@article{SollfrankHartGoodselletal.2015, author = {Sollfrank, Teresa and Hart, Daniel and Goodsell, Rachel and Foster, Jonathan and Tan, Tele}, title = {3D visualization of movements can amplify motor cortex activation during subsequent motor imagery}, series = {Frontiers in Human Neuroscience}, volume = {9}, journal = {Frontiers in Human Neuroscience}, number = {463}, doi = {10.3389/fnhum.2015.00463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126058}, year = {2015}, abstract = {A repetitive movement practice by motor imagery (MI) can influence motor cortical excitability in the electroencephalogram (EEG). This study investigated if a realistic visualization in 3D of upper and lower limb movements can amplify motor related potentials during subsequent MI. We hypothesized that a richer sensory visualization might be more effective during instrumental conditioning, resulting in a more pronounced event related desynchronization (ERD) of the upper alpha band (10-12 Hz) over the sensorimotor cortices thereby potentially improving MI based brain-computer interface (BCI) protocols for motor rehabilitation. The results show a strong increase of the characteristic patterns of ERD of the upper alpha band components for left and right limb MI present over the sensorimotor areas in both visualization conditions. Overall, significant differences were observed as a function of visualization modality (VM; 2D vs. 3D). The largest upper alpha band power decrease was obtained during MI after a 3-dimensional visualization. In total in 12 out of 20 tasks the end-user of the 3D visualization group showed an enhanced upper alpha ERD relative to 2D VM group, with statistical significance in nine tasks.With a realistic visualization of the limb movements, we tried to increase motor cortex activation during subsequent MI. The feedback and the feedback environment should be inherently motivating and relevant for the learner and should have an appeal of novelty, real-world relevance or aesthetic value (Ryan and Deci, 2000; Merrill, 2007). Realistic visual feedback, consistent with the participant's MI, might be helpful for accomplishing successful MI and the use of such feedback may assist in making BCI a more natural interface for MI based BCI rehabilitation.}, language = {en} } @article{LueckerathLapaAlbertetal.2015, author = {L{\"u}ckerath, Katharina and Lapa, Constantin and Albert, Christa and Herrmann, Ken and J{\"o}rg, Gerhard and Samnick, Samuel and Einsele, Herrmann and Knop, Stefan and Buck, Andreas K.}, title = {\(^{11}\)C-Methionine-PET: a novel and sensitive tool for monitoring of early response to treatment in multiple myeloma}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {10}, doi = {10.18632/oncotarget.3053}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148688}, pages = {8418-8429}, year = {2015}, abstract = {Multiple myeloma (MM) remains an essentially incurable hematologic malignancy. However, new treatment modalities and novel drugs have been introduced and thus additional tools for therapy monitoring are increasingly needed. Therefore, we evaluated the radiotracers \(^{11}\)C-Methionine (paraprotein-biosynthesis) and \(^{18}\)F-FDG (glucose-utilization) for monitoring response to anti-myeloma-therapy and outcome prediction. Influence of proteasome-inhibition on radiotracer-uptake of different MM cell-lines and patient-derived CD138\(^{+}\) plasma cells was analyzed and related to tumor-biology. Mice xenotransplanted with MM. 1S tumors underwent MET- and FDG-\(\mu\)PET. Tumor-to-background ratios before and after 24 h, 8 and 15 days treatment with bortezomib were correlated to survival. Treatment reduced both MET and FDG uptake; changes in tracer-retention correlated with a switch from high to low CD138-expression. In xenotransplanted mice, MET-uptake significantly decreased by 30-79\% as early as 24 h after bortezomib injection. No significant differences were detected thus early with FDG. This finding was confirmed in patient-derived MM cells. Importantly, early reduction of MET-but not FDG-uptake correlated with improved survival and reduced tumor burden in mice. Our results suggest that MET is superior to FDG in very early assessment of response to anti-myeloma-therapy. Early changes in MET-uptake have predictive potential regarding response and survival. MET-PET holds promise to individualize therapies in MM in future.}, language = {en} } @article{BaurSchedelbeckPulzeretal.2015, author = {Baur, Johannes and Schedelbeck, Ulla and Pulzer, Alina and Bluemel, Christina and Wild, Vanessa and Fassnacht, Martin and Steger, U.}, title = {A case report of a solitary pancreatic metastasis of an adrenocortical carcinoma}, series = {BMC Surgery}, volume = {15}, journal = {BMC Surgery}, number = {93}, doi = {10.1186/s12893-015-0076-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126130}, year = {2015}, abstract = {Background Solitary metastases to the pancreas are rare. Therefore the value of resection in curative intention remains unclear. In the literature there are several promising reports about resection of solitary metastasis to the pancreas mainly of renal origin. Case presentation Here we report for the first time on the surgical therapy of a 1.5 cm solitary pancreatic metastasis of an adrenocortical carcinoma. The metastasis occurred almost 6 years after resection of the primary tumor. A partial pancreatoduodenectomy was performed and postoperatively adjuvant mitotane treatment was initiated. During the follow-up of 3 years after surgery no evidence of tumor recurrence occurred. Conclusion Resection of pancreatic tumors should be considered, even if the mass is suspicious for metastatic disease including recurrence of adrenocortical cancer.}, language = {en} } @article{KleikersHooijmansGoebetal.2015, author = {Kleikers, Pamela W. M. and Hooijmans, Carlijn and G{\"o}b, Eva and Langhauser, Friederike and Rewell, Sarah S. J. and Radermacher, Kim and Ritskes-Hoitinga, Merel and Howells, David W. and Kleinschnitz, Christoph and Schmidt, Harald H. H. W.}, title = {A combined pre-clinical meta-analysis and randomized confirmatory trial approach to improve data validity for therapeutic target validation}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {13428}, doi = {10.1038/srep13428}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151401}, year = {2015}, abstract = {Biomedical research suffers from a dramatically poor translational success. For example, in ischemic stroke, a condition with a high medical need, over a thousand experimental drug targets were unsuccessful. Here, we adopt methods from clinical research for a late-stage pre-clinical meta-analysis (MA) and randomized confirmatory trial (pRCT) approach. A profound body of literature suggests NOX\(_{2}\) to be a major therapeutic target in stroke. Systematic review and MA of all available NOX\(_{2}\)\(^{-/y}\) studies revealed a positive publication bias and lack of statistical power to detect a relevant reduction in infarct size. A fully powered multi-center pRCT rejects NOX\(_{2}\) as a target to improve neurofunctional outcomes or achieve a translationally relevant infarct size reduction. Thus stringent statistical thresholds, reporting negative data and a MA-pRCT approach can ensure biomedical data validity and overcome risks of bias.}, language = {en} } @phdthesis{Lewandowska2015, author = {Lewandowska, Natalia Ewelina}, title = {A Correlation Study of Radio Giant Pulses and Very High Energy Photons from the Crab Pulsar}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123533}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Pulsars (in short for Pulsating Stars) are magnetized, fast rotating neutron stars. The basic picture of a pulsar describes it as a neutron star which has a rotation axis that is not aligned with its magnetic field axis. The emission is assumed to be generated near the magnetic poles of the neutron star and emitted along the open magnetic field lines. Consequently, the corresponding beam of photons is emitted along the magnetic field line axis. The non-alignment of both, the rotation and the magnetic field axis, results in the effect that the emission of the pulsar is only seen if its beam points towards the observer. The emission from a pulsar is therefore perceived as being pulsed although its generation is not. This rather simple geometrical model is commonly referred to as Lighthouse Model and has been widely accepted. However, it does not deliver an explanation of the precise mechanisms behind the emission from pulsars (see below for more details). Nowadays more than 2000 pulsars are known. They are observed at various wavelengths. Multiwavelength studies have shown that some pulsars are visible only at certain wavelengths while the emission from others can be observed throughout large parts of the electromagnetic spectrum. An example of the latter case is the Crab pulsar which is also the main object of interest in this thesis. Originating from a supernova explosion observed in 1054 A.D. and discovered in 1968, the Crab pulsar has been the central subject of numerous studies. Its pulsed emission is visible throughout the whole electromagnetic spectrum which makes it a key figure in understanding the possible mechanisms of multiwavelength emission from pulsars. The Crab pulsar is also well known for its radio emission strongly varying on long as well as on short time scales. While long time scale behaviour from a pulsar is usually examined through the use of its average profile (a profile resulting from averaging of a large number of individual pulses resulting from single rotations), short time scale behaviour is examined via its single pulses. The short time scale anomalous behaviour of its radio emission is commonly referred to as Giant Pulses and represents the central topic of this thesis. While current theoretical approaches place the origin of the radio emission from a pulsar like the Crab near its magnetic poles (Polar Cap Model) as already indicated by the Lighthouse model, its emission at higher frequencies, especially its gamma-ray emission, is assumed to originate further away in the geometrical region surrounding a pulsar which is commonly referred to as a pulsar magnetosphere (Outer Gap Model). Consequently, the respective emission regions are usually assumed not to be connected. However, past observational results from the Crab pulsar represent a contradiction to this assumption. Radio giant pulses from the Crab pulsar have been observed to emit large amounts of energy on very short time scales implying small emission regions on the surface of the pulsar. Such energetic events might also leave a trace in the gamma-ray emission of the Crab pulsar. The aim of this thesis is to search for this connection in the form of a correlation study between radio giant pulses and gamma-photons from the Crab pulsar. To make such a study possible, a multiwavelength observational campaign was organized for which radio observations were independently applied for, coordinated and carried out with the Effelsberg radio telescope and the Westerbork Synthesis Radio Telescope and gamma-ray observations with the Major Atmospheric Imaging Cherenkov telescopes. The corresponding radio and gamma-ray data sets were reduced and the correlation analysis thereafter consisted of three different approaches: 1) The search for a clustering in the differences of the times of arrival of radio giant pulses and gamma-photons; 2) The search for a linear correlation between radio giant pulses and gamma-photons using the Pearson correlation approach; 3) A search for an increase of the gamma-ray flux around occurring radio giant pulses. In the last part of the correlation study an increase of the number of gamma-photons centered on a radio giant pulse by about 17\% (in contrast with the number of gamma-photons when no radio giant pulse occurs in the same time window) was discovered. This finding suggests that a new theoretical approach for the emission of young pulsars like the Crab pulsar, is necessary.}, subject = {Pulsar}, language = {en} } @article{StangeDesirKakaretal.2015, author = {Stange, Katja and D{\´e}sir, Julie and Kakar, Naseebullah and Mueller, Thomas D. and Budde, Birgit S. and Gordon, Christopher T. and Horn, Denise and Seemann, Petra and Borck, Guntram}, title = {A hypomorphic BMPR1B mutation causes du Pan acromesomelic dysplasia}, series = {Orphanet Journal of Rare Diseases}, volume = {10}, journal = {Orphanet Journal of Rare Diseases}, number = {84}, doi = {10.1186/s13023-015-0299-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151650}, year = {2015}, abstract = {Background: Grebe dysplasia, Hunter-Thompson dysplasia, and du Pan dysplasia constitute a spectrum of skeletal dysplasias inherited as an autosomal recessive trait characterized by short stature, severe acromesomelic shortening of the limbs, and normal axial skeleton. The majority of patients with these disorders have biallelic loss-of-function mutations of GDF5. In single instances, Grebe dysplasia and a Grebe dysplasia-like phenotype with genital anomalies have been shown to be caused by mutations in BMPR1B, encoding a GDF5 receptor. Methods: We clinically and radiologically characterised an acromesomelic chondrodysplasia in an adult woman born to consanguineous parents. We sequenced GDF5 and BMPR1B on DNA of the proposita. We performed 3D structural analysis and luciferase reporter assays to functionally investigate the identified BMPR1B mutation. Results: We extend the genotype-phenotype correlation in the acromesomelic chondrodysplasias by showing that the milder du Pan dysplasia can be caused by a hypomorphic BMPR1B mutation. We show that the homozygous c.91C>T, p.(Arg31Cys) mutation causing du Pan dysplasia leads to a significant loss of BMPR1B function, but to a lesser extent than the previously reported p.Cys53Arg mutation that results in the more severe Grebe dysplasia. Conclusions: The phenotypic severity gradient of the clinically and radiologically related acromesomelic chondrodysplasia spectrum of skeletal disorders may be due to the extent of functional impairment of the ligand-receptor pair GDF5-BMPR1B.}, language = {en} } @article{PlanesNinolesRubioetal.2015, author = {Planes, Maria D. and Ni{\~n}oles, Regina and Rubio, Lourdes and Bissoli, Gaetano and Bueso, Eduardo and Garc{\´i}a-S{\´a}nchez, Mar{\´i}a J. and Alejandro, Santiago and Gonzalez-Guzm{\´a}n, Miguel and Hedrich, Rainer and Rodriguez, Pedro L. and Fern{\´a}ndez, Jos{\´e} A. and Serrano, Ram{\´o}n}, title = {A mechanism of growth inhibition by abscisic acid in germinating seeds of Arabidopsis thaliana based on inhibition of plasma membrane \(H^+\)-ATPase and decreased cytosolic pH, \(K^+\), and anions}, series = {Journal of Experimental Botany}, volume = {66}, journal = {Journal of Experimental Botany}, number = {3}, doi = {10.1093/jxb/eru442}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121221}, pages = {813-25}, year = {2015}, abstract = {The stress hormone abscisic acid (ABA) induces expression of defence genes in many organs, modulates ion homeostasis and metabolism in guard cells, and inhibits germination and seedling growth. Concerning the latter effect, several mutants of Arabidopsis thaliana with improved capability for \(H^+\) efflux (wat1-1D, overexpression of AKT1 and ost2-1D) are less sensitive to inhibition by ABA than the wild type. This suggested that ABA could inhibit \(H^+\) efflux (\(H^+\)-ATPase) and induce cytosolic acidification as a mechanism of growth inhibition. Measurements to test this hypothesis could not be done in germinating seeds and we used roots as the most convenient system. ABA inhibited the root plasma-membrane H+-ATPase measured in vitro (ATP hydrolysis by isolated vesicles) and in vivo (\(H^+\) efflux from seedling roots). This inhibition involved the core ABA signalling elements: PYR/PYL/RCAR ABA receptors, ABA-inhibited protein phosphatases (HAB1), and ABA-activated protein kinases (SnRK2.2 and SnRK2.3). Electrophysiological measurements in root epidermal cells indicated that ABA, acting through the PYR/PYL/RCAR receptors, induced membrane hyperpolarization (due to \(K^+\) efflux through the GORK channel) and cytosolic acidification. This acidification was not observed in the wat1-1D mutant. The mechanism of inhibition of the \(H^+\)-ATPase by ABA and its effects on cytosolic pH and membrane potential in roots were different from those in guard cells. ABA did not affect the in vivo phosphorylation level of the known activating site (penultimate threonine) of (\(H^+\)-ATPase in roots, and SnRK2.2 phosphorylated in vitro the C-terminal regulatory domain of (\(H^+\)-ATPase while the guard-cell kinase SnRK2.6/OST1 did not.}, language = {en} } @phdthesis{Nguyen2015, author = {Nguyen, Thanh Nam}, title = {A model system for carbohydrates interactions on single-crystalline Ru surfaces}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111485}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {In this thesis, I present a model system for carbohydrate interactions with single-crystalline Ru surfaces. Geometric and electronic properties of copper phthalocyanine (CuPc) on top of graphene on hexagonal Ru(0001), rectangular Ru(10-10) and vicinal Ru(1,1,-2,10) surfaces have been studied. First, the Fermi surfaces and band structures of the three Ru surfaces were investigated by high-resolution angle-resolved photoemission spectroscopy. The experimental data and theoretical calculations allow to derive detailed information about the momentum-resolved electronic structure. The results can be used as a reference to understand the chemical and catalytic properties of Ru surfaces. Second, graphene layers were prepared on the three different Ru surfaces. Using low-energy electron diffraction and scanning tunneling microscopy, it was found that graphene can be grown in well-ordered structures on all three surfaces, hexagonal Ru(0001), rectangular Ru(10-10) and vicinal Ru(1,1,-2,10), although they have different surface symmetries. Evidence for a strong interaction between graphene and Ru surfaces is a 1.3-1.7e V increase in the graphene pi-bands binding energy with respect to free-standing graphene sheets. This energy variation is due to the hybridization between the graphene pi bands and the Ru 4d electrons, while the lattice mismatch does not play an important role in the bonding between graphene and Ru surfaces. Finally, the geometric and electronic structures of CuPc on Ru(10-10), graphene/Ru(10-10), and graphene/Ru(0001) have been studied in detail. CuPc molecules can be grown well-ordered on Ru(10-10) but not on Ru(0001). The growth of CuPc on graphene/Ru(10-10) and Ru(0001) is dominated by the Moire pattern of graphene. CuPc molecules form well-ordered structures with rectangular unit cells on graphene/Ru(10-10) and Ru(0001). The distance of adjacent CuPc molecules is 1.5 and 1.3 nm on graphene/Ru(0001) and 1.54 and 1.37 nm on graphene/Ru(10-10). This indicates that the molecule-substrate interaction dominates over the intermolecular interaction for CuPc molecules on graphene/Ru(10-10) and graphene/Ru(0001).}, subject = {Ruthenium}, language = {en} } @article{ZahoGhirlandoAlfonsoetal.2015, author = {Zaho, Huaying and Ghirlando, Rodolfo and Alfonso, Carlos and Arisaka, Fumio and Attali, Ilan and Bain, David L. and Bakhtina, Marina M. and Becker, Donald F. and Bedwell, Gregory J. and Bekdemir, Ahmet and Besong, Tabot M. D. and Birck, Catherine and Brautigam, Chad A. and Brennerman, William and Byron, Olwyn and Bzowska, Agnieszka and Chaires, Jonathan B. and Chaton, Catherine T. and Coelfen, Helmbut and Connaghan, Keith D. and Crowley, Kimberly A. and Curth, Ute and Daviter, Tina and Dean, William L. and Diez, Ana I. and Ebel, Christine and Eckert, Debra M. and Eisele, Leslie E. and Eisenstein, Edward and England, Patrick and Escalante, Carlos and Fagan, Jeffrey A. and Fairman, Robert and Finn, Ron M. and Fischle, Wolfgang and Garcia de la Torre, Jose and Gor, Jayesh and Gustafsson, Henning and Hall, Damien and Harding, Stephen E. and Hernandez Cifre, Jose G. and Herr, Andrew B. and Howell, Elizabeth E. and Isaac, Richard S. and Jao, Shu-Chuan and Jose, Davis and Kim, Soon-Jong and Kokona, Bashkim and Kornblatt, Jack A. and Kosek, Dalibor and Krayukhina, Elena and Krzizike, Daniel and Kusznir, Eric A. and Kwon, Hyewon and Larson, Adam and Laue, Thomas M. and Le Roy, Aline and Leech, Andrew P. and Lilie, Hauke and Luger, Karolin and Luque-Ortega, Juan R. and Ma, Jia and May, Carrie A. and Maynard, Ernest L. and Modrak-Wojcik, Anna and Mok, Yee-Foong and M{\"u}cke, Norbert and Nagel-Steger, Luitgard and Narlikar, Geeta J. and Noda, Masanori and Nourse, Amanda and Obsil, Thomas and Park, Chad K and Park, Jin-Ku and Pawelek, Peter D. and Perdue, Erby E. and Perkins, Stephen J. and Perugini, Matthew A. and Peterson, Craig L. and Peverelli, Martin G. and Piszczek, Grzegorz and Prag, Gali and Prevelige, Peter E. and Raynal, Bertrand D. E. and Rezabkova, Lenka and Richter, Klaus and Ringel, Alison E. and Rosenberg, Rose and Rowe, Arthur J. and Rufer, Arne C. and Scott, David J. and Seravalli, Javier G. and Solovyova, Alexandra S. and Song, Renjie and Staunton, David and Stoddard, Caitlin and Stott, Katherine and Strauss, Holder M. and Streicher, Werner W. and Sumida, John P. and Swygert, Sarah G. and Szczepanowski, Roman H. and Tessmer, Ingrid and Toth, Ronald T. and Tripathy, Ashutosh and Uchiyama, Susumu and Uebel, Stephan F. W. and Unzai, Satoru and Gruber, Anna Vitlin and von Hippel, Peter H. and Wandrey, Christine and Wang, Szu-Huan and Weitzel, Steven E and Wielgus-Kutrowska, Beata and Wolberger, Cynthia and Wolff, Martin and Wright, Edward and Wu, Yu-Sung and Wubben, Jacinta M. and Schuck, Peter}, title = {A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {5}, doi = {10.1371/journal.pone.0126420}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151903}, pages = {e0126420}, year = {2015}, abstract = {Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4\%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7\%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.}, language = {en} } @article{MatsudaUnoKondoetal.2015, author = {Matsuda, Yoichi and Uno, Yoshinobu and Kondo, Mariko and Gilchrist, Michael J. and Zorn, Aaron M. and Rokhsar, Daniel S. and Schmid, Michael and Taira, Masanori}, title = {A New Nomenclature of Xenopus laevis Chromosomes Based on the Phylogenetic Relationship to Silurana/Xenopus tropicalis}, series = {Cytogenetic and Genome Research}, volume = {145}, journal = {Cytogenetic and Genome Research}, number = {3-4}, issn = {1424-8581}, doi = {10.1159/000381292}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196748}, pages = {187-191}, year = {2015}, abstract = {Xenopus laevis (XLA) is an allotetraploid species which appears to have undergone whole-genome duplication after the interspecific hybridization of 2 diploid species closely related to Silurana/Xenopus tropicalis (XTR). Previous cDNA fluorescence in situ hybridization (FISH) experiments have identified 9 sets of homoeologous chromosomes in X. laevis, in which 8 sets correspond to chromosomes 1-8 of X. tropicalis (XTR1-XTR8), and the last set corresponds to a fusion of XTR9 and XTR10. In addition, recent X. laevis genome sequencing and BAC-FISH experiments support this physiological relationship and show no gross chromosome translocation in the X. laevis karyotype. Therefore, for the benefit of both comparative cytogenetics and genome research, we here propose a new chromosome nomenclature for X. laevis based on the phylogenetic relationship and chromosome length, i.e. XLA1L, XLA1S, XLA2L, XLA2S, and so on, in which the numbering of XLA chromosomes corresponds to that in X. tropicalis and the postfixes 'L' and 'S' stand for 'long' and 'short' chromosomes in the homoeologous pairs, which can be distinguished cytologically by their relative size. The last chromosome set is named XLA9L and XLA9S, in which XLA9 corresponds to both XTR9 and XTR10, and hence, to emphasize the phylogenetic relationship to X. tropicalis, XLA9_10L and XLA9_10S are also used as synonyms.}, language = {en} } @article{KoziolRadioSmircichetal.2015, author = {Koziol, Uriel and Radio, Santiago and Smircich, Pablo and Zarowiecki, Magdalena and Fern{\´a}ndez, Cecilia and Brehm, Klaus}, title = {A novel terminal-repeat retrotransposon in miniature (TRIM) is massively expressed in Echinococcus multilocularis stem cells}, series = {Genome Biology and Evolution}, volume = {7}, journal = {Genome Biology and Evolution}, number = {8}, doi = {10.1093/gbe/evv126}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148306}, pages = {2136-2153}, year = {2015}, abstract = {Taeniid cestodes (including the human parasites Echinococcus spp. and Taenia solium) have very few mobile genetic elements (MGEs) in their genome, despite lacking a canonical PIWI pathway. The MGEs of these parasites are virtually unexplored, and nothing is known about their expression and silencing. In this work, we report the discovery of a novel family of small nonautonomous long terminal repeat retrotransposons (also known as terminal-repeat retrotransposons in miniature, TRIMs) which we have named ta-TRIM (taeniid TRIM). ta-TRIMs are only the second family of TRIM elements discovered in animals, and are likely the result of convergent reductive evolution in different taxonomic groups. These elements originated at the base of the taeniid tree and have expanded during taeniid diversification, including after the divergence of closely related species such as Echinococcus multilocularis and Echinococcus granulosus. They are massively expressed in larval stages, from a small proportion of full-length copies and from isolated terminal repeats that show transcriptional read-through into downstream regions, generating novel noncoding RNAs and transcriptional fusions to coding genes. In E. multilocularis, ta-TRIMs are specifically expressed in the germinative cells (the somatic stem cells) during asexual reproduction of metacestode larvae. This would provide a developmental mechanism for insertion of ta-TRIMs into cells that will eventually generate the adult germ line. Future studies of active and inactive ta-TRIM elements could give the first clues on MGE silencing mechanisms in cestodes.}, language = {en} } @article{WinklerFischerSchadeetal.2015, author = {Winkler, Karol and Fischer, Julian and Schade, Anne and Amthor, Matthias and Dall, Robert and Geßler, Jonas and Emmerling, Monika and Ostrovskaya, Elena A. and Kamp, Martin and Schneider, Christian and H{\"o}fling, Sven}, title = {A polariton condensate in a photonic crystal potential landscape}, series = {New Journal of Physics}, volume = {17}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/17/2/023001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125050}, pages = {023001}, year = {2015}, abstract = {The possibility of investigating macroscopic coherent quantum states in polariton condensates and of engineering polariton landscapes in semiconductors has triggered interest in using polaritonic systems to simulate complex many-body phenomena. However, advanced experiments require superior trapping techniques that allow for the engineering of periodic and arbitrary potentials with strong on-site localization, clean condensate formation, and nearest-neighbor coupling. Here we establish a technology that meets these demands and enables strong, potentially tunable trapping without affecting the favorable polariton characteristics. The traps are based on a locally elongated microcavity which can be formed by standard lithography. We observe polariton condensation with non-resonant pumping in single traps and photonic crystal square lattice arrays. In the latter structures, we observe pronounced energy bands, complete band gaps, and spontaneous condensation at the M-point of the Brillouin zone.}, language = {en} } @article{DjuzenovaZimmermannKatzeretal.2015, author = {Djuzenova, Cholpon S. and Zimmermann, Marcus and Katzer, Astrid and Fiedler, Vanessa and Distel, Luitpold V. and Gasser, Martin and Waaga-Gasser, Anna-Maria and Flentje, Michael and Polat, B{\"u}lent}, title = {A prospective study on histone γ-H2AX and 53BP1 foci expression in rectal carcinoma patients: correlation with radiation therapy-induced outcome}, series = {BMC Cancer}, volume = {15}, journal = {BMC Cancer}, number = {856}, doi = {10.1186/s12885-015-1890-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125303}, year = {2015}, abstract = {Background The prognostic value of histone γ-H2AX and 53BP1 proteins to predict the radiotherapy (RT) outcome of patients with rectal carcinoma (RC) was evaluated in a prospective study. High expression of the constitutive histone γ-H2AX is indicative of defective DNA repair pathway and/or genomic instability, whereas 53BP1 (p53-binding protein 1) is a conserved checkpoint protein with properties of a DNA double-strand breaks sensor. Methods Using fluorescence microscopy, we assessed spontaneous and radiation-induced foci of γ-H2AX and 53BP1 in peripheral blood mononuclear cells derived from unselected RC patients (n = 53) undergoing neoadjuvant chemo- and RT. Cells from apparently healthy donors (n = 12) served as references. Results The γ-H2AX assay of in vitro irradiated lymphocytes revealed significantly higher degree of DNA damage in the group of unselected RC patients with respect to the background, initial (0.5 Gy, 30 min) and residual (0.5 Gy and 2 Gy, 24 h post-radiation) damage compared to the control group. Likewise, the numbers of 53BP1 foci analyzed in the samples from 46 RC patients were significantly higher than in controls except for the background DNA damage. However, both markers were not able to predict tumor stage, gastrointestinal toxicity or tumor regression after curative RT. Interestingly, the mean baseline and induced DNA damage was found to be lower in the group of RC patients with tumor stage IV (n = 7) as compared with the stage III (n = 35). The difference, however, did not reach statistical significance, apparently, because of the limited number of patients. Conclusions The study shows higher expression of γ-H2AX and 53BP1 foci in rectal cancer patients compared with healthy individuals. Yet the data in vitro were not predictive in regard to the radiotherapy outcome.}, language = {en} } @inproceedings{AliMontenegro2015, author = {Ali, Qasim and Montenegro, Sergio}, title = {A Simple Approach to Quadrocopter Formation Flying Test Setup for Education and Development}, series = {INTED2015 Proceedings}, booktitle = {INTED2015 Proceedings}, publisher = {International Academy of Technology, Education and Development (IATED)}, isbn = {978-84-606-5763-7}, issn = {2340-1079}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-114495}, pages = {2776 -- 2784}, year = {2015}, abstract = {A simple test setup has been developed at Institute of Aerospace Information Technology, University of W{\"u}rzburg, Germany to realize basic functionalities for formation flight of quadrocopters. The test environment is planned to be utilized for developing and validating the algorithms for formation flying capability in real environment as well as for education purpose. An already existing test bed for single quadrocopter was extended with necessary inter-communication and distributed control mechanism to test the algorithms for formation flights in 2 degrees of freedom (roll / pitch). This study encompasses the domain of communication, control engineering and embedded systems programming. Bluetooth protocol has been used for inter-communication between two quadrocopters. A simple approach of PID control in combination with Kalman filter has been exploited. MATLAB Instrument Control Toolbox has been used for data display, plotting and analysis. Plots can be drawn in real-time and received information can also be stored in the form of files for later use and analysis. The test setup has been developed indigenously and at considerably low cost. Emphasis has been placed on simplicity to facilitate students learning process. Several lessons have been learnt during the course of development of this setup. Proposed setup is quite flexible that can be modified as per changing requirements.}, subject = {Flugk{\"o}rper}, language = {en} } @phdthesis{Yang2015, author = {Yang, Zhenghong}, title = {A systematic study of learned helplessness in Drosophila melanogaster}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112424}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The learned helplessness phenomenon is a specific animal behavior induced by prior exposure to uncontrollable aversive stimuli. It was first found by Seligman and Maier (1967) in dogs and then has been reported in many other species, e.g. in rats (Vollmayr and Henn, 2001), in goldfishes (Padilla, 1970), in cockroaches (Brown, 1988) and also in fruit flies (Brown, 1996; Bertolucci, 2008). However, the learned helplessness effect in fruit flies (Drosophila melanogaster) has not been studied in detail. Thus, in this doctoral study, we investigated systematically learned helplessness behavior of Drosophila for the first time. Three groups of flies were tested in heatbox. Control group was in the chambers experiencing constant, mild temperature. Second group, master flies were punished in their chambers by being heated if they stopped walking for 0.9s. The heat pulses ended as soon as they resumed walking again. A third group, the yoked fly, was in their chambers at the same time. However, their behavior didn't affect anything: yoked flies were heated whenever master flies did, with same timing and durations. After certain amount of heating events, yoked flies associated their own behavior with the uncontrollability of the environment. They suppressed their innate responses such as reducing their walking time and walking speed; making longer escape latencies and less turning around behavior under heat pulses. Even after the conditioning phase, yoked flies showed lower activity level than master and control flies. Interestingly, we have also observed sex dimorphisms in flies. Male flies expressed learned helplessness not like female flies. Differences between master and yoked flies were smaller in male than in female flies. Another interesting finding was that prolonged or even repetition of training phases didn't enhance learned helplessness effect in flies. Furthermore, we investigated serotonergic and dopaminergic nervous systems in learned helplessness. Using genetic and pharmacological manipulations, we altered the levels of serotonin and dopamine in flies' central nervous system. Female flies with reduced serotonin concentration didn't show helpless behavior, while the learned helplessness effect in male flies seems not to be affected by a reduction of serotonin. Flies with lower dopamine level do not display the learned helplessness effect in the test phase, suggesting that with low dopamine the motivational change in learned helplessness in Drosophila may decline faster than with a normal dopamine level.}, subject = {Taufliege}, language = {en} } @article{LamatschAdolfssonSenioretal.2015, author = {Lamatsch, Dunja K. and Adolfsson, Sofia and Senior, Alistair M. and Christiansen, Guntram and Pichler, Maria and Ozaki, Yuichi and Smeds, Linnea and Schartl, Manfred and Nakagawa, Shinichi}, title = {A transcriptome derived female-specific marker from the invasive Western mosquitofish (Gambusia affinis)}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {2}, doi = {10.1371/journal.pone.0118214}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144004}, pages = {e0118214}, year = {2015}, abstract = {Sex-specific markers are a prerequisite for understanding reproductive biology, genetic factors involved in sex differences, mechanisms of sex determination, and ultimately the evolution of sex chromosomes. The Western mosquitofish, Gambusia affinis, may be considered a model species for sex-chromosome evolution, as it displays female heterogamety (ZW/ZZ), and is also ecologically interesting as a worldwide invasive species. Here, de novo RNA-sequencing on the gonads of sexually mature G. affinis was used to identify contigs that were highly transcribed in females but not in males (i.e., transcripts with ovary-specific expression). Subsequently, 129 primer pairs spanning 79 contigs were tested by PCR to identify sex-specific transcripts. Of those primer pairs, one female-specific DNA marker was identified, Sanger sequenced and subsequently validated in 115 fish. Sequence analyses revealed a high similarity between the identified sex-specific marker and the 3' UTR of the aminomethyl transferase (amt) gene of the closely related platyfish (Xiphophorus maculatus). This is the first time that RNA-seq has been used to successfully characterize a sex-specific marker in a fish species in the absence of a genome map. Additionally, the identified sex-specific marker represents one of only a handful of such markers in fishes.}, language = {en} } @article{vonBohlKuehnSimonetal.2015, author = {von Bohl, Andreas and Kuehn, Andrea and Simon, Nina and Nkwouano Ngongang, Vanesa and Spehr, Marc and Baumeister, Stefan and Przyborski, Jude M. and Fischer, Rainer and Pradel, Gabriele}, title = {A WD40-repeat protein unique to malaria parasites associates with adhesion protein complexes and is crucial for blood stage progeny}, series = {Malaria Journal}, volume = {14}, journal = {Malaria Journal}, number = {435}, doi = {10.1186/s12936-015-0967-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139728}, year = {2015}, abstract = {Background During development in human erythrocytes, Plasmodium falciparum parasites display a remarkable number of adhesive proteins on their plasma membrane. In the invasive merozoites, these include members of the PfMSP1 and PfAMA1/RON complexes, which facilitate contact between merozoites and red blood cells. In gametocytes, sexual precursor cells mediating parasite transmission to the mosquito vector, plasma membrane-associated proteins primarily belong to the PfCCp and 6-cys families with roles in fertilization. This study describes a newly identified WD40-repeat protein unique to Plasmodium species that associates with adhesion protein complexes of both merozoites and gametocytes. Methods The WD40-repeat protein-like protein PfWLP1 was identified via co-immunoprecipitation assays followed by mass spectrometry and characterized using biochemical and immunohistochemistry methods. Reverse genetics were employed for functional analysis. Results PfWLP1 is expressed both in schizonts and gametocytes. In mature schizonts, the protein localizes underneath the merozoite micronemes and interacts with PfAMA1, while in gametocytes PfWLP1 primarily accumulates underneath the plasma membrane and associates with PfCCp1 and Pfs230. Reverse genetics failed to disrupt the pfwlp1 gene, while haemagglutinin-tagging was feasible, suggesting a crucial function for PfWLP1 during blood stage replication. Conclusions This is the first report on a plasmodial WD40-repeat protein associating with cell adhesion proteins. Since WD40 domains are known to mediate protein-protein contact by serving as a rigid scaffold for protein interactions, the presented data suggest that PfWLP1 supports the stability of adhesion protein complexes of the plasmodial blood stages.}, language = {en} } @article{SchattonYangKleffeletal.2015, author = {Schatton, Tobias and Yang, Jun and Kleffel, Sonja and Uehara, Mayuko and Barthel, Steven R. and Schlapbach, Christoph and Zhan, Qian and Dudeney, Stephen and Mueller, Hansgeorg and Lee, Nayoung and de Vries, Juliane C. and Meier, Barbara and Beken, Seppe Vander and Kluth, Mark A. and Ganss, Christoph and Sharpe, Arlene H. and Waaga-Gasser, Ana Maria and Sayegh, Mohamed H. and Abdi, Reza and Scharffetter-Kochanek, Karin and Murphy, George F. and Kupper, Thomas S. and Frank, Natasha Y. and Frank, Markus H.}, title = {ABCB5 Identifies Immunoregulatory Dermal Cells}, series = {Cell Reports}, volume = {12}, journal = {Cell Reports}, doi = {10.1016/j.celrep.2015.08.010}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149989}, pages = {1564 -- 1574}, year = {2015}, abstract = {Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5\(^+\) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5\(^+\) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.}, language = {en} } @inproceedings{HoeggerXiao2015, author = {H{\"o}gger, Petra and Xiao, Jianbo}, title = {Abstracts of the International Symposium on Phytochemicals in Medicine and Food}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121585}, year = {2015}, abstract = {The International Symposium on Phytochemicals in Medicine and Food (ISPMF2015), organized by the Phytochemical Society of Europe (PSE) and the Phytochemical Society of Asia (PSA), was held June 26-29, 2015, in Shanghai of China. This was the first time that a PSE meeting has been held in Asia and a PSE-PSA joint symposium provided an opportunity for communication between scientists from Europe and Asia and other continents. ISPMF2015 has been jointly sponsored by Fujian Agriculture and Forestry University, Guizhou Medical University, Shanghai Normal University, Yancheng Institute of Technology, Beijing Normal University, and Fudan University. More than 270 scientists from 48 countries attended this meeting and presented their research and opinions on phytochemistry, phytomedicine and phytoneering. The international organizing committee and scientific advisory board of ISPMF 2015 comprised of outstanding scientists from around the globe. Dr. Jianbo Xiao was the chairman of the International Organizing Committee of ISPMF2015 and moderated the open address on June 26. The organizing committee of ISPMF2015 assembled an exciting and diverse program, featuring 16 sessions including 12 plenary lectures, 20 invited talks, 55 short oral presentations, and more than 130 posters, which were dedicated to creating a podium for exchanging the latest research results in the phytochemicals for food and human health.}, language = {en} } @article{ElsterPlattThomaleetal.2015, author = {Elster, Lars and Platt, Christian and Thomale, Ronny and Hanke, Werner and Hankiewicz, Ewelina M.}, title = {Accessing topological superconductivity via a combined STM and renormalization group analysis}, series = {Nature Communications}, volume = {6}, journal = {Nature Communications}, number = {8232}, doi = {10.1038/ncomms9232}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148181}, year = {2015}, abstract = {The search for topological superconductors has recently become a key issue in condensed matter physics, because of their possible relevance to provide a platform for Majorana bound states, non-Abelian statistics, and quantum computing. Here we propose a new scheme which links as directly as possible the experimental search to a material-based microscopic theory for topological superconductivity. For this, the analysis of scanning tunnelling microscopy, which typically uses a phenomenological ansatz for the superconductor gap functions, is elevated to a theory, where a multi-orbital functional renormalization group analysis allows for an unbiased microscopic determination of the material-dependent pairing potentials. The combined approach is highlighted for paradigmatic hexagonal systems, such as doped graphene and water-intercalated sodium cobaltates, where lattice symmetry and electronic correlations yield a propensity for a chiral singlet topological superconductor. We demonstrate that our microscopic material-oriented procedure is necessary to uniquely resolve a topological superconductor state.}, language = {en} } @article{FluriFleischerKleinschnitz2015, author = {Fluri, Felix and Fleischer, Michael and Kleinschnitz, Christoph}, title = {Accidental Thrombolysis in a Stroke Patient Receiving Apixaban}, series = {Cerebrovascular Diseases Extra}, volume = {5}, journal = {Cerebrovascular Diseases Extra}, doi = {10.1159/000375181}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126326}, pages = {55-56}, year = {2015}, abstract = {No abstract available.}, language = {en} } @article{StepniakKaestnerPoggietal.2015, author = {Stepniak, Beata and K{\"a}stner, Anne and Poggi, Giulia and Mitjans, Marina and Begemann, Martin and Hartmann, Annette and Van der Auwera, Sandra and Sananbenesi, Farahnaz and Kr{\"u}ger-Burg, Dilja and Matuszko, Gabriela and Brosi, Cornelia and Homuth, Georg and V{\"o}lzke, Henry and Benseler, Fritz and Bagni, Claudia and Fischer, Utz and Dityatev, Alexander and Grabe, Hans-J{\"o}rgen and Rujescu, Dan and Fischer, Andre and Ehrenreich, Hannelore}, title = {Accumulated common variants in the broader fragile X gene family modulate autistic phenotypes}, series = {EMBO Molecular Medicine}, volume = {7}, journal = {EMBO Molecular Medicine}, number = {12}, doi = {10.15252/emmm.201505696}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136893}, pages = {1565-1579}, year = {2015}, abstract = {Fragile X syndrome (FXS) is mostly caused by a CGG triplet expansion in the fragile X mental retardation 1 gene (FMR1). Up to 60\% of affected males fulfill criteria for autism spectrum disorder (ASD), making FXS the most frequent monogenetic cause of syndromic ASD. It is unknown, however, whether normal variants (independent of mutations) in the fragile X gene family (FMR1, FXR1, FXR2) and in FMR2 modulate autistic features. Here, we report an accumulation model of 8 SNPs in these genes, associated with autistic traits in a discovery sample of male patients with schizophrenia (N = 692) and three independent replicate samples: patients with schizophrenia (N = 626), patients with other psychiatric diagnoses (N = 111) and a general population sample (N = 2005). For first mechanistic insight, we contrasted microRNA expression in peripheral blood mononuclear cells of selected extreme group subjects with high-versus low-risk constellation regarding the accumulation model. Thereby, the brain-expressed miR-181 species emerged as potential "umbrella regulator", with several seed matches across the fragile X gene family and FMR2. To conclude, normal variation in these genes contributes to the continuum of autistic phenotypes.}, language = {en} } @article{KollertDombertDoeringetal.2015, author = {Kollert, Sina and Dombert, Benjamin and D{\"o}ring, Frank and Wischmeyer, Erhard}, title = {Activation of TRESK channels by the inflammatory mediator lysophosphatidic acid balances nociceptive signalling}, series = {Scientific Reports}, volume = {5}, journal = {Scientific Reports}, number = {12548}, doi = {10.1038/srep12548}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148312}, year = {2015}, abstract = {In dorsal root ganglia (DRG) neurons TRESK channels constitute a major current component of the standing outward current IK\(_{SO}\). A prominent physiological role of TRESK has been attributed to pain sensation. During inflammation mediators of pain e.g. lysophosphatidic acid (LPA) are released and modulate nociception. We demonstrate co-expression of TRESK and LPA receptors in DRG neurons. Heterologous expression of TRESK and LPA receptors in Xenopus oocytes revealed augmentation of basal K\(^{+}\) currents upon LPA application. In DRG neurons nociception can result from TRPV\(_{1}\) activation by capsaicin or LPA. Upon co-expression in Xenopus oocytes LPA simultaneously increased both depolarising TRPV\(_{1}\) and hyperpolarising TRESK currents. Patch-clamp recordings in cultured DRG neurons from TRESK[wt] mice displayed increased IK\(_{SO}\) after application of LPA whereas under these conditions IK\(_{SO}\) in neurons from TRESK[ko] mice remained unaltered. Under current-clamp conditions LPA application differentially modulated excitability in these genotypes upon depolarising pulses. Spike frequency was attenuated in TRESK[wt] neurons and, in contrast, augmented in TRESK[ko] neurons. Accordingly, excitation of nociceptive neurons by LPA is balanced by co-activation of TRESK channels. Hence excitation of sensory neurons is strongly controlled by the activity of TRESK channels, which therefore are good candidates for the treatment of pain disorders.}, language = {en} } @article{EbertBenischKrugetal.2015, author = {Ebert, Regina and Benisch, Peggy and Krug, Melanie and Zeck, Sabine and Meißner-Weigl, Jutta and Steinert, Andre and Rauner, Martina and Hofbauer, Lorenz and Jakob, Franz}, title = {Acute phase serum amyloid A induces proinflammatory cytokines and mineralization via toll-like receptor 4 in mesenchymal stem cells}, series = {Stem Cell Research}, volume = {15}, journal = {Stem Cell Research}, doi = {10.1016/j.scr.2015.06.008}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148491}, pages = {231-239}, year = {2015}, abstract = {The role of serum amyloid A (SAA) proteins, which are ligands for toll-like receptors, was analyzed in human bone marrow-derived mesenchymal stem cells (hMSCs) and their osteogenic offspring with a focus on senescence, differentiation andmineralization. In vitro aged hMSC developed a senescence-associated secretory phenotype (SASP), resulting in enhanced SAA1/2, TLR2/4 and proinflammatory cytokine (IL6, IL8, IL1\(\beta\), CXCL1, CXCL2) expression before entering replicative senescence. Recombinant human SAA1 (rhSAA1) induced SASP-related genes and proteins in MSC, which could be abolished by cotreatment with the TLR4-inhibitor CLI-095. The same pattern of SASP-resembling genes was stimulated upon induction of osteogenic differentiation, which is accompanied by autocrine SAA1/2 expression. In this context additional rhSAA1 enhanced the SASP-like phenotype, accelerated the proinflammatory phase of osteogenic differentiation and enhanced mineralization. Autocrine/paracrine and rhSAA1 via TLR4 stimulate a proinflammatory phenotype that is both part of the early phase of osteogenic differentiation and the development of senescence. This signaling cascade is tightly involved in bone formation and mineralization, but may also propagate pathological extraosseous calcification conditions such as calcifying inflammation and atherosclerosis.}, language = {en} } @article{HochleitnerJuengstBrownetal.2015, author = {Hochleitner, Gernot and J{\"u}ngst, Tomasz and Brown, Toby D and Hahn, Kathrin and Moseke, Claus and Jakob, Franz and Dalton, Paul D and Groll, J{\"u}rgen}, title = {Additive manufacturing of scaffolds with sub-micron filaments via melt electrospinning writing}, series = {Biofabrication}, volume = {7}, journal = {Biofabrication}, number = {3}, doi = {10.1088/1758-5090/7/3/035002}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254053}, year = {2015}, abstract = {The aim of this study was to explore the lower resolution limits of an electrohydrodynamic process combined with direct writing technology of polymer melts. Termed melt electrospinning writing, filaments are deposited layer-by-layer to produce discrete three-dimensional scaffolds for in vitro research. Through optimization of the parameters (flow rate, spinneret diameter, voltage, collector distance) for poly-ϵ-caprolactone, we could direct-write coherent scaffolds with ultrafine filaments, the smallest being 817 ± 165 nm. These low diameter filaments were deposited to form box-structures with a periodicity of 100.6 ± 5.1 μm and a height of 80 μm (50 stacked filaments; 100 overlap at intersections). We also observed oriented crystalline regions within such ultrafine filaments after annealing at 55 °C. The scaffolds were printed upon NCO-sP(EO-stat-PO)-coated glass slide surfaces and withstood frequent liquid exchanges with negligible scaffold detachment for at least 10 days in vitro.}, language = {en} } @article{LugerHohmannNiemannetal.2015, author = {Luger, Sebastian and Hohmann, Carina and Niemann, Daniela and Kraft, Peter and Gunreben, Ignaz and Neumann-Haefelin, Tobias and Kleinschnitz, Christoph and Steinmetz, Helmuth and Foerch, Christian and Pfeilschifter, Waltraud}, title = {Adherence to oral anticoagulant therapy in secondary stroke prevention - impact of the novel oral anticoagulants}, series = {Patient Preference and Adherence}, volume = {9}, journal = {Patient Preference and Adherence}, doi = {10.2147/PPA.S88994}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144477}, pages = {1695-1705}, year = {2015}, abstract = {Background: Oral anticoagulant therapy (OAT) potently prevents strokes in patients with atrial fibrillation. Vitamin K antagonists (VKA) have been the standard of care for long-term OAT for decades, but non-VKA oral anticoagulants (NOAC) have recently been approved for this indication, and raised many questions, among them their influence on medication adherence. We assessed adherence to VKA and NOAC in secondary stroke prevention. Methods: All patients treated from October 2011 to September 2012 for ischemic stroke or transient ischemic attack with a subsequent indication for OAT, at three academic hospitals were entered into a prospective registry, and baseline data and antithrombotic treatment at discharge were recorded. At the 1-year follow-up, we assessed the adherence to different OAT strategies and patients' adherence to their respective OAT. We noted OAT changes, reasons to change treatment, and factors that influence persistence to the prescribed OAT. Results: In patients discharged on OAT, we achieved a fatality corrected response rate of 73.3\% (n=209). A total of 92\% of these patients received OAT at the 1-year follow-up. We observed good adherence to both VKA and NOAC (VKA, 80.9\%; NOAC, 74.8\%; P=0.243) with a statistically nonsignificant tendency toward a weaker adherence to dabigatran. Disability at 1-year follow-up was an independent predictor of lower adherence to any OAT after multivariate analysis, whereas the choice of OAT did not have a relevant influence. Conclusion: One-year adherence to OAT after stroke is strong (>90\%) and patients who switch therapy most commonly switch toward another OAT. The 1-year adherence rates to VKA and NOAC in secondary stroke prevention do not differ significantly between both therapeutic strategies.}, language = {en} } @phdthesis{Geiselhart2015, author = {Geiselhart, Roman}, title = {Advances in the stability analysis of large-scale discrete-time systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-112963}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Several aspects of the stability analysis of large-scale discrete-time systems are considered. An important feature is that the right-hand side does not have have to be continuous. In particular, constructive approaches to compute Lyapunov functions are derived and applied to several system classes. For large-scale systems, which are considered as an interconnection of smaller subsystems, we derive a new class of small-gain results, which do not require the subsystems to be robust in some sense. Moreover, we do not only study sufficiency of the conditions, but rather state an assumption under which these conditions are also necessary. Moreover, gain construction methods are derived for several types of aggregation, quantifying how large a prescribed set of interconnection gains can be in order that a small-gain condition holds.}, subject = {Ljapunov-Funktion}, language = {en} } @article{KnollSchramm2015, author = {Knoll, Johannes and Schramm, Holger}, title = {Advertising in social network sites - Investigating the social influence of user-generated content on online advertising effects}, series = {Communications}, volume = {40}, journal = {Communications}, number = {3}, issn = {1613-4087}, doi = {10.1515/commun-2015-0011}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-194192}, pages = {341-360}, year = {2015}, abstract = {In today's social online world there is a variety of interaction and participatory possibilities which enable web users to actively produce content themselves. This user-generated content is omnipresent in the web and there is growing evidence that it is used to select or evaluate professionally created online information. The present study investigated how this surrounding content affects online advertising by drawing from social influence theory. Specifically, it was assumed that web users sharing an interpersonal relationship (interpersonal influence) and/or a group membership (collective influence) with authors of user-generated content which appears next to advertising on the web page are more strongly influenced in their response to the advertising than unrelated users. These assumptions were tested in a 2 × 2 between-subject experiment with 118 students who were exposed to four different Facebook profiles that differed in terms of interpersonal connection to the source (existent/non-existent) and collective connection to the source (existent/non-existent). The results show a significant impact in the case of collective influence, but not in the case of interpersonal influence. The underlying mechanisms of this effect and implications of the results for online advertising are discussed.}, language = {en} } @phdthesis{Sun2015, author = {Sun, Ping}, title = {Alzheimer`s disease and brain insulin resistance: The diabetes inducing drug streptozotocin diminishes adult neurogenesis in the rat hippocampus - an in vivo and in vitro study}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119252}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of the brain, which is characterized by a progressive loss of memory and spatial orientation. Only less than 5-10\% of AD sufferers are familial cases due to genetic mutations in the amyloid precursor protein (APP) gene or presenilin (PS) 1 and 2 genes. The cause of sporadic AD (sAD) which covers > 95\% of AD patients is still unknown. Current research found interactions between aging, diabetes and cognitive decline including dementia in general and in AD in particular. Disturbances of brain glucose uptake, glucose tolerance and utilization and impairment of the insulin/insulin receptor (IR) signaling cascade are thought to be key targets for the development of sAD. In the brain of AD patients, neural plasticity is impaired indicated by synaptic and neuronal loss. Adult neurogenesis (AN), the generation of functional neurons in the adult brain, may be able to restore neurological function deficits through the integration of newborn neurons into existing neural networks. The dentate gyrus of the hippocampus is one out of few brain regions where life-long AN exists. However, there is a big controversy in literature regarding the involvement of AN in AD pathology. Most animal studies used transgenic mice based on the Amyloid ß (Aß) hypothesis which primarily act as models for the familial form of AD. Findings from human post mortem AN studies were also inconstistent. In this thesis, we focused on the possible involvement of AN in the pathogenesis of the sporadic form of AD. Streptozotocin intracerebroventricularily (STZ icv) treated rats, which develop an insulin-resistant brain state and learning and memory deficits preceding Aß pathology act as an appropriate animal model for sAD. We used STZ treatment for both parts of my work, for the in vivo and in vitro study. In the first part of my thesis, my coworkers and I investigated STZ icv treatment effects on different stages of AN in an in vivo approach. Even if STZ icv treatment does not seem to considerably influence stem cell proliferation over a short-term (1 month after STZ icv treatment) as well as in a long-term (3 months after STZ icv treatment) period, it results in significantly less immature and newborn mature neurons 3 months after STZ icv treatment. This reduction detected after 3 months was specific for the septal hippocampus, discussed to be important for spatial learning. Subsequently we performed co-localization studies with antibodies detecting BrdU (applied appr. 27 days before sacrifice) and cell-type specific markers such as NeuN, and GFAP, we found that STZ treatment does not affect the differentiation fate of newly generated cells. Phenotype analysis of BrdU-positive cells in the hilus and molecular layer revealed that some of the BrdU-positive cells are newborn oligodendrocytes but not newborn microglia. In the second part of my thesis I worked with cultured neural stem cells (NSCs) isolated from the adult rat hippocampus to reveal STZ effects on the proliferation of of NSCs, and on the survival and differentiation of their progeny. Furthermore, this in vitro approach enabled me to study cellular mechanisms underlying the observed impaired neurogenesis in the hippocampus of STZ-treated rats. In contrast to our findings of the STZ icv in vivo study we revealed that STZ supplied with the cell culture medium inhibits the proliferation of NSCs in a dose-dependent and time-dependent manner. Moreover, performing immunofluorescence studies with antibodies detecting cell-type specific markers after triggering NSCs to differentiate, we could show that STZ treatment affects the number of newly generated neurons but not of astrocytes. Analyzing newborn cells starting to differentiate and migrate I was able to demonstrate that STZ has no effect on the migration of newborn cells. Trying to reveal cellular mechanisms underlying the negative influence of STZ on hippocampal AN, we performed qRT-PCR and immunofluorescence staining and thus could show that in NSCs the expression of glucose transporter (GLUT)3 mRNA as well as IR and GLUT3 protein levels are reduced after STZ treatment. Therefore, the inhibition of the proliferation of NSCs may be (at least partially) caused by these two molecules. Interestingly, the effect of STZ on differentiating cells was shown to be different, as IR protein expression was not significantly changed but GLUT3 protein levels were decreased in consequence of STZ treatment. In summary, this project delivered further insights into the interrelation between AN the sporadic form of sAD and thus provides a basis of new therapeutic approaches in sAD treatment through intervening AN. Discrepancies between the results of the two parts of my thesis, the in vivo and in vitro part, were certainly caused to a certain extent by the missing microenvironment in the in vitro approach with cultured NSCs. Future studies e.g. using co-culture systems could at least minimize the effect of a missing natural microenvironment of cultured NSCs, so that the use of an in vitro approach for the investigation of STZ treatment underlying cellular mechanisms can be improved.}, subject = {Alzheimerkrankheit}, language = {en} } @article{HansenKahnZelleretal.2015, author = {Hansen, Niels and Kahn, Ann-Kathrin and Zeller, Daniel and Katsarava, Zaza and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan}, title = {Amplitudes of pain-related evoked potentials are useful to detect small fiber involvement in painful mixed fiber neuropathies in addition to quantitative sensory testing - an electrophysiological study}, series = {Frontiers in Neurology}, volume = {6}, journal = {Frontiers in Neurology}, doi = {10.3389/fneur.2015.00244}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124824}, pages = {244}, year = {2015}, abstract = {To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls underwent clinical and electrophysiological evaluation. Small fiber function, electrical conductivity and morphology were examined by quantitative sensory testing (QST), PREP, and skin punch biopsy. MFN was diagnosed following clinical and electrophysiological examination (chronic inflammatory demyelinating neuropathy: n = 6; vasculitic neuropathy: n = 3; chronic axonal ­neuropathy: n = 2). The majority of patients with MFN characterized their pain by descriptors that mainly represent C-fiber-mediated pain. In QST, patients displayed elevated cold, warm, mechanical, and vibration detection thresholds and cold pain thresholds indicative of MFN. PREP amplitudes in patients correlated with cold (p < 0.05) and warm detection thresholds (p < 0.05). Burning pain and the presence of par-/dysesthesias correlated negatively with PREP amplitudes (p < 0.05). PREP amplitudes correlating with cold and warm detection thresholds, burning pain, and par-/dysesthesias support employing PREP amplitudes as an additional tool in conjunction with QST for detecting small fiber impairment in patients with MFN.}, language = {en} } @article{ArdeltEbbingAdamsetal.2015, author = {Ardelt, Peter U. and Ebbing, Jan and Adams, Fabian and Reiss, Cora and Arap, Wadih and Pasqualini, Renata and Bachmann, Alexander and Wetterauer, Ulrich and Riedmiller, Hubertus and Kneitz, Burkard}, title = {An anti-ubiquitin antibody response in transitional cell carcinoma of the urinary bladder}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {3}, doi = {10.1371/journal.pone.0118646}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143711}, pages = {e0118646}, year = {2015}, abstract = {Background To use combinatorial epitope mapping ("fingerprinting") of the antibody response to identify targets of the humoral immune response in patients with transitional cell carcinoma (TCC) of the bladder. Methods A combinatorial random peptide library was screened on the circulating pool of immunoglobulins purified from an index patient with a high risk TCC (pTa high grade plus carcinoma in situ) to identify corresponding target antigens. A patient cohort was investigated for antibody titers against ubiquitin. Results We selected, isolated, and validated an immunogenic peptide motif from ubiquitin as a dominant epitope of the humoral response. Patients with TCC had significantly higher antibody titers against ubiquitin than healthy donors (p<0.007), prostate cancer patients (p<0.0007), and all patients without TCC taken together (p<0.0001). Titers from superficial tumors were not significantly different from muscle invasive tumors (p = 0.0929). For antibody response against ubiquitin, sensitivity for detection of TCC was 0.44, specificity 0.96, positive predictive value 0.96 and negative predictive value 0.41. No significant titer changes were observed during the standard BCG induction immunotherapy. Conclusions This is the first report to demonstrate an anti-ubiquitin antibody response in patients with TCC. Although sensitivity of antibody production was low, a high specificity and positive predictive value make ubiquitin an interesting candidate for further diagnostic and possibly immune modulating studies.}, language = {en} } @article{SimonKaethnerRufetal.2015, author = {Simon, Nadine and K{\"a}thner, Ivo and Ruf, Carolin A. and Pasqualotto, Emanuele and K{\"u}bler, Andrea and Halder, Sebastian}, title = {An auditory multiclass brain-computer interface with natural stimuli: Usability evaluation with healthy participants and a motor impaired end user}, series = {Frontiers in Human Neuroscience}, volume = {8}, journal = {Frontiers in Human Neuroscience}, number = {1039}, doi = {10.3389/fnhum.2014.01039}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-126450}, year = {2015}, abstract = {Brain-computer interfaces (BCIs) can serve as muscle independent communication aids. Persons, who are unable to control their eye muscles (e.g., in the completely locked-in state) or have severe visual impairments for other reasons, need BCI systems that do not rely on the visual modality. For this reason, BCIs that employ auditory stimuli were suggested. In this study, a multiclass BCI spelling system was implemented that uses animal voices with directional cues to code rows and columns of a letter matrix. To reveal possible training effects with the system, 11 healthy participants performed spelling tasks on 2 consecutive days. In a second step, the system was tested by a participant with amyotrophic lateral sclerosis (ALS) in two sessions. In the first session, healthy participants spelled with an average accuracy of 76\% (3.29 bits/min) that increased to 90\% (4.23 bits/min) on the second day. Spelling accuracy by the participant with ALS was 20\% in the first and 47\% in the second session. The results indicate a strong training effect for both the healthy participants and the participant with ALS. While healthy participants reached high accuracies in the first session and second session, accuracies for the participant with ALS were not sufficient for satisfactory communication in both sessions. More training sessions might be needed to improve spelling accuracies. The study demonstrated the feasibility of the auditory BCI with healthy users and stresses the importance of training with auditory multiclass BCIs, especially for potential end-users of BCI with disease.}, language = {en} } @article{BleinBardelDanjeanetal.2015, author = {Blein, Sophie and Bardel, Claire and Danjean, Vincent and McGuffog, Lesley and Healay, Sue and Barrowdale, Daniel and Lee, Andrew and Dennis, Joe and Kuchenbaecker, Karoline B. and Soucy, Penny and Terry, Mary Beth and Chung, Wendy K. and Goldgar, David E. and Buys, Saundra S. and Janavicius, Ramunas and Tihomirova, Laima and Tung, Nadine and Dorfling, Cecilia M. and van Rensburg, Elizabeth J. and Neuhausen, Susan L. and Ding, Yuan Chun and Gerdes, Anne-Marie and Ejlertsen, Bent and Nielsen, Finn C. and Hansen, Thomas V. O. and Osorio, Ana and Benitez, Javier and Andreas Conejero, Raquel and Segota, Ena and Weitzel, Jeffrey N. and Thelander, Margo and Peterlongo, Paolo and Radice, Paolo and Pensotti, Valeria and Dolcetti, Riccardo and Bonanni, Bernardo and Peissel, Bernard and Zaffaroni, Daniela and Scuvera, Giulietta and Manoukian, Siranoush and Varesco, Liliana and Capone, Gabriele L. and Papi, Laura and Ottini, Laura and Yannoukakos, Drakoulis and Konstantopoulou, Irene and Garber, Judy and Hamann, Ute and Donaldson, Alan and Brady, Angela and Brewer, Carole and Foo, Claire and Evans, D. Gareth and Frost, Debra and Eccles, Diana and Douglas, Fiona and Cook, Jackie and Adlard, Julian and Barwell, Julian and Walker, Lisa and Izatt, Louise and Side, Lucy E. and Kennedy, M. John and Tischkowitz, Marc and Rogers, Mark T. and Porteous, Mary E. and Morrison, Patrick J. and Platte, Radka and Eeles, Ros and Davidson, Rosemarie and Hodgson, Shirley and Cole, Trevor and Godwin, Andrew K and Isaacs, Claudine and Claes, Kathleen and De Leeneer, Kim and Meindl, Alfons and Gehrig, Andrea and Wappenschmidt, Barbara and Sutter, Christian and Engel, Christoph and Niederacher, Dieter and Steinemann, Doris and Plendl, Hansjoerg and Kast, Karin and Rhiem, Kerstin and Ditsch, Nina and Arnold, Norbert and Varon-Mateeva, Raymonda and Schmutzler, Rita K. and Preisler-Adams, Sabine and Markov, Nadja Bogdanova and Wang-Gohrke, Shan and de Pauw, Antoine and Lefol, Cedrick and Lasset, Christine and Leroux, Dominique and Rouleau, Etienne and Damiola, Francesca and Dreyfus, Helene and Barjhoux, Laure and Golmard, Lisa and Uhrhammer, Nancy and Bonadona, Valerie and Sornin, Valerie and Bignon, Yves-Jean and Carter, Jonathan and Van Le, Linda and Piedmonte, Marion and DiSilvestro, Paul A. and de la Hoya, Miguel and Caldes, Trinidad and Nevanlinna, Heli and Aittom{\"a}ki, Kristiina and Jager, Agnes and van den Ouweland, Ans M. W. and Kets, Carolien M. and Aalfs, Cora M. and van Leeuwen, Flora E. and Hogervorst, Frans B. L. and Meijers-Heijboer, Hanne E. J. and Oosterwijk, Jan C. and van Roozendaal, Kees E. P. and Rookus, Matti A. and Devilee, Peter and van der Luijt, Rob B. and Olah, Edith and Diez, Orland and Teule, Alex and Lazaro, Conxi and Blanco, Ignacio and Del Valle, Jesus and Jakubowska, Anna and Sukiennicki, Grzegorz and Gronwald, Jacek and Spurdle, Amanda B. and Foulkes, William and Olswold, Curtis and Lindor, Noralene M. and Pankratz, Vernon S. and Szabo, Csilla I. and Lincoln, Anne and Jacobs, Lauren and Corines, Marina and Robson, Mark and Vijai, Joseph and Berger, Andreas and Fink-Retter, Anneliese and Singer, Christian F. and Rappaport, Christine and Geschwantler Kaulich, Daphne and Pfeiler, Georg and Tea, Muy-Kheng and Greene, Mark H. and Mai, Phuong L. and Rennert, Gad and Imyanitov, Evgeny N. and Mulligan, Anna Marie and Glendon, Gord and Andrulis, Irene L. and Tchatchou, Andrine and Toland, Amanda Ewart and Pedersen, Inge Sokilde and Thomassen, Mads and Kruse, Torben A. and Jensen, Uffe Birk and Caligo, Maria A. and Friedman, Eitan and Zidan, Jamal and Laitman, Yael and Lindblom, Annika and Melin, Beatrice and Arver, Brita and Loman, Niklas and Rosenquist, Richard and Olopade, Olufunmilayo I. and Nussbaum, Robert L. and Ramus, Susan J. and Nathanson, Katherine L. and Domchek, Susan M. and Rebbeck, Timothy R. and Arun, Banu K. and Mitchell, Gillian and Karlan, Bethy Y. and Lester, Jenny and Orsulic, Sandra and Stoppa-Lyonnet, Dominique and Thomas, Gilles and Simard, Jacques and Couch, Fergus J. and Offit, Kenenth and Easton, Douglas F. and Chenevix-Trench, Georgia and Antoniou, Antonis C. and Mazoyer, Sylvie and Phelan, Catherine M. and Sinilnikova, Olga M. and Cox, David G.}, title = {An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers}, series = {Breast Cancer Research}, volume = {17}, journal = {Breast Cancer Research}, number = {61}, doi = {10.1186/s13058-015-0567-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145458}, year = {2015}, abstract = {Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95\% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95\% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.}, language = {en} } @article{TimmermansvanderTolTimmermansetal.2015, author = {Timmermans, Wim J. and van der Tol, Christiaan and Timmermans, Joris and Ucer, Murat and Chen, Xuelong and Alonso, Luis and Moreno, Jose and Carrara, Arnaud and Lopez, Ramon and Fernando de la Cruz, Tercero and Corcoles, Horacio L. and de Miguel, Eduardo and Sanchez, Jose A. G. and Perez, Irene and Belen, Perez and Munoz, Juan-Carlos J. and Skokovic, Drazen and Sobrino, Jose and Soria, Guillem and MacArthur, Alasdair and Vescovo, Loris and Reusen, Ils and Andreu, Ana and Burkart, Andreas and Cilia, Chiara and Contreras, Sergio and Corbari, Chiara and Calleja, Javier F. and Guzinski, Radoslaw and Hellmann, Christine and Herrmann, Ittai and Kerr, Gregoire and Lazar, Adina-Laura and Leutner, Benjamin and Mendiguren, Gorka and Nasilowska, Sylwia and Nieto, Hector and Pachego-Labrador, Javier and Pulanekar, Survana and Raj, Rahul and Schikling, Anke and Siegmann, Bastian and von Bueren, Stefanie and Su, Zhongbo (Bob)}, title = {An Overview of the Regional Experiments for Land-atmosphere Exchanges 2012 (REFLEX 2012) Campaign}, series = {Acta Geophysica}, volume = {63}, journal = {Acta Geophysica}, number = {6}, doi = {10.2478/s11600-014-0254-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136491}, pages = {1465-1484}, year = {2015}, abstract = {The REFLEX 2012 campaign was initiated as part of a training course on the organization of an airborne campaign to support advancement of the understanding of land-atmosphere interaction processes. This article describes the campaign, its objectives and observations, remote as well as in situ. The observations took place at the experimental Las Tiesas farm in an agricultural area in the south of Spain. During the period of ten days, measurements were made to capture the main processes controlling the local and regional land-atmosphere exchanges. Apart from multi-temporal, multi-directional and multi-spatial space-borne and airborne observations, measurements of the local meteorology, energy fluxes, soil temperature profiles, soil moisture profiles, surface temperature, canopy structure as well as leaf-level measurements were carried out. Additional thermo-dynamical monitoring took place at selected sites. After presenting the different types of measurements, some examples are given to illustrate the potential of the observations made.}, language = {en} } @article{OrthCazesButtetal.2015, author = {Orth, Martin F. and Cazes, Alex and Butt, Elke and Grunewald, Thomas G. P.}, title = {An update on the LIM and SH3 domain protein 1 (LASP1): a versatile structural, signaling, and biomarker protein}, series = {Oncotarget}, volume = {6}, journal = {Oncotarget}, number = {1}, doi = {10.18632/oncotarget.3083}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144546}, pages = {26-42}, year = {2015}, abstract = {The gene encoding the LIM and SH3 domain protein (LASP1) was cloned two decades ago from a cDNA library of breast cancer metastases. As the first protein of a class comprising one N-terminal LIM and one C-terminal SH3 domain, LASP1 founded a new LIM-protein subfamily of the nebulin group. Since its discovery LASP1 proved to be an extremely versatile protein because of its exceptional structure allowing interaction with various binding partners, its ubiquitous expression in normal tissues, albeit with distinct expression patterns, and its ability to transmit signals from the cytoplasm into the nucleus. As a result, LASP1 plays key roles in cell structure, physiological processes, and cell signaling. Furthermore, LASP1 overexpression contributes to cancer aggressiveness hinting to a potential value of LASP1 as a cancer biomarker. In this review we summarize published data on structure, regulation, function, and expression pattern of LASP1, with a focus on its role in human cancer and as a biomarker protein. In addition, we provide a comprehensive transcriptome analysis of published microarrays (n=2,780) that illustrates the expression profile of LASP1 in normal tissues and its overexpression in a broad range of human cancer entities.}, language = {en} } @article{BoesSpiegelVoepeletal.2015, author = {Boes, Alexander and Spiegel, Holger and Voepel, Nadja and Edgue, Gueven and Beiss, Veronique and Kapelski, Stephanie and Fendel, Rolf and Scheuermayer, Matthias and Pradel, Gabriele and Bolscher, Judith M. and Behet, Marije C. and Dechering, Koen J. and Hermsen, Cornelus C. and Sauerwein, Robert W. and Schillberg, Stefan and Reimann, Andreas and Fischer, Rainer}, title = {Analysis of a multi-component multi-stage malaria vaccine candidate—tackling the cocktail challenge}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0131456}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173092}, pages = {e0131456}, year = {2015}, abstract = {Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80\%), blood (up to 90\%) and sexual parasite stages (100\%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml), the blood stage (40-60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.}, language = {en} } @phdthesis{Mohammadi2015, author = {Mohammadi, Masoumeh}, title = {Analysis of discretization schemes for Fokker-Planck equations and related optimality systems}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111494}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {The Fokker-Planck (FP) equation is a fundamental model in thermodynamic kinetic theories and statistical mechanics. In general, the FP equation appears in a number of different fields in natural sciences, for instance in solid-state physics, quantum optics, chemical physics, theoretical biology, and circuit theory. These equations also provide a powerful mean to define robust control strategies for random models. The FP equations are partial differential equations (PDE) describing the time evolution of the probability density function (PDF) of stochastic processes. These equations are of different types depending on the underlying stochastic process. In particular, they are parabolic PDEs for the PDF of Ito processes, and hyperbolic PDEs for piecewise deterministic processes (PDP). A fundamental axiom of probability calculus requires that the integral of the PDF over all the allowable state space must be equal to one, for all time. Therefore, for the purpose of accurate numerical simulation, a discretized FP equation must guarantee conservativeness of the total probability. Furthermore, since the solution of the FP equation represents a probability density, any numerical scheme that approximates the FP equation is required to guarantee the positivity of the solution. In addition, an approximation scheme must be accurate and stable. For these purposes, for parabolic FP equations on bounded domains, we investigate the Chang-Cooper (CC) scheme for space discretization and first- and second-order backward time differencing. We prove that the resulting space-time discretization schemes are accurate, conditionally stable, conservative, and preserve positivity. Further, we discuss a finite difference discretization for the FP system corresponding to a PDP process in a bounded domain. Next, we discuss FP equations in unbounded domains. In this case, finite-difference or finite-element methods cannot be applied. By employing a suitable set of basis functions, spectral methods allow to treat unbounded domains. Since FP solutions decay exponentially at infinity, we consider Hermite functions as basis functions, which are Hermite polynomials multiplied by a Gaussian. To this end, the Hermite spectral discretization is applied to two different FP equations; the parabolic PDE corresponding to Ito processes, and the system of hyperbolic PDEs corresponding to a PDP process. The resulting discretized schemes are analyzed. Stability and spectral accuracy of the Hermite spectral discretization of the FP problems is proved. Furthermore, we investigate the conservativity of the solutions of FP equations discretized with the Hermite spectral scheme. In the last part of this thesis, we discuss optimal control problems governed by FP equations on the characterization of their solution by optimality systems. We then investigate the Hermite spectral discretization of FP optimality systems in unbounded domains. Within the framework of Hermite discretization, we obtain sparse-band systems of ordinary differential equations. We analyze the accuracy of the discretization schemes by showing spectral convergence in approximating the state, the adjoint, and the control variables that appear in the FP optimality systems. To validate our theoretical estimates, we present results of numerical experiments.}, subject = {Fokker-Planck-Gleichung}, language = {en} } @article{FluriSchuhmannKleinschnitz2015, author = {Fluri, Felix and Schuhmann, Michael K and Kleinschnitz, Christoph}, title = {Animal models of ischemic stroke and their application in clinical research}, series = {Drug Design, Development and Therapy}, volume = {9}, journal = {Drug Design, Development and Therapy}, doi = {10.2147/DDDT.S56071}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149157}, pages = {3445-3454}, year = {2015}, abstract = {This review outlines the most frequently used rodent stroke models and discusses their strengths and shortcomings. Mimicking all aspects of human stroke in one animal model is not feasible because ischemic stroke in humans is a heterogeneous disorder with a complex pathophysiology. The transient or permanent middle cerebral artery occlusion (MCAo) model is one of the models that most closely simulate human ischemic stroke. Furthermore, this model is characterized by reliable and well-reproducible infarcts. Therefore, the MCAo model has been involved in the majority of studies that address pathophysiological processes or neuroprotective agents. Another model uses thromboembolic clots and thus is more convenient for investigating thrombolytic agents and pathophysiological processes after thrombolysis. However, for many reasons, preclinical stroke research has a low translational success rate. One factor might be the choice of stroke model. Whereas the therapeutic responsiveness of permanent focal stroke in humans declines significantly within 3 hours after stroke onset, the therapeutic window in animal models with prompt reperfusion is up to 12 hours, resulting in a much longer action time of the investigated agent. Another major problem of animal stroke models is that studies are mostly conducted in young animals without any comorbidity. These models differ from human stroke, which particularly affects elderly people who have various cerebrovascular risk factors. Choosing the most appropriate stroke model and optimizing the study design of preclinical trials might increase the translational potential of animal stroke models.}, language = {en} } @article{GlaserSchurigtSuzukietal.2015, author = {Glaser, Jan and Schurigt, Uta and Suzuki, Brian M. and Caffrey, Connor R. and Holzgrabe, Ulrike}, title = {Anti-Schistosomal Activity of Cinnamic Acid Esters: Eugenyl}, series = {Molecules}, volume = {20}, journal = {Molecules}, doi = {10.3390/molecules200610873}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125712}, pages = {10873-10883}, year = {2015}, abstract = {Bornyl caffeate (1) was previously isolated by us from Valeriana (V.) wallichii rhizomes and identified as an anti-leishmanial substance. Here, we screened a small compound library of synthesized derivatives 1-30 for activity against schistosomula of Schistosoma (S.) mansoni. Compound 1 did not show any anti-schistosomal activity. However, strong phenotypic changes, including the formation of vacuoles, degeneration and death were observed after in vitro treatment with compounds 23 (thymyl cinnamate) and 27 (eugenyl cinnamate). Electron microscopy analysis of the induced vacuoles in the dying parasites suggests that 23 and 27 interfere with autophagy.}, language = {en} } @article{LeonCalvijoLealCastroAlmanzarReinaetal.2015, author = {Le{\´o}n-Calvijo, Mar{\´i}a A. and Leal-Castro, Aura L. and Almanzar-Reina, Giovanni A. and Rosas-P{\´e}rez, Jaiver E. and Garc{\´i}a-Casta{\~n}eda, Javier E. and Rivera-Monroy, Zuly J.}, title = {Antibacterial activity of synthetic peptides derived from lactoferricin against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212}, series = {BioMed Research International}, journal = {BioMed Research International}, number = {453826}, doi = {10.1155/2015/453826}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-144591}, year = {2015}, abstract = {Peptides derived from human and bovine lactoferricin were designed, synthesized, purified, and characterized using RP-HPLC and MALDI-TOF-MS. Specific changes in the sequences were designed as (i) the incorporation of unnatural amino acids in the sequence, the (ii) reduction or (iii) elongation of the peptide chain length, and (iv) synthesis of molecules with different number of branches containing the same sequence. For each peptide, the antibacterial activity against Escherichia coli ATCC 25922 and Enterococcus faecalis ATCC 29212 was evaluated. Our results showed that Peptides I.2 (RWQWRWQWR) and I.4 ((RRWQWR)\(_{4}\)K\(_{2}\)Ahx\(_{2}\)C\(_{2}\)) exhibit bigger or similar activity against E. coli (MIC 4-33 μM) and E. faecalis (MIC 10-33 μM) when they were compared with lactoferricin protein (LF) and some of its derivate peptides as II.1 (FKCRRWQWRMKKLGA) and IV.1 (FKCRRWQWRMKKLGAPSITCVRRAE). It should be pointed out that Peptides I.2 and I.4, containing the RWQWR motif, are short and easy to synthesize; our results demonstrate that it is possible to design and obtain synthetic peptides that exhibit enhanced antibacterial activity using a methodology that is fast and low-cost and that allows obtaining products with a high degree of purity and high yield.}, language = {en} } @article{GlaserSchultheisMolletal.2015, author = {Glaser, Jan and Schultheis, Martina and Moll, Heidrun and Hazra, Banasri and Holzgrabe, Ulrike}, title = {Antileishmanial and Cytotoxic Compounds from Valeriana wallichii and Identification of a Novel Nepetolactone Derivative}, series = {Molecules}, volume = {20}, journal = {Molecules}, number = {4}, doi = {10.3390/molecules20045740}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125320}, pages = {5740-5753}, year = {2015}, abstract = {The chloroform extract of Valeriana wallichii (V. wallichii) rhizomes was investigated to elucidate the structures responsible for reported antileishmanial activity. Besides bornyl caffeate (1, already been reported by us previously), bioassay-guided fractionation resulted in two additional cinnamic acid derivatives 2-3 with moderate leishmanicidal activity. The structure of a novel nepetolactone derivative 4 having a cinnamic acid moiety was elucidated by means of spectral analysis. To the best of our knowledge villoside aglycone (5) was isolated from this plant for the first time. The bioassay-guided fractionation yielded two new (compounds 6-7) and two known valtrates (compounds 8-9) with leishmanicidal potential against Leishmania major (L. major) promastigotes. In addition, β-bisabolol (10), α-kessyl alcohol (11), valeranone (12), bornyl isovalerate (13) and linarin-2-O-methylbutyrate (14) were identified. This is the first report on the isolation of 4'-demethylpodophyllotoxin (15), podophyllotoxin (16) and pinoresinol (17) in V. wallichii. In total thirteen known and four new compounds were identified from the extract and their cytotoxic and antileishmanial properties were evaluated.}, language = {en} } @phdthesis{Glaser2015, author = {Glaser, Jan}, title = {Antileishmanial compounds from Nature - Elucidation of the active principles of an extract from Valeriana wallichii rhizomes}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-129140}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {This study is dealing with the bioactivity-guided fractionation of a chloroform extract from pulverized rhizomes of Valeriana wallichii with focus on isolation and structure elucidation of the antileishmanial active principles.}, subject = {Leishmaniose}, language = {en} } @article{AndreattaPauli2015, author = {Andreatta, Marta and Pauli, Paul}, title = {Appetitive vs. aversive conditioning in humans}, series = {Frontiers in Behavioral Neuroscience}, volume = {9}, journal = {Frontiers in Behavioral Neuroscience}, number = {128}, doi = {10.3389/fnbeh.2015.00128}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148614}, year = {2015}, abstract = {In classical conditioning, an initially neutral stimulus (conditioned stimulus, CS) becomes associated with a biologically salient event (unconditioned stimulus, US), which might be pain (aversive conditioning) or food (appetitive conditioning). After a few associations, the CS is able to initiate either defensive or consummatory responses, respectively. Contrary to aversive conditioning, appetitive conditioning is rarely investigated in humans, although its importance for normal and pathological behaviors (e.g., obesity, addiction) is undeniable. The present study intents to translate animal findings on appetitive conditioning to humans using food as an US. Thirty-three participants were investigated between 8 and 10 am without breakfast in order to assure that they felt hungry. During two acquisition phases, one geometrical shape (avCS+) predicted an aversive US (painful electric shock), another shape (appCS+) predicted an appetitive US (chocolate or salty pretzel according to the participants' preference), and a third shape (CS) predicted neither US. In a extinction phase, these three shapes plus a novel shape (NEW) were presented again without US delivery. Valence and arousal ratings as well as startle and skin conductance (SCR) responses were collected as learning indices. We found successful aversive and appetitive conditioning. On the one hand, the avCS+ was rated as more negative and more arousing than the CS and induced startle potentiation and enhanced SCR. On the other hand, the appCS+ was rated more positive than the CS and induced startle attenuation and larger SCR. In summary, we successfully confirmed animal findings in (hungry) humans by demonstrating appetitive learning and normal aversive learning.}, language = {en} } @article{RamachandranVivaresKlieberetal.2015, author = {Ramachandran, Sarada D. and Vivar{\`e}s, Aur{\´e}lie and Klieber, Sylvie and Hewitt, Nicola J. and Muenst, Bernhard and Heinz, Stefan and Walles, Heike and Braspenning, Joris}, title = {Applicability of second-generation upcyte\(^{®}\) human hepatocytes for use in CYP inhibition and induction studies}, series = {Pharmacology Research \& Perspectives}, volume = {3}, journal = {Pharmacology Research \& Perspectives}, number = {5}, doi = {10.1002/prp2.161}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149564}, pages = {e00161}, year = {2015}, abstract = {Human upcyte\(^{®}\) hepatocytes are proliferating hepatocytes that retain many characteristics of primary human hepatocytes. We conducted a comprehensive evaluation of the application of second-generation upcyte\(^{®}\) hepatocytes from four donors for inhibition and induction assays using a selection of reference inhibitors and inducers. CYP1A2, CYP2B6, CYP2C9, and CYP3A4 were reproducibly inhibited in a concentration-dependent manner and the calculated IC\(_{50}\) values for each compound correctly classified them as potent inhibitors. Upcyte\(^{®}\) hepatocytes were responsive to prototypical CYP1A2, CYP2B6, CYP2C9, and CYP3A4 inducers, confirming that they have functional AhR-, CAR-, and PXR-mediated CYP regulation. A panel of 11 inducers classified as potent, moderate or noninducers of CYP3A4 and CYP2B6 were tested. There was a good fit of data from upcyte\(^{®}\) hepatocytes to three different predictive models for CYP3A4 induction, namely the Relative Induction Score (RIS), AUC\(_{u}\)/F\(_{2}\), and C\(_{max,u}\)/Ind\(_{50}\). In addition, PXR (rifampicin) and CAR-selective (carbamazepine and phenytoin) inducers of CYP3A4 and CYP2B6 induction, respectively, were demonstrated. In conclusion, these data support the use of second-generation upcyte\(^{®}\) hepatocytes for CYP inhibition and induction assays. Under the culture conditions used, these cells expressed CYP activities that were equivalent to or higher than those measured in primary human hepatocyte cultures, which could be inhibited or induced by prototypical CYP inhibitors and inducers, respectively. Moreover, they can be used to predict in vivo CYP3A4 induction potential using three prediction models. Bulk availability of cells from multiple donors makes upcyte\(^{®}\) hepatocytes suitable for DDI screening, as well as more in-depth mechanistic investigations.}, language = {en} } @article{SchroederPfister2015, author = {Schroeder, Philipp A. and Pfister, Roland}, title = {Arbitrary numbers counter fair decisions: trails of markedness in card distribution}, series = {Frontiers in Psychology}, volume = {6}, journal = {Frontiers in Psychology}, doi = {10.3389/fpsyg.2015.00240}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143481}, pages = {240}, year = {2015}, abstract = {Converging evidence from controlled experiments suggests that the mere processing of a number and its attributes such as value or parity might affect free choice decisions between different actions. For example the spatial numerical associations of response codes (SNARC) effect indicates the magnitude of a digit to be associated with a spatial representation and might therefore affect spatial response choices (i.e., decisions between a "left" and a "right" option). At the same time, other (linguistic) features of a number such as parity are embedded into space and might likewise prime left or right responses through feature words [odd or even, respectively; markedness association of response codes (MARC) effect]. In this experiment we aimed at documenting such influences in a natural setting. We therefore assessed number space and parity space association effects by exposing participants to a fair distribution task in a card playing scenario. Participants drew cards, read out loud their number values, and announced their response choice, i.e., dealing it to a left vs. right player, indicated by Playmobil characters. Not only did participants prefer to deal more cards to the right player, the card's digits also affected response choices and led to a slightly but systematically unfair distribution, supported by a regular SNARC effect and counteracted by a reversed MARC effect. The experiment demonstrates the impact of SNARC- and MARC-like biases in free choice behavior through verbal and visual numerical information processing even in a setting with high external validity.}, language = {en} } @article{CheethamWuPaulietal.2015, author = {Cheetham, Marcus and Wu, Lingdan and Pauli, Paul and Jancke, Lutz}, title = {Arousal, valence, and the uncanny valley: psychophysiological and self-report findings}, series = {Frontiers in Psychology}, volume = {6}, journal = {Frontiers in Psychology}, number = {981}, doi = {10.3389/fpsyg.2015.00981}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151519}, year = {2015}, abstract = {The main prediction of the Uncanny Valley Hypothesis (UVH) is that observation of humanlike characters that are difficult to distinguish from the human counterpart will evoke a state of negative affect. Well-established electrophysiological [late positive potential (LPP) and facial electromyography (EMG)] and self-report [Self-Assessment Manikin (SAM)] indices of valence and arousal, i.e., the primary orthogonal dimensions of affective experience, were used to test this prediction by examining affective experience in response to categorically ambiguous compared with unambiguous avatar and human faces (N = 30). LPP and EMG provided direct psychophysiological indices of affective state during passive observation and the SAM provided self-reported indices of affective state during explicit cognitive evaluation of static facial stimuli. The faces were drawn from well-controlled morph continua representing the UVH' dimension of human likeness (DHL). The results provide no support for the notion that category ambiguity along the DHL is specifically associated with enhanced experience of negative affect. On the contrary, the LPP and SAM-based measures of arousal and valence indicated a general increase in negative affective state (i.e., enhanced arousal and negative valence) with greater morph distance from the human end of the DHL. A second sample (N = 30) produced the same finding, using an ad hoc self-rating scale of feelings of familiarity, i.e., an oft-used measure of affective experience along the UVH' familiarity dimension. In conclusion, this multi-method approach using well-validated psychophysiological and self-rating indices of arousal and valence rejects for passive observation and for explicit affective evaluation of static faces the main prediction of the UVH.}, language = {en} } @article{BassetCizekCuenoudetal.2015, author = {Basset, Yves and Cizek, Lukas and Cu{\´e}noud, Philippe and Didham, Raphael K. and Novotny, Vojtech and {\O}degaard, Frode and Roslin, Tomas and Tishechkin, Alexey K. and Schmidl, J{\"u}rgen and Winchester, Neville N. and Roubik, David W. and Aberlenc, Henri-Pierre and Bail, Johannes and Barrios, Hector and Bridle, Jonathan R. and Casta{\~n}o-Meneses, Gabriela and Corbara, Bruno and Curletti, Gianfranco and da Rocha, Wesley Duarte and De Bakker, Domir and Delabie, Jacques H. C. and Dejean, Alain and Fagan, Laura L. and Floren, Andreas and Kitching, Roger L. and Medianero, Enrique and de Oliveira, Evandro Gama and Orivel, Jerome and Pollet, Marc and Rapp, Mathieu and Ribeiro, Servio P. and Roisin, Yves and Schmidt, Jesper B. and S{\o}rensen, Line and Lewinsohn, Thomas M. and Leponce, Maurice}, title = {Arthropod Distribution in a Tropical Rainforest: Tackling a Four Dimensional Puzzle}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {12}, doi = {10.1371/journal.pone.0144110}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-136393}, pages = {e0144110}, year = {2015}, abstract = {Quantifying the spatio-temporal distribution of arthropods in tropical rainforests represents a first step towards scrutinizing the global distribution of biodiversity on Earth. To date most studies have focused on narrow taxonomic groups or lack a design that allows partitioning of the components of diversity. Here, we consider an exceptionally large dataset (113,952 individuals representing 5,858 species), obtained from the San Lorenzo forest in Panama, where the phylogenetic breadth of arthropod taxa was surveyed using 14 protocols targeting the soil, litter, understory, lower and upper canopy habitats, replicated across seasons in 2003 and 2004. This dataset is used to explore the relative influence of horizontal, vertical and seasonal drivers of arthropod distribution in this forest. We considered arthropod abundance, observed and estimated species richness, additive decomposition of species richness, multiplicative partitioning of species diversity, variation in species composition, species turnover and guild structure as components of diversity. At the scale of our study (2km of distance, 40m in height and 400 days), the effects related to the vertical and seasonal dimensions were most important. Most adult arthropods were collected from the soil/litter or the upper canopy and species richness was highest in the canopy. We compared the distribution of arthropods and trees within our study system. Effects related to the seasonal dimension were stronger for arthropods than for trees. We conclude that: (1) models of beta diversity developed for tropical trees are unlikely to be applicable to tropical arthropods; (2) it is imperative that estimates of global biodiversity derived from mass collecting of arthropods in tropical rainforests embrace the strong vertical and seasonal partitioning observed here; and (3) given the high species turnover observed between seasons, global climate change may have severe consequences for rainforest arthropods.}, language = {en} } @phdthesis{Muenz2015, author = {M{\"u}nz, Thomas Sebastian}, title = {Aspects of neuronal plasticity in the mushroom body calyx during adult maturation in the honeybee Apis mellifera}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111611}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Division of labor represents a major advantage of social insect communities that accounts for their enormous ecological success. In colonies of the honeybee, Apis mellifera, division of labor comprises different tasks of fertile queens and drones (males) and, in general, sterile female workers. Division of labor also occurs among workers in form of an age-related polyethism. This helps them to deal with the great variety of tasks within the colony. After adult eclosion, workers spend around three weeks with various duties inside the hive such as tending the brood or cleaning and building cells. After this period workers switch to outdoor tasks and become foragers collecting nectar, pollen and water. With this behavioral transition, workers face tremendous changes in their sensory environment. In particular, visual sensory stimuli become important, but also the olfactory world changes. Foragers have to perform a completely new behavioral repertoire ranging from long distance navigation based on landmark orientation and polarized-skylight information to learning and memory tasks associated with finding profitable food sources. However, behavioral maturation is not a purely age-related internal program associated with a change, for example, in juvenile hormone titers. External factors such as primer pheromones like the brood pheromone or queen mandibular pheromone can modulate the timing of this transition. In this way colonies are able to flexibly adjust their work force distribution between indoor and outdoor tasks depending on the actual needs of the colony. Besides certain physiological changes, mainly affecting glandular tissue, the transition from indoor to outdoor tasks requires significant adaptations in sensory and higher-order integration centers of the brain. The mushroom bodies integrate olfactory, visual, gustatory and mechanosensory information. Furthermore, they play important roles in learning and memory processes. It is therefore not surprising that the mushroom bodies, in particular their main input region, the calyx, undergo volumetric neuronal plasticity. Similar to behavioral maturation, plastic changes of the mushroom bodies are associated with age, but are also to be affected by modulating factors such as task and experience. In my thesis, I analyzed in detail the neuronal processes underlying volumetric plasticity in the mushroom body. Immunohistochemical labeling of synaptic proteins combined with quantitative 3D confocal imaging revealed that the volume increase of the mushroom body calyx is largely caused by the growth of the Kenyon cell dendritic network. This outgrowth is accompanied by changes in the synaptic architecture of the mushroom body calyx, which is organized in a distinct pattern of synaptic complexes, so called microglomeruli. During the first week of natural adult maturation microglomeruli remain constant in total number. With subsequent behavioral transition from indoor duties to foraging, microglomeruli are pruned while the Kenyon cell dendritic network is still growing. As a result of these processes, the mushroom body calyx neuropil volume enlarges while the total number of microgloumeruli becomes reduced in foragers compared to indoor workers. In the visual subcompartments (calyx collar) this process is induced by visual sensory stimuli as the beginning of pruning correlates with the time window when workers start their first orientation flights. The high level of analysis of cellular and subcellular process underlying structural plasticity of the mushroom body calyx during natural maturation will serve as a framework for future investigations of behavioral plasticity in the honeybee. The transition to foraging is not purely age-dependent, but gets modulated, for example, by the presence of foragers. Ethyl oleate, a primer pheromone that is present only in foragers, was shown to delay the onset of foraging in nurse bees. Using artificial application of additional ethyl oleate in triple cohort colonies, I tested whether it directly affects adult neuronal plasticity in the visual input region of the mushroom body calyx. As the pheromonal treatment failed to induce a clear behavioral phenotype (delayed onset of foraging) it was not possible to show a direct link between the exposure to additional ethyl oleate and neuronal plasticity in mushroom body calyx. However, the general results on synaptic maturation confirmed my data of natural maturation processes in the mushroom body calyx. Given the result that dendritic plasticity is a major contributor to neuronal plasticity in the mushroom body calyx associated with division of labor, the question arose which proteins could be involved in mediating these effects. Calcium/calmodulin-dependent protein kinase II (CaMKII) especially in mammals, but also in insects (Drosophila, Cockroach), was shown to be involved in facilitating learning and memory processes like long-term synaptic potentiation. In addition to presynaptic effects, the protein was also revealed to directly interact with cytoskeleton elements in the postsynapse. It therefore is a likely candidate to mediate structural synaptic plasticity. As part of my thesis, the presence and distribution of CaMKII was analyzed, and the results showed that the protein is highly concentrated in a distinct subpopulation of the mushroom body intrinsic neurons, the noncompact Kenyon cells. The dendritic network of this population arborizes in two calyx subregions: one receiving mainly olfactory input - the lip - and the collar receiving visual input. This distribution pattern did not change with age or task. The high concentration of CaMKII in dendritic spines and its overlap with f-actin indicates that CaMKII could be a key player inducing structural neuronal plasticity associated with learning and memory formation and/or behavioral transitions related to division of labor. Interestingly CaMKII immunoreactivity was absent in the basal ring, another subregion of the mushroom body calyx formed almost exclusively by the inner compact Kenyon cells and known to receive combined visual and olfactory input. This indicates differences of this mushroom body subregion regarding the molecular mechanisms controlling plastic changes in corresponding Kenyon cells. How is timing of behavioral and neuronal plasticity regulated? The primer pheromone ethyl oleate was found in high concentrations on foragers and was shown to influence behavioral maturation by delaying the onset of foraging when artificially applied in elevated concentrations. But how is ethyl oleate transferred and how does it shift the work force distribution between indoor and outdoor tasks? Previous work showed that ethyl oleate concentrations are highest in the honeycrop of foragers and suggested that it is transferred and communicated inside the colony via trophallaxis. The results of this thesis however clearly show, that ethyl oleate was not present inside the honey crop or the regurgitate, but rather in the surrounding tissue of the honey crop. As additionally the second highest concentration of ethyl oleate was measured on the surface of the cuticle of forgers, trophallaxis was ruled out as a mode of transmission. Neurophysiological measurements at the level of the antennae (electroantennogram recordings) and the first olfactory neuropil (calcium imaging of activity in the antennal lobe) revealed that the primer pheromone ethyl oleate is received and processed as an olfactory stimulus. Appetitive olfactory conditioning using the proboscis extension response as a behavioral paradigm showed that ethyl oleate can be associated with a sugar reward. This indicates that workers are able to perceive, learn and memorize the presence of this pheromone. As ethyl oleate had to be presented by a heated stimulation device at close range, it can be concluded that this primer pheromone acts via close range/contact chemoreception through the olfactory system. This is also supported by previous behavioral observations. Taken together, the findings presented in this thesis revealed structural changes in the synaptic architecture of the mushroom body calyx associated with division of labor. For the primer pheromone ethyl oleate, which modulates the transition from nursing to foraging, the results clearly showed that it is received via the olfactory system and presumably acts via this pathway. However, manipulation experiments did not indicate a direct effect of ethyl oleate on synaptic plasticity. At the molecular level, CaMKII is a prime candidate to mediate structural synaptic plasticity in the mushroom body calyx. Future combined structural and functional experiments are needed to finally link the activity of primer pheromones like ethyl oleate to the molecular pathways mediating behavioral and synaptic plasticity associated with division of labor in Apis mellifera. The here identified underlying processes will serve as excellent models for a general understanding of fundamental mechanisms promoting behavioral plasticity.}, subject = {Biene}, language = {en} } @article{BlancoKuchenbaeckerCuadrasetal.2015, author = {Blanco, Ignacio and Kuchenbaecker, Karoline and Cuadras, Daniel and Wang, Xianshu and Barrowdale, Daniel and Ruiz de Garibay, Gorka and Librado, Pablo and Sanchez-Gracia, Alejandro and Rozas, Julio and Bonifaci, N{\´u}ria and McGuffog, Lesley and Pankratz, Vernon S. and Islam, Abul and Mateo, Francesca and Berenguer, Antoni and Petit, Anna and Catal{\`a}, Isabel and Brunet, Joan and Feliubadal{\´o}, Lidia and Tornero, Eva and Ben{\´i}tez, Javier and Osorio, Ana and Ram{\´o}n y Cajal, Teresa and Nevanlinna, Heli and Aittom{\"a}ki, Kristina and Arun, Banu K. and Toland, Amanda E. and Karlan, Beth Y. and Walsh, Christine and Lester, Jenny and Greene, Mark H. and Mai, Phuong L. and Nussbaum, Robert L. and Andrulis, Irene L. and Domchek, Susan M. and Nathanson, Katherine L. and Rebbeck, Timothy R. and Barkardottir, Rosa B. and Jakubowska, Anna and Lubinski, Jan and Durda, Katarzyna and Jaworska-Bieniek, Katarzyna and Claes, Kathleen and Van Maerken, Tom and D{\´i}ez, Orland and Hansen, Thomas V. and J{\o}nson, Lars and Gerdes, Anne-Marie and Ejlertsen, Bent and De la Hoya, Miguel and Cald{\´e}s, Trinidad and Dunning, Alison M. and Oliver, Clare and Fineberg, Elena and Cook, Margaret and Peock, Susan and McCann, Emma and Murray, Alex and Jacobs, Chris and Pichert, Gabriella and Lalloo, Fiona and Chu, Carol and Dorkins, Huw and Paterson, Joan and Ong, Kai-Ren and Teixeira, Manuel R. and Hogervorst, Frans B. L. and Van der Hout, Annemarie H. and Seynaeve, Caroline and Van der Luijt, Rob B. and Ligtenberg, Marjolijn J. L. and Devilee, Peter and Wijnen, Juul T. and Rookus, Matti A. and Meijers-Heijboer, Hanne E. J. and Blok, Marinus J. and Van den Ouweland, Ans M. W. and Aalfs, Cora M. and Rodriguez, Gustavo C. and Phillips, Kelly-Anne A. and Piedmonte, Marion and Nerenstone, Stacy R. and Bae-Jump, Victoria L. and O'Malley, David M. and Schmutzler, Rita K. and Wappenschmidt, Barbara and Rhiem, Kerstin and Engel, Christoph and Meindl, Alfons and Ditsch, Nina and Arnold, Norbert and Plendl, Hansjoerg J. and Niederacher, Dieter and Sutter, Christian and Wang-Gohrke, Shan and Steinemann, Doris and Preisler-Adams, Sabine and Kast, Karin and Varon-Mateeva, Raymonda and Gehrig, Andrea and Bojesen, Anders and Pedersen, Inge Sokilde and Sunde, Lone and Birk Jensen, Uffe and Thomassen, Mads and Kruse, Torben A. and Foretova, Lenka and Peterlongo, Paolo and Bernard, Loris and Peissel, Bernard and Scuvera, Giulietta and Manoukian, Siranoush and Radice, Paolo and Ottini, Laura and Montagna, Marco and Agata, Simona and Maugard, Christine and Simard, Jacques and Soucy, Penny and Berger, Andreas and Fink-Retter, Anneliese and Singer, Christian F. and Rappaport, Christine and Geschwantler-Kaulich, Daphne and Tea, Muy-Kheng and Pfeiler, Georg and John, Esther M. and Miron, Alex and Neuhausen, Susan L. and Terry, Mary Beth and Chung, Wendy K. and Daly, Mary B. and Goldgar, David E. and Janavicius, Ramunas and Dorfling, Cecilia M. and Van Rensburg, Elisabeth J. and Fostira, Florentia and Konstantopoulou, Irene and Garber, Judy and Godwin, Andrew K. and Olah, Edith and Narod, Steven A. and Rennert, Gad and Paluch, Shani Shimon and Laitman, Yael and Friedman, Eitan and Liljegren, Annelie and Rantala, Johanna and Stenmark-Askmalm, Marie and Loman, Niklas and Imyanitov, Evgeny N. and Hamann, Ute and Spurdle, Amanda B. and Healey, Sue and Weitzel, Jeffrey N. and Herzog, Josef and Margileth, David and Gorrini, Chiara and Esteller, Manel and G{\´o}mez, Antonio and Sayols, Sergi and Vidal, Enrique and Heyn, Holger and Stoppa-Lyonnet, Dominique and L{\´e}on{\´e}, Melanie and Barjhoux, Laure and Fassy-Colcombet, Marion and Pauw, Antoine de and Lasset, Christine and Fert Ferrer, Sandra and Castera, Laurent and Berthet, Pascaline and Cornelis, Fran{\c{c}}ois and Bignon, Yves-Jean and Damiola, Francesca and Mazoyer, Sylvie and Sinilnikova, Olga M. and Maxwell, Christopher A. and Vijai, Joseph and Robson, Mark and Kauff, Noah and Corines, Marina J. and Villano, Danylko and Cunningham, Julie and Lee, Adam and Lindor, Noralane and L{\´a}zaro, Conxi and Easton, Douglas F. and Offit, Kenneth and Chenevix-Trench, Georgia and Couch, Fergus J. and Antoniou, Antonis C. and Pujana, Miguel Angel}, title = {Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {4}, doi = {10.1371/journal.pone.0120020}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-143469}, pages = {e0120020}, year = {2015}, abstract = {While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95\% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95\% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.}, language = {en} } @phdthesis{Kastner2015, author = {Kastner, Anna Katharina}, title = {Attention mechanisms in contextual anxiety and cued fear and their influence on processing of social cues}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-123747}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Anxiety is an affective state characterized by a sustained, long-lasting defensive response, induced by unpredictable, diffuse threat. In comparison, fear is a phasic response to predictable threat. Fear can be experimentally modeled with the help of cue conditioning. Context conditioning, in which the context serves as the best predictor of a threat due to the absence of any conditioned cues, is seen as an operationalization of sustained anxiety. This thesis used a differential context conditioning paradigm to examine sustained attention processes in a threat context compared to a safety context for the first time. In three studies, the attention mechanisms during the processing of contextual anxiety were examined by measuring heart rate responses and steady-state-visually evoked potentials (ssVEPs). An additional focus was set on the processing of social cues (i.e. faces) and the influence of contextual information on these cues. In a last step, the correlates of sustained anxiety were compared to evoked responses by phasic fear, which was realized in a previously established paradigm combining predictable and unpredictable threat. In the first study, a contextual stimulus was associated with an aversive loud noise, while a second context remained unpaired. This conditioning paradigm created an anxiety context (CTX+) and a safety context (CTX-). After acquisition, a social agent vs. an object was presented as a distractor in both contexts. Heart rate and cortical responses, with ssVEPs by using frequency tagging, to the contexts and the distractors were assessed. Results revealed enhanced ssVEP amplitudes for the CTX+ compared to the CTX- during acquisition and during presentation of distractor stimuli. Additionally, the heart rate was accelerated in the acquisition phase, followed by a heart rate deceleration as a psychophysiological marker of contextual anxiety. Study 2 used the same context conditioning paradigm as Study 1. In contrast to the first study, persons with different emotional facial expressions were presented in the anxiety and safety contexts in order to compare the differential processing of these cues within periods of threat and safety. A similar anxiety response was found in the second study, although only participants who Abstract VIII were aware of the contingency between contexts and aversive event showed a sensory amplification of the threat context, indicated by heart rate response and ssVEP activation. All faces irrespective of their emotional expression received increased attentional resources when presented within the anxiety context, which suggests a general hypervigilance in anxiety contexts. In the third study, the differentiation of predictable and unpredictable threat as an operationalization of fear and anxiety was examined on a cortical and physiological level. In the predictable condition, a social cue was paired with an aversive event, while in the unpredictable condition the aversive event remained unpaired with the respective cue. A fear response to the predictable cue was found, indicated by increased oscillatory response and accelerated heart rate. Both predictable and unpredictable threat yielded increased ssVEP amplitudes evoked by the context stimuli, while the response in the unpredictable context showed longer-lasting ssVEP activation to the threat context. To sum up, all three studies endorsed anxiety as a long-lasting defensive response. Due to the unpredictability of the aversive events, the individuals reacted with hypervigilance in the anxiety context, reflected in a facilitated processing of sensory information and an orienting response. This hypervigilance had an impact on the processing of novel cues, which appeared in the anxiety context. Considering the compared stimuli categories, the stimuli perceived in a state of anxiety received increased attentional resources, irrespective of the emotional arousal conveyed by the facial expression. Both predictable and unpredictable threat elicited sensory amplification of the contexts, while the response in the unpredictable context showed longer-lasting sensory facilitation of the threat context.}, subject = {Angst}, language = {en} }