ante investment incentives, while there are no transaction costs that might restrain ex post negotiations. We explore the implications of such transaction costs. Prominent conclusions of the property rights theory may be overturned: A party may have stronger investment incentives when a non investing party is the owner, and joint ownership can be the uniquely optimal ownership structure. Intuitively, an ownership structure that is unattractive in the standard model may now be desirable, because it implies large gains from trade, such that the parties are more inclined to incur the transaction costs.}, language = {en} } @article{BeerSteffanDewenterHaerteletal.2016, author = {Beer, Katharina and Steffan-Dewenter, Ingolf and H{\"a}rtel, Stephan and Helfrich-F{\"o}rster, Charlotte}, title = {A new device for monitoring individual activity rhythms of honey bees reveals critical effects of the social environment on behavior}, series = {Journal of Comparative Physiology A}, volume = {202}, journal = {Journal of Comparative Physiology A}, number = {8}, doi = {10.1007/s00359-016-1103-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188030}, pages = {555-565}, year = {2016}, abstract = {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.}, language = {en} } @article{ReynoldsHofmeisterCliffeetal.2016, author = {Reynolds, David L. and Hofmeister, Brigitte T. and Cliffe, Laura and Siegel, T. Nicolai and Andersson, Britta A. and Beverley, Stephen M. and Schmitz, Robert J. and Sabatini, Robert}, title = {Base J represses genes at the end of polycistronic gene clusters in Leishmania major by promoting RNAP II termination}, series = {Molecular Microbiology}, volume = {101}, journal = {Molecular Microbiology}, number = {4}, doi = {10.1111/mmi.13408}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187727}, pages = {559-574}, year = {2016}, abstract = {The genomes of kinetoplastids are organized into polycistronic gene clusters that are flanked by the modified DNA base J. Previous work has established a role of base J in promoting RNA polymerase II termination in Leishmania spp. where the loss of J leads to termination defects and transcription into adjacent gene clusters. It remains unclear whether these termination defects affect gene expression and whether read through transcription is detrimental to cell growth, thus explaining the essential nature of J. We now demonstrate that reduction of base J at specific sites within polycistronic gene clusters in L. major leads to read through transcription and increased expression of downstream genes in the cluster. Interestingly, subsequent transcription into the opposing polycistronic gene cluster does not lead to downregulation of sense mRNAs. These findings indicate a conserved role for J regulating transcription termination and expression of genes within polycistronic gene clusters in trypanosomatids. In contrast to the expectations often attributed to opposing transcription, the essential nature of J in Leishmania spp. is related to its role in gene repression rather than preventing transcriptional interference resulting from read through and dual strand transcription.}, language = {en} } @article{SteigerwaldMuellerJohannesetal.2016, author = {Steigerwald, Frank and M{\"u}ller, Lorenz and Johannes, Silvia and Matthies, Cordula and Volkmann, Jens}, title = {Directional deep brain stimulation of the subthalamic nucleus: a pilot study using a novel neurostimulation device}, series = {Movement Disorders}, volume = {31}, journal = {Movement Disorders}, number = {8}, doi = {10.1002/mds.26669}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187683}, pages = {1240-1243}, year = {2016}, abstract = {Introduction A novel neurostimulation system allows steering current in horizontal directions by combining segmented leads and multiple independent current control. The aim of this study was to evaluate directional DBS effects on parkinsonian motor features and adverse effects of subthalamic neurostimulation. Methods Seven PD patients implanted with the novel directional DBS system for bilateral subthalamic DBS underwent an extended monopolar review session during the first postoperative week, in which current thresholds were determined for rigidity control and stimulation-induced adverse effects using either directional or ring-mode settings. Results Effect or adverse effect thresholds were modified by directional settings for each of the 14 STN leads. Magnitude of change varied markedly between leads, as did orientation of optimal horizontal current steering. Conclusion Directional current steering through chronically implanted segmented electrodes is feasible, alters adverse effect and efficacy thresholds in a highly individual manner, and expands the therapeutic window in a monopolar review as compared to ring-mode DBS.}, language = {en} } @article{HarkinBrochSchrecketal.2016, author = {Harkin, David J. and Broch, Katharina and Schreck, Maximilian and Ceyman, Harald and Stoy, Andreas and Yong, Chaw-Keong and Nikolka, Mark and McCulloch, Ian and Stingelin, Natalie and Lambert, Christoph and Sirringhaus, Henning}, title = {Decoupling charge transport and electroluminescence in a high mobility polymer semiconductor}, series = {Advanced Materials}, volume = {28}, journal = {Advanced Materials}, number = {30}, doi = {10.1002/adma.201600851}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187670}, pages = {6378-6285}, year = {2016}, abstract = {Fluorescence enhancement of a high-mobility polymer semiconductor is achieved via energy transfer to a higher fluorescence quantum yield squaraine dye molecule on 50 ps timescales. In organic light-emitting diodes, an order of magnitude enhancement of the external quantum efficiency is observed without reduction in the charge-carrier mobility resulting in radiances of up to 5 W str\(^{-1}\) m\(^{-2}\) at 800 nm.}, language = {en} } @article{ChopraBiehlSteinfattetal.2016, author = {Chopra, Martin and Biehl, Marlene and Steinfatt, Tim and Brandl, Andreas and Kums, Juliane and Amich, Jorge and Vaeth, Martin and Kuen, Janina and Holtappels, Rafaela and Podlech, J{\"u}rgen and Mottok, Anja and Kraus, Sabrina and Jord{\´a}n-Garotte, Ana-Laura and B{\"a}uerlein, Carina A. and Brede, Christian and Ribechini, Eliana and Fick, Andrea and Seher, Axel and Polz, Johannes and Ottmueller, Katja J. and Baker, Jeannette and Nishikii, Hidekazu and Ritz, Miriam and Mattenheimer, Katharina and Schwinn, Stefanie and Winter, Thorsten and Sch{\"a}fer, Viktoria and Krappmann, Sven and Einsele, Hermann and M{\"u}ller, Thomas D. and Reddehase, Matthias J. and Lutz, Manfred B. and M{\"a}nnel, Daniela N. and Berberich-Siebelt, Friederike and Wajant, Harald and Beilhack, Andreas}, title = {Exogenous TNFR2 activation protects from acute GvHD via host T reg cell expansion}, series = {Journal of Experimental Medicine}, volume = {213}, journal = {Journal of Experimental Medicine}, number = {9}, doi = {10.1084/jem.20151563}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187640}, pages = {1881-1900}, year = {2016}, abstract = {Donor CD4\(^+\)Foxp3\(^+\) regulatory T cells (T reg cells) suppress graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (HCT allo-HCT]). Current clinical study protocols rely on the ex vivo expansion of donor T reg cells and their infusion in high numbers. In this study, we present a novel strategy for inhibiting GvHD that is based on the in vivo expansion of recipient T reg cells before allo-HCT, exploiting the crucial role of tumor necrosis factor receptor 2 (TNFR2) in T reg cell biology. Expanding radiation-resistant host T reg cells in recipient mice using a mouse TNFR2-selective agonist before allo-HCT significantly prolonged survival and reduced GvHD severity in a TNFR2-and T reg cell-dependent manner. The beneficial effects of transplanted T cells against leukemia cells and infectious pathogens remained unaffected. A corresponding human TNFR2-specific agonist expanded human T reg cells in vitro. These observations indicate the potential of our strategy to protect allo-HCT patients from acute GvHD by expanding T reg cells via selective TNFR2 activation in vivo.}, language = {en} } @article{BuckDecristoforo2016, author = {Buck, Andreas and Decristoforo, Clemens}, title = {Highlights lecture EANM 2015: the search for nuclear medicine's superheroes}, series = {European Journal of Nuclear Medicine and Molecular Imaging}, volume = {43}, journal = {European Journal of Nuclear Medicine and Molecular Imaging}, number = {10}, doi = {10.1007/s00259-016-3423-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187613}, pages = {1910-1927}, year = {2016}, abstract = {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).}, language = {en} } @article{WalzMuehlbergerPauli2016, author = {Walz, Nora and M{\"u}hlberger, Andreas and Pauli, Paul}, title = {A human open field test reveals thigmotaxis related to agoraphobic fear}, series = {Biological Psychiatry}, volume = {80}, journal = {Biological Psychiatry}, number = {5}, doi = {10.1016/j.biopsych.2015.12.016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187607}, pages = {390-397}, year = {2016}, abstract = {BACKGROUND: Thigmotaxis refers to a specific behavior of animals (i.e., to stay close to walls when exploring an open space). Such behavior can be assessed with the open field test (OFT), which is a well-established indicator of animal fear. The detection of similar open field behavior in humans may verify the translational validity of this paradigm. Enhanced thigmotaxis related to anxiety may suggest the relevance of such behavior for anxiety disorders, especially agoraphobia. METHODS: A global positioning system was used to analyze the behavior of 16 patients with agoraphobia and 18 healthy individuals with a risk for agoraphobia (i.e., high anxiety sensitivity) during a human OFT and compare it with appropriate control groups (n = 16 and n = 19). We also tracked 17 patients with agoraphobia and 17 control participants during a city walk that involved walking through an open market square. RESULTS: Our human OFT triggered thigmotaxis in participants; patients with agoraphobia and participants with high anxiety sensitivity exhibited enhanced thigmotaxis. This behavior was evident in increased movement lengths along the wall of the natural open field and fewer entries into the center of the field despite normal movement speed and length. Furthermore, participants avoided passing through the market square during the city walk, indicating again that thigmotaxis is related to agoraphobia. CONCLUSIONS: This study is the first to our knowledge to verify the translational validity of the OFT and to reveal that thigmotaxis, an evolutionarily adaptive behavior shown by most species, is related to agoraphobia, a pathologic fear of open spaces, and anxiety sensitivity, a risk factor for agoraphobia.}, language = {en} } @article{UllmannSchmidtHieberBertzetal.2016, author = {Ullmann, Andrew J. and Schmidt-Hieber, Martin and Bertz, Hartmut and Heinz, Werner J. and Kiehl, Michael and Kr{\"u}ger, William and Mousset, Sabine and Neuburger, Stefan and Neumann, Silke and Penack, Olaf and Silling, Gerda and Vehreschild, J{\"o}rg Janne and Einsele, Hermann and Maschmeyer, Georg}, title = {Infectious diseases in allogeneic haematopoietic stem cell transplantation: prevention and prophylaxis strategy guidelines 2016}, series = {Annals of Hematology}, volume = {95}, journal = {Annals of Hematology}, number = {9}, organization = {Infectious Diseases Working Party of the German Society for Hematology and Medical Oncology (AGIHO/DGHO) and the DAG-KBT (German Working Group for Blood and Marrow Transplantation)}, doi = {10.1007/s00277-016-2711-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187587}, pages = {1435-1455}, year = {2016}, abstract = {Infectious complications after allogeneic haematopoietic stem cell transplantation (allo-HCT) remain a clinical challenge. This is a guideline provided by the AGIHO (Infectious Diseases Working Group) of the DGHO (German Society for Hematology and Medical Oncology). A core group of experts prepared a preliminary guideline, which was discussed, reviewed, and approved by the entire working group. The guideline provides clinical recommendations for the preventive management including prophylactic treatment of viral, bacterial, parasitic, and fungal diseases. The guideline focuses on antimicrobial agents but includes recommendations on the use of vaccinations. This is the updated version of the AGHIO guideline in the field of allogeneic haematopoietic stem cell transplantation utilizing methods according to evidence-based medicine criteria.}, language = {en} } @article{GoncharovaRuzhenkovaPetrovetal.2016, author = {Goncharova, Elena P. and Ruzhenkova, Julia S. and Petrov, Ivan S. and Shchelkunov, Sergey N. and Zenkova, Marina A.}, title = {Oncolytic virus efficiency inhibited growth of tumour cells with multiple drug resistant phenotype in vivo and in vitro}, series = {Journal of Translational Medicine}, volume = {14}, journal = {Journal of Translational Medicine}, number = {241}, doi = {10.1186/s12967-016-1002-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165714}, pages = {1-14}, year = {2016}, abstract = {Background Tumour resistance to a wide range of drugs (multiple drug resistant, MDR) acquired after intensive chemotherapy is considered to be the main obstacle of the curative treatment of cancer patients. Recent work has shown that oncolytic viruses demonstrated prominent potential for effective treatment of diverse cancers. Here, we evaluated whether genetically modified vaccinia virus (LIVP-GFP) may be effective in treatment of cancers displaying MDR phenotype. Methods LIVP-GFP replication, transgene expression and cytopathic effects were analysed in human cervical carcinomas KB-3-1 (MDR-), KB-8-5 (MDR+) and in murine melanoma B-16 (MDR-), murine lymphosarcomas RLS and RLS-40 (MDR+). To investigate the efficacy of this therapy in vivo, we treated immunocompetent mice bearing murine lymphosarcoma RLS-40 (MDR+) (6- to 8-week-old female CBA mice; n = 10/group) or melanoma B-16 (MDR-) (6- to 8-week-old female C57Bl mice; n = 6/group) with LIVP-GFP (5 × 107 PFU of virus in 0.1 mL of IMDM immediately and 4 days after tumour implantation). Results We demonstrated that LIVP-GFP replication was effective in human cervical carcinomas KB-3-1 (MDR-) and KB-8-5 (MDR+) and in murine melanoma B-16 (MDR-), whereas active viral production was not detected in murine lymphosarcomas RLS and RLS-40 (MDR+). Additionally, it was found that in tumour models in immunocompetent mice under the optimized regimen intratumoural injections of LIVP-GFP significantly inhibited melanoma B16 (33 \% of mice were with complete response after 90 days) and RLS-40 tumour growth (fourfold increase in tumour doubling time) as well as metastasis. Conclusion The anti-tumour activity of LIVP-GFP is a result of direct oncolysis of tumour cells in case of melanoma B-16 because the virus effectively replicates and destroys these cells, and virus-mediated activation of the host immune system followed by immunologically mediated destruction of of tumour cells in case of lymphosarcoma RLS-40. Thus, the recombinant vaccinia virus LIVP-GFP is able to inhibit the growth of malignant cells with the MDR phenotype and tumour metastasis when administered in the early stages of tumour development.}, language = {en} } @article{YadavSelvarajBenderetal.2016, author = {Yadav, Preeti and Selvaraj, Bhuvaneish T. and Bender, Florian L. P. and Behringer, Marcus and Moradi, Mehri and Sivadasan, Rajeeve and Dombert, Benjamin and Blum, Robert and Asan, Esther and Sauer, Markus and Julien, Jean-Pierre and Sendtner, Michael}, title = {Neurofilament depletion improves microtubule dynamics via modulation of Stat3/stathmin signaling}, series = {Acta Neuropathologica}, volume = {132}, journal = {Acta Neuropathologica}, number = {1}, doi = {10.1007/s00401-016-1564-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188234}, pages = {93-110}, year = {2016}, abstract = {In neurons, microtubules form a dense array within axons, and the stability and function of this microtubule network is modulated by neurofilaments. Accumulation of neurofilaments has been observed in several forms of neurodegenerative diseases, but the mechanisms how elevated neurofilament levels destabilize axons are unknown so far. Here, we show that increased neurofilament expression in motor nerves of pmn mutant mice, a model of motoneuron disease, causes disturbed microtubule dynamics. The disease is caused by a point mutation in the tubulin-specific chaperone E (Tbce) gene, leading to an exchange of the most C-terminal amino acid tryptophan to glycine. As a consequence, the TBCE protein becomes instable which then results in destabilization of axonal microtubules and defects in axonal transport, in particular in motoneurons. Depletion of neurofilament increases the number and regrowth of microtubules in pmn mutant motoneurons and restores axon elongation. This effect is mediated by interaction of neurofilament with the stathmin complex. Accumulating neurofilaments associate with stathmin in axons of pmn mutant motoneurons. Depletion of neurofilament by Nefl knockout increases Stat3-stathmin interaction and stabilizes the microtubules in pmn mutant motoneurons. Consequently, counteracting enhanced neurofilament expression improves axonal maintenance and prolongs survival of pmn mutant mice. We propose that this mechanism could also be relevant for other neurodegenerative diseases in which neurofilament accumulation and loss of microtubules are prominent features.}, language = {en} } @article{OrtizAbioseBichetetal.2016, author = {Ortiz, Alberto and Abiose, Ademola and Bichet, Daniel G. and Cabrera, Gustavo and Charrow, Joel and Germain, Dominique P. and Hopkin, Robert J. and Jovanovic, Ana and Linhart, Aleš and Maruti, Sonia S. and Mauer, Michael and Oliveira, Jo{\~a}o P. and Patel, Manesh R. and Politei, Juan and Waldek, Stephen and Wanner, Christoph and Yoo, Han-Wook and Warnock, David G.}, title = {Time to treatment benefit for adult patients with Fabry disease receiving agalsidase beta: data from the Fabry Registry}, series = {Journal of Medical Genetics}, volume = {53}, journal = {Journal of Medical Genetics}, number = {7}, doi = {10.1136/jmedgenet-2015-103486}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188241}, pages = {495-502}, year = {2016}, abstract = {Background Agalsidase beta is a form of enzyme replacement therapy for Fabry disease, a genetic disorder characterised by low alpha-galactosidase A activity, accumulation of glycosphingolipids and life-threatening cardiovascular, renal and cerebrovascular events. In clinical trials, agalsidase beta cleared glycolipid deposits from endothelial cells within 6 months; clearance from other cell types required sustained treatment. We hypothesised that there might be a 'lag time' to clinical benefit after initiating agalsidase beta treatment, and analysed the incidence of severe clinical events over time in patients receiving agalsidase beta. Methods The incidence of severe clinical events (renal failure, cardiac events, stroke, death) was studied in 1044 adult patients (641 men, 403 women) enrolled in the Fabry Registry who received agalsidase beta (average dose 1 mg/kg every 2 weeks) for up to 5 years. Results The incidence of all severe clinical events was 111 per 1000 person-years (95\% CI 84 to 145) during the first 6 months. After 6 months, the incidence decreased and remained stable within the range of 40-58 events per 1000 patient-years. The largest decrease in incidence rates was among male patients and those aged >= 40 years when agalsidase beta was initiated. Conclusions Contrary to the expected increased incidence of severe clinical events with time, adult patients with Fabry disease had decreased incidence of severe clinical events after 6 months treatment with agalsidase beta 1 mg/kg every 2 weeks.}, language = {en} } @article{BemmBeckerLarischetal.2016, author = {Bemm, Felix and Becker, Dirk and Larisch, Christina and Kreuzer, Ines and Escalante-Perez, Maria and Schulze, Waltraud X. and Ankenbrand, Markus and Van de Weyer, Anna-Lena and Krol, Elzbieta and Al-Rasheid, Khaled A. and Mith{\"o}fer, Axel and Weber, Andreas P. and Schultz, J{\"o}rg and Hedrich, Rainer}, title = {Venus flytrap carnivorous lifestyle builds on herbivore defense strategies}, series = {Genome Research}, volume = {26}, journal = {Genome Research}, number = {6}, doi = {10.1101/gr.202200.115}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188799}, pages = {812-825}, year = {2016}, abstract = {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.}, language = {en} } @article{RechHueberFinzeletal.2016, author = {Rech, Juergen and Hueber, Axel J. and Finzel, Stephanie and Englbrecht, Matthias and Haschka, Judith and Manger, Bernhard and Kleyer, Arnd and Reiser, Michaela and Cobra, Jayme Fogagnolo and Figueiredo, Camille and Tony, Hans-Peter and Kleinert, Stefan and Wendler, Joerg and Schuch, Florian and Ronneberger, Monika and Feuchtenberger, Martin and Fleck, Martin and Manger, Karin and Ochs, Wolfgang and Schmitt-Haendle, Matthias and Lorenz, Hanns-Martin and Nuesslein, Hubert and Alten, Rieke and Henes, Joerg and Krueger, Klaus and Schett, Georg}, title = {Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment}, series = {Annals of the Rheumatic Diseases}, volume = {75}, journal = {Annals of the Rheumatic Diseases}, number = {9}, doi = {10.1136/annrheumdis-2015-207900}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187519}, pages = {1637-1644}, year = {2016}, abstract = {Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33\% of patients with RA overall. Twice as many patients who relapsed (58\%) had moderate/high MBDA compared with patients who remained in remission (21\%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13\%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3\%) and MBDA-ACPA+ (31.8\%) and high in patients who were MBDA+/ACPA+ (76.4\%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80\% of the patients. Trial registration number EudraCT 2009-015740-42.}, language = {en} } @article{LepetaLourencoSchweitzeretal.2016, author = {Lepeta, Katarzyna and Lourenco, Mychael V. and Schweitzer, Barbara C. and Martino Adami, Pamela V. and Banerjee, Priyanjalee and Catuara-Solarz, Silvina and de la Fuente Revenga, Mario and Marc Guillem, Alain and Haider, Mouna and Ijomone, Omamuyovwi M. and Nadorp, Bettina and Qi, Lin and Perera, Nirma D. and Refsgaard, Louise K. and Reid, Kimberley M. and Sabbar, Mariam and Sahoo, Arghyadip and Schaefer, Natascha and Sheean, Rebecca K. and Suska, Anna and Verma, Rajkumar and Vicidomini, Cinzia and Wright, Dean and Zhang, Xing-Ding and Seidenbecher, Constanze}, title = {Synaptopathies: synaptic dysfunction in neurological disorders - a review from students to students}, series = {Journal of Neurochemistry}, volume = {138}, journal = {Journal of Neurochemistry}, number = {6}, doi = {10.1111/jnc.13713}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187509}, pages = {785-805}, year = {2016}, abstract = {Synapses are essential components of neurons and allow information to travel coordinately throughout the nervous system to adjust behavior to environmental stimuli and to control body functions, memories, and emotions. Thus, optimal synaptic communication is required for proper brain physiology, and slight perturbations of synapse function can lead to brain disorders. In fact, increasing evidence has demonstrated the relevance of synapse dysfunction as a major determinant of many neurological diseases. This notion has led to the concept of synaptopathies as brain diseases with synapse defects as shared pathogenic features. In this review, which was initiated at the 13th International Society for Neurochemistry Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental disorders (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer and Parkinson disease). We finally discuss the appropriateness and potential implications of gathering synapse diseases under a single term. Understanding common causes and intrinsic differences in disease-associated synaptic dysfunction could offer novel clues toward synapse-based therapeutic intervention for neurological and neuropsychiatric disorders. In this Review, which was initiated at the 13th International Society for Neurochemistry (ISN) Advanced School, we discuss basic concepts of synapse structure and function, and provide a critical view of how aberrant synapse physiology may contribute to neurodevelopmental (autism, Down syndrome, startle disease, and epilepsy) as well as neurodegenerative disorders (Alzheimer's and Parkinson's diseases), gathered together under the term of synaptopathies. Read the Editorial Highlight for this article on page .}, language = {en} } @article{SabelFleischhackTippeltetal.2016, author = {Sabel, Magnus and Fleischhack, Gudrun and Tippelt, Stephan and Gustafsson, G{\"o}ran and Doz, Fran{\c{c}}ois and Kortmann, Rolf and Massimino, Maura and Navajas, Aurora and von Hoff, Katja and Rutkowski, Stefan and Warmuth-Metz, Monika and Clifford, Steven C. and Pietsch, Torsten and Pizer, Barry and Linnering, Birgitta}, title = {Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study}, series = {Journal of Neurooncology}, volume = {129}, journal = {Journal of Neurooncology}, number = {3}, organization = {SIOP-E Brain Tumour Group}, doi = {10.1007/s11060-016-2202-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187498}, pages = {515-524}, year = {2016}, abstract = {The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 +/- 2 \% and 78 +/- 2 \% respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 \%) were isolated local relapses in the posterior fossa (PF) and 59 (82 \%) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. > 5 years from diagnosis, occurred in six patients (8 \%). Relapse treatment consisted of combinations of surgery (25 \%), focal radiotherapy (RT 22 \%), high dose chemotherapy with stem cell rescue (HDSCR 21 \%) and conventional chemotherapy (90 \%). OS at 5 years after relapse was 6.0 +/- 4 \%. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour.}, language = {en} } @article{KupperStigloherFeldhaaretal.2016, author = {Kupper, Maria and Stigloher, Christian and Feldhaar, Heike and Gross, Roy}, title = {Distribution of the obligate endosymbiont Blochmannia floridanus and expression analysis of putative immune genes in ovaries of the carpenter ant Camponotus floridanus}, series = {Arthropod Structure \& Development}, volume = {45}, journal = {Arthropod Structure \& Development}, number = {5}, doi = {10.1016/j.asd.2016.09.004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187482}, pages = {475-487}, year = {2016}, abstract = {The bacterial endosymbiont Blochmannia floridanus of the carpenter ant Camponotus floridanus contributes to its hosts' ontogeny via nutritional upgrading during metamorphosis. This primary endosymbiosis is essential for both partners and vertical transmission of the endosymbionts is guaranteed by bacterial infestation of oocytes. Here we present a detailed analysis of the presence and localisation of B. floridanus in the ants' ovaries obtained by FISH and TEM analyses. The most apical part of the germarium harbouring germ-line stem cells (GSCs) is not infected by the bacteria. The bacteria are detectable for the first time in lower parts of the germarium when cystocytes undergo the 4th and 5th division and B. floridanus infects somatic cells lying under the basal lamina surrounding the ovarioles. With the beginning of cystocyte differentiation, the endosymbionts are exclusively transported from follicle cells into the growing oocytes. This infestation of the oocytes by bacteria very likely involves exocytosis endocytosis processes between follicle cells and the oocytes. Nurse cells were never found to harbour the endosymbionts. Furthermore we present first gene expression data in C floridanus ovaries. These data indicate a modulation of immune gene expression which may facilitate tolerance towards the endosymbionts and thus may contribute to their transovarial transmission.}, language = {en} } @article{ChagtaiZillDaineseetal.2016, author = {Chagtai, Tasnim and Zill, Christina and Dainese, Linda and Wegert, Jenny and Savola, Suvi and Popov, Sergey and Mifsud, William and Vujanic, Gordan and Sebire, Neil and Le Bouc, Yves and Ambros, Peter F. and Kager, Leo and O`Sullivan, Maureen J. and Blaise, Annick and Bergeron, Christophe and Holmquist Mengelbier, Linda and Gisselsson, David and Kool, Marcel and Tytgat, Godelieve A.M. and van den Heuvel-Eibrink, Marry M. and Graf, Norbert and van Tinteren, Harm and Coulomb, Aurore and Gessler, Manfred and Williams, Richard Dafydd and Pritchard-Jones, Kathy}, title = {Gain of 1q As a Prognostic Biomarker in Wilms Tumors (WTs) Treated With Preoperative Chemotherapy in the International Society of Paediatric Oncology (SIOP) WT 2001 Trial: a SIOP Renal Tumours Biology Consortium Study}, series = {Journal of Clinical Oncology}, volume = {34}, journal = {Journal of Clinical Oncology}, number = {26}, doi = {10.1200/JCO.2015.66.0001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187478}, pages = {3195-3205}, year = {2016}, abstract = {Purpose Wilms tumor (WT) is the most common pediatric renal tumor. Treatment planning under International Society of Paediatric Oncology (SIOP) protocols is based on staging and histologic assessment of response to preoperative chemotherapy. Despite high overall survival (OS), many relapses occur in patients without specific risk factors, and many successfully treated patients are exposed to treatments with significant risks of late effects. To investigate whether molecular biomarkers could improve risk stratification, we assessed 1q status and other potential copy number biomarkers in a large WT series. Materials and Methods WT nephrectomy samples from 586 SIOP WT 2001 patients were analyzed using a multiplex ligation-dependent probe amplification (MLPA) assay that measured the copy number of 1q and other regions of interest. Results One hundred sixty-seven (28\%) of 586 WTs had 1q gain. Five-year event-free survival (EFS) was 75.0\% in patients with 1q gain (95\% CI, 68.5\% to 82.0\%) and 88.2\% in patients without gain (95\% CI, 85.0\% to 91.4\%). OS was 88.4\% with gain (95\% CI, 83.5\% to 93.6\%) and 94.4\% without gain (95\% CI, 92.1\% to 96.7\%). In univariable analysis, 1q gain was associated with poorer EFS (P<.001; hazard ratio, 2.33) and OS (P=.01; hazard ratio, 2.16). The association of 1q gain with poorer EFS retained significance in multivariable analysis adjusted for 1p and 16q loss, sex, stage, age, and histologic risk group. Gain of 1q remained associated with poorer EFS in tumor subsets limited to either intermediate-risk localized disease or nonanaplastic localized disease. Other notable aberrations associated with poorer EFS included MYCN gain and TP53 loss. Conclusion Gain of 1q is a potentially valuable prognostic biomarker in WT, in addition to histologic response to preoperative chemotherapy and tumor stage.}, language = {en} } @article{DreinerKraussO'Learyetal.2016, author = {Dreiner, Herbi K. and Krauss, Manuel E. and O'Leary, Ben and Opferkuch, Toby and Staub, Florian}, title = {Validity of the CMSSM interpretation of the diphoton excess}, series = {Physical Review D}, volume = {94}, journal = {Physical Review D}, number = {5}, doi = {10.1103/PhysRevD.94.055013}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187429}, pages = {055013}, year = {2016}, abstract = {It has been proposed that the observed diphoton excess at 750 GeV could be explained within the constrained minimal supersymmetric standard model via resonantly produced stop bound states. We reanalyze this scenario critically and extend previous work to include the constraints from the stability of the electroweak vacuum and from the decays of the stoponium into a pair of Higgs bosons. It is shown that the interesting regions of parameter space with a light stop and Higgs of the desired mass are ruled out by these constraints. This conclusion is not affected by the presence of the bound states because the binding energy is usually very small in the regions of parameter space which can explain the Higgs mass. Thus, this also leads to strong constraints on the diphoton production cross section which is in general too small.}, language = {en} } @article{BurnsGoldsteinNewgreenetal.2016, author = {Burns, Alan J. and Goldstein, Allan M. and Newgreen, Donald F. and Stamp, Lincon and Sch{\"a}fer, Karl-Herbert and Metzger, Marco and Hotta, Ryo and Young, Heather M. and Andrews, Peter W. and Thapar, Nikhil and Belkind-Gerson, Jaime and Bondurand, Nadege and Bornstein, Joel C. and Chan, Wood Yee and Cheah, Kathryn and Gershon, Michael D. and Heuckeroth, Robert O. and Hofstra, Robert M.W. and Just, Lothar and Kapur, Raj P. and King, Sebastian K. and McCann, Conor J. and Nagy, Nandor and Ngan, Elly and Obermayr, Florian and Pachnis, Vassilis and Pasricha, Pankaj J. and Sham, Mai Har and Tam, Paul and Vanden Berghe, Pieter}, title = {White paper on guidelines concerning enteric nervous system stem cell therapy for enteric neuropathies}, series = {Developmental Biology}, volume = {417}, journal = {Developmental Biology}, number = {2}, doi = {10.1016/j.ydbio.2016.04.001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187415}, pages = {229-251}, year = {2016}, abstract = {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.}, language = {en} } @article{SzczerbaZukrowskiPrzybylskietal.2016, author = {Szczerba, Wojciech and Zukrowski, Jan and Przybylski, Marek and Sikora, Marcin and Safonova, Olga and Shmeliov, Aleksey and Nicolosi, Valeria and Schneider, Michael and Granath, Tim and Oppmann, Maximilian and Straßer, Marion and Mandel, Karl}, title = {Pushing up the magnetisation values for iron oxide nanoparticles via zinc doping: X-ray studies on the particle's sub-nano structure of different synthesis routes}, series = {Physical Chemistry Chemical Physics}, volume = {18}, journal = {Physical Chemistry Chemical Physics}, number = {36}, doi = {10.1039/c6cp04221j}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187390}, pages = {25221-25229}, year = {2016}, abstract = {The maximum magnetisation (saturation magnetisation) obtainable for iron oxide nanoparticles can be increased by doping the nanocrystals with non-magnetic elements such as zinc. Herein, we closely study how only slightly different synthesis approaches towards such doped nanoparticles strongly influence the resulting sub-nano/atomic structure. We compare two co-precipitation approaches, where we only vary the base (NaOH versus NH\(_3\)), and a thermal decomposition route. These methods are the most commonly applied ones for synthesising doped iron oxide nanoparticles. The measurable magnetisation change upon zinc doping is about the same for all systems. However, the sub-nano structure, which we studied with Mossbauer and X-ray absorption near edge spectroscopy, differs tremendously. We found evidence that a much more complex picture has to be drawn regarding what happens upon Zn doping compared to what textbooks tell us about the mechanism. Our work demonstrates that it is crucial to study the obtained structures very precisely when "playing'' with the atomic order in iron oxide nanocrystals.}, language = {en} } @article{PloetzPolyutovIvanovetal.2016, author = {Pl{\"o}tz, P.-A. and Polyutov, S. P. and Ivanov, S. D. and Fennel, F. and Wolter, S. and Niehaus, T. and Xie, Z. and Lochbrunner, S. and W{\"u}rthner, Frank and K{\"u}hn, O.}, title = {Biphasic aggregation of a perylene bisimide dye identified by exciton-vibrational spectra}, series = {Physical Chemistry Chemical Physics}, volume = {18}, journal = {Physical Chemistry Chemical Physics}, number = {36}, doi = {10.1039/c6cp04898f}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187387}, pages = {25110-25119}, year = {2016}, abstract = {The quantum efficiency of light emission is a crucial parameter of supramolecular aggregates that can be tuned by the molecular design of the monomeric species. Here, we report on a strong variation of the fluorescence quantum yield due to different phases of aggregation for the case of a perylene bisimide dye. In particular, a change of the dominant aggregation character from H- to J-type within the first aggregation steps is found, explaining the observed dramatic change in quantum yield. This behaviour is rationalised by means of a systematic study of the intermolecular potential energy surfaces using the time-dependent density functional based tight-binding (TD-DFTB) method. This provides a correlation between structural changes and a coupling strength and supports the notion of H- type stacked dimers and J-type stack-slipped dimers. The exciton-vibrational level structure is modelled by means of an excitonic dimer model including two effective vibrational modes per monomer. Calculated absorption and fluorescence spectra are found to be in reasonable agreement with experimental ones, thus supporting the conclusion on the aggregation behaviour.}, language = {en} } @article{WieserReichertsJuravleetal.2016, author = {Wieser, Matthias J. and Reicherts, Philipp and Juravle, Georgiana and von Leupoldt, Andreas}, title = {Attention mechanisms during predictable and unpredictable threat - a steady-state visual evoked potential approach}, series = {NeuroImage}, volume = {139}, journal = {NeuroImage}, doi = {10.1016/j.neuroimage.2016.06.026}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187365}, pages = {167-175}, year = {2016}, abstract = {Fear is elicited by imminent threat and leads to phasic fear responses with selective attention, whereas anxiety is characterized by a sustained state of heightened vigilance due to uncertain danger. In the present study, we investigated attention mechanisms in fear and anxiety by adapting the NPU-threat test to measure steady-state visual evoked potentials (ssVEPs). We investigated ssVEPs across no aversive events (N), predictable aversive events (P), and unpredictable aversive events (U), signaled by four-object arrays (30 s). In addition, central cues were presented during all conditions but predictably signaled imminent threat only during the P condition. Importantly, cues and context events were flickered at different frequencies (15 Hz vs. 20 Hz) in order to disentangle respective electrocortical responses. The onset of the context elicited larger electrocortical responses for U compared to P context. Conversely, P cues elicited larger electrocortical responses compared to N cues. Interestingly, during the presence of the P cue, visuocortical processing of the concurrent context was also enhanced. The results support the notion of enhanced initial hypervigilance to unpredictable compared to predictable threat contexts, while predictable cues show electrocortical enhancement of the cues themselves but additionally a boost of context processing.}, language = {en} } @article{HolzschuhDaineseGonzalezVaroetal.2016, author = {Holzschuh, Andrea and Dainese, Matteo and Gonzalez-Varo, Juan P. and Mudri-Stojnic, Sonja and Riedinger, Verena and Rundl{\"o}f, Maj and Scheper, Jeroen and Wickens, Jennifer B. and Wickens, Victoria J. and Bommarco, Riccardo and Kleijn, David and Potts, Simon G. and Roberts, Stuart P. M. and Smith, Henrik G. and Vil{\`a}, Montserrat and Vujic, Ante and Steffan-Dewenter, Ingolf}, title = {Mass-flowering crops dilute pollinator abundance in agricultural landscapes across Europe}, series = {Ecology Letters}, volume = {19}, journal = {Ecology Letters}, number = {10}, doi = {10.1111/ele.12657}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187356}, pages = {1228-1236}, year = {2016}, abstract = {Mass-flowering crops (MFCs) are increasingly cultivated and might influence pollinator communities in MFC fields and nearby semi-natural habitats (SNHs). Across six European regions and 2 years, we assessed how landscape-scale cover of MFCs affected pollinator densities in 408 MFC fields and adjacent SNHs. In MFC fields, densities of bumblebees, solitary bees, managed honeybees and hoverflies were negatively related to the cover of MFCs in the landscape. In SNHs, densities of bumblebees declined with increasing cover of MFCs but densities of honeybees increased. The densities of all pollinators were generally unrelated to the cover of SNHs in the landscape. Although MFC fields apparently attracted pollinators from SNHs, in landscapes with large areas of MFCs they became diluted. The resulting lower densities might negatively affect yields of pollinator- dependent crops and the reproductive success of wild plants. An expansion of MFCs needs to be accompanied by pollinator-supporting practices in agricultural landscapes.}, language = {en} } @article{SchmittFunkBlumetal.2016, author = {Schmitt, Dominique and Funk, Natalia and Blum, Robert and Asan, Esther and Andersen, Lill and R{\"u}licke, Thomas and Sendtner, Michael and Buchner, Erich}, title = {Initial characterization of a Syap1 knock-out mouse and distribution of Syap1 in mouse brain and cultured motoneurons}, series = {Histochemistry and Cell Biology}, volume = {146}, journal = {Histochemistry and Cell Biology}, number = {4}, doi = {10.1007/s00418-016-1457-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-187258}, pages = {489-512}, year = {2016}, abstract = {Synapse-associated protein 1 (Syap1/BSTA) is the mammalian homologue of Sap47 (synapse-associated protein of 47 kDa) in Drosophila. Sap47 null mutant larvae show reduced short-term synaptic plasticity and a defect in associative behavioral plasticity. In cultured adipocytes, Syap1 functions as part of a complex that phosphorylates protein kinase B alpha/Akt1 (Akt1) at Ser\(^{473}\) and promotes differentiation. The role of Syap1 in the vertebrate nervous system is unknown. Here, we generated a Syap1 knock-out mouse and show that lack of Syap1 is compatible with viability and fertility. Adult knock-out mice show no overt defects in brain morphology. In wild-type brain, Syap1 is found widely distributed in synaptic neuropil, notably in regions rich in glutamatergic synapses, but also in perinuclear structures associated with the Golgi apparatus of specific groups of neuronal cell bodies. In cultured motoneurons, Syap1 is located in axons and growth cones and is enriched in a perinuclear region partially overlapping with Golgi markers. We studied in detail the influence of Syap1 knockdown and knockout on structure and development of these cells. Importantly, Syap1 knockout does not affect motoneuron survival or axon growth. Unexpectedly, neither knockdown nor knockout of Syap1 in cultured motoneurons is associated with reduced Ser\(^{473}\) or Thr\(^{308}\) phosphorylation of Akt. Our findings demonstrate a widespread expression of Syap1 in the mouse central nervous system with regionally specific distribution patterns as illustrated in particular for olfactory bulb, hippocampus, and cerebellum.}, language = {en} }