@article{ArnholdtKamawalHolzapfeletal.2018, author = {Arnholdt, J{\"o}rg and Kamawal, Yama and Holzapfel, Boris Michael and Ripp, Axel and Rudert, Maximilian and Steinert, Andre Friedrich}, title = {Evaluation of implant fit and frontal plane alignment after bi-compartmental knee arthroplasty using patient-specific instruments and implants}, series = {Archives of Medical Science}, volume = {14}, journal = {Archives of Medical Science}, number = {6}, doi = {10.5114/aoms.2018.79007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159668}, pages = {1424-1431}, year = {2018}, abstract = {Introduction The goals of successful bi-compartmental knee arthroplasty are to achieve correct fit and positioning of the implant, while appropriately correcting the mechanical alignment of the leg after surgery. As these requirements are not always reliably fulfilled using off-the-shelf implant systems, newer approaches for bi-compartmental resurfacing have been explored. Material and methods In this article we report the radiographic results of 30 patients with anteromedial osteoarthritis (OA) who were treated with a novel patient-specific fixed-bearing bi-compartmental knee resurfacing system using custom-made implants and instruments. Utilizing standardized pre- and postoperative radiographic analyses (based on anterior-posterior and lateral, anterior-posterior weight-bearing full-length radiographs, patella skyline views and preoperative computed tomography (CT) scanning) implant fit and positioning as well as correction of the mechanical axis (hip-knee-ankle angle, HKA) were determined. Results On average, HKA was corrected from 173.4 ±3.47° preoperatively to 179.4 ±2.85° postoperatively. The coronal femoro-tibial angle was corrected on average 5.61°. The preoperative tibial slope measured on lateral views was 6.38 ±2.4°, while the average slope in the CT-based planning protocol (iView) was 6.14 ±2.40°. Postoperative lateral tibial slope was determined to be 5.77 ±1.97°. The thickness of the posterior femoral cuts was measured intraoperatively and, in all cases, corresponded well to the targeted thickness of the cuts provided by the iView. The joint line was preserved in all cases and the average Insall-Salvati index was 1.078 ±0.11 pre- and 1.072 ±0.11 postoperatively. The fit of the implant components measured by over- or underhang was excellent throughout (< 1.01 mm). Conclusions Custom-made bicompartmental knee arthroplasty can ensure optimized fitting and positioning of the implant with restoration of the leg axis. These implants could be considered as an alternative primary solution for knee surgeons treating bi-compartmental disease.}, language = {en} } @article{KohlmorgenEliasSchoen2017, author = {Kohlmorgen, Britta and Elias, Johannes and Schoen, Christoph}, title = {Improved performance of the artus Mycobacterium tuberculosis RG PCR kit in a low incidence setting: a retrospective monocentric study}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {14127}, doi = {10.1038/s41598-017-14367-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159248}, year = {2017}, abstract = {Tuberculosis (TB) and the spread of Mycobacterium tuberculosis complex (MTBC) strains resistant against rifampin (RIF) and isoniazid (INH) pose a serious threat to global health. However, rapid and reliable MTBC detection along with RIF/INH susceptibility testing are challenging in low prevalence countries due to the higher rate of false positives. Here, we provide the first performance data for the artus MTBC PCR assay in a low prevalence setting. We analyze 1323 respiratory and 311 non-respiratory samples with the artus MTBC PCR assay as well as by mycobacterial culture and microscopy. We propose retesting of specimens in duplicate and consideration of a determined cycle-threshold value cut-off greater than 34, as this significantly increases accuracy, specificity, and negative predictive value without affecting sensitivity. Furthermore, we tested fourteen MTBC positive samples with the GenoType MTBDRplus test and demonstrate that using an identical DNA extraction protocol for both assays does not impair downstream genotypic testing for RIF and INH susceptibility. In conclusion, our procedure optimizes the use of the artus MTB assay with workload efficient methods in a low incidence setting. Combining the modified artus MTB with the GenoType MTBDRplus assays allows rapid and accurate detection of MTBC and RIF/INH resistance.}, language = {en} } @article{LapaAriasLozaHayakawaetal.2017, author = {Lapa, Constantin and Arias-Loza, Paula and Hayakawa, Nobuyuki and Wakabayashi, Hiroshi and Werner, Rudolf A. and Chen, Xinyu and Shinaji, Tetsuya and Herrmann, Ken and Pelzer, Theo and Higuchi, Takahiro}, title = {Whitening and impaired glucose utilization of brown adipose tissue in a rat model of type 2 diabetes mellitus}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-17148-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159066}, pages = {16795}, year = {2017}, abstract = {Brown adipose tissue (BAT) is an attractive therapeutic target to combat diabetes and obesity due to its ability to increase glucose expenditure. In a genetic rat model (ZDF fa/fa) of type-2 diabetes and obesity, we aimed to investigate glucose utilization of BAT by \(^{18}\)F-FDG PET imaging. Male Zucker diabetic fatty (ZDF) and Male Zucker lean (ZL) control rats were studied at 13 weeks. Three weeks prior to imaging, ZDF rats were randomized into a no-restriction (ZDF-ND) and a mild calorie restriction (ZDF-CR) group. Dynamic \(^{18}\)F-FDG PET using a dedicated small animal PET system was performed under hyperinsulinemic-euglycemic clamp. \(^{18}\)F-FDG PET identified intense inter-scapular BAT glucose uptake in all ZL control rats, while no focally increased \(^{18}\)F-FDG uptake was detected in all ZDF-ND rats. Mild but significant improved BAT tracer uptake was identified after calorie restriction in diabetic rats (ZDF-CR). The weight of BAT tissue and fat deposits were significantly increased in ZDF-CR and ZDF-ND rats as compared to ZL controls, while UCP-1 and mitochondrial concentrations were significantly decreased. Whitening and severely impaired insulin-stimulated glucose uptake in BAT was confirmed in a rat model of type-2 diabetes. Additionally, calorie restriction partially restored the impaired BAT glucose uptake.}, language = {en} } @article{HefnerBerberichLanversetal.2017, author = {Hefner, Jochen and Berberich, Sara and Lanvers, Elena and Sanning, Maria and Steimer, Ann-Kathrin and Kunzmann, Volker}, title = {New insights into frequency and contents of fear of cancer progression/recurrence (FOP/FCR) in outpatients with colorectal carcinoma (CRC) receiving oral capecitabine: a pilot study at a comprehensive cancer center}, series = {Patient Preference and Adherence}, volume = {11}, journal = {Patient Preference and Adherence}, doi = {10.2147/PPA.S142784}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158476}, pages = {1907-1914}, year = {2017}, abstract = {Background: Fear of cancer progression/recurrence (FOP/FCR) is considered one of the most prevalent sources of distress in cancer survivors and associated with lower quality of life and functional impairment. Detailed measures of FOP/FCR are needed because little is known about the knowledge of FOP/FCR, its associations with the patient-doctor relationship, and the rate of adequate therapy. Colorectal cancer (CRC) is one of the most prevalent cancer entities, and oral capecitabine is widely prescribed as treatment. Therefore, we initiated a pilot study to expand the literature on FOP/FCR in CRC outpatients receiving capecitabine and to generate hypotheses for future investigations. Methods: This study included 58 patients treated at a comprehensive cancer center. FOP/FCR was assessed with the Fear of Progression Questionnaire (FOP-Q-SF). Satisfaction with the relationships with doctors was assessed with the Patient-Doctor Relationship Questionnaire-9 (PRDQ-9). Levels of side effects were rated by the patients on a visual analog scale. Clinical data were extracted from the charts. Results: A total of 19 out of 58 patients (36\%) suffered from FOP/FCR according to our assessment. Levels of FOP/FCR seemed to be mostly moderate to high. Only four out of the 19 distressed patients (21\%) were treated accordingly. Typical side effects of oncological treatment were associated with higher FOP/FCR. Satisfaction with doctor-patient relationships was not associated with FOP/FCR. Regarding single items of FOP/FCR, three out of the five most prevalent fears were associated with close relatives. Discussion: FOP/FCR occurred frequently in more than one in three patients, but was mostly untreated in this sample of consecutive outpatients with CRC receiving oral capecitabine. In detail, most fears were related to family and friends. In addition to an unmet need of patients, our data indicate sources of distress not considered thus far. If replicated in larger studies, results may help to inform intervention development and improve patient care.}, language = {en} } @article{LapaKircherSchirbeletal.2017, author = {Lapa, Constantin and Kircher, Stefan and Schirbel, Andreas and Rosenwald, Andreas and Kropf, Saskia and Pelzer, Theo and Walles, Thorsten and Buck, Andreas K. and Weber, Wolfgang A. and Wester, Hans-Juergen and Herrmann, Ken and L{\"u}ckerath, Katharina}, title = {Targeting CXCR4 with [\(^{68}\)Ga]Pentixafor: a suitable theranostic approach in pleural mesothelioma?}, series = {Oncotarget}, volume = {8}, journal = {Oncotarget}, number = {57}, doi = {10.18632/oncotarget.18235}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169989}, pages = {96732-96737}, year = {2017}, abstract = {C-X-C motif chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. This study investigated the feasibility of CXCR4-directed imaging with positron emission tomography/computed tomography (PET/CT) using [\(^{68}\)Ga]Pentixafor in malignant pleural mesothelioma. Six patients with pleural mesothelioma underwent [\(^{68}\)Ga]Pentixafor-PET/CT. 2′-[\(^{18}\)F]fluoro-2′-deoxy-D-glucose ([\(^{18}\)F]FDG)-PET/CT (4/6 patients) and immunohistochemistry obtained from biopsy or surgery (all) served as standards of reference. Additionally, 9 surgical mesothelioma samples were available for histological work-up. Whereas [\(^{18}\)F]FDG-PET depicted active lesions in all patients, [\(^{68}\)Ga]Pentixafor-PET/CT recorded physiologic tracer distribution and none of the 6 patients presented [\(^{68}\)Ga]Pentixafor-positive lesions. This finding paralleled results of immunohistochemistry which also could not identify relevant CXCR4 surface expression in the samples analyzed. In contrast to past reports, our data suggest widely absence of CXCR4 expression in pleural mesothelioma. Hence, robust cell surface expression should be confirmed prior to targeting this chemokine receptor for diagnosis and/or therapy.}, language = {en} } @article{SunkavalliAguilarSilvaetal.2017, author = {Sunkavalli, Ushasree and Aguilar, Carmen and Silva, Ricardo Jorge and Sharan, Malvika and Cruz, Ana Rita and Tawk, Caroline and Maudet, Claire and Mano, Miguel and Eulalio, Ana}, title = {Analysis of host microRNA function uncovers a role for miR-29b-2-5p in Shigella capture by filopodia}, series = {PLoS Pathogens}, volume = {13}, journal = {PLoS Pathogens}, number = {4}, doi = {10.1371/journal.ppat.1006327}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158204}, pages = {e1006327}, year = {2017}, abstract = {MicroRNAs play an important role in the interplay between bacterial pathogens and host cells, participating as host defense mechanisms, as well as exploited by bacteria to subvert host cellular functions. Here, we show that microRNAs modulate infection by Shigella flexneri, a major causative agent of bacillary dysentery in humans. Specifically, we characterize the dual regulatory role of miR-29b-2-5p during infection, showing that this microRNA strongly favors Shigella infection by promoting both bacterial binding to host cells and intracellular replication. Using a combination of transcriptome analysis and targeted high-content RNAi screening, we identify UNC5C as a direct target of miR-29b-2-5p and show its pivotal role in the modulation of Shigella binding to host cells. MiR-29b-2-5p, through repression of UNC5C, strongly enhances filopodia formation thus increasing Shigella capture and promoting bacterial invasion. The increase of filopodia formation mediated by miR-29b-2-5p is dependent on RhoF and Cdc42 Rho-GTPases. Interestingly, the levels of miR-29b-2-5p, but not of other mature microRNAs from the same precursor, are decreased upon Shigella replication at late times post-infection, through degradation of the mature microRNA by the exonuclease PNPT1. While the relatively high basal levels of miR-29b-2-5p at the start of infection ensure efficient Shigella capture by host cell filopodia, dampening of miR-29b-2-5p levels later during infection may constitute a bacterial strategy to favor a balanced intracellular replication to avoid premature cell death and favor dissemination to neighboring cells, or alternatively, part of the host response to counteract Shigella infection. Overall, these findings reveal a previously unappreciated role of microRNAs, and in particular miR-29b-2-5p, in the interaction of Shigella with host cells.}, language = {en} } @article{PieczykolanHuestegge2017, author = {Pieczykolan, Aleks and Huestegge, Lynn}, title = {Cross-modal Action Complexity: Action- and Rule-related Memory Retrieval in Dual-response Control}, series = {Frontiers in Psychology}, volume = {8}, journal = {Frontiers in Psychology}, number = {529}, doi = {10.3389/fpsyg.2017.00529}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157794}, year = {2017}, abstract = {Normally, we do not act within a single effector system only, but rather coordinate actions across several output modules (cross-modal action). Such cross-modal action demands can vary substantially with respect to their complexity in terms of the number of task-relevant response combinations and to-be-retrieved stimulus-response (S-R) mapping rules. In the present study, we study the impact of these two types of cross-modal action complexity on dual-response costs (i.e., performance differences between single- and dual-action demands). In Experiment 1, we combined a manual and an oculomotor task, each involving four response alternatives. Crucially, one (unconstrained) condition involved all 16 possible combinations of response alternatives, whereas a constrained condition involved only a subset of possible response combinations. The results revealed that preparing for a larger number of response combinations yielded a significant, but moderate increase in dual-response costs. In Experiment 2, we utilized one common lateralized auditory (e.g., left) stimulus to trigger incompatible response compounds (e.g., left saccade and right key press or vice versa). While one condition only involved one set of task-relevant S-R rules, another condition involved two sets of task-relevant rules (coded by stimulus type: noise/tone), while the number of task-relevant response combinations was the same in both conditions. Here, an increase in the number of to-be-retrieved S-R rules was associated with a substantial increase in dual-response costs that were also modulated on a trial-by-trial basis when switching between rules. Taken together, the results shed further light on the dependency of cross-modal action control on both action- and rule-related memory retrieval processes.}, language = {en} } @article{SchmidtSkafGavriletal.2017, author = {Schmidt, Marianne and Skaf, Josef and Gavril, Georgiana and Polednik, Christine and Roller, Jeanette and Kessler, Michael and Holzgrabe, Ulrike}, title = {The influence of Osmunda regalis root extract on head and neck cancer cell proliferation, invasion and gene expression}, series = {BMC Complementary and Alternative Medicine}, volume = {17}, journal = {BMC Complementary and Alternative Medicine}, number = {518}, doi = {10.1186/s12906-017-2009-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158704}, year = {2017}, abstract = {Background: According to only a handful of historical sources, Osmunda regalis, the royal fern, has been used already in the middle age as an anti-cancer remedy. To examine this ancient cancer cure, an ethanolic extract of the roots was prepared and analysed in vitro on its effectiveness against head and neck cancer cell lines. Methods: Proliferation inhibition was measured with the MTT assay. Invasion inhibition was tested in a spheroid-based 3-D migration assay on different extracellular matrix surfaces. Corresponding changes in gene expression were analysed by qRT-PCR array. Induction of apoptosis was measured by fluorescence activated cell sorting (FACS) with the Annexin V binding method. The plant extract was analysed by preliminary phytochemical tests, liquid chromatography/mass spectroscopy (LC-MS) and thin layer chromatography (TLC). Anti-angiogenetic activity was determined by the tube formation assay. Results: O. regalis extract revealed a growth inhibiting effect on the head and neck carcinoma cell lines HLaC78 and FaDu. The toxic effect seems to be partially modulated by p-glycoprotein, as the MDR-1 expressing HLaC79-Tax cells were less sensitive. O. regalis extract inhibited the invasion of cell lines on diverse extracellular matrix substrates significantly. Especially the dispersion of the highly motile cell line HlaC78 on laminin was almost completely abrogated. Motility inhibition on laminin was accompanied by differential gene regulation of a variety of genes involved in cell adhesion and metastasis. Furthermore, O. regalis extract triggered apoptosis in HNSCC cell lines and inhibited tube formation of endothelial cells. Preliminary phytochemical analysis proved the presence of tannins, glycosides, steroids and saponins. Liquid chromatography/mass spectroscopy (LC-MS) revealed a major peak of an unknown substance with a molecular mass of 864.15 Da, comprising about 50\% of the total extract. Thin layer chromatography identified ferulic acid to be present in the extract. Conclusion: The presented results justify the use of royal fern extracts as an anti-cancer remedy in history and imply a further analysis of ingredients.}, language = {en} } @article{WernerWeichHiguchietal.2017, author = {Werner, Rudolf A. and Weich, Alexander and Higuchi, Takahiro and Schmid, Jan S. and Schirbel, Andreas and Lassmann, Michael and Wild, Vanessa and Rudelius, Martina and Kudlich, Theodor and Herrmann, Ken and Scheurlen, Michael and Buck, Andreas K. and Kropf, Saskia and Wester, Hans-J{\"u}rgen and Lapa, Constantin}, title = {Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors - a Triple Tracer Comparative Approach}, series = {Theranostics}, volume = {7}, journal = {Theranostics}, number = {6}, doi = {10.7150/thno.18754}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158008}, pages = {1489-1498}, year = {2017}, abstract = {C-X-C motif chemokine receptor 4 (CXCR4) and somatostatin receptors (SSTR) are overexpressed in gastro-entero-pancreatic neuroendocrine tumors (GEP-NET). In this study, we aimed to elucidate the feasibility of non-invasive CXCR4 positron emission tomography/computed tomography (PET/CT) imaging in GEP-NET patients using [\(^{68}\)Ga]Pentixafor in comparison to \(^{68}\)Ga-DOTA-D-Phe-Tyr3-octreotide ([\(^{68}\)Ga]DOTATOC) and \(^{18}\)F-fluorodeoxyglucose ([\(^{18}\)F]FDG). Twelve patients with histologically proven GEP-NET (3xG1, 4xG2, 5xG3) underwent [\(^{68}\)Ga]DOTATOC, [\(^{18}\)F]FDG, and [\(^{68}\)Ga]Pentixafor PET/CT for staging and planning of the therapeutic management. Scans were analyzed on a patient as well as on a lesion basis and compared to immunohistochemical staining patterns of CXCR4 and somatostatin receptors SSTR2a and SSTR5. [\(^{68}\)Ga]Pentixafor visualized tumor lesions in 6/12 subjects, whereas [\(^{18}\)F]FDG revealed sites of disease in 10/12 and [\(^{68}\)Ga]DOTATOC in 11/12 patients, respectively. Regarding sensitivity, SSTR-directed PET was the superior imaging modality in all G1 and G2 NET. CXCR4-directed PET was negative in all G1 NET. In contrast, 50\% of G2 and 80\% of G3 patients exhibited [\(^{68}\)Ga]Pentixafor-positive tumor lesions. Whereas CXCR4 seems to play only a limited role in detecting well-differentiated NET, increasing receptor expression could be non-invasively observed with increasing tumor grade. Thus, [\(^{68}\)Ga]Pentixafor PET/CT might serve as non-invasive read-out for evaluating the possibility of CXCR4-directed endoradiotherapy in advanced dedifferentiated SSTR-negative tumors.}, subject = {Positronen-Emissions-Tomografie}, language = {en} } @article{EmmertKneisel2017, author = {Emmert, Adrian and Kneisel, Christof}, title = {Internal structure of two alpine rock glaciers investigated by quasi-3-D electrical resistivity imaging}, series = {The Cryosphere}, volume = {11}, journal = {The Cryosphere}, doi = {10.5194/tc-11-841-2017}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157569}, pages = {841-855}, year = {2017}, abstract = {Interactions between different formative processes are reflected in the internal structure of rock glaciers. Therefore, the detection of subsurface conditions can help to enhance our understanding of landform development. For an assessment of subsurface conditions, we present an analysis of the spatial variability of active layer thickness, ground ice content and frost table topography for two different rock glaciers in the Eastern Swiss Alps by means of quasi-3-D electrical resistivity imaging (ERI). This approach enables an extensive mapping of subsurface structures and a spatial overlay between site-specific surface and subsurface characteristics. At Nair rock glacier, we discovered a gradual descent of the frost table in a downslope direction and a constant decrease of ice content which follows the observed surface topography. This is attributed to ice formation by refreezing meltwater from an embedded snow bank or from a subsurface ice patch which reshapes the permafrost layer. The heterogeneous ground ice distribution at Uertsch rock glacier indicates that multiple processes on different time domains were involved in the development. Resistivity values which represent frozen conditions vary within a wide range and indicate a successive formation which includes several advances, past glacial overrides and creep processes on the rock glacier surface. In combination with the observed topography, quasi-3-D ERI enables us to delimit areas of extensive and compressive flow in close proximity. Excellent data quality was provided by a good coupling of electrodes to the ground in the pebbly material of the investigated rock glaciers. Results show the value of the quasi-3-D ERI approach but advise the application of complementary geophysical methods for interpreting the results.}, language = {en} } @article{KraftFleischerWiedmannetal.2017, author = {Kraft, Peter and Fleischer, Anna and Wiedmann, Silke and R{\"u}cker, Viktoria and Mackenrodt, Daniel and Morbach, Caroline and Malzahn, Uwe and Kleinschnitz, Christoph and St{\"o}rk, Stefan and Heuschmann, Peter U.}, title = {Feasibility and diagnostic accuracy of point-of-care handheld echocardiography in acute ischemic stroke patients - a pilot study}, series = {BMC Neurology}, volume = {17}, journal = {BMC Neurology}, number = {159}, doi = {10.1186/s12883-017-0937-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158081}, year = {2017}, abstract = {Background: Standard echocardiography (SE) is an essential part of the routine diagnostic work-up after ischemic stroke (IS) and also serves for research purposes. However, access to SE is often limited. We aimed to assess feasibility and accuracy of point-of-care (POC) echocardiography in a stroke unit (SU) setting. Methods: IS patients were recruited on the SU of the University Hospital W{\"u}rzburg, Germany. Two SU team members were trained in POC echocardiography for a three-month period to assess a set of predefined cardiac parameters including left ventricular ejection fraction (LVEF). Diagnostic agreement was assessed by comparing POC with SE executed by an expert sonographer, and intraclass correlation coefficient (ICC) or kappa (κ) with 95\% confidence intervals (95\% CI) were calculated. Results: In the 78 patients receiving both POC and SE agreement for cardiac parameters was good, with ICC varying from 0.82 (95\% CI 0.71-0.89) to 0.93 (95\% CI 0.87-0.96), and κ from 0.39 (-95\% CI 0.14-0.92) to 0.79 (95\% CI 0.67-0.91). Detection of systolic dysfunction with POC echocardiography compared to SE was very good, with an area under the curve of 0.99 (0.96-1.00). Interrater agreement for LVEF measured by POC echocardiography was good with κ 0.63 (95\% CI 0.40-0.85). Conclusions: POC echocardiography in a SU setting is feasible enabling reliable quantification of LVEF and preliminary assessment of selected cardiac parameters that might be used for research purposes. Its potential clinical utility in triaging stroke patients who should undergo or do not necessarily require SE needs to be investigated in larger prospective diagnostic studies.}, language = {en} } @article{LaglerElMeseryKuebleretal.2017, author = {Lagler, Charlotte and El-Mesery, Mohamed and K{\"u}bler, Alexander Christian and M{\"u}ller-Richter, Urs Dietmar Achim and St{\"u}hmer, Thorsten and Nickel, Joachim and M{\"u}ller, Thomas Dieter and Wajant, Harald and Seher, Axel}, title = {The anti-myeloma activity of bone morphogenetic protein 2 predominantly relies on the induction of growth arrest and is apoptosis-independent}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {10}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158993}, pages = {e0185720}, year = {2017}, abstract = {Multiple myeloma (MM), a malignancy of the bone marrow, is characterized by a pathological increase in antibody-producing plasma cells and an increase in immunoglobulins (plasmacytosis). In recent years, bone morphogenetic proteins (BMPs) have been reported to be activators of apoptotic cell death in neoplastic B cells in MM. Here, we use bone morphogenetic protein 2 (BMP2) to show that the "apoptotic" effect of BMPs on human neoplastic B cells is dominated by anti-proliferative activities and cell cycle arrest and is apoptosis-independent. The anti-proliferative effect of BMP2 was analysed in the human cell lines KMS12-BM and L363 using WST-1 and a Coulter counter and was confirmed using CytoTox assays with established inhibitors of programmed cell death (zVAD-fmk and necrostatin-1). Furthermore, apoptotic activity was compared in both cell lines employing western blot analysis for caspase 3 and 8 in cells treated with BMP2 and FasL. Additionally, expression profiles of marker genes of different cell death pathways were analysed in both cell lines after stimulation with BMP2 for 48h using an RT-PCR-based array. In our experiments we observed that there was rather no reduction in absolute cell number, but cells stopped proliferating following treatment with BMP2 instead. The time frame (48-72 h) after BMP2 treatment at which a reduction in cell number is detectable is too long to indicate a directly BMP2-triggered apoptosis. Moreover, in comparison to robust apoptosis induced by the approved apoptotic factor FasL, BMP2 only marginally induced cell death. Consistently, neither the known inhibitor of apoptotic cell death zVAD-fmk nor the necroptosis inhibitor necrostatin-1 was able to rescue myeloma cell growth in the presence of BMP2.}, language = {en} } @article{MorbachWagnerGuentneretal.2017, author = {Morbach, Caroline and Wagner, Martin and G{\"u}ntner, Stefan and Malsch, Carolin and Oezkur, Mehmet and Wood, David and Kotseva, Kornelia and Leyh, Rainer and Ertl, Georg and Karmann, Wolfgang and Heuschmann, Peter U and St{\"o}rk, Stefan}, title = {Heart failure in patients with coronary heart disease: Prevalence, characteristics and guideline implementation - Results from the German EuroAspire IV cohort}, series = {BMC Cardiovascular Disorders}, volume = {17}, journal = {BMC Cardiovascular Disorders}, number = {108}, doi = {10.1186/s12872-017-0543-0}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157738}, year = {2017}, abstract = {Background: Adherence to pharmacotherapeutic treatment guidelines in patients with heart failure (HF) is of major prognostic importance, but thorough implementation of guidelines in routine care remains insufficient. Our aim was to investigate prevalence and characteristics of HF in patients with coronary heart disease (CHD), and to assess the adherence to current HF guidelines in patients with HF stage C, thus identifying potential targets for the optimization of guideline implementation. Methods: Patients from the German sample of the European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EuroAspire) IV survey with a hospitalization for CHD within the previous six to 36 months providing valid data on echocardiography as well as on signs and symptoms of HF were categorized into stages of HF: A, prevalence of risk factors for developing HF; B, asymptomatic but with structural heart disease; C, symptomatic HF. A Guideline Adherence Indicator (GAI-3) was calculated for patients with reduced (≤40\%) left ventricular ejection fraction (HFrEF) as number of drugs taken per number of drugs indicated; beta-blockers, angiotensin converting enzyme inhibitors/angiotensin receptor blockers, and mineralocorticoid receptor antagonists (MRA) were considered. Results: 509/536 patients entered analysis. HF stage A was prevalent in n = 20 (3.9\%), stage B in n = 264 (51.9\%), and stage C in n = 225 (44.2\%) patients; 94/225 patients were diagnosed with HFrEF (42\%). Stage C patients were older, had a longer duration of CHD, and a higher prevalence of arterial hypertension. Awareness of pre-diagnosed HF was low (19\%). Overall GAI-3 of HFrEF patients was 96.4\% with a trend towards lower GAI-3 in patients with lower LVEF due to less thorough MRA prescription. Conclusions: In our sample of CHD patients, prevalence of HF stage C was high and a sizable subgroup suffered from HFrEF. Overall, pharmacotherapy was fairly well implemented in HFrEF patients, although somewhat worse in patients with more reduced ejection fraction. Two major targets were identified possibly suited to further improve the implementation of HF guidelines: 1) increase patients´ awareness of diagnosis and importance of HF; and 2) disseminate knowledge about the importance of appropriately implementing the use of mineralocorticoid receptor antagonists. Trial registration: This is a cross-sectional analysis of a non-interventional study. Therefore, it was not registered as an interventional trial.}, language = {en} } @article{WegertVokuhZiegleretal.2017, author = {Wegert, Jenny and Vokuh, Christian and Ziegler, Barbara and Ernestus, Karen and Leuschner, Ivo and Furtw{\"a}ngler, Rhoikos and Graf, Norbert and Gessler, Manfred}, title = {TP53 alterations in Wilms tumour represent progression events with strong intratumour heterogeneity that are closely linked but not limited to anaplasia}, series = {The Journal of Pathology: Clinical Research}, volume = {3}, journal = {The Journal of Pathology: Clinical Research}, doi = {10.1002/cjp2.77}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158302}, pages = {234-248}, year = {2017}, abstract = {TP53 mutations have been associated with anaplasia in Wilms tumour, which conveys a high risk for relapse and fatal outcome. Nevertheless, TP53 alterations have been reported in no more than 60\% of anaplastic tumours, and recent data have suggested their presence in tumours that do not fulfil the criteria for anaplasia, questioning the clinical utility of TP53 analysis. Therefore, we characterized the TP53 status in 84 fatal cases of Wilms tumour, irrespective of histological subtype. We identified TP53 alterations in at least 90\% of fatal cases of anaplastic Wilms tumour, and even more when diffuse anaplasia was present, indicating a very strong if not absolute coupling between anaplasia and deregulation of p53 function. Unfortunately, TP53 mutations do not provide additional predictive value in anaplastic tumours since the same mutation rate was found in a cohort of non-fatal anaplastic tumours. When classified according to tumour stage, patients with stage I diffuse anaplastic tumours still had a high chance of survival (87\%), but this rate dropped to 26\% for stages II-IV. Thus, volume of anaplasia or possible spread may turn out to be critical parameters. Importantly, among non-anaplastic fatal tumours, 26\% had TP53 alterations, indicating that TP53 screening may identify additional cases at risk. Several of these non-anaplastic tumours fulfilled some criteria for anaplasia, for example nuclear unrest, suggesting that such partial phenotypes should be under special scrutiny to enhance detection of high-risk tumours via TP53 screening. A major drawback is that these alterations are secondary changes that occur only later in tumour development, leading to striking intratumour heterogeneity that requires multiple biopsies and analysis guided by histological criteria. In conclusion, we found a very close correlation between histological signs of anaplasia and TP53 alterations. The latter may precede development of anaplasia and thereby provide diagnostic value pointing towards aggressive disease.}, language = {en} } @article{JessbergerHoeggerGenestetal.2017, author = {Jessberger, Steffen and H{\"o}gger, Petra and Genest, Franca and Salter, Donald M. and Seefried, Lothar}, title = {Cellular pharmacodynamic effects of Pycnogenol\(^{®}\) in patients with severe osteoarthritis: a randomized controlled pilot study}, series = {BMC Complementary and Alternative Medicine}, volume = {17}, journal = {BMC Complementary and Alternative Medicine}, number = {537}, doi = {10.1186/s12906-017-2044-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159532}, year = {2017}, abstract = {Background: The standardized maritime pine bark extract (Pycnogenol\(^{®}\)) has previously shown symptom alleviating effects in patients suffering from moderate forms of knee osteoarthritis (OA). The cellular mechanisms for this positive impact are so far unknown. The purpose of the present randomized pilot controlled study was to span the knowledge gap between the reported clinical effects of Pycnogenol\(^{®}\) and its in vivo mechanism of action in OA patients. Methods: Thirty three patients with severe OA scheduled for a knee arthroplasty either received 100 mg of Pycnogenol\(^{®}\) twice daily or no treatment (control group) three weeks before surgery. Cartilage, synovial fluid and serum samples were collected during surgical intervention. Relative gene expression of cartilage homeostasis markers were analyzed in the patients' chondrocytes. Inflammatory and cartilage metabolism mediators were investigated in serum and synovial fluid samples. Results: The oral intake of Pycnogenol\(^{®}\) downregulated the gene expression of various cartilage degradation markers in the patients' chondrocytes, the decrease of MMP3, MMP13 and the pro-inflammatory cytokine IL1B were statistically significant (p ≤ 0.05). Additionally, protein concentrations of ADAMTS-5 in serum were reduced significantly (p ≤ 0.05) after three weeks intake of the pine bark extract. Conclusions: This is the first report about positive cellular effects of a dietary supplement on key catabolic and inflammatory markers in patients with severe OA. The results provide a rational basis for understanding previously reported clinical effects of Pycnogenol\(^{®}\) on symptom scores of patients suffering from OA.}, language = {en} } @article{PolatKaiserWohllebenetal.2017, author = {Polat, B{\"u}lent and Kaiser, Philipp and Wohlleben, Gisela and Gehrke, Thomas and Scherzad, Agmal and Scheich, Matthias and Malzahn, Uwe and Fischer, Thomas and Vordermark, Dirk and Flentje, Michael}, title = {Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer}, series = {BMC Cancer}, volume = {17}, journal = {BMC Cancer}, number = {6}, doi = {10.1186/s12885-016-3024-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157529}, year = {2017}, abstract = {Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). Results: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Conclusions: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.}, language = {en} } @article{SayedSchimmerShadeetal.2017, author = {Sayed, Sameh and Schimmer, Christoph and Shade, Ina and Leyh, Rainer and Aleksic, Ivan}, title = {Combined pulmonary and left ventricular support with veno-pulmonary ECMO and impella 5.0 for cardiogenic shock after coronary surgery}, series = {Journal of Cardiothoracic Surgery}, volume = {12}, journal = {Journal of Cardiothoracic Surgery}, number = {38}, doi = {10.1186/s13019-017-0594-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157598}, year = {2017}, abstract = {Background: Mechanical circulatory support is a common practice nowadays in the management of patients after cardiogenic shock due to myocardial infarction. The single or combined use of one or more devices for mechanical support depends not only on the advantage or disadvantage of these devices but also on the timing of use of these devices before the development of multi organ failure. In our case we used more than one tool for mechanical circulatory support during the prolonged and complicated course of our patient with postcardiotomy cardiogenic shock after coronary artery bypass surgery. Case Presentation: We describe the combined use of Impella 5.0 and veno- pulmonary extra corporeal membrane oxygenation (VP-ECMO) for biventricular failure in a 52 years—old man. He presented with cardiogenic shock after inferior wall ST-elevation myocardial infarction. After emergency coronary artery bypass surgery and failure to wean from extracorporeal circulation we employed V-P ECMO and consecutively Impella 5.0 to manage the primarily failing right and secondarily failing left ventricles. He remained hemodynamically stable on both Impella 5.0 and VP-ECMO until Heart Mate II left ventricular assist device implantation on the 14th postoperative day. Right sided support was weaned on 66th postoperative day. The patient remained in the intensive care unit for 77 days. During his prolonged stay, he underwent renal replacement therapy and tracheostomy with complete recovery. Six months later, he was successfully heart transplanted and has completed three and half years of unremarkable follow up. Conclusions: The combined use of VP ECMO and Impella 5.0 is effective in the management of postcardiotomy biventricular failure as a bridge for further mechanical support or heart transplantation.}, language = {en} } @article{DoehlerSchneiderEckertetal.2017, author = {D{\"o}hler, Anja and Schneider, Theresa and Eckert, Ina and Ribechini, Eliana and Andreas, Nico and Riemann, Marc and Reizis, Boris and Weih, Falk and Lutz, Manfred B.}, title = {RelB\(^{+}\) Steady-State Migratory Dendritic Cells Control the Peripheral Pool of the Natural Foxp3\(^{+}\) Regulatory T Cells}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {726}, doi = {10.3389/fimmu.2017.00726}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158121}, year = {2017}, abstract = {Thymus-derived natural Foxp3\(^{+}\) CD4\(^{+}\) regulatory T cells (nTregs) play a key role in maintaining immune tolerance and preventing autoimmune disease. Several studies indicate that dendritic cells (DCs) are critically involved in the maintenance and proliferation of nTregs. However, the mechanisms how DCs manage to keep the peripheral pool at constant levels remain poorly understood. Here, we describe that the NF-κB/Rel family transcription factor RelB controls the frequencies of steady-state migratory DCs (ssmDCs) in peripheral lymph nodes and their numbers control peripheral nTreg homeostasis. DC-specific RelB depletion was investigated in CD11c-Cre × RelB\(^{fl/fl}\) mice (RelB\(^{DCko}\)), which showed normal frequencies of resident DCs in lymph nodes and spleen while the subsets of CD103\(^{-}\) Langerin\(^{-}\) dermal DCs (dDCs) and Langerhans cells but not CD103\(^{+}\) Langerin\(^{+}\) dDC of the ssmDCs in skin-draining lymph nodes were increased. Enhanced frequencies and proliferation rates were also observed for nTregs and a small population of CD4\(^{+}\) CD44\(^{high}\) CD25\(^{low}\) memory-like T cells (Tml). Interestingly, only the Tml but not DCs showed an increase in IL-2-producing capacity in lymph nodes of RelB\(^{DCko}\) mice. Blocking of IL-2 in vivo reduced the frequency of nTregs but increased the Tml frequencies, followed by a recovery of nTregs. Taken together, by employing RelB\(^{DCko}\) mice with increased frequencies of ssmDCs our data indicate a critical role for specific ssmDC subsets for the peripheral nTreg and IL-2\(^{+}\) Tml frequencies during homeostasis.}, language = {en} } @article{LangenhorstTabaresGuldeetal.2018, author = {Langenhorst, Daniela and Tabares, Paula and Gulde, Tobias and Becklund, Bryan R. and Berr, Susanne and Surh, Charles D. and Beyersdorf, Niklas and H{\"u}nig, Thomas}, title = {Self-recognition sensitizes mouse and human regulatory T cells to low-dose CD28 superagonist stimulation}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {1985}, doi = {10.3389/fimmu.2017.01985}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159387}, year = {2018}, abstract = {In rodents, low doses of CD28-specific superagonistic monoclonal antibodies (CD28 superagonists, CD28SA) selectively activate regulatory T cells (Treg). This observation has recently been extended to humans, suggesting an option for the treatment of autoimmune and inflammatory diseases. However, a mechanistic explanation for this phenomenon is still lacking. Given that CD28SA amplify T cell receptor (TCR) signals, we tested the hypothesis that the weak tonic TCR signals received by conventional CD4\(^{+}\) T cells (Tconv) in the absence of cognate antigen require more CD28 signaling input for full activation than the stronger TCR signals received by self-reactive Treg. We report that in vitro, the response of mouse Treg and Tconv to CD28SA strongly depends on MHC class II expression by antigen-presenting cells. To separate the effect of tonic TCR signals from self-peptide recognition, we compared the response of wild-type Treg and Tconv to low and high CD28SA doses upon transfer into wild-type or H-2M knockout mice, which lack a self-peptide repertoire. We found that the superior response of Treg to low CD28SA doses was lost in the absence of self-peptide presentation. We also tested if potentially pathogenic autoreactive Tconv would benefit from self-recognition-induced sensitivity to CD28SA stimulation by transferring TCR transgenic OVA-specific Tconv into OVA-expressing mice and found that low-dose CD28SA application inhibited, rather than supported, their expansion, presumably due to the massive concomitant activation of Treg. Finally, we report that also in the in vitro response of human peripheral blood mononuclear cells to CD28SA, HLA II blockade interferes with the expansion of Treg by low-dose CD28SA stimulation. These results provide a rational basis for the further development of low-dose CD28SA therapy for the improvement of Treg activity.}, language = {en} } @article{BornZinnerSperlich2017, author = {Born, Dennis-Peter and Zinner, Christoph and Sperlich, Billy}, title = {The mucosal immune function is not compromised during a period of high-intensity interval training. Is it time to reconsider an old assumption?}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, number = {485}, doi = {10.3389/fphys.2017.00485}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158025}, year = {2017}, abstract = {Purpose: The aim of the study was to evaluate the mucosal immune function and circadian variation of salivary cortisol, Immunoglobin-A (sIgA) secretion rate and mood during a period of high-intensity interval training (HIIT) compared to long-slow distance training (LSD). Methods: Recreational male runners (n = 28) completed nine sessions of either HIIT or LSD within 3 weeks. The HIIT involved 4 × 4 min of running at 90-95\% of maximum heart rate interspersed with 3 min of active recovery while the LSD comprised of continuous running at 70-75\% of maximum heart rate for 60-80 min. The psycho-immunological stress-response was investigated with a full daily profile of salivary cortisol and immunoglobin-A (sIgA) secretion rate along with the mood state on a baseline day, the first and last day of training and at follow-up 4 days after the last day of training. Before and after the training period, each athlete's running performance and peak oxygen uptake (V·O\(_{2peak}\)) was determined with an incremental exercise test. Results: The HIIT resulted in a longer time-to-exhaustion (P = 0.02) and increased V·O\(_{2peak}\) compared to LSD (P = 0.01). The circadian variation of sIgA secretion rate showed highest values in the morning immediately after waking up followed by a decrease throughout the day in both groups (P < 0.05). With HIIT, the wake-up response of sIgA secretion rate was higher on the last day of training (P < 0.01) as well as the area under the curve (AUC\(_{G}\)) higher on the first and last day of training and follow-up compared to the LSD (P = 0.01). Also the AUC\(_{G}\) for the sIgA secretion rate correlated with the increase in V·O\(_{2peak}\) and running performance. The AUC\(_{G}\) for cortisol remained unaffected on the first and last day of training but increased on the follow-up day with both, HIIT and LSD (P < 0.01). Conclusion: The increased sIgA secretion rate with the HIIT indicates no compromised mucosal immune function compared to LSD and shows the functional adaptation of the mucosal immune system in response to the increased stress and training load of nine sessions of HIIT.}, language = {en} } @article{ZinnerBornSperlich2017, author = {Zinner, Christoph and Born, Dennis-Peter and Sperlich, Billy}, title = {Ischemic preconditioning does not alter performance in multidirectional high-intensity intermittent exercise}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, doi = {10.3389/fphys.2017.01029}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159348}, pages = {1029}, year = {2017}, abstract = {Purpose: Research dealing with ischemic preconditioning (IPC) has primarily focused on variables associated to endurance performance with little research about the acute responses of IPC on repeated multidirectional running sprint performance. Here we aimed to investigate the effects of IPC of the arms and the legs on repeated running sprint performance with changes-of-direction (COD) movements. Methods: Thirteen moderately-to-well-trained team-sport athletes (7 males; 6 females; age: 24 ± 2 years, size: 175 ± 8 cm, body mass: 67.9 ± 8.1 kg) performed 16 × 30 m all-out sprints (15 s rest) with multidirectional COD movements on a Speedcourt\(^{©}\) with IPC (3 × 5 min) of the legs (IPC\(_{leg}\); 240 mm Hg) or of the arms (remote IPC: IPC\(_{remote}\); 180-190 mm Hg) 45 min before the sprints and a control trial (CON; 20 mm Hg). Results: The mean (±SD) time for the 16 × 30 m multidirectional COD sprints was similar between IPC\(_{leg}\) (Mean t: 16.0 ± 1.8 s), IPC\(_{remote}\) (16.2 ± 1.7 s), and CON (16.0 ± 1.6 s; p = 0.50). No statistical differences in oxygen uptake (mean difference: 0\%), heart rate (1.1\%) nor muscle oxygen saturation of the vastus lateralis (4.7\%) and biceps brachii (7.8\%) between the three conditions were evident (all p > 0.05). Conclusions: IPC (3 × 5 min) of the legs (220 mm Hg) or arms (180-190 mm Hg; remote IPC) applied 45 min before 16 × 30 m repeated multidirectional running sprint exercise does not improve sprint performance, oxygen uptake, heart rate nor muscle oxygen saturation of the vastus lateralis muscle when compared to a control trial.}, language = {en} } @article{SchuhmannFluri2017, author = {Schuhmann, Michael K. and Fluri, Felix}, title = {Effects of fullerenols on mouse brain microvascular endothelial cells}, series = {International Journal of Molecular Sciences}, volume = {18}, journal = {International Journal of Molecular Sciences}, number = {8}, issn = {1422-0067}, doi = {10.3390/ijms18081783}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158072}, year = {2017}, abstract = {Fullerenols, water-soluble C60-fullerene derivatives, have been shown to exert neuroprotective effects in vitro and in vivo, most likely due to their capability to scavenge free radicals. However, little is known about the effects of fullerenols on the blood-brain barrier (BBB), especially on cerebral endothelial cells under inflammatory conditions. Here, we investigated whether the treatment of primary mouse brain microvascular endothelial cells with fullerenols impacts basal and inflammatory blood-brain barrier (BBB) properties in vitro. While fullerenols (1, 10, and 100 µg/mL) did not change transendothelial electrical resistance under basal and inflammatory conditions, 100 µg/mL of fullerenol significantly reduced erk1/2 activation and resulted in an activation of NFκB in an inflammatory milieu. Our findings suggest that fullerenols might counteract oxidative stress via the erk1/2 and NFκB pathways, and thus are able to protect microvascular endothelial cells under inflammatory conditions.}, language = {en} } @article{DaineseSchneiderKraussetal.2017, author = {Dainese, Matteo and Schneider, Gudrun and Krauss, Jochen and Steffan-Dewenter, Ingolf}, title = {Complementarity among natural enemies enhances pest suppression}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-08316-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158621}, pages = {8172}, year = {2017}, abstract = {Natural enemies have been shown to be effective agents for controlling insect pests in crops. However, it remains unclear how different natural enemy guilds contribute to the regulation of pests and how this might be modulated by landscape context. In a field exclusion experiment in oilseed rape (OSR), we found that parasitoids and ground-dwelling predators acted in a complementary way to suppress pollen beetles, suggesting that pest control by multiple enemies attacking a pest during different periods of its occurrence in the field improves biological control efficacy. The density of pollen beetle significantly decreased with an increased proportion of non-crop habitats in the landscape. Parasitism had a strong effect on pollen beetle numbers in landscapes with a low or intermediate proportion of non-crop habitats, but not in complex landscapes. Our results underline the importance of different natural enemy guilds to pest regulation in crops, and demonstrate how biological control can be strengthened by complementarity among natural enemies. The optimization of natural pest control by adoption of specific management practices at local and landscape scales, such as establishing non-crop areas, low-impact tillage, and temporal crop rotation, could significantly reduce dependence on pesticides and foster yield stability through ecological intensification in agriculture.}, language = {en} } @article{HampeFriedmanEdgertonetal.2017, author = {Hampe, Irene A. I. and Friedman, Justin and Edgerton, Mira and Morschh{\"a}user, Joachim}, title = {An acquired mechanism of antifungal drug resistance simultaneously enables Candida albicans to escape from intrinsic host defenses}, series = {PLoS Pathogens}, volume = {13}, journal = {PLoS Pathogens}, number = {9}, doi = {10.1371/journal.ppat.1006655}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158883}, pages = {e1006655}, year = {2017}, abstract = {The opportunistic fungal pathogen Candida albicans frequently produces genetically altered variants to adapt to environmental changes and new host niches in the course of its life-long association with the human host. Gain-of-function mutations in zinc cluster transcription factors, which result in the constitutive upregulation of their target genes, are a common cause of acquired resistance to the widely used antifungal drug fluconazole, especially during long-term therapy of oropharyngeal candidiasis. In this study, we investigated if C. albicans also can develop resistance to the antimicrobial peptide histatin 5, which is secreted in the saliva of humans to protect the oral mucosa from pathogenic microbes. As histatin 5 has been shown to be transported out of C. albicans cells by the Flu1 efflux pump, we screened a library of C. albicans strains that contain artificially activated forms of all zinc cluster transcription factors of this fungus for increased FLU1 expression. We found that a hyperactive Mrr1, which confers fluconazole resistance by upregulating the multidrug efflux pump MDR1 and other genes, also causes FLU1 overexpression. Similarly to the artificially activated Mrr1, naturally occurring gain-of-function mutations in this transcription factor also caused FLU1 upregulation and increased histatin 5 resistance. Surprisingly, however, Mrr1-mediated histatin 5 resistance was mainly caused by the upregulation of MDR1 instead of FLU1, revealing a previously unrecognized function of the Mdr1 efflux pump. Fluconazole-resistant clinical C. albicans isolates with different Mrr1 gain-of-function mutations were less efficiently killed by histatin 5, and this phenotype was reverted when MRR1 was deleted. Therefore, antimycotic therapy can promote the evolution of strains that, as a consequence of drug resistance mutations, simultaneously have acquired increased resistance against an innate host defense mechanism and are thereby better adapted to certain host niches.}, language = {en} } @article{SharanFoerstnerEulalioetal.2017, author = {Sharan, Malvika and F{\"o}rstner, Konrad U. and Eulalio, Ana and Vogel, J{\"o}rg}, title = {APRICOT: an integrated computational pipeline for the sequence-based identification and characterization of RNA-binding proteins}, series = {Nucleic Acids Research}, volume = {45}, journal = {Nucleic Acids Research}, number = {11}, doi = {10.1093/nar/gkx137}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157963}, pages = {e96}, year = {2017}, abstract = {RNA-binding proteins (RBPs) have been established as core components of several post-transcriptional gene regulation mechanisms. Experimental techniques such as cross-linking and co-immunoprecipitation have enabled the identification of RBPs, RNA-binding domains (RBDs) and their regulatory roles in the eukaryotic species such as human and yeast in large-scale. In contrast, our knowledge of the number and potential diversity of RBPs in bacteria is poorer due to the technical challenges associated with the existing global screening approaches. We introduce APRICOT, a computational pipeline for the sequence-based identification and characterization of proteins using RBDs known from experimental studies. The pipeline identifies functional motifs in protein sequences using position-specific scoring matrices and Hidden Markov Models of the functional domains and statistically scores them based on a series of sequence-based features. Subsequently, APRICOT identifies putative RBPs and characterizes them by several biological properties. Here we demonstrate the application and adaptability of the pipeline on large-scale protein sets, including the bacterial proteome of Escherichia coli. APRICOT showed better performance on various datasets compared to other existing tools for the sequence-based prediction of RBPs by achieving an average sensitivity and specificity of 0.90 and 0.91 respectively. The command-line tool and its documentation are available at https://pypi.python.org/pypi/bio-apricot.}, language = {en} } @article{SilvaVilchesPletinckxLohnertetal.2017, author = {Silva-Vilches, Cinthia and Pletinckx, Katrien and Lohnert, Miriam and Pavlovic, Vladimir and Ashour, Diyaaeldin and John, Vini and Vendelova, Emilia and Kneitz, Susanne and Zhou, Jie and Chen, Rena and Reinheckel, Thomas and Mueller, Thomas D. and Bodem, Jochen and Lutz, Manfred B.}, title = {Low doses of cholera toxin and its mediator cAMP induce CTLA-2 secretion by dendritic cells to enhance regulatory T cell conversion}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0178114}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158244}, pages = {e0178114}, year = {2017}, abstract = {Immature or semi-mature dendritic cells (DCs) represent tolerogenic maturation stages that can convert naive T cells into Foxp3\(^{+}\) induced regulatory T cells (iTreg). Here we found that murine bone marrow-derived DCs (BM-DCs) treated with cholera toxin (CT) matured by up-regulating MHC-II and costimulatory molecules using either high or low doses of CT (CT\(^{hi}\), CT\(^{lo}\)) or with cAMP, a known mediator CT signals. However, all three conditions also induced mRNA of both isoforms of the tolerogenic molecule cytotoxic T lymphocyte antigen 2 (CTLA-2α and CTLA-2β). Only DCs matured under CT\(^{hi}\) conditions secreted IL-1β, IL-6 and IL-23 leading to the instruction of Th17 cell polarization. In contrast, CT\(^{lo}\)- or cAMP-DCs resembled semi-mature DCs and enhanced TGF-β-dependent Foxp3\(^{+}\) iTreg conversion. iTreg conversion could be reduced using siRNA blocking of CTLA-2 and reversely, addition of recombinant CTLA-2α increased iTreg conversion in vitro. Injection of CT\(^{lo}\)- or cAMP-DCs exerted MOG peptide-specific protective effects in experimental autoimmune encephalomyelitis (EAE) by inducing Foxp3\(^{+}\) Tregs and reducing Th17 responses. Together, we identified CTLA-2 production by DCs as a novel tolerogenic mediator of TGF-β-mediated iTreg induction in vitro and in vivo. The CT-induced and cAMP-mediated up-regulation of CTLA-2 also may point to a novel immune evasion mechanism of Vibrio cholerae.}, language = {en} } @article{HergovitsMaisHaanetal.2017, author = {Hergovits, Sabine and Mais, Christine and Haan, Claude and Costa-Pereira, Ana P. and Hermanns, Heike M.}, title = {Oncostatin M induces RIG-I and MDA5 expression and enhances the double-stranded RNA response in fibroblasts}, series = {Journal of Cellular and Molecular Medicine}, volume = {21}, journal = {Journal of Cellular and Molecular Medicine}, number = {11}, doi = {10.1111/jcmm.13221}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159558}, pages = {3087-3099}, year = {2017}, abstract = {Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts. Induction of the helicases depends on tyrosine as well as serine phosphorylation of STAT1. Moreover, we could show that the OSM-induced STAT1 phosphorylation is predominantly counter-regulated by a strong STAT3-dependent SOCS3 induction, as Stat3 as well as Socs3 knock-down results in an enhanced and prolonged helicase and IRF expression. Other factors involved in regulation of STAT1 or IRF1 activity, like protein tyrosine phosphatase, non-receptor type 2 (PTPN2), promyelocytic leukaemia protein (PML) or small ubiquitin-related modifier 1 (SUMO1), play a minor role in OSM-mediated induction of RLR. Remarkably, OSM and interferon-γ (IFN-γ) synergize to mediate transcription of RLR and pre-treatment of fibroblasts with OSM fosters the type I interferon production in response to a subsequent encounter with double-stranded RNA. Together, these findings suggest that the OSM-induced JAK/STAT1 signalling is implicated in virus protection of non-professional immune cells and may cooperate with interferons to enhance RLR expression in these cells.}, language = {en} } @article{ZellerHeidemeierGrigoleitetal.2017, author = {Zeller, Daniel and Heidemeier, Anke and Grigoleit, G{\"o}tz Ulrich and M{\"u}llges, Wolfgang}, title = {Case report: subacute tetraplegia in an immunocompromised patient}, series = {BMC Neurology}, volume = {17}, journal = {BMC Neurology}, number = {31}, doi = {10.1186/s12883-017-0814-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157576}, year = {2017}, abstract = {Background: Clinical reasoning in Neurology is based on general associations which help to deduce the site of the lesion. However, even "golden principles" may occasionally be deceptive. Here, we describe the case of subacute flaccid tetraparesis due to motor cortical lesions. To our knowledge, this is the first report to include an impressive illustration of nearly symmetric motor cortical involvement of encephalitis on brain MRI. Case presentation: A 51 year old immunocompromized man developed a high-grade pure motor flaccid tetraparesis over few days. Based on clinical presentation, critical illness polyneuromyopathy was suspected. However, brain MRI revealed symmetrical hyperintensities strictly limited to the subcortical precentral gyrus. An encephalitis, possibly due to CMV infection, turned out to be the most likely cause. Conclusion: While recognition of basic clinical patterns is indispensable in neurological reasoning, awareness of central conditions mimicking peripheral nervous disease may be crucial to detect unsuspected, potentially treatable conditions.}, language = {en} } @article{CollenburgBeyersdorfWieseetal.2017, author = {Collenburg, Lena and Beyersdorf, Niklas and Wiese, Teresa and Arenz, Christoph and Saied, Essa M. and Becker-Flegler, Katrin Anne and Schneider-Schaulies, Sibylle and Avota, Elita}, title = {The activity of the neutral sphingomyelinase is important in T cell recruitment and directional migration}, series = {Frontiers in Immunology}, volume = {8}, journal = {Frontiers in Immunology}, number = {1007}, doi = {10.3389/fimmu.2017.01007}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158944}, year = {2017}, abstract = {Breakdown of sphingomyelin as catalyzed by the activity of sphingomyelinases profoundly affects biophysical properties of cellular membranes which is particularly important with regard to compartmentalization of surface receptors and their signaling relay. As it is activated both upon TCR ligation and co-stimulation in a spatiotemporally controlled manner, the neutral sphingomyelinase (NSM) has proven to be important in T cell activation, where it appears to play a particularly important role in cytoskeletal reorganization and cell polarization. Because these are important parameters in directional T cell migration and motility in tissues, we analyzed the role of the NSM in these processes. Pharmacological inhibition of NSM interfered with early lymph node homing of T cells in vivo indicating that the enzyme impacts on endothelial adhesion, transendothelial migration, sensing of chemokine gradients or, at a cellular level, acquisition of a polarized phenotype. NSM inhibition reduced adhesion of T cells to TNF-α/IFN-γ activated, but not resting endothelial cells, most likely via inhibiting high-affinity LFA-1 clustering. NSM activity proved to be highly important in directional T cell motility in response to SDF1-α, indicating that their ability to sense and translate chemokine gradients might be NSM dependent. In fact, pharmacological or genetic NSM ablation interfered with T cell polarization both at an overall morphological level and redistribution of CXCR4 and pERM proteins on endothelial cells or fibronectin, as well as with F-actin polymerization in response to SDF1-α stimulation, indicating that efficient directional perception and signaling relay depend on NSM activity. Altogether, these data support a central role of the NSM in T cell recruitment and migration both under homeostatic and inflamed conditions by regulating polarized redistribution of receptors and their coupling to the cytoskeleton.}, language = {en} } @article{AwadOthmanStopper2017, author = {Awad, Eman and Othman, Eman M. and Stopper, Helga}, title = {Effects of resveratrol, lovastatin and the mTOR-inhibitor RAD-001 on insulin-induced genomic damage in vitro}, series = {Molecules}, volume = {22}, journal = {Molecules}, number = {12}, doi = {10.3390/molecules22122207}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159260}, pages = {2207}, year = {2017}, abstract = {Diabetes mellitus (DM) is one of the major current health problems due to lifestyle changes. Before diagnosis and in the early years of disease, insulin blood levels are elevated. However, insulin generates low levels of reactive oxygen species (ROS) which are integral to the regulation of a variety of intracellular signaling pathways, but excess levels of insulin may also lead to DNA oxidation and DNA damage. Three pharmaceutical compounds, resveratrol, lovastatin and the mTOR-inhibitor RAD-001, were investigated due to their known beneficial effects. They showed protective properties against genotoxic damage and significantly reduced ROS after in vitro treatment of cultured cells with insulin. Therefore, the selected pharmaceuticals may be attractive candidates to be considered for support of DM therapy.}, language = {en} } @article{Kramer2017, author = {Kramer, Susanne}, title = {The ApaH-like phosphatase TbALPH1 is the major mRNA decapping enzyme of trypanosomes}, series = {PLoS Pathogens}, volume = {13}, journal = {PLoS Pathogens}, number = {6}, doi = {10.1371/journal.ppat.1006456}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158482}, pages = {e1006456}, year = {2017}, abstract = {5'-3' decay is the major mRNA decay pathway in many eukaryotes, including trypanosomes. After deadenylation, mRNAs are decapped by the nudix hydrolase DCP2 of the decapping complex and finally degraded by the 5'-3' exoribonuclease. Uniquely, trypanosomes lack homologues to all subunits of the decapping complex, while deadenylation and 5'-3' degradation are conserved. Here, I show that the parasites use an ApaH-like phosphatase (ALPH1) as their major mRNA decapping enzyme. The protein was recently identified as a novel trypanosome stress granule protein and as involved in mRNA binding. A fraction of ALPH1 co-localises exclusively with the trypanosome 5'-3' exoribonuclease XRNA to a special granule at the posterior pole of the cell, indicating a connection between the two enzymes. RNAi depletion of ALPH1 is lethal and causes a massive increase in total mRNAs that are deadenylated, but have not yet started 5'-3' decay. These data suggest that ALPH1 acts downstream of deadenylation and upstream of mRNA degradation, consistent with a function in mRNA decapping. In vitro experiments show that recombinant, N-terminally truncated ALHP1 protein, but not a catalytically inactive mutant, sensitises the capped trypanosome spliced leader RNA to yeast Xrn1, but only if an RNA 5' polyphosphatase is included. This indicates that the decapping mechanism of ALPH1 differs from the decapping mechanism of Dcp2 by leaving more than one phosphate group at the mRNA's 5' end. This is the first reported function of a eukaryotic ApaH-like phosphatase, a bacterial-derived class of enzymes present in all phylogenetic super-groups of the eukaryotic kingdom. The substrates of eukaryotic ApaH-like phosphatases are unknown. However, the substrate of the related bacterial enzyme ApaH, diadenosine tetraphosphate, is highly reminiscent of a eukaryotic mRNA cap.}, language = {en} } @article{KunzGoettlichWallesetal.2017, author = {Kunz, Meik and G{\"o}ttlich, Claudia and Walles, Thorsten and Nietzer, Sarah and Dandekar, Gudrun and Dandekar, Thomas}, title = {MicroRNA-21 versus microRNA-34: Lung cancer promoting and inhibitory microRNAs analysed in silico and in vitro and their clinical impact}, series = {Tumor Biology}, volume = {39}, journal = {Tumor Biology}, number = {7}, doi = {10.1177/1010428317706430}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158399}, year = {2017}, abstract = {MicroRNAs are well-known strong RNA regulators modulating whole functional units in complex signaling networks. Regarding clinical application, they have potential as biomarkers for prognosis, diagnosis, and therapy. In this review, we focus on two microRNAs centrally involved in lung cancer progression. MicroRNA-21 promotes and microRNA-34 inhibits cancer progression. We elucidate here involved pathways and imbed these antagonistic microRNAs in a network of interactions, stressing their cancer microRNA biology, followed by experimental and bioinformatics analysis of such microRNAs and their targets. This background is then illuminated from a clinical perspective on microRNA-21 and microRNA-34 as general examples for the complex microRNA biology in lung cancer and its diagnostic value. Moreover, we discuss the immense potential that microRNAs such as microRNA-21 and microRNA-34 imply by their broad regulatory effects. These should be explored for novel therapeutic strategies in the clinic.}, language = {en} } @article{MumcuogluSiverinoTabiszetal.2017, author = {Mumcuoglu, Didem and Siverino, Claudia and Tabisz, Barbara and Kluijtmans, Bas and Nickel, Joachim}, title = {How to use BMP-2 for clinical applications? A review on pros and cons of existing delivery strategies}, series = {Journal of Translational Science}, volume = {3}, journal = {Journal of Translational Science}, number = {5}, doi = {10.15761/JTS.1000195}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158678}, year = {2017}, abstract = {No abstract available.}, language = {en} } @article{SchusterKruegerSubotaetal.2017, author = {Schuster, Sarah and Kr{\"u}ger, Timothy and Subota, Ines and Thusek, Sina and Rotureau, Brice and Beilhack, Andreas and Engstler, Markus}, title = {Developmental adaptations of trypanosome motility to the tsetse fly host environments unravel a multifaceted in vivo microswimmer system}, series = {eLife}, volume = {6}, journal = {eLife}, doi = {10.7554/eLife.27656}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158662}, pages = {e27656}, year = {2017}, abstract = {The highly motile and versatile protozoan pathogen Trypanosoma brucei undergoes a complex life cycle in the tsetse fly. Here we introduce the host insect as an expedient model environment for microswimmer research, as it allows examination of microbial motion within a diversified, secluded and yet microscopically tractable space. During their week-long journey through the different microenvironments of the fly´s interior organs, the incessantly swimming trypanosomes cross various barriers and confined surroundings, with concurrently occurring major changes of parasite cell architecture. Multicolour light sheet fluorescence microscopy provided information about tsetse tissue topology with unprecedented resolution and allowed the first 3D analysis of the infection process. High-speed fluorescence microscopy illuminated the versatile behaviour of trypanosome developmental stages, ranging from solitary motion and near-wall swimming to collective motility in synchronised swarms and in confinement. We correlate the microenvironments and trypanosome morphologies to high-speed motility data, which paves the way for cross-disciplinary microswimmer research in a naturally evolved environment.}, language = {en} } @article{GrobFleischmannGruebeletal.2017, author = {Grob, Robin and Fleischmann, Pauline N. and Gr{\"u}bel, Kornelia and Wehner, R{\"u}diger and R{\"o}ssler, Wolfgang}, title = {The role of celestial compass information in Cataglyphis ants during learning walks and for neuroplasticity in the central complex and mushroom bodies}, series = {Frontiers in Behavioral Neuroscience}, volume = {11}, journal = {Frontiers in Behavioral Neuroscience}, number = {226}, doi = {10.3389/fnbeh.2017.00226}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159235}, year = {2017}, abstract = {Central place foragers are faced with the challenge to learn the position of their nest entrance in its surroundings, in order to find their way back home every time they go out to search for food. To acquire navigational information at the beginning of their foraging career, Cataglyphis noda performs learning walks during the transition from interior worker to forager. These small loops around the nest entrance are repeatedly interrupted by strikingly accurate back turns during which the ants stop and precisely gaze back to the nest entrance—presumably to learn the landmark panorama of the nest surroundings. However, as at this point the complete navigational toolkit is not yet available, the ants are in need of a reference system for the compass component of the path integrator to align their nest entrance-directed gazes. In order to find this directional reference system, we systematically manipulated the skylight information received by ants during learning walks in their natural habitat, as it has been previously suggested that the celestial compass, as part of the path integrator, might provide such a reference system. High-speed video analyses of distinct learning walk elements revealed that even exclusion from the skylight polarization pattern, UV-light spectrum and the position of the sun did not alter the accuracy of the look back to the nest behavior. We therefore conclude that C. noda uses a different reference system to initially align their gaze directions. However, a comparison of neuroanatomical changes in the central complex and the mushroom bodies before and after learning walks revealed that exposure to UV light together with a naturally changing polarization pattern was essential to induce neuroplasticity in these high-order sensory integration centers of the ant brain. This suggests a crucial role of celestial information, in particular a changing polarization pattern, in initially calibrating the celestial compass system.}, language = {en} } @article{RoemerBollazziRoces2017, author = {R{\"o}mer, Daniela and Bollazzi, Martin and Roces, Flavio}, title = {Carbon dioxide sensing in an obligate insect-fungus symbiosis: CO\(_{2}\) preferences of leaf-cutting ants to rear their mutualistic fungus}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0174597}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159561}, pages = {e0174597}, year = {2017}, abstract = {Defense against biotic or abiotic stresses is one of the benefits of living in symbiosis. Leaf-cutting ants, which live in an obligate mutualism with a fungus, attenuate thermal and desiccation stress of their partner through behavioral responses, by choosing suitable places for fungus-rearing across the soil profile. The underground environment also presents hypoxic (low oxygen) and hypercapnic (high carbon dioxide) conditions, which can negatively influence the symbiont. Here, we investigated whether workers of the leaf-cutting ant Acromyrmex lundii use the CO\(_{2}\) concentration as an orientation cue when selecting a place to locate their fungus garden, and whether they show preferences for specific CO\(_{2}\) concentrations. We also evaluated whether levels preferred by workers for fungus-rearing differ from those selected for themselves. In the laboratory, CO\(_{2}\) preferences were assessed in binary choices between chambers with different CO\(_{2}\) concentrations, by quantifying number of workers in each chamber and amount of relocated fungus. Leaf-cutting ants used the CO\(_{2}\) concentration as a spatial cue when selecting places for fungus-rearing. A. lundii preferred intermediate CO\(_{2}\) levels, between 1 and 3\%, as they would encounter at soil depths where their nest chambers are located. In addition, workers avoided both atmospheric and high CO\(_{2}\) levels as they would occur outside the nest and at deeper soil layers, respectively. In order to prevent fungus desiccation, however, workers relocated fungus to high CO\(_{2}\) levels, which were otherwise avoided. Workers' CO\(_{2}\) preferences for themselves showed no clear-cut pattern. We suggest that workers avoid both atmospheric and high CO\(_{2}\) concentrations not because they are detrimental for themselves, but because of their consequences for the symbiotic partner. Whether the preferred CO\(_{2}\) concentrations are beneficial for symbiont growth remains to be investigated, as well as whether the observed preferences for fungus-rearing influences the ants' decisions where to excavate new chambers across the soil profile.}, language = {en} } @article{HalbothRoces2017, author = {Halboth, Florian and Roces, Flavio}, title = {The construction of ventilation turrets in Atta vollenweideri leaf-cutting ants: Carbon dioxide levels in the nest tunnels, but not airflow or air humidity, influence turret structure}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0188162}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159133}, pages = {e0188162}, year = {2017}, abstract = {Nest ventilation in the leaf-cutting ant Atta vollenweideri is driven via a wind-induced mechanism. On their nests, workers construct small turrets that are expected to facilitate nest ventilation. We hypothesized that the construction and structural features of the turrets would depend on the colony's current demands for ventilation and thus might be influenced by the prevailing environmental conditions inside the nest. Therefore, we tested whether climate-related parameters, namely airflow, air humidity and CO\(_{2}\) levels in the outflowing nest air influenced turret construction in Atta vollenweideri. In the laboratory, we simulated a semi-natural nest arrangement with fungus chambers, a central ventilation tunnel providing outflow of air and an aboveground building arena for turret construction. In independent series, different climatic conditions inside the ventilation tunnel were experimentally generated, and after 24 hours, several features of the built turret were quantified, i.e., mass, height, number and surface area (aperture) of turret openings. Turret mass and height were similar in all experiments even when no airflow was provided in the ventilation tunnel. However, elevated CO\(_{2}\) levels led to the construction of a turret with several minor openings and a larger total aperture. This effect was statistically significant at higher CO\(_{2}\) levels of 5\% and 10\% but not at 1\% CO\(_{2}\). The construction of a turret with several minor openings did not depend on the strong differences in CO\(_{2}\) levels between the outflowing and the outside air, since workers also built permeated turrets even when the CO\(_{2}\) levels inside and outside were both similarly high. We propose that the construction of turrets with several openings and larger opening surface area might facilitate the removal of CO\(_{2}\) from the underground nest structure and could therefore be involved in the control of nest climate in leaf-cutting ants.}, language = {en} } @article{FrankSchmittHovestadtetal.2017, author = {Frank, Erik Thomas and Schmitt, Thomas and Hovestadt, Thomas and Mitesser, Oliver and Stiegler, Jonas and Linsenmair, Karl Eduard}, title = {Saving the injured: Rescue behavior in the termite-hunting ant Megaponera analis}, series = {Science Advances}, volume = {3}, journal = {Science Advances}, number = {4}, doi = {10.1126/sciadv.1602187}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157933}, pages = {e1602187}, year = {2017}, abstract = {Predators of highly defensive prey likely develop cost-reducing adaptations. The ant Megaponera analis is a specialized termite predator, solely raiding termites of the subfamily Macrotermitinae (in this study, mostly colonies of Pseudocanthotermes sp.) at their foraging sites. The evolutionary arms race between termites and ants led to various defensive mechanisms in termites (for example, a caste specialized in fighting predators). Because M. analis incurs high injury/mortality risks when preying on termites, some risk-mitigating adaptations seem likely to have evolved. We show that a unique rescue behavior in M. analis, consisting of injured nestmates being carried back to the nest, reduces combat mortality. After a fight, injured ants are carried back by their nestmates; these ants have usually lost an extremity or have termites clinging to them and are able to recover within the nest. Injured ants that are forced experimentally to return without help, die in 32\% of the cases. Behavioral experiments show that two compounds, dimethyl disulfide and dimethyl trisulfide, present in the mandibular gland reservoirs, trigger the rescue behavior. A model accounting for this rescue behavior identifies the drivers favoring its evolution and estimates that rescuing enables maintenance of a 28.7\% larger colony size. Our results are the first to explore experimentally the adaptive value of this form of rescue behavior focused on injured nestmates in social insects and help us to identify evolutionary drivers responsible for this type of behavior to evolve in animals.}, language = {en} } @article{HeibyRajabRatetal.2017, author = {Heiby, Julia C. and Rajab, Suhaila and Rat, Charlotte and Johnson, Christopher M. and Neuweiler, Hannes}, title = {Conservation of folding and association within a family of spidroin N-terminal domains}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-16881-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159272}, pages = {16789}, year = {2017}, abstract = {Web spiders synthesize silk fibres, nature's toughest biomaterial, through the controlled assembly of fibroin proteins, so-called spidroins. The highly conserved spidroin N-terminal domain (NTD) is a pH-driven self-assembly device that connects spidroins to super-molecules in fibres. The degree to which forces of self-assembly is conserved across spider glands and species is currently unknown because quantitative measures are missing. Here, we report the comparative investigation of spidroin NTDs originating from the major ampullate glands of the spider species Euprosthenops australis, Nephila clavipes, Latrodectus hesperus, and Latrodectus geometricus. We characterized equilibrium thermodynamics and kinetics of folding and self-association using dynamic light scattering, stopped-flow fluorescence and circular dichroism spectroscopy in combination with thermal and chemical denaturation experiments. We found cooperative two-state folding on a sub-millisecond time scale through a late transition state of all four domains. Stability was compromised by repulsive electrostatic forces originating from clustering of point charges on the NTD surface required for function. pH-driven dimerization proceeded with characteristic fast kinetics yielding high affinities. Results showed that energetics and kinetics of NTD self-assembly are highly conserved across spider species despite the different silk mechanical properties and web geometries they produce.}, language = {en} } @article{SperlichHolmberg2017, author = {Sperlich, Billy and Holmberg, Hans-Christer}, title = {The responses of elite athletes to exercise: an all-day, 24-h integrative view is required!}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, number = {564}, doi = {10.3389/fphys.2017.00564}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158655}, year = {2017}, abstract = {No abstract available.}, language = {en} } @article{SperlichDuekingHolmberg2017, author = {Sperlich, Billy and D{\"u}king, Peter and Holmberg, Hans-Christer}, title = {A SWOT analysis of the use and potential misuse of implantable monitoring devices by athletes}, series = {Frontiers in Physiology}, volume = {8}, journal = {Frontiers in Physiology}, number = {629}, doi = {10.3389/fphys.2017.00629}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158742}, year = {2017}, abstract = {Kein Abstract vorhanden.}, language = {en} } @article{BecamWalterBurgertetal.2017, author = {Becam, J{\´e}r{\^o}me and Walter, Tim and Burgert, Anne and Schlegel, Jan and Sauer, Markus and Seibel, J{\"u}rgen and Schubert-Unkmeir, Alexandra}, title = {Antibacterial activity of ceramide and ceramide analogs against pathogenic Neisseria}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, doi = {10.1038/s41598-017-18071-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159367}, pages = {17627}, year = {2017}, abstract = {Certain fatty acids and sphingoid bases found at mucosal surfaces are known to have antibacterial activity and are thought to play a more direct role in innate immunity against bacterial infections. Herein, we analysed the antibacterial activity of sphingolipids, including the sphingoid base sphingosine as well as short-chain C\(_{6}\) and long-chain C\(_{16}\)-ceramides and azido-functionalized ceramide analogs against pathogenic Neisseriae. Determination of the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) demonstrated that short-chain ceramides and a ω-azido-functionalized C\(_{6}\)-ceramide were active against Neisseria meningitidis and N. gonorrhoeae, whereas they were inactive against Escherichia coli and Staphylococcus aureus. Kinetic assays showed that killing of N. meningitidis occurred within 2 h with ω-azido-C\(_{6}\)-ceramide at 1 X the MIC. Of note, at a bactericidal concentration, ω-azido-C\(_{6}\)-ceramide had no significant toxic effect on host cells. Moreover, lipid uptake and localization was studied by flow cytometry and confocal laser scanning microscopy (CLSM) and revealed a rapid uptake by bacteria within 5 min. CLSM and super-resolution fluorescence imaging by direct stochastic optical reconstruction microscopy demonstrated homogeneous distribution of ceramide analogs in the bacterial membrane. Taken together, these data demonstrate the potent bactericidal activity of sphingosine and synthetic short-chain ceramide analogs against pathogenic Neisseriae.}, language = {en} } @article{GoosDejungJanzenetal.2017, author = {Goos, Carina and Dejung, Mario and Janzen, Christian J. and Butter, Falk and Kramer, Susanne}, title = {The nuclear proteome of Trypanosoma brucei}, series = {PLoS ONE}, volume = {12}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0181884}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158572}, pages = {e0181884}, year = {2017}, abstract = {Trypanosoma brucei is a protozoan flagellate that is transmitted by tsetse flies into the mammalian bloodstream. The parasite has a huge impact on human health both directly by causing African sleeping sickness and indirectly, by infecting domestic cattle. The biology of trypanosomes involves some highly unusual, nuclear-localised processes. These include polycistronic transcription without classical promoters initiated from regions defined by histone variants, trans-splicing of all transcripts to the exon of a spliced leader RNA, transcription of some very abundant proteins by RNA polymerase I and antigenic variation, a switch in expression of the cell surface protein variants that allows the parasite to resist the immune system of its mammalian host. Here, we provide the nuclear proteome of procyclic Trypanosoma brucei, the stage that resides within the tsetse fly midgut. We have performed quantitative label-free mass spectrometry to score 764 significantly nuclear enriched proteins in comparison to whole cell lysates. A comparison with proteomes of several experimentally characterised nuclear and non-nuclear structures and pathways confirmed the high quality of the dataset: the proteome contains about 80\% of all nuclear proteins and less than 2\% false positives. Using motif enrichment, we found the amino acid sequence KRxR present in a large number of nuclear proteins. KRxR is a sub-motif of a classical eukaryotic monopartite nuclear localisation signal and could be responsible for nuclear localization of proteins in Kinetoplastida species. As a proof of principle, we have confirmed the nuclear localisation of six proteins with previously unknown localisation by expressing eYFP fusion proteins. While proteome data of several T. brucei organelles have been published, our nuclear proteome closes an important gap in knowledge to study trypanosome biology, in particular nuclear-related processes.}, language = {en} } @article{ErlbeckMochtyKuebleretal.2017, author = {Erlbeck, Helena and Mochty, Ursula and K{\"u}bler, Andrea and Real, Ruben G. L.}, title = {Circadian course of the P300 ERP in patients with amyotrophic lateral sclerosis - implications for brain-computer interfaces (BCI)}, series = {BMC Neurology}, volume = {17}, journal = {BMC Neurology}, number = {3}, doi = {10.1186/s12883-016-0782-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157423}, year = {2017}, abstract = {Background: Accidents or neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) can lead to progressing, extensive, and complete paralysis leaving patients aware but unable to communicate (locked-in state). Brain-computer interfaces (BCI) based on electroencephalography represent an important approach to establish communication with these patients. The most common BCI for communication rely on the P300, a positive deflection arising in response to rare events. To foster broader application of BCIs for restoring lost function, also for end-users with impaired vision, we explored whether there were specific time windows during the day in which a P300 driven BCI should be preferably applied. Methods: The present study investigated the influence of time of the day and modality (visual vs. auditory) on P300 amplitude and latency. A sample of 14 patients (end-users) with ALS and 14 healthy age matched volunteers participated in the study and P300 event-related potentials (ERP) were recorded at four different times (10, 12 am, 2, \& 4 pm) during the day. Results: Results indicated no differences in P300 amplitudes or latencies between groups (ALS patients v. healthy participants) or time of measurement. In the auditory condition, latencies were shorter and amplitudes smaller as compared to the visual condition. Conclusion: Our findings suggest applicability of EEG/BCI sessions in patients with ALS throughout normal waking hours. Future studies using actual BCI systems are needed to generalize these findings with regard to BCI effectiveness/efficiency and other times of day.}, language = {en} } @article{GulveFrankKlepschetal.2017, author = {Gulve, Nitish and Frank, Celina and Klepsch, Maximilian and Prusty, Bhupesh K.}, title = {Chromosomal integration of HHV-6A during non-productive viral infection}, series = {Scientific Reports}, volume = {7}, journal = {Scientific Reports}, number = {512}, doi = {10.1038/s41598-017-00658-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158117}, year = {2017}, abstract = {Human herpesvirus 6A (HHV-6A) and 6B (HHV-6B) are two different species of betaherpesviruses that integrate into sub-telomeric ends of human chromosomes, for which different prevalence rates of integration have been reported. It has been demonstrated that integrated viral genome is stable and is fully retained. However, study of chromosomally integrated viral genome in individuals carrying inherited HHV-6 (iciHHV-6) showed unexpected number of viral DR copies. Hence, we created an in vitro infection model and studied retention of full or partial viral genome over a period of time. We observed an exceptional event where cells retained viral direct repeats (DRs) alone in the absence of the full viral genome. Finally, we found evidence for non-telomeric integration of HHV-6A DR in both cultured cells and in an iciHHV-6 individual. Our results shed light on several novel features of HHV-6A chromosomal integration and provide valuable information for future screening techniques.}, language = {en} } @article{HeroldHerzWinteretal.2017, author = {Herold, Volker and Herz, Stefan and Winter, Patrick and Gutjahr, Fabian Tobias and Andelovic, Kristina and Bauer, Wolfgang Rudolf and Jakob, Peter Michael}, title = {Assessment of local pulse wave velocity distribution in mice using k-t BLAST PC-CMR with semi-automatic area segmentation.}, series = {Journal of Cardiovascular Magnetic Resonance}, volume = {19}, journal = {Journal of Cardiovascular Magnetic Resonance}, number = {77}, doi = {10.1186/s12968-017-0382-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157696}, year = {2017}, abstract = {Background: Local aortic pulse wave velocity (PWV) is a measure for vascular stiffness and has a predictive value for cardiovascular events. Ultra high field CMR scanners allow the quantification of local PWV in mice, however these systems are yet unable to monitor the distribution of local elasticities. Methods: In the present study we provide a new accelerated method to quantify local aortic PWV in mice with phase-contrast cardiovascular magnetic resonance imaging (PC-CMR) at 17.6 T. Based on a k-t BLAST (Broad-use Linear Acquisition Speed-up Technique) undersampling scheme, total measurement time could be reduced by a factor of 6. The fast data acquisition enables to quantify the local PWV at several locations along the aortic blood vessel based on the evaluation of local temporal changes in blood flow and vessel cross sectional area. To speed up post processing and to eliminate operator bias, we introduce a new semi-automatic segmentation algorithm to quantify cross-sectional areas of the aortic vessel. The new methods were applied in 10 eight-month-old mice (4 C57BL/6J-mice and 6 ApoE\(^{(-/-)}\)-mice) at 12 adjacent locations along the abdominal aorta. Results: Accelerated data acquisition and semi-automatic post-processing delivered reliable measures for the local PWV, similiar to those obtained with full data sampling and manual segmentation. No statistically significant differences of the mean values could be detected for the different measurement approaches. Mean PWV values were elevated for the ApoE\(^{(-/-)}\)-group compared to the C57BL/6J-group (3.5 ± 0.7 m/s vs. 2.2 ± 0.4 m/s, p < 0.01). A more heterogeneous PWV-distribution in the ApoE \(^{(-/-)}\)-animals could be observed compared to the C57BL/6J-mice, representing the local character of lesion development in atherosclerosis. Conclusion: In the present work, we showed that k-t BLAST PC-MRI enables the measurement of the local PWV distribution in the mouse aorta. The semi-automatic segmentation method based on PC-CMR data allowed rapid determination of local PWV. The findings of this study demonstrate the ability of the proposed methods to non-invasively quantify the spatial variations in local PWV along the aorta of ApoE\(^{(-/-)}\)-mice as a relevant model of atherosclerosis.}, language = {en} } @article{OezkurMagyarThomasetal.2017, author = {Oezkur, Mehmet and Magyar, Attila and Thomas, Phillip and Stork, Tabea and Schneider, Reinhard and Bening, Constanze and St{\"o}rk, Stefan and Heuschmann, Peter U. and Leyh, Rainer G. and Wagner, Martin}, title = {TIMP-2*IGFBP7 (Nephrocheck®) Measurements at Intensive Care Unit Admission After Cardiac Surgery are Predictive for Acute Kidney Injury Within 48 Hours}, series = {Kidney \& Blood Pressure Research}, volume = {42}, journal = {Kidney \& Blood Pressure Research}, doi = {10.1159/000479298}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157988}, pages = {456-467}, year = {2017}, abstract = {Background/Aims: Acute kidney injury (AKI) is a postoperative complication after cardiac surgery with a high impact on mortality and morbidity. Nephrocheck® [TIMP-2*IGFBP7] determines markers of tubular stress, which occurs prior to tubular damage. It is unknown at which time-point [TIMP-2*IGFBP7] measurement should be performed to ideally predict AKI. We investigated the association of [TIMP-2*IGFBP7] at various time-points with the incidence of AKI in patients undergoing elective cardiac surgery including cardio-pulmonary bypass. Methods: In a prospective cohort study, serial blood and urine samples were collected from 150 patients: pre-operative, at ICU-admission, 24h and 48h post-surgery. AKI was defined as Serum-Creatinine rise >0.3 mg/dl within 48hrs. Urinary [TIMP-2*IGFBP7] was measured at pre-operative, ICU-admission and 24h post-surgery; medical staff was kept blinded to these results. Results: A total of 35 patients (23.5\%) experienced AKI, with a higher incidence in those with high [TIMP-2*IGFBP7] values at ICU admission (57.1\% vs. 10.1\%, p<0.001). In logistic regression [TIMP-2*IGFBP7] at ICU admission was independently associated with the occurrence of AKI (Odds Ratio 11.83; p<0.001, C-statistic= 0.74) after adjustment for EuroSCORE II and CBP-time. Conclusions: Early detection of elevated [TIMP-2*IGFBP7] at ICU admission was strongly predictive for postoperative AKI and appeared to be more precise as compared to subsequent measurements.}, language = {en} } @article{SauerLiHollWiedenetal.2017, author = {Sauer, Alexander and Li, Mengxia and Holl-Wieden, Annette and Pabst, Thomas and Neubauer, Henning}, title = {Readout-segmented multi-shot diffusion-weighted MRI of the knee joint in patients with juvenile idiopathic arthritis}, series = {Pediatric Rheumatology}, volume = {15}, journal = {Pediatric Rheumatology}, number = {73}, doi = {10.1186/s12969-017-0203-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158095}, year = {2017}, abstract = {Background: Diffusion-weighted MRI has been proposed as a new technique for imaging synovitis without intravenous contrast application. We investigated diagnostic utility of multi-shot readout-segmented diffusion-weighted MRI (multi-shot DWI) for synovial imaging of the knee joint in patients with juvenile idiopathic arthritis (JIA). Methods: Thirty-two consecutive patients with confirmed or suspected JIA (21 girls, median age 13 years) underwent routine 1.5 T MRI with contrast-enhanced T1w imaging (contrast-enhanced MRI) and with multi-shot DWI (RESOLVE, b-values 0-50 and 800 s/mm\(^2\)). Contrast-enhanced MRI, representing the diagnostic standard, and diffusion-weighted images at b = 800 s/mm\(^2\) were separately rated by three independent blinded readers at different levels of expertise for the presence and the degree of synovitis on a modified 5-item Likert scale along with the level of subjective diagnostic confidence. Results: Fourteen (44\%) patients had active synovitis and joint effusion, nine (28\%) patients showed mild synovial enhancement not qualifying for arthritis and another nine (28\%) patients had no synovial signal alterations on contrast-enhanced imaging. Ratings by the 1st reader on contrast-enhanced MRI and on DWI showed substantial agreement (κ = 0.74). Inter-observer-agreement was high for diagnosing, or ruling out, active arthritis of the knee joint on contrast-enhanced MRI and on DWI, showing full agreement between 1st and 2nd reader and disagreement in one case (3\%) between 1st and 3rd reader. In contrast, ratings in cases of absent vs. little synovial inflammation were markedly inconsistent on DWI. Diagnostic confidence was lower on DWI, compared to contrast-enhanced imaging. Conclusion: Multi-shot DWI of the knee joint is feasible in routine imaging and reliably diagnoses, or rules out, active arthritis of the knee joint in paediatric patients without the need of gadolinium-based i.v. contrast injection. Possibly due to "T2w shine-through" artifacts, DWI does not reliably differentiate non-inflamed joints from knee joints with mild synovial irritation.}, language = {en} } @article{BaurMatheGesierichetal.2017, author = {Baur, Johannes and Mathe, Katrin and Gesierich, Anja and Weyandt, Gerhard and Wiegering, Armin and Germer, Christoph-Thomas and Gasser, Martin and Pelz, J{\"o}rg O. W.}, title = {Morbidity and oncologic outcome after saphenous vein-sparing inguinal lymphadenectomy in melanoma patients}, series = {World Journal of Surgical Oncology}, volume = {15}, journal = {World Journal of Surgical Oncology}, number = {99}, doi = {10.1186/s12957-017-1164-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157687}, year = {2017}, abstract = {Background: Inguinal lymph node dissection (LND) is a surgical procedure with a high morbidity rate. Variations in surgical procedure, such as sparing of the saphenous vein, have been proposed to reduce surgical morbidity. While sparing of the saphenous vein has shown promising results in earlier studies, data for this procedure in melanoma patients are rare. In this retrospective study, we report 10-year findings on the effects of saphenous vein-sparing LND on surgical morbidity and oncologic outcomes in melanoma patients. Methods: A retrospective analysis of melanoma patients receiving inguinal LND in our facility between 2003 and 2013 was performed. Patients were divided into two groups: the saphenous vein resection group and the vein sparing group. Surgical morbidity, including wound infection, lymphatic fistula, severe bleeding, neurological complications, and chronic lymphedema, as well as regional recurrence-free survival were investigated. Results: A total of 106 patients were included in this study; of these, the saphenous vein was spared in 41 patients (38.7\%). The rate of lymphatic fistula was 51.6 vs. 48.8\%, wound infection occurred in 31.3 vs. 24.4\%, and patients suffered from chronic lymphedema in 30.0 vs. 26.5\% in V. saphena magna resection vs. sparing group. Differences observed, however, were not significant. No difference in regional recurrence-free survival between the two study groups was detected. Conclusions: The results of our retrospective analysis could not confirm the promising results reported in earlier studies. Thus, sparing of the saphenous vein appears to be optional.}, language = {en} } @article{KaethnerHalderHintermuelleretal.2017, author = {K{\"a}thner, Ivo and Halder, Sebastian and Hinterm{\"u}ller, Christoph and Espinosa, Arnau and Guger, Christoph and Miralles, Felip and Vargiu, Eloisa and Dauwalder, Stefan and Rafael-Palou, Xavier and Sol{\`a}, Marc and Daly, Jean M. and Armstrong, Elaine and Martin, Suzanne and K{\"u}bler, Andrea}, title = {A Multifunctional Brain-Computer Interface Intended for Home Use: An Evaluation with Healthy Participants and Potential End Users with Dry and Gel-Based Electrodes}, series = {Frontiers in Neuroscience}, volume = {11}, journal = {Frontiers in Neuroscience}, number = {286}, doi = {10.3389/fnins.2017.00286}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157925}, year = {2017}, abstract = {Current brain-computer interface (BCIs) software is often tailored to the needs of scientists and technicians and therefore complex to allow for versatile use. To facilitate home use of BCIs a multifunctional P300 BCI with a graphical user interface intended for non-expert set-up and control was designed and implemented. The system includes applications for spelling, web access, entertainment, artistic expression and environmental control. In addition to new software, it also includes new hardware for the recording of electroencephalogram (EEG) signals. The EEG system consists of a small and wireless amplifier attached to a cap that can be equipped with gel-based or dry contact electrodes. The system was systematically evaluated with a healthy sample, and targeted end users of BCI technology, i.e., people with a varying degree of motor impairment tested the BCI in a series of individual case studies. Usability was assessed in terms of effectiveness, efficiency and satisfaction. Feedback of users was gathered with structured questionnaires. Two groups of healthy participants completed an experimental protocol with the gel-based and the dry contact electrodes (N = 10 each). The results demonstrated that all healthy participants gained control over the system and achieved satisfactory to high accuracies with both gel-based and dry electrodes (average error rates of 6 and 13\%). Average satisfaction ratings were high, but certain aspects of the system such as the wearing comfort of the dry electrodes and design of the cap, and speed (in both groups) were criticized by some participants. Six potential end users tested the system during supervised sessions. The achieved accuracies varied greatly from no control to high control with accuracies comparable to that of healthy volunteers. Satisfaction ratings of the two end-users that gained control of the system were lower as compared to healthy participants. The advantages and disadvantages of the BCI and its applications are discussed and suggestions are presented for improvements to pave the way for user friendly BCIs intended to be used as assistive technology by persons with severe paralysis.}, language = {en} }