@article{BhavsarSinghSharmaetal.2016, author = {Bhavsar, Shefalee K. and Singh, Yogesh and Sharma, Piyush and Khairnar, Vishal and Hosseinzadeh, Zohreh and Zhang, Shaqiu and Palmada, Monica and Sabolic, Ivan and Koepsell, Hermann and Lang, Karl S. and Lang, Philipp A. and Lang, Florian}, title = {Expression of JAK3 Sensitive Na\(^+\) Coupled Glucose Carrier SGLT1 in Activated Cytotoxic T Lymphocytes}, series = {Cellular Physiology and Biochemistry}, volume = {39}, journal = {Cellular Physiology and Biochemistry}, number = {3}, doi = {10.1159/000447827}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164900}, pages = {1209-1228}, year = {2016}, abstract = {Background: Similar to tumor cells, activated T-lymphocytes generate ATP mainly by glycolytic degradation of glucose. Lymphocyte glucose uptake involves non-concentrative glucose carriers of the GLUT family. In contrast to GLUT isoforms, Na+-coupled glucose-carrier SGLT1 accumulates glucose against glucose gradients and is effective at low extracellular glucose concentrations. The present study explored expression and regulation of SGLT1 in activated murine splenic cytotoxic T cells (CTLs) and human Jurkat T cells. Methods: FACS analysis, immunofluorescence, confocal microscopy, chemiluminescence and Western blotting were employed to estimate SGLT1 expression, function and regulation in lymphocytes, as well as dual electrode voltage clamp in SGLT1 ± JAK3 expressing Xenopus oocytes to quantify the effect of janus kinase3 (JAK3) on SGLT1 function. Results: SGLT1 is expressed in murine CTLs and also in human Jurkat T cells. 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose uptake was significantly decreased by SGLT1-blocker phloridzin (0.2 mM) and by pharmacological inhibition of JAK3 with WHI-P131 (156 µM), WHI-P154 (11.2 µM) and JAK3 inhibitor VI (0.5 µM). Electrogenic glucose transport (Iglucose) in Xenopus oocytes expressing human SGLT1 was increased by additional expression of human wild type JAK3, active A568VJAK3 but not inactive K851AJAK3. Coexpression of JAK3 enhanced the maximal transport rate without significantly modifying affinity of the carrier. Iglucose in SGLT1+JAK3 expressing oocytes was significantly decreased by WHI-P154 (11.2 µM). JAK3 increased the SGLT1 protein abundance in the cell membrane. Inhibition of carrier insertion by brefeldin A (5 µM) in SGLT1+JAK3 expressing oocytes resulted in a decline of Iglucose, which was similar in presence and absence of JAK3. Conclusions: SGLT1 is expressed in murine cytotoxic T cells and human Jurkat T cells and significantly contributes to glucose uptake in those cells post activation. JAK3 up-regulates SGLT1 activity by increasing the carrier protein abundance in the cell membrane, an effect enforcing cellular glucose uptake into activated lymphocytes and thus contributing to the immune response.}, language = {en} } @article{SchleicherPaduchDebusetal.2016, author = {Schleicher, Ulrike and Paduch, Katrin and Debus, Andrea and Obermeyer, Stephanie and K{\"o}nig, Till and Kling, Jessica C. and Ribechini, Eliana and Dudziak, Diana and Mougiakakos, Dimitrios and Murray, Peter J. and Ostuni, Renato and K{\"o}rner, Heinrich and Bogdan, Christian}, title = {TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection}, series = {Cell Reports}, volume = {15}, journal = {Cell Reports}, number = {5}, doi = {10.1016/j.celrep.2016.04.001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164897}, pages = {1062-1075}, year = {2016}, abstract = {Neutralization or deletion of tumor necrosis factor (TNF) causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1) expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO) synthase (NOS2) was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg) was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control.}, language = {en} } @article{GattoSchulzeNielsen2016, author = {Gatto, Francesco and Schulze, Almut and Nielsen, Jens}, title = {Systematic Analysis Reveals that Cancer Mutations Converge on Deregulated Metabolism of Arachidonate and Xenobiotics}, series = {Cell Reports}, volume = {16}, journal = {Cell Reports}, number = {3}, doi = {10.1016/j.celrep.2016.06.038}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164814}, pages = {878-895}, year = {2016}, abstract = {Mutations are the basis of the clonal evolution of most cancers. Nevertheless, a systematic analysis of whether mutations are selected in cancer because they lead to the deregulation of specific biological processes independent of the type of cancer is still lacking. In this study, we correlated the genome and transcriptome of 1,082 tumors. We found that nine commonly mutated genes correlated with substantial changes in gene expression, which primarily converged on metabolism. Further network analyses circumscribed the convergence to a network of reactions, termed AraX, that involves the glutathione- and oxygen-mediated metabolism of arachidonic acid and xenobiotics. In an independent cohort of 4,462 samples, all nine mutated genes were consistently correlated with the deregulation of AraX. Among all of the metabolic pathways, AraX deregulation represented the strongest predictor of patient survival. These findings suggest that oncogenic mutations drive a selection process that converges on the deregulation of the AraX network.}, language = {en} } @article{ChilloKleinertLautzetal.2016, author = {Chillo, Omary and Kleinert, Eike Christian and Lautz, Thomas and Lasch, Manuel and Pagel, Judith-Irina and Heun, Yvonn and Troidl, Kerstin and Fischer, Silvia and Caballero-Martinez, Amelia and Mauer, Annika and Kurz, Angela R. M. and Assmann, Gerald and Rehberg, Markus and Kanse, Sandip M. and Nieswandt, Bernhard and Walzog, Barbara and Reichel, Christoph A. and Mannell, Hanna and Preissner, Klaus T. and Deindl, Elisabeth}, title = {Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function}, series = {Cell Reports}, volume = {16}, journal = {Cell Reports}, number = {8}, doi = {10.1016/j.celrep.2016.07.040}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164800}, pages = {2197-2207}, year = {2016}, abstract = {The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases.}, language = {en} } @article{BartelheimNemesSeeringeretal.2016, author = {Bartelheim, Kerstin and Nemes, Karolina and Seeringer, Angela and Kerl, Kornelius and Buechner, Jochen and Boos, Joachim and Graf, Norbert and D{\"u}rken, Matthias and Gerss, Joachim and Hasselblatt, Martin and Kortmann, Rolf-Dieter and Teichert von Luettichau, Irene and Nagel, Inga and Nygaard, Randi and Oyen, Florian and Quiroga, Eduardo and Schlegel, Paul-Gerhardt and Schmid, Irene and Schneppenheim, Reinhard and Siebert, Reiner and Solano-Paez, Palma and Timmermann, Beate and Warmuth-Metz, Monika and Fr{\"u}hwald, Michael Christoph}, title = {Improved 6-year overall survival in AT/RT - results of the registry study Rhabdoid 2007}, series = {Cancer Medicine}, volume = {5}, journal = {Cancer Medicine}, number = {8}, doi = {10.1002/cam4.741}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164799}, pages = {1765-1775}, year = {2016}, abstract = {Atypical teratoid rhabdoid tumors (AT/RT) are characterized by mutations and subsequent inactivation of SMARCB1 (INI1, hSNF5), a predilection for very young children and an unfavorable outcome. The European Registry for rhabdoid tumors (EU-RHAB) was established to generate a common European database and to establish a standardized treatment regimen as the basis for phase I/II trials. Thus, genetic analyses, neuropathologic and radiologic diagnoses, and a consensus treatment regimen were prospectively evaluated. From 2005 to 2009, 31 patients with AT/RT from four countries were recruited into the registry study Rhabdoid 2007 and treated with systemic and intraventricular chemotherapy. Eight patients received high-dose chemotherapy, 23 radiotherapy, and 17 maintenance therapy. Reference evaluations were performed in 64\% (genetic analyses, FISH, MLPA, sequencing) up to 97\% (neuropathology, INI1 stain). Germ-line mutations (GLM) were detected in 6/21 patients. Prolonged overall survival was associated with age above 3 years, radiotherapy and achievement of a complete remission. 6-year overall and event-free survival rates were 46\% (±0.10) and 45\% (±0.09), respectively. Serious adverse events and one treatment-related death due to insufficiency of a ventriculo peritoneal shunt (VP-shunt) and consecutive herniation were noted. Acquisition of standardized data including reference diagnosis and a standard treatment schedule improved data quality along with a survival benefit. Treatment was feasible with significant but manageable toxicity. Although our analysis is biased due to heterogeneous adherence to therapy, EU-RHAB provides the best available basis for phase I/II clinical trials.}, language = {en} } @article{SilvestriBarrowdaleMulliganetal.2016, author = {Silvestri, Valentina and Barrowdale, Daniel and Mulligan, Anna Marie and Neuhausen, Susan L. and Fox, Stephen and Karlan, Beth Y. and Mitchell, Gillian and James, Paul and Thull, Darcy L. and Zorn, Kristin K. and Carter, Natalie J. and Nathanson, Katherine L. and Domchek, Susan M. and Rebbeck, Timothy R. and Ramus, Susan J. and Nussbaum, Robert L. and Olopade, Olufunmilayo I. and Rantala, Johanna and Yoon, Sook-Yee and Caligo, Maria A. and Spugnesi, Laura and Bojesen, Anders and Pedersen, Inge Sokilde and Thomassen, Mads and Jensen, Uffe Birk and Toland, Amanda Ewart and Senter, Leigha and Andrulis, Irene L. and Glendon, Gord and Hulick, Peter J. and Imyanitov, Evgeny N. and Greene, Mark H. and Mai, Phuong L. and Singer, Christian F. and Rappaport-Fuerhauser, Christine and Kramer, Gero and Vijai, Joseph and Offit, Kenneth and Robson, Mark and Lincoln, Anne and Jacobs, Lauren and Machackova, Eva and Foretova, Lenka and Navratilova, Marie and Vasickova, Petra and Couch, Fergus J. and Hallberg, Emily and Ruddy, Kathryn J. and Sharma, Priyanka and Kim, Sung-Won and Teixeira, Manuel R. and Pinto, Pedro and Montagna, Marco and Matricardi, Laura and Arason, Adalgeir and Johannsson, Oskar Th and Barkardottir, Rosa B. and Jakubowska, Anna and Lubinski, Jan and Izquierdo, Angel and Pujana, Miguel Angel and Balma{\~n}a, Judith and Diez, Orland and Ivady, Gabriella and Papp, Janos and Olah, Edith and Kwong, Ava and Nevanlinna, Heli and Aittom{\"a}ki, Kristiina and Segura, Pedro Perez and Caldes, Trinidad and Van Maerken, Tom and Poppe, Bruce and Claes, Kathleen B. M. and Isaacs, Claudine and Elan, Camille and Lasset, Christine and Stoppa-Lyonnet, Dominique and Barjhoux, Laure and Belotti, Muriel and Meindl, Alfons and Gehrig, Andrea and Sutter, Christian and Engel, Christoph and Niederacher, Dieter and Steinemann, Doris and Hahnen, Eric and Kast, Karin and Arnold, Norbert and Varon-Mateeva, Raymonda and Wand, Dorothea and Godwin, Andrew K. and Evans, D. Gareth and Frost, Debra and Perkins, Jo and Adlard, Julian and Izatt, Louise and Platte, Radka and Eeles, Ros and Ellis, Steve and Hamann, Ute and Garber, Judy and Fostira, Florentia and Fountzilas, George and Pasini, Barbara and Giannini, Giuseppe and Rizzolo, Piera and Russo, Antonio and Cortesi, Laura and Papi, Laura and Varesco, Liliana and Palli, Domenico and Zanna, Ines and Savarese, Antonella and Radice, Paolo and Manoukian, Siranoush and Peissel, Bernard and Barile, Monica and Bonanni, Bernardo and Viel, Alessandra and Pensotti, Valeria and Tommasi, Stefania and Peterlongo, Paolo and Weitzel, Jeffrey N. and Osorio, Ana and Benitez, Javier and McGuffog, Lesley and Healey, Sue and Gerdes, Anne-Marie and Ejlertsen, Bent and Hansen, Thomas V. O. and Steele, Linda and Ding, Yuan Chun and Tung, Nadine and Janavicius, Ramunas and Goldgar, David E. and Buys, Saundra S. and Daly, Mary B. and Bane, Anita and Terry, Mary Beth and John, Esther M. and Southey, Melissa and Easton, Douglas F. and Chenevix-Trench, Georgia and Antoniou, Antonis C. and Ottini, Laura}, title = {Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2}, series = {Breast Cancer Research}, volume = {18}, journal = {Breast Cancer Research}, number = {15}, doi = {10.1186/s13058-016-0671-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164769}, year = {2016}, abstract = {Background BRCA1 and, more commonly, BRCA2 mutations are associated with increased risk of male breast cancer (MBC). However, only a paucity of data exists on the pathology of breast cancers (BCs) in men with BRCA1/2 mutations. Using the largest available dataset, we determined whether MBCs arising in BRCA1/2 mutation carriers display specific pathologic features and whether these features differ from those of BRCA1/2 female BCs (FBCs). Methods We characterised the pathologic features of 419 BRCA1/2 MBCs and, using logistic regression analysis, contrasted those with data from 9675 BRCA1/2 FBCs and with population-based data from 6351 MBCs in the Surveillance, Epidemiology, and End Results (SEER) database. Results Among BRCA2 MBCs, grade significantly decreased with increasing age at diagnosis (P = 0.005). Compared with BRCA2 FBCs, BRCA2 MBCs were of significantly higher stage (P for trend = 2 × 10-5) and higher grade (P for trend = 0.005) and were more likely to be oestrogen receptor-positive [odds ratio (OR) 10.59; 95 \% confidence interval (CI) 5.15-21.80] and progesterone receptor-positive (OR 5.04; 95 \% CI 3.17-8.04). With the exception of grade, similar patterns of associations emerged when we compared BRCA1 MBCs and FBCs. BRCA2 MBCs also presented with higher grade than MBCs from the SEER database (P for trend = 4 × 10-12). Conclusions On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs, and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.}, language = {en} } @article{WeigandBoosTasbihietal.2016, author = {Weigand, Annika and Boos, Anja M. and Tasbihi, Kereshmeh and Beier, Justus P. and Dalton, Paul D. and Schrauder, Michael and Horch, Raymund E. and Beckmann, Matthias W. and Strissel, Pamela L. and Strick, Reiner}, title = {Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells}, series = {Breast Cancer Research}, volume = {18}, journal = {Breast Cancer Research}, number = {32}, doi = {10.1186/s13058-016-0688-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164759}, year = {2016}, abstract = {Background There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors. Methods A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds. Results Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering. Conclusion Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine.}, language = {en} } @article{DuenasEspinVelaPauwsetal.2016, author = {Due{\~n}as-Esp{\´i}n, Ivan and Vela, Emili and Pauws, Steffen and Bescos, Cristina and Cano, Isaac and Cleries, Montserrat and Contel, Joan Carles and Keenoy, Esteban de Manuel and Garcia-Aymerich, Judith and Gomez-Cabrero, David and Kaye, Rachelle and Lahr, Maarten M. H. and Lluch-Ariet, Mag{\´i} and Moharra, Montserrat and Monterde, David and Mora, Joana and Nalin, Marco and Pavlickova, Andrea and Piera, Jordi and Ponce, Sara and Santaeugenia, Sebasti{\`a} and Schonenberg, Helen and St{\"o}rk, Stefan and Tegner, Jesper and Velickovski, Filip and Westerteicher, Christoph and Roca, Josep}, title = {Proposals for enhanced health risk assessment and stratification in an integrated care scenario}, series = {BMJ Open}, volume = {6}, journal = {BMJ Open}, number = {e010301}, doi = {10.1136/bmjopen-2015-010301}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164743}, year = {2016}, abstract = {Objectives Population-based health risk assessment and stratification are considered highly relevant for large-scale implementation of integrated care by facilitating services design and case identification. The principal objective of the study was to analyse five health-risk assessment strategies and health indicators used in the five regions participating in the Advancing Care Coordination and Telehealth Deployment (ACT) programme (http://www.act-programme.eu). The second purpose was to elaborate on strategies toward enhanced health risk predictive modelling in the clinical scenario. Settings The five ACT regions: Scotland (UK), Basque Country (ES), Catalonia (ES), Lombardy (I) and Groningen (NL). Participants Responsible teams for regional data management in the five ACT regions. Primary and secondary outcome measures We characterised and compared risk assessment strategies among ACT regions by analysing operational health risk predictive modelling tools for population-based stratification, as well as available health indicators at regional level. The analysis of the risk assessment tool deployed in Catalonia in 2015 (GMAs, Adjusted Morbidity Groups) was used as a basis to propose how population-based analytics could contribute to clinical risk prediction. Results There was consensus on the need for a population health approach to generate health risk predictive modelling. However, this strategy was fully in place only in two ACT regions: Basque Country and Catalonia. We found marked differences among regions in health risk predictive modelling tools and health indicators, and identified key factors constraining their comparability. The research proposes means to overcome current limitations and the use of population-based health risk prediction for enhanced clinical risk assessment. Conclusions The results indicate the need for further efforts to improve both comparability and flexibility of current population-based health risk predictive modelling approaches. Applicability and impact of the proposals for enhanced clinical risk assessment require prospective evaluation.}, language = {en} } @article{HammerleHussErnstetal.2016, author = {Hammerle, Florian and Huss, Michael and Ernst, Verena and B{\"u}rger, Arne}, title = {Thinking dimensional: prevalence of DSM-5 early adolescent full syndrome, partial and subthreshold eating disorders in a cross-sectional survey in German schools}, series = {BMJ Open}, volume = {6}, journal = {BMJ Open}, number = {e010843}, doi = {10.1136/bmjopen-2015-010843}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164734}, year = {2016}, abstract = {Objectives Investigating for the first time in Germany Diagnostic and Statistical Manual Fifth Edition (DSM-5) prevalences of adolescent full syndrome, Other Specified Feeding or Eating Disorder (OSFED), partial and subthreshold anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED). Method A national school-based cross-sectional survey with nine schools in Germany was undertaken that was aimed at students from grades 7 and 8. Of the 1775 students who were contacted to participate in the study, 1654 participated (participation rate: 93.2\%). The sample consisted of 873 female and 781 male adolescents (mean age=13.4 years). Prevalence rates were established using direct symptom criteria with a structured inventory (SIAB-S) and an additional self-report questionnaire (Eating Disorder Inventory 2 (EDI-2)). Results Prevalences for full syndrome were 0.3\% for AN, 0.4\% for BN, 0.5\% for BED and 3.6\% for OSFED-atypical AN, 0\% for BN (low frequency/limited duration), 0\% for BED (low frequency/limited duration) and 1.9\% for purging disorder (PD). Prevalences of partial syndrome were 10.9\% for AN (7.1\% established with cognitive symptoms only, excluding weight criteria), 0.2\% for BN and 2.1\% for BED, and of subthreshold syndrome were 0.8\% for AN, 0.3\% for BN and 0.2\% for BED. Cases on EDI-2 scales were much more pronounced with 12.6-21.1\% of the participants with significant sex differences. Conclusions The findings were in accordance with corresponding international studies but were in contrast to other German studies showing much higher prevalence rates. The study provides, for the first time, estimates for DSM-5 prevalences of eating disorders in adolescents for Germany, and evidence in favour of using valid measures for improving prevalence estimates."}, language = {en} } @article{KolarHammerleJenetzkyetal.2016, author = {Kolar, David R. and Hammerle, Florian and Jenetzky, Ekkehart and Huss, Michael and B{\"u}rger, Arne}, title = {Aversive tension in female adolescents with Anorexia Nervosa: a controlled ecological momentary assessment using smartphones}, series = {BMC Psychiatry}, volume = {16}, journal = {BMC Psychiatry}, number = {97}, doi = {10.1186/s12888-016-0807-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164720}, year = {2016}, abstract = {Background Current models of Anorexia Nervosa (AN) emphasize the role of emotion regulation. Aversive tension, described as a state of intense arousal and negative valence, is considered to be a link between emotional events and disordered eating. Recent research focused only on adult patients, and mainly general emotion regulation traits were studied. However, the momentary occurrence of aversive tension, particularly in adolescents with AN, has not been previously studied. Method 20 female adolescents with AN in outpatient treatment and 20 healthy adolescents aged 12 to 19 years participated in an ecological momentary assessment using their smartphones. Current states of aversive tension and events were assessed hourly for two consecutive weekdays. Mean and maximum values of aversive tension were compared. Multilevel analyses were computed to test the influence of time and reported events on aversive tension. The effect of reported events on subsequent changes of aversive tension in patients with AN were additionally tested in a multilevel model. Results AN patients showed higher mean and maximum levels of aversive tension. In a multilevel model, reported food intake was associated with higher levels of aversive tension in the AN group, whereas reported school or sport-related events were not linked to specific states of aversive tension. After food intake, subsequent increases of aversive tension were diminished and decreases of aversive tension were induced in adolescents with AN. Conclusions Aversive tension may play a substantial role in the psychopathology of AN, particular in relation with food intake. Therefore, treatment should consider aversive tension as a possible intervening variable during refeeding. Our findings encourage further research on aversive tension and its link to disordered eating.}, language = {en} } @article{TuerpSchlenkerSchroederetal.2016, author = {T{\"u}rp, Jens C. and Schlenker, Anna and Schr{\"o}der, Johannes and Essig, Marco and Schmitter, Marc}, title = {Disk displacement, eccentric condylar position, osteoarthrosis - misnomers for variations of normality? Results and interpretations from an MRI study in two age cohorts}, series = {BMC Oral Health}, volume = {16}, journal = {BMC Oral Health}, number = {124}, doi = {10.1186/s12903-016-0319-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164710}, year = {2016}, abstract = {Background Clinical decision-making and prognostic statements in individuals with manifest or suspected temporomandibular disorders (TMDs) may involve assessment of (a) the position of articular disc relative to the mandibular condyle, (b) the location of the condyle relative to the temporal joint surfaces, and (c) the depth of the glenoid fossa of the temporomandibular joints (TMJs). The aim of this study was twofold: (1) Determination of the prevalence of these variables in two representative population-based birth cohorts. (2) Reinterpretation of the clinical significance of the findings. Methods From existing magnetic resonance imaging (MRI) scans of the TMJs that had been taken in 2005 and 2006 from 72 subjects born between 1930 and 1932 and between 1950 and 1952, respectively, the condylar position at closed jaw was calculated as percentage displacement of the condyle from absolute centricity. By using the criteria introduced by Orsini et al. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 86:489-97, 1998), a textbook-like disc position at closed jaw was distinguished from an anterior location. TMJ morphology of the temporal joint surfaces was assessed at open jaw by measuring the depth of the glenoid fossa, using the method proposed by Muto et al. (J Oral Maxillofac Surg 52:1269-72, 1994). Frequency distributions were recorded for the condylar and disc positions at closed jaw. Student's t-test with independent samples was used as test of significance to detect differences of condylar positions between the age cohorts (1930 vs. 1950) and the sexes. The significance levels were set at 5\%. First, the results from the measurement of the age cohorts were compared without differentiation of sexes, i.e., age cohort 1930-1932 versus age cohort 1950-1952. Subsequently, the age cohorts were compared by sex, i.e., men in cohort 1930-1932 versus men in cohort 1950-1952, and women in cohort 1930-1932 women men in cohort 1950-1952. Results In both cohorts, condylar position was characterized by great variability. About 50\% of the condyles were located centrically, while the other half was either in an anterior or in a posterior position. In both female cohorts, a posterior position predominated, whereas a centric position prevailed among men. Around 75\% of the discs were positioned textbook-like, while the remaining forth was located anteriorly. Age had no statistically significant influence on condylar or on disc position. Conversely, comparison between the age groups revealed a statistically significant decrease of the depth of the glenoid fossa in both older cohorts. This age-dependent changes may be interpreted as flattening of the temporal joint surfaces. Conclusions We call for a re-interpretation of imaging findings because they may insinuate pathology which usually is not present. Instead, anterior or posterior positions of the mandibular condyle as well as an anterior location of the articular disc should be construed as a variation of normalcy. Likewise, flattening of articular surfaces of the TMJs may be considered as normal adaptive responses to increased loading, rather than pathological degenerative changes.}, language = {en} } @article{AlnawaisehSchubertNelisetal.2016, author = {Alnawaiseh, Maged and Schubert, Friederike and Nelis, Pieter and Wirths, Gabriele and Rosentreter, Andr{\´e} and Eter, Nicole}, title = {Optical coherence tomography (OCT) angiography findings in retinal arterial macroaneurysms}, series = {BMC Ophthalmology}, volume = {16}, journal = {BMC Ophthalmology}, number = {120}, doi = {10.1186/s12886-016-0293-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164702}, year = {2016}, abstract = {Background Optical coherence tomography angiography is a novel imaging technique that allows dyeless in vivo visualization of the retinal and choroidal vasculature. The purpose of this study was to describe optical coherence tomography (OCT) angiography findings in patients with retinal arterial macroaneurysms (RAMs). Methods Three eyes of three patients with RAMs were retrospectively included. Fundus photography, OCT, fluorescein angiography (FA), and OCT angiography were performed. The entire imaging data was analyzed in detail. Results OCT angiography could detect the RAMs noninvasively without dye injection. By simultaneously observing the OCT scans, it was possible to determine the depth of the RAMs in the retina, to detect the exact localization in relation to the main vessel, and to determine the level of blood flow in the RAMs. Conclusions OCT angiography can clearly visualize RAMs without use of a dye. It also allows layer-specific observation of blood flow in each layer of the RAM. OCT angiography provides additional dynamic information on RAMs, which is not obtained with FA and facilitates a better understanding of its morphology and activity. This information in combination with ICG and fluorescein angiography can help to optimize direct laser treatment.}, language = {en} } @article{PadbergKnispelZoellneretal.2016, author = {Padberg, Inken and Knispel, Petra and Z{\"o}llner, Susanne and Sieveking, Meike and Schneider, Alice and Steinbrink, Jens and Heuschmann, Peter U. and Wellwood, Ian and Meisel, Andreas}, title = {Social work after stroke: identifying demand for support by recording stroke patients' and carers' needs in different phases after stroke}, series = {BMC Neurology}, volume = {16}, journal = {BMC Neurology}, number = {111}, doi = {10.1186/s12883-016-0626-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164691}, year = {2016}, abstract = {Background Previous studies examining social work interventions in stroke often lack information on content, methods and timing over different phases of care including acute hospital, rehabilitation and out-patient care. This limits our ability to evaluate the impact of social work in multidisciplinary stroke care. We aimed to quantify social-work-related support in stroke patients and their carers in terms of timing and content, depending on the different phases of stroke care. Methods We prospectively collected and evaluated data derived from a specialized "Stroke-Service-Point" (SSP); a "drop in" center and non-medical stroke assistance service, staffed by social workers and available to all stroke patients, their carers and members of the public in the metropolitan region of Berlin, Germany. Results Enquiries from 257 consenting participants consulting the SSP between March 2010 and April 2012 related to out-patient and in-patient services, therapeutic services, medical questions, medical rehabilitation, self-help groups and questions around obtaining benefits. Frequency of enquiries for different topics depended on whether patients were located in an in-patient or out-patient setting. The majority of contacts involved information provision. While the proportion of male and female patients with stroke was similar, about two thirds of the carers contacting the SSP were female. Conclusion The social-work-related services provided by a specialized center in a German metropolitan area were diverse in terms of topic and timing depending on the phase of stroke care. Targeting the timing of interventions might be important to increase the impact of social work on patient's outcome.}, language = {en} } @article{BuschNadalSchmidetal.2016, author = {Busch, Martin and Nadal, Jennifer and Schmid, Matthias and Paul, Katharina and Titze, Stephanie and H{\"u}bner, Silvia and K{\"o}ttgen, Anna and Schultheiss, Ulla T. and Baid-Agrawal, Seema and Lorenzen, Johan and Schlieper, Georg and Sommerer, Claudia and Krane, Vera and Hilge, Robert and Kielstein, Jan T. and Kronenberg, Florian and Wanner, Christoph and Eckardt, Kai-Uwe and Wolf, Gunter}, title = {Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort}, series = {BMC Nephrology}, volume = {17}, journal = {BMC Nephrology}, number = {59}, doi = {10.1186/s12882-016-0273-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164687}, year = {2016}, abstract = {Background Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. Methods The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m2 or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. Results At baseline, DM was present in 1842 patients (35 \%) and the median HbA1C was 7.0 \% (25th-75th percentile: 6.8-7.9 \%), equalling 53 mmol/mol (51, 63); 24.2 \% of patients received dietary treatment only, 25.5 \% oral antidiabetic drugs but not insulin, 8.4 \% oral antidiabetic drugs with insulin, and 41.8 \% insulin alone. Metformin was used by 18.8 \%. Factors associated with an HbA1C level >7.0 \% (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m2, 95 \% CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 \% CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 \% CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 \% CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. Conclusions Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 \% receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.}, language = {en} } @article{DienemannFujiiOrlandietal.2016, author = {Dienemann, Thomas and Fujii, Naohiko and Orlandi, Paula and Nessel, Lisa and Furth, Susan L. and Hoy, Wendy E. and Matsuo, Seiichi and Mayer, Gert and Methven, Shona and Schaefer, Franz and Schaeffner, Elke S. and Sol{\´a}, Laura and Stengel, B{\´e}n{\´e}dicte and Wanner, Christoph and Zhang, Luxia and Levin, Adeera and Eckardt, Kai-Uwe and Feldman, Harold I.}, title = {International Network of Chronic Kidney Disease cohort studies (iNET-CKD): a global network of chronic kidney disease cohorts}, series = {BMC Nephrology}, volume = {17}, journal = {BMC Nephrology}, doi = {10.1186/s12882-016-0335-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164604}, pages = {121}, year = {2016}, abstract = {Background Chronic kidney disease (CKD) is a global health burden, yet it is still underrepresented within public health agendas in many countries. Studies focusing on the natural history of CKD are challenging to design and conduct, because of the long time-course of disease progression, a wide variation in etiologies, and a large amount of clinical variability among individuals with CKD. With the difference in health-related behaviors, healthcare delivery, genetics, and environmental exposures, this variability is greater across countries than within one locale and may not be captured effectively in a single study. Methods Studies were invited to join the network. Prerequisites for membership included: 1) observational designs with a priori hypotheses and defined study objectives, patient-level information, prospective data acquisition and collection of bio-samples, all focused on predialysis CKD patients; 2) target sample sizes of 1,000 patients for adult cohorts and 300 for pediatric cohorts; and 3) minimum follow-up of three years. Participating studies were surveyed regarding design, data, and biosample resources. Results Twelve prospective cohort studies and two registries covering 21 countries were included. Participants age ranges from >2 to >70 years at inclusion, CKD severity ranges from stage 2 to stage 5. Patient data and biosamples (not available in the registry studies) are measured yearly or biennially. Many studies included multiple ethnicities; cohort size ranges from 400 to more than 13,000 participants. Studies' areas of emphasis all include but are not limited to renal outcomes, such as progression to ESRD and death. Conclusions iNET-CKD (International Network of CKD cohort studies) was established, to promote collaborative research, foster exchange of expertise, and create opportunities for research training. Participating studies have many commonalities that will facilitate comparative research; however, we also observed substantial differences. The diversity we observed across studies within this network will be able to be leveraged to identify genetic, behavioral, and health services factors associated with the course of CKD. With an emerging infrastructure to facilitate interactions among the investigators of iNET-CKD and a broadly defined research agenda, we are confident that there will be great opportunity for productive collaborative investigations involving cohorts of individuals with CKD.}, language = {en} } @article{KuhlmannHussBuergeretal.2016, author = {Kuhlmann, S.M. and Huss, M. and B{\"u}rger, A. and Hammerle, F.}, title = {Coping with stress in medical students: results of a randomized controlled trial using a mindfulness-based stress prevention training (MediMind) in Germany}, series = {BMC Medical Education}, volume = {16}, journal = {BMC Medical Education}, doi = {10.1186/s12909-016-0833-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164593}, pages = {316}, year = {2016}, abstract = {Background High prevalence rates of psychological distress in medical training and later professional life indicate a need for prevention. Different types of intervention were shown to have good effects, but little is known about the relative efficacy of different types of stress management interventions, and methodological limitations have been reported. In order to overcome some of these limitations, the present study aimed at evaluating the effect of a specifically developed mindfulness-based stress prevention training for medical students (MediMind) on measures of distress, coping and psychological morbidity. Methods We report on a prospective randomized controlled trial with three study conditions: experimental treatment (MediMind), standard treatment (Autogenic Training) and a control group without treatment. The sample consisted of medical or dental students in the second or eighth semester. They completed self-report questionnaires at baseline, after the training and at one year follow-up. Distress (Trier Inventory for the Assessment of Chronic Stress, TICS) was assessed as the primary outcome and coping (Brief COPE) as a co-primary outcome. Effects on the psychological morbidity (Brief Symptom Inventory, BSI) as a secondary outcome were expected one year after the trainings. Results Initially, N = 183 students were randomly allocated to the study groups. At one year follow-up N = 80 could be included into the per-protocol analysis: MediMind (n =31), Autogenic Training (n = 32) and control group (n = 17). A selective drop-out for students who suffered more often from psychological symptoms was detected (p = .020). MANCOVA's on TICS and Brief COPE revealed no significant interaction effects. On the BSI, a significant overall interaction effect became apparent (p = .002, η2partial = .382), but post hoc analyses were not significant. Means of the Global Severity Index (BSI) indicated that MediMind may contribute to a decrease in psychological morbidity. Conclusion Due to the high and selective dropout rates, the results cannot be generalized and further research is necessary. Since the participation rate of the trainings was high, a need for further prevention programs is indicated. The study gives important suggestions on further implementation and evaluation of stress prevention in medical schools.}, language = {en} } @article{ShenChalopinGarciaetal.2016, author = {Shen, Yingjia and Chalopin, Domitille and Garcia, Tzintzuni and Boswell, Mikki and Boswell, William and Shiryev, Sergey A. and Agarwala, Richa and Volff, Jean-Nicolas and Postlethwait, John H. and Schartl, Manfred and Minx, Patrick and Warren, Wesley C. and Walter, Ronald B.}, title = {X. couchianus and X. hellerii genome models provide genomic variation insight among Xiphophorus species}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, doi = {10.1186/s12864-015-2361-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164582}, pages = {37}, year = {2016}, abstract = {Background Xiphophorus fishes are represented by 26 live-bearing species of tropical fish that express many attributes (e.g., viviparity, genetic and phenotypic variation, ecological adaptation, varied sexual developmental mechanisms, ability to produce fertile interspecies hybrids) that have made attractive research models for over 85 years. Use of various interspecies hybrids to investigate the genetics underlying spontaneous and induced tumorigenesis has resulted in the development and maintenance of pedigreed Xiphophorus lines specifically bred for research. The recent availability of the X. maculatus reference genome assembly now provides unprecedented opportunities for novel and exciting comparative research studies among Xiphophorus species. Results We present sequencing, assembly and annotation of two new genomes representing Xiphophorus couchianus and Xiphophorus hellerii. The final X. couchianus and X. hellerii assemblies have total sizes of 708 Mb and 734 Mb and correspond to 98 \% and 102 \% of the X. maculatus Jp 163 A genome size, respectively. The rates of single nucleotide change range from 1 per 52 bp to 1 per 69 bp among the three genomes and the impact of putatively damaging variants are presented. In addition, a survey of transposable elements allowed us to deduce an ancestral TE landscape, uncovered potential active TEs and document a recent burst of TEs during evolution of this genus. Conclusions Two new Xiphophorus genomes and their corresponding transcriptomes were efficiently assembled, the former using a novel guided assembly approach. Three assembled genome sequences within this single vertebrate order of new world live-bearing fishes will accelerate our understanding of relationship between environmental adaptation and genome evolution. In addition, these genome resources provide capability to determine allele specific gene regulation among interspecies hybrids produced by crossing any of the three species that are known to produce progeny predisposed to tumor development.}, language = {en} } @article{daCruzRodriguezCasuriagaSantinaqueetal.2016, author = {da Cruz, Irene and Rodr{\´i}guez-Casuriaga, Rosana and Santi{\~n}aque, Frederico F. and Far{\´i}as, Joaquina and Curti, Gianni and Capoano, Carlos A. and Folle, Gustavo A. and Benavente, Ricardo and Sotelo-Silveira, Jos{\´e} Roberto and Geisinger, Adriana}, title = {Transcriptome analysis of highly purified mouse spermatogenic cell populations: gene expression signatures switch from meiotic-to postmeiotic-related processes at pachytene stage}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, doi = {10.1186/s12864-016-2618-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164574}, pages = {294}, year = {2016}, abstract = {Background Spermatogenesis is a complex differentiation process that involves the successive and simultaneous execution of three different gene expression programs: mitotic proliferation of spermatogonia, meiosis, and spermiogenesis. Testicular cell heterogeneity has hindered its molecular analyses. Moreover, the characterization of short, poorly represented cell stages such as initial meiotic prophase ones (leptotene and zygotene) has remained elusive, despite their crucial importance for understanding the fundamentals of meiosis. Results We have developed a flow cytometry-based approach for obtaining highly pure stage-specific spermatogenic cell populations, including early meiotic prophase. Here we combined this methodology with next generation sequencing, which enabled the analysis of meiotic and postmeiotic gene expression signatures in mouse with unprecedented reliability. Interestingly, we found that a considerable number of genes involved in early as well as late meiotic processes are already on at early meiotic prophase, with a high proportion of them being expressed only for the short time lapse of lepto-zygotene stages. Besides, we observed a massive change in gene expression patterns during medium meiotic prophase (pachytene) when mostly genes related to spermiogenesis and sperm function are already turned on. This indicates that the transcriptional switch from meiosis to post-meiosis takes place very early, during meiotic prophase, thus disclosing a higher incidence of post-transcriptional regulation in spermatogenesis than previously reported. Moreover, we found that a good proportion of the differential gene expression in spermiogenesis corresponds to up-regulation of genes whose expression starts earlier, at pachytene stage; this includes transition protein-and protamine-coding genes, which have long been claimed to switch on during spermiogenesis. In addition, our results afford new insights concerning X chromosome meiotic inactivation and reactivation. Conclusions This work provides for the first time an overview of the time course for the massive onset and turning off of the meiotic and spermiogenic genetic programs. Importantly, our data represent a highly reliable information set about gene expression in pure testicular cell populations including early meiotic prophase, for further data mining towards the elucidation of the molecular bases of male reproduction in mammals.}, 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}, doi = {10.5194/acp-16-7813-2016}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-198547}, 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{ČuklinaHahnImakaevetal.2016, author = {Čuklina, Jelena and Hahn, Julia and Imakaev, Maxim and Omasits, Ulrich and F{\"o}rstner, Konrad U. and Ljubimov, Nikolay and Goebel, Melanie and Pessi, Gabriella and Fischer, Hans-Martin and Ahrens, Christian H. and Gelfand, Mikhail S. and Evguenieva-Hackenberg, Elena}, title = {Genome-wide transcription start site mapping of Bradyrhizobium japonicum grown free-living or in symbiosis - a rich resource to identify new transcripts, proteins and to study gene regulation}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, doi = {10.1186/s12864-016-2602-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164565}, pages = {302}, year = {2016}, abstract = {Background Differential RNA-sequencing (dRNA-seq) is indispensable for determination of primary transcriptomes. However, using dRNA-seq data to map transcriptional start sites (TSSs) and promoters genome-wide is a bioinformatics challenge. We performed dRNA-seq of Bradyrhizobium japonicum USDA 110, the nitrogen-fixing symbiont of soybean, and developed algorithms to map TSSs and promoters. Results A specialized machine learning procedure for TSS recognition allowed us to map 15,923 TSSs: 14,360 in free-living bacteria, 4329 in symbiosis with soybean and 2766 in both conditions. Further, we provide proteomic evidence for 4090 proteins, among them 107 proteins corresponding to new genes and 178 proteins with N-termini different from the existing annotation (72 and 109 of them with TSS support, respectively). Guided by proteomics evidence, previously identified TSSs and TSSs experimentally validated here, we assign a score threshold to flag 14 \% of the mapped TSSs as a class of lower confidence. However, this class of lower confidence contains valid TSSs of low-abundant transcripts. Moreover, we developed a de novo algorithm to identify promoter motifs upstream of mapped TSSs, which is publicly available, and found motifs mainly used in symbiosis (similar to RpoN-dependent promoters) or under both conditions (similar to RpoD-dependent promoters). Mapped TSSs and putative promoters, proteomic evidence and updated gene annotation were combined into an annotation file. Conclusions The genome-wide TSS and promoter maps along with the extended genome annotation of B. japonicum represent a valuable resource for future systems biology studies and for detailed analyses of individual non-coding transcripts and ORFs. Our data will also provide new insights into bacterial gene regulation during the agriculturally important symbiosis between rhizobia and legumes.}, language = {en} } @article{BabskiHaasNaetherSchindleretal.2016, author = {Babski, Julia and Haas, Karina A. and N{\"a}ther-Schindler, Daniela and Pfeiffer, Friedhelm and F{\"o}rstner, Konrad U. and Hammelmann, Matthias and Hilker, Rolf and Becker, Anke and Sharma, Cynthia M. and Marchfelder, Anita and Soppa, J{\"o}rg}, title = {Genome-wide identification of transcriptional start sites in the haloarchaeon Haloferax volcanii based on differential RNA-Seq (dRNA-Seq)}, series = {BMC Genomics}, volume = {17}, journal = {BMC Genomics}, number = {629}, doi = {10.1186/s12864-016-2920-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164553}, year = {2016}, abstract = {Background Differential RNA-Seq (dRNA-Seq) is a recently developed method of performing primary transcriptome analyses that allows for the genome-wide mapping of transcriptional start sites (TSSs) and the identification of novel transcripts. Although the transcriptomes of diverse bacterial species have been characterized by dRNA-Seq, the transcriptome analysis of archaeal species is still rather limited. Therefore, we used dRNA-Seq to characterize the primary transcriptome of the model archaeon Haloferax volcanii. Results Three independent cultures of Hfx. volcanii grown under optimal conditions to the mid-exponential growth phase were used to determine the primary transcriptome and map the 5′-ends of the transcripts. In total, 4749 potential TSSs were detected. A position weight matrix (PWM) was derived for the promoter predictions, and the results showed that 64 \% of the TSSs were preceded by stringent or relaxed basal promoters. Of the identified TSSs, 1851 belonged to protein-coding genes. Thus, fewer than half (46 \%) of the 4040 protein-coding genes were expressed under optimal growth conditions. Seventy-two percent of all protein-coding transcripts were leaderless, which emphasized that this pathway is the major pathway for translation initiation in haloarchaea. A total of 2898 of the TSSs belonged to potential non-coding RNAs, which accounted for an unexpectedly high fraction (61 \%) of all transcripts. Most of the non-coding TSSs had not been previously described (2792) and represented novel sequences (59 \% of all TSSs). A large fraction of the potential novel non-coding transcripts were cis-antisense RNAs (1244 aTSSs). A strong negative correlation between the levels of antisense transcripts and cognate sense mRNAs was found, which suggested that the negative regulation of gene expression via antisense RNAs may play an important role in haloarchaea. The other types of novel non-coding transcripts corresponded to internal transcripts overlapping with mRNAs (1153 iTSSs) and intergenic small RNA (sRNA) candidates (395 TSSs). Conclusion This study provides a comprehensive map of the primary transcriptome of Hfx. volcanii grown under optimal conditions. Fewer than half of all protein-coding genes have been transcribed under these conditions. Unexpectedly, more than half of the detected TSSs belonged to several classes of non-coding RNAs. Thus, RNA-based regulation appears to play a more important role in haloarchaea than previously anticipated.}, language = {en} } @article{SchofferSchueleinArandetal.2016, author = {Schoffer, Olaf and Sch{\"u}lein, Stefanie and Arand, Gerlinde and Arnholdt, Hans and Baaske, Dieter and Bargou, Ralf C. and Becker, Nikolaus and Beckmann, Matthias W. and Bodack, Yves and B{\"o}hme, Beatrix and Bozkurt, Tayfun and Breitsprecher, Regine and Buchali, Andre and Burger, Elke and Burger, Ulrike and Dommisch, Klaus and Elsner, Gudrun and Fernschild, Karin and Flintzer, Ulrike and Funke, Uwe and Gerken, Michael and G{\"o}bel, Hubert and Grobe, Norbert and Gumpp, Vera and Heinzerling, Lucie and Kempfer, Lana Raffaela and Kiani, Alexander and Klinkhammer-Schalke, Monika and Kl{\"o}cking, Sabine and Kreibich, Ute and Knabner, Katrin and Kuhn, Peter and Lutze, Stine and M{\"a}der, Uwe and Maisel, Tanja and Maschke, Jan and Middeke, Martin and Neubauer, Andreas and Niedostatek, Antje and Opazo-Saez, Anabelle and Peters, Christoph and Schell, Beatrice and Schenkirsch, Gerhard and Schmalenberg, Harald and Schmidt, Peter and Schneider, Constanze and Schubotz, Birgit and Seide, Anika and Strecker, Paul and Taubenheim, Sabine and Wackes, Matthias and Weiß, Steffen and Welke, Claudia and Werner, Carmen and Wittekind, Christian and Wulff, J{\"o}rg and Zettl, Heike and Klug, Stefanie J.}, title = {Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011}, series = {BMC Cancer}, volume = {16}, journal = {BMC Cancer}, number = {936}, doi = {10.1186/s12885-016-2963-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164544}, year = {2016}, abstract = {Background Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results The number of annually documented cases increased by 53.2\% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95\% CI 0.97-0.97), sex (OR 1.18, 95\% CI 1.11-1.25), date of diagnosis (OR 1.05, 95\% CI 1.04-1.06), 'diagnosis during screening' (OR 3.24, 95\% CI 2.50-4.19) and place of residence (OR 1.23, 95\% CI 1.16-1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4\% (95\% CI 82.8-83.9\%). Conclusions No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008. "}, language = {en} } @article{StoelzelMohrKrameretal.2016, author = {St{\"o}lzel, F. and Mohr, B. and Kramer, M. and Oelschl{\"a}gel, U. and Bochtler, T. and Berdel, W. E. and Kaufmann, M. and Baldus, C. D. and Sch{\"a}fer-Eckart, K. and Stuhlmann, R. and Einsele, H. and Krause, S. W. and Serve, H. and H{\"a}nel, M. and Herbst, R. and Neubauer, A. and Sohlbach, K. and Mayer, J. and Middeke, J. M. and Platzbecker, U. and Schaich, M. and Kr{\"a}mer, A. and R{\"o}llig, C. and Schetelig, J. and Bornh{\"a}user, M. and Ehninger, G.}, title = {Karyotype complexity and prognosis in acute myeloid leukemia}, series = {Blood Cancer Journal}, volume = {6}, journal = {Blood Cancer Journal}, doi = {10.1038/bcj.2015.114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164530}, pages = {e386}, year = {2016}, abstract = {A complex aberrant karyotype consisting of multiple unrelated cytogenetic abnormalities is associated with poor prognosis in patients with acute myeloid leukemia (AML). The European Leukemia Net classification and the UK Medical Research Council recommendation provide prognostic categories that differ in the definition of unbalanced aberrations as well as the number of single aberrations. The aim of this study on 3526 AML patients was to redefine and validate a cutoff for karyotype complexity in AML with regard to adverse prognosis. Our study demonstrated that (1) patients with a pure hyperdiploid karyotype have an adverse risk irrespective of the number of chromosomal gains, (2) patients with translocation t(9;11)(p21∼22;q23) have an intermediate risk independent of the number of additional aberrations, (3) patients with 4 abnormalities have an adverse risk per se and (4) patients with three aberrations in the absence of abnormalities of strong influence (hyperdiploid karyotype, t(9;11)(p21∼22;q23), CBF-AML, unique adverse-risk aberrations) have borderline intermediate/adverse risk with a reduced overall survival compared with patients with a normal karyotype.}, language = {en} } @article{WilhelmSmetakReimeretal.2016, author = {Wilhelm, M. and Smetak, M. and Reimer, P. and Geissinger, E. and Ruediger, T. and Metzner, B. and Schmitz, N. and Engert, A. and Schaefer-Eckart, K. and Birkmann, J.}, title = {First-line therapy of peripheral T-cell lymphoma: extension and long-term follow-up of a study investigating the role of autologous stem cell transplantation}, series = {Blood Cancer Journal}, volume = {6}, journal = {Blood Cancer Journal}, doi = {10.1038/bcj.2016.63}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164506}, pages = {e452}, year = {2016}, abstract = {Current guidelines recommend consolidation with autologous stem cell transplantation (autoSCT) after induction chemotherapy for most patients with peripheral T-cell lymphoma (PTCL). This assumption is based on five prospective phase II studies, three of which included <50 patients with limited follow-up. Here we present the final analysis of the prospective German study. The treatment regimen consisted of four to six cycles of CHOP chemotherapy followed by mobilizing therapy and stem cell collection. Patients in complete remission (CR) or partial remission (PR) underwent myeloablative chemo(radio)therapy and autoSCT. From January 2001 to July 2010, 111 patients were enrolled in the study. The main subgroups were PTCL not specified (n=42) and angioimmunoblastic T-cell lymphoma (n=37). Seventy-five (68\%) of the 111 patients received transplantation. The main reason for not receiving autoSCT was progressive disease. In an intent-to-treat analysis, the complete response rate after myeloablative therapy was 59\%. The estimated 5-year overall survival, disease-free survival and progression-free survival rates were 44\%, 54\% and 39\%, respectively. The results of this study confirm that upfront autoSCT can result in long-term remissions in patients with all major subtypes of PTCL and therefore should be part of first-line therapy whenever possible.}, language = {en} } @article{GoekbugetKelshChiaetal.2016, author = {G{\"o}kbuget, N. and Kelsh, M. and Chia, V. and Advani, A. and Bassan, R. and Dombret, H. and Doubek, M. and Fielding, A. K. and Giebel, S. and Haddad, V. and Hoelzer, D. and Holland, C. and Ifrah, N. and Katz, A. and Maniar, T. and Martinelli, G. and Morgades, M. and O'Brien, S. and Ribera, J.-M. and Rowe, J. M. and Stein, A. and Topp, M. and Wadleigh, M. and Kantarjian, H.}, title = {Blinatumomab vs historical standard therapy of adult relapsed/refractory acute lymphoblastic leukemia}, series = {Blood Cancer Journal}, volume = {6}, journal = {Blood Cancer Journal}, doi = {10.1038/bcj.2016.84}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164495}, pages = {e473}, year = {2016}, abstract = {We compared outcomes from a single-arm study of blinatumomab in adult patients with B-precursor Ph-negative relapsed/refractory acute lymphoblastic leukemia (R/R ALL) with a historical data set from Europe and the United States. Estimates of complete remission (CR) and overall survival (OS) were weighted by the frequency distribution of prognostic factors in the blinatumomab trial. Outcomes were also compared between the trial and historical data using propensity score methods. The historical cohort included 694 patients with CR data and 1112 patients with OS data compared with 189 patients with CR and survival data in the blinatumomab trial. The weighted analysis revealed a CR rate of 24\% (95\% CI: 20-27\%) and a median OS of 3.3 months (95\% CI: 2.8-3.6) in the historical cohort compared with a CR/CRh rate of 43\% (95\% CI: 36-50\%) and a median OS of 6.1 months (95\% CI: 4.2-7.5) in the blinatumomab trial. Propensity score analysis estimated increased odds of CR/CRh (OR=2.68, 95\% CI: 1.67-4.31) and improved OS (HR=0.536, 95\% CI: 0.394-0.730) with blinatumomab. The analysis demonstrates the application of different study designs and statistical methods to compare novel therapies for R/R ALL with historical data.}, language = {en} } @article{FornariRapplMorelhaoetal.2016, author = {Fornari, C. I. and Rappl, P. H. O. and Morelhao, S. L. and Peixoto, T. R. F. and Bentmann, H. and Reinert, F. and Abramof, E.}, title = {Preservation of pristine Bi\(_2\)Te\(_3\) thin film topological insulator surface after ex situ mechanical removal of Te capping layer}, series = {APL Materials}, volume = {4}, journal = {APL Materials}, doi = {10.1063/1.4964610}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164468}, pages = {106107}, year = {2016}, abstract = {Ex situ analyses on topological insulator films require protection against surface contamination during air exposure. This work reports on a technique that combines deposition of protective capping just after epitaxial growth and its mechanical removal inside ultra-high vacuum systems. This method was applied to Bi2Te3 films with thickness varying from 8 to 170 nm. Contrarily to other methods, this technique does not require any sputtering or thermal annealing setups installed inside the analyzing system and preserves both film thickness and surface characteristics. These results suggest that the technique presented here can be expanded to other topological insulator materials.}, language = {en} } @article{TrudzinskiMinkoRappetal.2016, author = {Trudzinski, Franziska C. and Minko, Peter and Rapp, Daniel and F{\"a}hndrich, Sebastian and Haake, Hendrik and Haab, Myriam and Bohle, Rainer M. and Flaig, Monika and Kaestner, Franziska and Bals, Robert and Wilkens, Heinrike and Muellenbach, Ralf M. and Link, Andreas and Groesdonk, Heinrich V. and Lensch, Christian and Langer, Frank and Lepper, Philipp M.}, title = {Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis}, series = {Annals of Intensive Care}, volume = {6}, journal = {Annals of Intensive Care}, doi = {10.1186/s13613-016-0172-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164455}, pages = {66}, year = {2016}, abstract = {Background Even though bleeding and thromboembolic events are major complications of extracorporeal membrane oxygenation (ECMO), data on the incidence of venous thrombosis (VT) and thromboembolism (VTE) under ECMO are scarce. This study analyzes the incidence and predictors of VTE in patients treated with ECMO due to respiratory failure. Methods Retrospective analysis of patients treated on ECMO in our center from 04/2010 to 11/2015. Patients with thromboembolic events prior to admission were excluded. Diagnosis was made by imaging in survivors and postmortem examination in deceased patients. Results Out of 102 screened cases, 42 survivors and 21 autopsy cases [mean age 46.0 ± 14.4 years; 37 (58.7 \%) males] fulfilling the above-mentioned criteria were included. Thirty-four patients (54.0 \%) underwent ECMO therapy due to ARDS, and 29 patients (46.0 \%) with chronic organ failure were bridged to lung transplantation. Despite systemic anticoagulation at a mean PTT of 50.6 ± 12.8 s, [VT/VTE 47.0 ± 12.3 s and no VT/VTE 53.63 ± 12.51 s (p = 0.037)], VT and/or VTE was observed in 29 cases (46.1 \%). The rate of V. cava thrombosis was 15/29 (51.7 \%). Diagnosis of pulmonary embolism prevailed in deceased patients [5/21 (23.8 \%) vs. 2/42 (4.8 \%) (p = 0.036)]. In a multivariable analysis, only aPTT and time on ECMO predicted VT/VTE. There was no difference in the incidence of clinically diagnosed VT in ECMO survivors and autopsy findings. Conclusions Venous thrombosis and thromboembolism following ECMO therapy are frequent. Quality of anticoagulation and ECMO runtime predicted thromboembolic events. "}, language = {en} } @article{LotzSchmidRossietal.2016, author = {Lotz, Christian and Schmid, Freia F. and Rossi, Angela and Kurdyn, Szymon and Kampik, Daniel and De Wever, Bart and Walles, Heike and Groeber, Florian K.}, title = {Alternative Methods for the Replacement of Eye Irritation Testing}, series = {ALTEX - Alternatives to Animal Experimentation}, volume = {33}, journal = {ALTEX - Alternatives to Animal Experimentation}, number = {1}, doi = {10.14573/altex.1508241}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164444}, pages = {55-67}, year = {2016}, abstract = {In the last decades significant regulatory attempts were made to replace, refine and reduce animal testing to assess the risk of consumer products for the human eye. As the original in vivo Draize eye test is criticized for limited predictivity, costs and ethical issues, several animal-free test methods have been developed to categorize substances according to the global harmonized system (GHS) for eye irritation. This review summarizes the progress of alternative test methods for the assessment of eye irritation. Based on the corneal anatomy and current knowledge of the mechanisms causing eye irritation, different ex vivo and in vitro methods will be presented and discussed with regard to possible limitations and status of regulatory acceptance. In addition to established in vitro models, this review will also highlight emerging, full thickness cornea models that might be suited to predict all GHS categories.}, language = {en} } @article{GroeberEngelhardtLangeetal.2016, author = {Groeber, Florian and Engelhardt, Lisa and Lange, Julia and Kurdyn, Szymon and Schmid, Freia F. and R{\"u}cker, Christoph and Mielke, Stephan and Walles, Heike and Hansmann, Jan}, title = {A First Vascularized Skin Equivalent as an Alternative to Animal Experimentation}, series = {ALTEX - Alternatives to Animal Experimentation}, volume = {33}, journal = {ALTEX - Alternatives to Animal Experimentation}, number = {4}, doi = {10.14573/altex.1604041}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164438}, pages = {415-422}, year = {2016}, abstract = {Tissue-engineered skin equivalents mimic key aspects of the human skin, and can thus be employed as wound coverage for large skin defects or as in vitro test systems as an alternative to animal models. However, current skin equivalents lack a functional vasculature limiting clinical and research applications. This study demonstrates the generation of a vascularized skin equivalent with a perfused vascular network by combining a biological vascularized scaffold (BioVaSc) based on a decellularized segment of a porcine jejunum and a tailored bioreactor system. Briefly, the BioVaSc was seeded with human fibroblasts, keratinocytes, and human microvascular endothelial cells. After 14 days at the air-liquid interface, hematoxylin \& eosin and immunohistological staining revealed a specific histological architecture representative of the human dermis and epidermis including a papillary-like architecture at the dermal-epidermal-junction. The formation of the skin barrier was measured non-destructively using impedance spectroscopy. Additionally, endothelial cells lined the walls of the formed vessels that could be perfused with a physiological volume flow. Due to the presence of a complex in-vivo-like vasculature, the here shown skin equivalent has the potential for skin grafting and represents a sophisticated in vitro model for dermatological research.}, language = {en} } @article{DePalmaAbrahamczykAizenetal.2016, author = {De Palma, Adriana and Abrahamczyk, Stefan and Aizen, Marcelo A. and Albrecht, Matthias and Basset, Yves and Bates, Adam and Blake, Robin J. and Boutin, C{\´e}line and Bugter, Rob and Connop, Stuart and Cruz-L{\´o}pez, Leopoldo and Cunningham, Saul A. and Darvill, Ben and Diek{\"o}tter, Tim and Dorn, Silvia and Downing, Nicola and Entling, Martin H. and Farwig, Nina and Felicioli, Antonio and Fonte, Steven J. and Fowler, Robert and Franzen, Markus Franz{\´e}n and Goulson, Dave and Grass, Ingo and Hanley, Mick E. and Hendrix, Stephen D. and Herrmann, Farina and Herzog, Felix and Holzschuh, Andrea and Jauker, Birgit and Kessler, Michael and Knight, M. E. and Kruess, Andreas and Lavelle, Patrick and Le F{\´e}on, Violette and Lentini, Pia and Malone, Louise A. and Marshall, Jon and Mart{\´i}nez Pach{\´o}n, Eliana and McFrederick, Quinn S. and Morales, Carolina L. and Mudri-Stojnic, Sonja and Nates-Parra, Guiomar and Nilsson, Sven G. and {\"O}ckinger, Erik and Osgathorpe, Lynne and Parra-H, Alejandro and Peres, Carlos A. and Persson, Anna S. and Petanidou, Theodora and Poveda, Katja and Power, Eileen F. and Quaranta, Marino and Quintero, Carolina and Rader, Romina and Richards, Miriam H. and Roulston, T'ai and Rousseau, Laurent and Sadler, Jonathan P. and Samneg{\aa}rd, Ulrika and Schellhorn, Nancy A. and Sch{\"u}epp, Christof and Schweiger, Oliver and Smith-Pardo, Allan H. and Steffan-Dewenter, Ingolf and Stout, Jane C. and Tonietto, Rebecca K. and Tscharntke, Teja and Tylianakis, Jason M. and Verboven, Hans A. F. and Vergara, Carlos H. and Verhulst, Jort and Westphal, Catrin and Yoon, Hyung Joo and Purvis, Andy}, title = {Predicting bee community responses to land-use changes: Effects of geographic and taxonomic biases}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, doi = {10.1038/srep31153}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167642}, pages = {31153}, year = {2016}, abstract = {Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises.}, language = {en} } @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} } @article{KochereshkoDurnevBesombesetal.2016, author = {Kochereshko, Vladimir P. and Durnev, Mikhail V. and Besombes, Lucien and Mariette, Henri and Sapega, Victor F. and Askitopoulos, Alexis and Savenko, Ivan G. and Liew, Timothy C. H. and Shelykh, Ivan A. and Platonov, Alexey V. and Tsintzos, Simeon I. and Hatzopoulos, Z. and Savvidis, Pavlos G. and Kalevich, Vladimir K. and Afanasiev, Mikhail M. and Lukoshkin, Vladimir A. and Schneider, Christian and Amthor, Matthias and Metzger, Christian and Kamp, Martin and Hoefling, Sven and Lagoudakis, Pavlos and Kavokin, Alexey}, title = {Lasing in Bose-Fermi mixtures}, series = {Scientific Reports}, volume = {6}, journal = {Scientific Reports}, number = {20091}, doi = {10.1038/srep20091}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168152}, year = {2016}, abstract = {Light amplification by stimulated emission of radiation, well-known for revolutionising photonic science, has been realised primarily in fermionic systems including widely applied diode lasers. The prerequisite for fermionic lasing is the inversion of electronic population, which governs the lasing threshold. More recently, bosonic lasers have also been developed based on Bose-Einstein condensates of exciton-polaritons in semiconductor microcavities. These electrically neutral bosons coexist with charged electrons and holes. In the presence of magnetic fields, the charged particles are bound to their cyclotron orbits, while the neutral exciton-polaritons move freely. We demonstrate how magnetic fields affect dramatically the phase diagram of mixed Bose-Fermi systems, switching between fermionic lasing, incoherent emission and bosonic lasing regimes in planar and pillar microcavities with optical and electrical pumping. We collected and analyzed the data taken on pillar and planar microcavity structures at continuous wave and pulsed optical excitation as well as injecting electrons and holes electronically. Our results evidence the transition from a Bose gas to a Fermi liquid mediated by magnetic fields and light-matter coupling.}, language = {en} }