@article{Schoech2016, author = {Sch{\"o}ch, Christof}, title = {Ein digitales Textformat f{\"u}r die Literaturwissenschaften. Die Richtlinien der Text Encoding Initiative und ihr Nutzen f{\"u}r Textedition und Textanalyse}, series = {Romanische Studien}, volume = {4}, journal = {Romanische Studien}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171351}, pages = {325-364}, year = {2016}, abstract = {Die stetig voranschreitende Digitalisierung literarischer Texte verschiedenster Sprachen, Epochen und Gattungen stellt die Literaturwissenschaften immer wieder vor die Frage, wie sie diese Entwicklung mitgestalten und zu ihrem Vorteil nutzen k{\"o}nnen. Dabei ist digital nicht gleich digital, sondern es existiert eine Vielzahl sehr unterschiedlicher, digitaler Repr{\"a}sentationsformen von Text. Nur wenige dieser Repr{\"a}sentationsformen werden literaturwissenschaftlichen Anforderungen tats{\"a}chlich gerecht, darunter diejenige, die den Richtlinien der Text Encoding Initiative folgt. Der vorliegende Beitrag vergleicht zun{\"a}chst einige derzeit g{\"a}ngige digitale Repr{\"a}sentationsformen von Text. F{\"u}r literaturwissenschaftliche Forschung besonders geeignet erweist sich hierbei eine Repr{\"a}sentationsform, die den Richtlinien der Text Encoding Initiative folgt. Daher informiert der Beitrag anschließend {\"u}ber deren Nutzen f{\"u}r die literaturwissenschaftliche Arbeit, sowohl im Bereich der wissenschaftlichen Textedition als auch im Bereich der Analyse und Interpretation von Texten. Nur wenn die Literaturwissenschaften in ihrer Breite den Nutzen von offenen, expressiven, flexiblen und standardisierten, langfristig nutzbaren Formaten f{\"u}r die Forschung erkennen, k{\"o}nnen sie sich mit dem erforderlichen Nachdruck f{\"u}r deren Verbreitung einsetzen und durch die zunehmende Verf{\"u}gbarkeit von Texten in solchen Formaten f{\"u}r die eigene Forschung und Lehre davon profitieren.}, language = {de} } @article{KestlerLuccaKrause2016, author = {Kestler, Thomas and Lucca, Juan Bautista and Krause, Silvana}, title = {'Break-In Parties' and Changing Patterns of Democracy in Latin America}, series = {Brazilian Political Science Review}, volume = {10}, journal = {Brazilian Political Science Review}, number = {1}, doi = {10.1590/1981-38212016000100004}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171333}, pages = {e0004}, year = {2016}, abstract = {Although Lijphart's typology of consensus and majoritarian democracy can be regarded as the most widely used tool to classify democratic regimes, it has been rarely applied to Latin America so far. We try to fill this gap by adapting Lijphart's typological framework to the Latin American context in the following way. In contrast to previous studies, we treat the type of democracy as an independent variable and include informal factors such as clientelism or informal employment in our assessment of democratic patterns. On this basis, we aim to answer the following questions. First, how did the patterns of democracy evolve in Latin America over the two decades between 1990 and 2010 and what kind of differences can be observed in the region? Second, what are the institutional determinants of the observed changes? We focus on the emergence of new parties because of their strong impact on the first dimension of Lijphart's typology. From our observations we draw the following tentative conclusions: If strong new parties established themselves in the party system but failed to gain the presidency, they pushed the system towards consensualism. Conversely, new parties that gained the presidency produced more majoritarian traits.}, language = {en} } @article{JoensuuAltimirHakolaetal.2016, author = {Joensuu, Johanna and Altimir, Nuria and Hakola, Hannele and Rost{\´a}s, Michael and Raivonen, Maarit and Vestenius, Mika and Aaltonen, Hermanni and Riederer, Markus and B{\"a}ck, Jaana}, title = {Role of needle surface waxes in dynamic exchange of mono- and sesquiterpenes}, series = {Atmospheric Chemistry and Physics}, volume = {16}, journal = {Atmospheric Chemistry and Physics}, number = {12}, doi = {10.5194/acp-2015-1024}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171324}, pages = {7813-7823}, year = {2016}, abstract = {Biogenic volatile organic compounds (BVOCs) produced by plants have a major role in atmospheric chemistry. The different physicochemical properties of BVOCs affect their transport within and out of the plant as well as their reactions along the way. Some of these compounds may accumulate in or on the waxy surface layer of conifer needles and participate in chemical reactions on or near the foliage surface. The aim of this work was to determine whether terpenes, a key category of BVOCs produced by trees, can be found on the epicuticles of Scots pine (Pinus sylvestris L.) and, if so, how they compare with the terpenes found in shoot emissions of the same tree. We measured shoot-level emissions of pine seedlings at a remote outdoor location in central Finland and subsequently analysed the needle surface waxes for the same compounds. Both emissions and wax extracts were clearly dominated by monoterpenes, but the proportion of sesquiterpenes was higher in the wax extracts. There were also differences in the terpene spectra of the emissions and the wax extracts. The results, therefore, support the existence of BVOC associated to the epicuticular waxes. We briefly discuss the different pathways for terpenes to reach the needle surfaces and the implications for air chemistry.}, language = {en} } @article{SchroederMeyerterVehnFassnachtRiederleetal.2016, author = {Schroeder, Katharina and Meyer-ter-Vehn, Tobias and Fassnacht-Riederle, Heidi and Guthoff, Rainer}, title = {Course of disease in multifocal choroiditis lacking sufficient immunosuppression: a case report}, series = {Journal of Medical Case Reports}, volume = {10}, journal = {Journal of Medical Case Reports}, number = {298}, doi = {10.1186/s13256-016-1069-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171317}, year = {2016}, abstract = {Background: Multifocal choroiditis with panuveitis is a rare disease. The educational merit of this case presentation results from the good documentation and the impressive ocular fundus pictures. Case presentation: We illustrate the 3-year course of disease in a 22-year-old myopic white woman with multifocal choroiditis with panuveitis and secondary choroidal neovascularization. The activity of the disease was evaluated clinically by optical coherence tomography and fluorescein angiography. Choroidal neovascularization was treated by intravitreal bevacizumab (2.5 mg/0.1 ml). Our patient lacked systemic therapy for the first 11 months because of noncompliance. Conclusions: The case is remarkable as the delayed onset of peripheral lesions and the additional existence of high myopia made diagnosis difficult. In addition, it demonstrates that full outbreak of disease with multiple central and peripheral fundus lesions and secondary choroidal neovascularization can develop without systemic treatment.}, language = {en} } @article{DietrichSteudeTropfetal.2016, author = {Dietrich, Christof P. and Steude, Anja and Tropf, Laura and Schubert, Marcel and Kronenberg, Nils M. and Ostermann, Kai and H{\"o}fling, Sven and Gather, Malte C.}, title = {An exciton-polariton laser based on biologically produced fluorescent protein}, series = {Science Advances}, volume = {2}, journal = {Science Advances}, number = {8}, doi = {10.1126/sciadv.1600666}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171305}, pages = {e1600666}, year = {2016}, abstract = {Under adequate conditions, cavity polaritons form a macroscopic coherent quantum state, known as polariton condensate. Compared to Wannier-Mott excitons in inorganic semiconductors, the localized Frenkel excitons in organic emitter materials show weaker interaction with each other but stronger coupling to light, which recently enabled the first realization of a polariton condensate at room temperature. However, this required ultrafast optical pumping, which limits the applications of organic polariton condensates. We demonstrate room temperature polariton condensates of cavity polaritons in simple laminated microcavities filled with biologically produced enhanced green fluorescent protein (eGFP). The unique molecular structure of eGFP prevents exciton annihilation even at high excitation densities, thus facilitating polariton condensation under conventional nanosecond pumping. Condensation is clearly evidenced by a distinct threshold, an interaction-induced blueshift of the condensate, long-range coherence, and the presence of a second threshold at higher excitation density that is associated with the onset of photon lasing.}, language = {en} } @article{SperlichAchtzehndeMareesetal.2016, author = {Sperlich, Billy and Achtzehn, Silvia and de Mar{\´e}es, Markus and von Papen, Henning and Mester, Joachim}, title = {Load management in elite German distance runners during 3-weeks of high-altitude training}, series = {Physiological Reports}, volume = {4}, journal = {Physiological Reports}, number = {12}, doi = {10.14814/phy2.12845}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171294}, pages = {e12845}, year = {2016}, abstract = {There is a debate on the optimal way of monitoring training loads in elite endurance athletes especially during altitude training camps. In this case report, including nine members of the German national middle distance running team, we describe a practical approach to monitor the psychobiological stress markers during 21 days of altitude training (~2100 m above sea-level) to estimate the training load and to control muscle damage, fatigue, and/or chronic overreaching. Daily examination included: oxygen saturation of hemoglobin, resting heart rate, body mass, body and sleep perception, capillary blood concentration of creatine kinase. Every other day, venous serum concentration of blood urea nitrogen, venous blood concentration of hemoglobin, hematocrit, red and white blood cell were measured. If two or more of the above-mentioned stress markers were beyond or beneath the athlete's normal individual range, the training load of the subsequent training session was reduced. Running speed at 3 mmol L\(^{-1}\) blood lactate (V\(_{3}\)) improved and no athlete showed any signs of underperformance, chronic muscle damage, decrease body and sleep perception as well as activated inflammatory process during the 21 days. The dense screening of biomarkers in the present case study may stimulate further research to identify candidate markers for load monitoring in elite middle- and long-distance runners during a training camp at altitude.}, language = {en} } @article{StolzeTrautmannGoebeleretal.2016, author = {Stolze, Ina and Trautmann, Axel and Goebeler, Matthias and Stoevesandt, Johanna}, title = {Dangerous Leg Cramps: Severe Pustular Exanthema Caused by an Over-the-Counter Drug}, series = {Acta Dermato-Venereologica}, volume = {96}, journal = {Acta Dermato-Venereologica}, doi = {10.2340/00015555-2324}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-171285}, pages = {703-704}, year = {2016}, abstract = {Abstract is missing}, language = {en} } @article{MeulePlatte2016, author = {Meule, Adrian and Platte, Petra}, title = {Attentional bias toward high-calorie food-cues and trait motor impulsivity interactively predict weight gain}, series = {Health Psychology Open}, journal = {Health Psychology Open}, doi = {10.1177/2055102916649585}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168504}, year = {2016}, abstract = {Strong bottom-up impulses and weak top-down control may interactively lead to overeating and, consequently, weight gain. In the present study, female university freshmen were tested at the start of the first semester and again at the start of the second semester. Attentional bias toward high- or low-calorie food-cues was assessed using a dot-probe paradigm and participants completed the Barratt Impulsiveness Scale. Attentional bias and motor impulsivity interactively predicted change in body mass index: motor impulsivity positively predicted weight gain only when participants showed an attentional bias toward high-calorie food-cues. Attentional and non-planning impulsivity were unrelated to weight change. Results support findings showing that weight gain is prospectively predicted by a combination of weak top-down control (i.e. high impulsivity) and strong bottom-up impulses (i.e. high automatic motivational drive toward high-calorie food stimuli). They also highlight the fact that only specific aspects of impulsivity are relevant in eating and weight regulation.}, language = {en} } @article{DeebGiordanoRossietal.2016, author = {Deeb, Wissam and Giordano, James J. and Rossi, Peter J. and Mogilner, Alon Y. and Gunduz, Aysegul and Judy, Jack W. and Klassen, Bryan T. and Butson, Christopher R. and Van Horne, Craig and Deny, Damiaan and Dougherty, Darin D. and Rowell, David and Gerhardt, Greg A. and Smith, Gwenn S. and Ponce, Francisco A. and Walker, Harrison C. and Bronte-Stewart, Helen M. and Mayberg, Helen S. and Chizeck, Howard J. and Langevin, Jean-Philippe and Volkmann, Jens and Ostrem, Jill L. and Shute, Jonathan B. and Jimenez-Shahed, Joohi and Foote, Kelly D. and Wagle Shukla, Aparna and Rossi, Marvin A. and Oh, Michael and Pourfar, Michael and Rosenberg, Paul B. and Silburn, Peter A. and de Hemptine, Coralie and Starr, Philip A. and Denison, Timothy and Akbar, Umer and Grill, Warren M. and Okun, Michael S.}, title = {Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies}, series = {Frontiers in Integrative Neuroscience}, volume = {10}, journal = {Frontiers in Integrative Neuroscience}, number = {38}, doi = {10.3389/fnint.2016.00038}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168493}, year = {2016}, abstract = {This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field.}, language = {en} } @article{HommersGoers2016, author = {Hommers, Wilfried and G{\"o}rs, Marijke}, title = {Information integration of Kohlbergian thoughts about consensual sex}, series = {Universitas Psychologica}, volume = {15}, journal = {Universitas Psychologica}, number = {3}, doi = {10.11144/Javeriana.upsy15-3.iikt}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168487}, year = {2016}, abstract = {The unification of two major approaches to moral judgment is the purpose of the present approach. Kohlberg's well-known stage theory assumes a sequence of discrete stages that underlie all moral judgment. Stage theory recognizes the problem of integrating considerations but gives no way to solve such integration, even with information from any one stage. And, of course, the stage concept denies any significant integration from different stages. Thus, research on moral judgment needs to study the integration problem which can be tested within Anderson's theory of information integration. The main purpose of the present study was to extend this unificationist approach to the issue of sexual morality. A novel task presents information from two very different stages. The results showed that in contrast to discreteness the stage informers were positively correlated in punishment judgments of both genders about consensual sex of juveniles. Furthermore, the subjects integrated considerations from those very different stages also in contrast to the hypothesis that only a single stage was operative at any time.}, language = {en} } @article{BergesKerkauWerneretal.2016, author = {Berges, Carsten and Kerkau, Thomas and Werner, Sandra and Wolf, Nelli and Winter, Nadine and H{\"u}nig, Thomas and Einsele, Hermann and Topp, Max S. and Beyersdorf, Niklas}, title = {Hsp90 inhibition ameliorates CD4\(^{+}\) T cell-mediated acute Graft versus Host disease in mice}, series = {Immunity, Inflammation and Disease}, volume = {4}, journal = {Immunity, Inflammation and Disease}, number = {4}, doi = {10.1002/iid3.127}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168318}, pages = {463-473}, year = {2016}, abstract = {Introduction: For many patients with leukemia only allogeneic bone marrow transplantion provides a chance of cure. Co-transplanted mature donor T cells mediate the desired Graft versus Tumor (GvT) effect required to destroy residual leukemic cells. The donor T cells very often, however, also attack healthy tissue of the patient inducing acute Graft versus Host Disease (aGvHD)—a potentially life-threatening complication. Methods: Therefore, we used the well established C57BL/6 into BALB/c mouse aGvHD model to evaluate whether pharmacological inhibition of heat shock protein 90 (Hsp90) would protect the mice from aGvHD. Results: Treatment of the BALB/c recipient mice from day 0 to +2 after allogeneic CD4\(^{+}\) T cell transplantation with the Hsp90 inhibitor 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (DMAG) partially protected the mice from aGvHD. DMAG treatment was, however, insufficient to prolong overall survival of leukemia-bearing mice after transplantation of allogeneic CD4\(^{+}\) and CD8\(^{+}\) T cells. Ex vivo analyses and in vitro experiments revealed that DMAG primarily inhibits conventional CD4\(^{+}\) T cells with a relative resistance of CD4\(^{+}\) regulatory and CD8\(^{+}\) T cells toward Hsp90 inhibition. Conclusions: Our data, thus, suggest that Hsp90 inhibition might constitute a novel approach to reduce aGvHD in patients without abrogating the desired GvT effect.}, language = {en} } @article{KappKosmalaKircheretal.2016, author = {Kapp, Markus and Kosmala, Aleksander and Kircher, Stefan and Luber, Verena and Kunzmann, Volker}, title = {Exceptional Response to Nanoparticle Albumin-Bound Paclitaxel and Gemcitabine in a Patient with a Refractory Adenocarcinoma of the Ampulla of Vater}, series = {Case Reports in Oncology}, volume = {9}, journal = {Case Reports in Oncology}, number = {1}, doi = {10.1159/000443304}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168358}, pages = {15-24}, year = {2016}, abstract = {Ampullary carcinoma is a rare tumor and evidence on the treatment of recurrent metastatic disease is scarce. We report the case of a 60-year-old patient with an R0-resected node-positive adenocarcinoma of the papilla of Vater of an initially diagnosed intestinal subtype who developed pulmonary metastases 2 months after adjuvant gemcitabine chemotherapy and, subsequently, liver metastases. Palliative combination chemotherapy with standard regimens for intestinal-type adenocarcinoma (FOLFOX and FOLFIRI) failed. However, subsequent combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine, a regimen with proven efficacy in metastatic adenocarcinoma of the pancreas, resulted in a durable, very good partial remission. Treatment was manageable and well tolerated. Primary tumor and metastatic tissue were reassessed by immunohistochemistry and had to be reclassified to a mixed phenotype containing predominant elements of the pancreatobiliary subtype. Our case suggests that combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine could represent a promising option for the treatment of this rare disease and warrants further investigation within controlled clinical trials. Moreover, thorough characterization of ampullary carcinomas by histomorphology and additional immunohistochemistry should become mandatory in order to start a chemotherapeutic regimen tailored for the definitive subtype.}, language = {en} } @article{DeelemanReinholdMillerFloren2016, author = {Deeleman-Reinhold, Christa L. and Miller, Jeremy and Floren, Andreas}, title = {Depreissia decipiens, an enigmatic canopy spider from Borneo revisited (Araneae, Salticidae), with remarks on the distribution and diversity of canopy spiders in Sabah, Borneo}, series = {ZooKeys}, volume = {556}, journal = {ZooKeys}, doi = {10.3897/zookeys.556.6174}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168342}, pages = {1-17}, year = {2016}, abstract = {Depreissia is a little known genus comprising two hymenopteran-mimicking species, one found in Central Africa and one in the north of Borneo. The male of D. decipiens is redescribed, the female is described for the first time. The carapace is elongated, dorsally flattened and rhombus-shaped, the rear of the thorax laterally depressed and transformed, with a pair of deep pits; the pedicel is almost as long as the abdomen. The male palp is unusual, characterized by the transverse deeply split membranous tegulum separating a ventral part which bears a sclerotized tegular apophysis and a large dagger-like retrodirected median apophysis. The female epigyne consists of one pair of large adjacent spermathecae and very long copulatory ducts arising posteriorly and rising laterally alongside the spermathecae continuing in several vertical and horizontal coils over the anterior surface. Relationships within the Salticidae are discussed and an affinity with the Cocalodinae is suggested. Arguments are provided for a hypothesis that D. decipiens is not ant-mimicking as was previously believed, but is a mimic of polistinine wasps. The species was found in the canopy in the Kinabalu area only, in primary and old secondary rainforest at 200-700 m.a.s.l. Overlap of canopy-dwelling spider species with those in the understorey are discussed and examples of species richness and endemism in the canopy are highlighted. Canopy fogging is a very efficient method of collecting for most arthropods. The canopy fauna adds an extra dimension to the known biodiversity of the tropical rainforest. In southeast Asia, canopy research has been neglected, inhibiting evaluation of comparative results of this canopy project with that from other regions. More use of fogging as a collecting method would greatly improve insight into the actual species richness and species distribution in general.}, language = {en} } @article{SchlinkertLudwigBataryetal.2016, author = {Schlinkert, Hella and Ludwig, Martin and Bat{\´a}ry, P{\´e}ter and Holzschuh, Andrea and Kov{\´a}cs-Hosty{\´a}nszki, Anik{\´o} and Tscharntke, Teja and Fischer, Christina}, title = {Forest specialist and generalist small mammals in forest edges and hedges}, series = {Wildlife Biology}, volume = {22}, journal = {Wildlife Biology}, number = {3}, doi = {10.2981/wlb.00176}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168333}, pages = {86-94}, year = {2016}, abstract = {Agricultural intensification often leads to fragmentation of natural habitats, such as forests, and thereby negatively affects forest specialist species. However, human introduced habitats, such as hedges, may counteract negative effects of forest fragmentation and increase dispersal, particularly of forest specialists. We studied effects of habitat type (forest edge versus hedge) and hedge isolation from forests (connected versus isolated hedge) in agricultural landscapes on abundance, species richness and community composition of mice, voles and shrews in forest edges and hedges. Simultaneously to these effects of forest edge/hedge type we analysed impacts of habitat structure, namely percentage of bare ground and forest edge/hedge width, on abundance, species richness and community composition of small mammals. Total abundance and forest specialist abundance (both driven by the most abundant species Myodes glareolus, bank vole) were higher in forest edges than in hedges, while hedge isolation had no effect. In contrast, abundance of habitat generalists was higher in isolated compared to connected hedges, with no effect of habitat type (forest edge versus hedge). Species richness as well as abundance of the most abundant habitat generalist Sorex araneus (common shrew), were not affected by habitat type or hedge isolation. Decreasing percentage of bare ground and increasing forest edge/hedge width was associated with increased abundance of forest specialists, while habitat structure was unrelated to species richness or abundance of any other group. Community composition was driven by forest specialists, which exceeded habitat generalist abundance in forest edges and connected hedges, while abundances were similar to each other in isolated hedges. Our results show that small mammal forest specialists prefer forest edges as habitats over hedges, while habitat generalists are able to use unoccupied ecological niches in isolated hedges. Consequently even isolated hedges can be marginal habitats for forest specialists and habitat generalists and thereby may increase regional farmland biodiversity.}, language = {en} } @article{BenAmiTongBhuiyanetal.2016, author = {Ben Ami, Tal and Tong, Yuehong and Bhuiyan, Alauddin and Huisingh, Carrie and Ablonczy, Zsolt and Ach, Thomas and Curcio, Christine A. and Smith, R. Theodore}, title = {Spatial and Spectral Characterization of Human Retinal Pigment Epithelium Fluorophore Families by Ex Vivo Hyperspectral Autofluorescence Imaging}, series = {Translational Vision Science \& Technology}, volume = {5}, journal = {Translational Vision Science \& Technology}, number = {3}, doi = {10.1167/tvst.5.3.5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168328}, pages = {5}, year = {2016}, abstract = {Purpose: Discovery of candidate spectra for abundant fluorophore families in human retinal pigment epithelium (RPE) by ex vivo hyperspectral imaging. Methods: Hyperspectral autofluorescence emission images were captured between 420 and 720 nm (10-nm intervals), at two excitation bands (436-460, 480-510 nm), from three locations (fovea, perifovea, near-periphery) in 20 normal RPE/Bruch's membrane (BrM) flatmounts. Mathematical factorization extracted a BrM spectrum (S0) and abundant lipofuscin/melanolipofuscin (LF/ML) spectra of RPE origin (S1, S2, S3) from each tissue. Results: Smooth spectra S1 to S3, with perinuclear localization consistent with LF/ML at all three retinal locations and both excitations in 14 eyes (84 datasets), were included in the analysis. The mean peak emissions of S0, S1, and S2 at λ\(_{ex}\) 436 nm were, respectively, 495 ± 14, 535 ± 17, and 576 ± 20 nm. S3 was generally trimodal, with peaks at either 580, 620, or 650 nm (peak mode, 650 nm). At λ\(_{ex}\) 480 nm, S0, S1, and S2 were red-shifted to 526 ± 9, 553 ± 10, and 588 ± 23 nm, and S3 was again trimodal (peak mode, 620 nm). S1 often split into two spectra, S1A and S1B. S3 strongly colocalized with melanin. There were no significant differences across age, sex, or retinal location. Conclusions: There appear to be at least three families of abundant RPE fluorophores that are ubiquitous across age, retinal location, and sex in this sample of healthy eyes. Further molecular characterization by imaging mass spectrometry and localization via super-resolution microscopy should elucidate normal and abnormal RPE physiology involving fluorophores. Translational Relevance: Our results help establish hyperspectral autofluorescence imaging of the human retinal pigment epithelium as a useful tool for investigating retinal health and disease.}, language = {en} } @article{LeiboldvandenHoveViechtbaueretal.2016, author = {Leibold, NK and van den Hove, DLA and Viechtbauer, W and Buchanan, GF and Goossens, L and Lange, I and Knuts, I and Lesch, KP and Steinbusch, HWM and Schruers, KRJ}, title = {CO\(_{2}\) exposure as translational cross-species experimental model for panic}, series = {Translational Psychiatry}, volume = {6}, journal = {Translational Psychiatry}, number = {e885}, doi = {10.1038/tp.2016.162}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168308}, year = {2016}, abstract = {The current diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders are being challenged by the heterogeneity and the symptom overlap of psychiatric disorders. Therefore, a framework toward a more etiology-based classification has been initiated by the US National Institute of Mental Health, the research domain criteria project. The basic neurobiology of human psychiatric disorders is often studied in rodent models. However, the differences in outcome measurements hamper the translation of knowledge. Here, we aimed to present a translational panic model by using the same stimulus and by quantitatively comparing the same outcome measurements in rodents, healthy human subjects and panic disorder patients within one large project. We measured the behavioral-emotional and bodily response to CO\(_{2}\) exposure in all three samples, allowing for a reliable cross-species comparison. We show that CO\(_{2}\) exposure causes a robust fear response in terms of behavior in mice and panic symptom ratings in healthy volunteers and panic disorder patients. To improve comparability, we next assessed the respiratory and cardiovascular response to CO\(_{2}\), demonstrating corresponding respiratory and cardiovascular effects across both species. This project bridges the gap between basic and human research to improve the translation of knowledge between these disciplines. This will allow significant progress in unraveling the etiological basis of panic disorder and will be highly beneficial for refining the diagnostic categories as well as treatment strategies.}, language = {en} } @article{ZayatsJacobsenKleppeetal.2016, author = {Zayats, T and Jacobsen, KK and Kleppe, R and Jacob, CP and Kittel-Schneider, S and Ribas{\´e}s, M and Ramos-Quiroga, JA and Richarte, V and Casas, M and Mota, NR and Grevet, EH and Klein, M and Corominas, J and Bralten, J and Galesloot, T and Vasquez, AA and Herms, S and Forstner, AJ and Larsson, H and Breen, G and Asherson, P and Gross-Lesch, S and Lesch, KP and Cichon, S and Gabrielsen, MB and Holmen, OL and Bau, CHD and Buitelaar, J and Kiemeney, L and Faraone, SV and Cormand, B and Franke, B and Reif, A and Haavik, J and Johansson, S}, title = {Exome chip analyses in adult attention deficit hyperactivity disorder}, series = {Translational Psychiatry}, volume = {6}, journal = {Translational Psychiatry}, number = {e923}, doi = {10.1038/tp.2016.196}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168297}, year = {2016}, abstract = {Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1\%); (2) single marker association tests of common variants (MAF⩾1\%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E-06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E-08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E-07); the PSD locus (P=7.58E-08) and ZCCHC4 locus (P=1.79E-06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E-05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.}, language = {en} } @article{KronhardtBeitzingerBarthetal.2016, author = {Kronhardt, Angelika and Beitzinger, Christoph and Barth, Holger and Benz, Roland}, title = {Chloroquine Analog Interaction with C2-and Iota-Toxin in Vitro and in Living Cells}, series = {Toxins}, volume = {8}, journal = {Toxins}, number = {8}, doi = {10.3390/toxins8080237}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168286}, pages = {237}, year = {2016}, abstract = {C2-toxin from Clostridium botulinum and Iota-toxin from Clostridium perfringens belong both to the binary A-B-type of toxins consisting of two separately secreted components, an enzymatic subunit A and a binding component B that facilitates the entry of the corresponding enzymatic subunit into the target cells. The enzymatic subunits are in both cases actin ADP-ribosyltransferases that modify R177 of globular actin finally leading to cell death. Following their binding to host cells' receptors and internalization, the two binding components form heptameric channels in endosomal membranes which mediate the translocation of the enzymatic components Iota a and C2I from endosomes into the cytosol of the target cells. The binding components form ion-permeable channels in artificial and biological membranes. Chloroquine and related 4-aminoquinolines were able to block channel formation in vitro and intoxication of living cells. In this study, we extended our previous work to the use of different chloroquine analogs and demonstrate that positively charged aminoquinolinium salts are able to block channels formed in lipid bilayer membranes by the binding components of C2- and Iota-toxin. Similarly, these molecules protect cultured mammalian cells from intoxication with C2- and Iota-toxin. The aminoquinolinium salts did presumably not interfere with actin ADP-ribosylation or receptor binding but blocked the pores formed by C2IIa and Iota b in living cells and in vitro. The blocking efficiency of pores formed by Iota b and C2IIa by the chloroquine analogs showed interesting differences indicating structural variations between the types of protein-conducting nanochannels formed by Iota b and C2IIa.}, language = {en} } @article{LapaLueckerathKleinleinetal.2016, author = {Lapa, Constantin and L{\"u}ckerath, Katharina and Kleinlein, Irene and Monoranu, Camelia Maria and Linsenmann, Thomas and Kessler, Almuth F. and Rudelius, Martina and Kropf, Saskia and Buck, Andreas K. and Ernestus, Ralf-Ingo and Wester, Hans-J{\"u}rgen and L{\"o}hr, Mario and Herrmann, Ken}, title = {\(^{68}\)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma}, series = {Theranostics}, volume = {6}, journal = {Theranostics}, number = {3}, doi = {10.7150/thno.13986}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168174}, pages = {428-434}, year = {2016}, abstract = {Chemokine receptor-4 (CXCR4) has been reported to be overexpressed in glioblastoma (GBM) and to be associated with poor survival. This study investigated the feasibility of non-invasive CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using the radiolabelled chemokine receptor ligand \(^{68}\)Ga-Pentixafor. 15 patients with clinical suspicion on primary or recurrent glioblastoma (13 primary, 2 recurrent tumors) underwent \(^{68}\)Ga-Pentixafor-PET/CT for assessment of CXCR4 expression prior to surgery. O-(2-\(^{18}\)F-fluoroethyl)-L-tyrosine (\(^{18}\)F-FET) PET/CT images were available in 11/15 cases and were compared visually and semi-quantitatively (SUV\(_{max}\), SUV\(_{mean}\)). Tumor-to-background ratios (TBR) were calculated for both PET probes. \(^{68}\)Ga-Pentixafor-PET/CT results were also compared to histological CXCR4 expression on neuronavigated surgical samples. \(^{68}\)Ga-Pentixafor-PET/CT was visually positive in 13/15 cases with SUV\(_{mean}\) and SUV\(_{max}\) of 3.0±1.5 and 3.9±2.0 respectively. Respective values for \(^{18}\)F-FET were 4.4±2.0 (SUV\(_{mean}\)) and 5.3±2.3 (SUV\(_{max}\)). TBR for SUV\(_{mean}\) and SUV\(_{max}\) were higher for \(^{68}\)Ga-Pentixafor than for \(^{18}\)F-FET (SUV\(_{mean}\) 154.0±90.7 vs. 4.1±1.3; SUV\(_{max}\) 70.3±44.0 and 3.8±1.2, p<0.01), respectively. Histological analysis confirmed CXCR4 expression in tumor areas with high \(^{68}\)Ga-Pentixafor uptake; regions of the same tumor without apparent \(^{68}\)Ga-Pentixafor uptake showed no or low receptor expression. In this pilot study, \(^{68}\)Ga-Pentixafor retention has been observed in the vast majority of glioblastoma lesions and served as readout for non-invasive determination of CXCR4 expression. Given the paramount importance of the CXCR4/SDF-1 axis in tumor biology, \(^{68}\)Ga-Pentixafor-PET/CT might prove a useful tool for sensitive, non-invasive in-vivo quantification of CXCR4 as well as selection of patients who might benefit from CXCR4-directed therapy.}, language = {en} } @article{ManukjanRippergerVenturinietal.2016, author = {Manukjan, Georgi and Ripperger, Tim and Venturini, Letizia and Stadler, Michael and G{\"o}hring, Gudrun and Schambach, Axel and Schlegelberger, Brigitte and Steinemann, Doris}, title = {GABP is necessary for stem/progenitor cell maintenance and myeloid differentiation in human hematopoiesis and chronic myeloid leukemia}, series = {Stem Cell Research}, volume = {16}, journal = {Stem Cell Research}, number = {3}, doi = {10.1016/j.scr.2016.04.007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168165}, pages = {677-681}, year = {2016}, abstract = {Maintenance of hematopoietic stem cells and their potential to give rise to progenitors of differentiated lymphoid and myeloid cells are accomplished by a network of regulatory processes. As a part of this network, the heteromeric transcription factor GA-binding protein (GABP) plays a crucial role in self-renewal of murine hematopoietic and leukemic stem cells. Here, we report the consequences of functional impairment of GABP in human hematopoietic and in leukemic stem/progenitor cells. Ectopic overexpression of a dominant-negative acting GABP mutant led to impaired myeloid differentiation of CD34\(^{+}\) hematopoietic stem/progenitor cells obtained from healthy donors. Moreover, drastically reduced clonogenic capacity of leukemic stem/progenitor cells isolated from bone marrow aspirates of chronic myeloid leukemia (CML) patients underlines the importance of GABP on stem/progenitor cell maintenance and confirms the relevance of GABP for human myelopoiesis in healthy and diseased states.}, language = {en} }