TY - JOUR A1 - Joensuu, Johanna A1 - Altimir, Nuria A1 - Hakola, Hannele A1 - Rostás, Michael A1 - Raivonen, Maarit A1 - Vestenius, Mika A1 - Aaltonen, Hermanni A1 - Riederer, Markus A1 - Bäck, Jaana T1 - Role of needle surface waxes in dynamic exchange of mono- and sesquiterpenes JF - Atmospheric Chemistry and Physics N2 - Biogenic volatile organic compounds (BVOCs) produced by plants have a major role in atmospheric chemistry. The different physicochemical properties of BVOCs affect their transport within and out of the plant as well as their reactions along the way. Some of these compounds may accumulate in or on the waxy surface layer of conifer needles and participate in chemical reactions on or near the foliage surface. The aim of this work was to determine whether terpenes, a key category of BVOCs produced by trees, can be found on the epicuticles of Scots pine (Pinus sylvestris L.) and, if so, how they compare with the terpenes found in shoot emissions of the same tree. We measured shoot-level emissions of pine seedlings at a remote outdoor location in central Finland and subsequently analysed the needle surface waxes for the same compounds. Both emissions and wax extracts were clearly dominated by monoterpenes, but the proportion of sesquiterpenes was higher in the wax extracts. There were also differences in the terpene spectra of the emissions and the wax extracts. The results, therefore, support the existence of BVOC associated to the epicuticular waxes. We briefly discuss the different pathways for terpenes to reach the needle surfaces and the implications for air chemistry. KW - needle surface waxes KW - biogenic volatile organic compounds KW - Pinus sylvestris L. KW - atmospheric chemistry Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171324 VL - 16 IS - 12 ER - TY - JOUR A1 - Lorenz, Sonja A1 - Bhattacharyya, Moitrayee A1 - Feiler, Christian A1 - Rape, Michael A1 - Kuriyan, John T1 - Crystal Structure of a Ube2S-Ubiquitin Conjugate JF - PLoS ONE N2 - Protein ubiquitination occurs through the sequential formation and reorganization of specific protein-protein interfaces. Ubiquitin-conjugating (E2) enzymes, such as Ube2S, catalyze the formation of an isopeptide linkage between the C-terminus of a “donor” ubiquitin and a primary amino group of an “acceptor” ubiquitin molecule. This reaction involves an intermediate, in which the C-terminus of the donor ubiquitin is thioester-bound to the active site cysteine of the E2 and a functionally important interface is formed between the two proteins. A docked model of a Ube2S-donor ubiquitin complex was generated previously, based on chemical shift mapping by NMR, and predicted contacts were validated in functional studies. We now present the crystal structure of a covalent Ube2S-ubiquitin complex. The structure contains an interface between Ube2S and ubiquitin in trans that resembles the earlier model in general terms, but differs in detail. The crystallographic interface is more hydrophobic than the earlier model and is stable in molecular dynamics (MD) simulations. Remarkably, the docked Ube2S-donor complex converges readily to the configuration seen in the crystal structure in 3 out of 8 MD trajectories. Since the crystallographic interface is fully consistent with mutational effects, this indicates that the structure provides an energetically favorable representation of the functionally critical Ube2S-donor interface. KW - crystal structure KW - protein ubiquitination KW - Ubiquitin-conjugating (E2) enzymes KW - Ube2S Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167265 VL - 11 IS - 2 ER - TY - JOUR A1 - Bahník, Štěpán A1 - Strack, Fritz T1 - Overlap of accessible information undermines the anchoring effect JF - Judgment and Decision Making N2 - According to the Selective Accessibility Model of anchoring, the comparison question in the standard anchoring paradigm activates information that is congruent with an anchor. As a consequence, this information will be more likely to become the basis for the absolute judgment which will therefore be assimilated toward the anchor. However, if the activated information overlaps with information that is elicited by the absolute judgment itself, the preceding comparative judgment should not exert an incremental effect and should fail to result in an anchoring effect. The present studies find this result when the comparative judgment refers to a general category and the absolute judgment refers to a subset of the general category that was activated by the anchor value. For example, participants comparing the average annual temperature in New York City to a high 102 °F judged the average winter, but not summer temperature to be higher than participants making no comparison. On the other hand, participants comparing the annual temperature to a low –4 °F judged the average summer, but not winter temperature to be lower than control participants. This pattern of results was shown also in another content domain. It is consistent with the Selective Accessibility Model but difficult to reconcile with other main explanations of the anchoring effect. KW - anchoring KW - judgment KW - heuristics and biases KW - selective accessibility Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169287 VL - 11 IS - 1 ER - TY - JOUR A1 - Bekes, Inga A1 - Friedl, Thomas W. P. A1 - Köhler, Tanja A1 - Möbus, Volker A1 - Janni, Wolfgang A1 - Wöckel, Achim A1 - Wulff, Christine T1 - Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer? JF - Molecular Cancer N2 - Background Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types. Methods Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition. Results VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5. Conclusions Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition. KW - ovarian cancer KW - vascular permeability KW - ascites KW - VEGF KW - claudin 5 KW - VE-cadherin Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169298 VL - 15 IS - 13 ER - TY - JOUR A1 - Huang, Guozheng A1 - Schramm, Simon A1 - Heilmann, Jörg A1 - Biedermann, David A1 - Kren, Vladimír A1 - Decker, Michael T1 - Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins JF - Beilstein Journal of Organic Chemistry N2 - Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields. KW - Mitsunobu KW - dehydration KW - flavonoid KW - hydnocarpin KW - silybin Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160986 VL - 12 ER - TY - JOUR A1 - Zinner, C. A1 - Krueger, M. A1 - Reed, J. L. A1 - Kohl-Bareis, M. A1 - Holmberg, H. C. A1 - Sperlich, B. T1 - Exposure to a combination of heat and hyperoxia during cycling at submaximal intensity does not alter thermoregulatory responses JF - Biology of Sport N2 - In this study, we tested the hypothesis that breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) while exercising in a hot environment exerts negative effects on the total tissue level of haemoglobin concentration (tHb); core (T\(_{core}\)) and skin (T\(_{skin}\)) temperatures; muscle activity; heart rate; blood concentration of lactate; pH; partial pressure of oxygen (P\(_a\)O\(_2\)) and carbon dioxide; arterial oxygen saturation (S\(_a\)O\(_2\)); and perceptual responses. Ten well-trained male athletes cycled at submaximal intensity at 21°C or 33°C in randomized order: first for 20 min while breathing normal air (FinO\(_2\) = 0.21) and then 10 min with F\(_{in}\)O\(_2\) = 0.40 (HOX). At both temperatures, S\(_a\)O\(_2\) and P\(_a\)O\(_2\), but not tHb, were increased by HOX. Tskin and perception of exertion and thermal discomfort were higher at 33°C than 21°C (p < 0.01), but independent of F\(_{in}\)O\(_2\). T\(_{core}\) and muscle activity were the same under all conditions (p > 0.07). Blood lactate and heart rate were higher at 33°C than 21°C. In conclusion, during 30 min of submaximal cycling at 21°C or 33°C, T\(_{core}\), T\(_{skin}\) and T\(_{body}\), tHb, muscle activity and ratings of perceived exertion and thermal discomfort were the same under normoxic and hyperoxic conditions. Accordingly, breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) did not affect thermoregulation under these conditions. KW - heat stress KW - hyperthermia KW - skin blood flow KW - thermoregulation KW - vasoconstriction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160993 VL - 33 IS - 1 ER - TY - JOUR A1 - Joukhadar, R. A1 - Wöckel, A. A1 - Herr, D. A1 - Paulus, V. A1 - Radosa, J. A1 - Hamza, A. A1 - Solomayer, E. A1 - Baum, S. T1 - Challenges of Longevity: Safety of Vaginal and Laparoscopic Urogynecological Procedures in Septuagenarians and Older Patients JF - BioMed Research International N2 - Introduction. Pelvic organ prolapse (POP) and urinary incontinence (UI) have increasing prevalence in the elderly population. The aim of this study was to compare the comorbidities of these procedures between <70 y/o and ≥70 y/o patients. Materials and Methods. In our retrospective study over a period of 2.5 years, 407 patients had received an urogynecological procedure. All patients with POP were treated by reconstructive surgery. Complications were reported using the standardized classification of Clavien-Dindo (CD). The study can be assigned to stage 2b Exploration IDEAL (Idea, Development, Exploration, Assessment, Long-term study)-system of surgical innovation. Results. Operation time, blood loss, and intraoperative complications have not been more frequent in the elderly, whereas hospital stay was significantly longer in ≥70 y/o patients. Regarding postoperative complications, we noticed that ≥70 y/o patients had an almost threefold risk to develop mild early postoperative complications compared to younger patients (OR: 2.86; 95% CI: 1.76–4.66). On the contrary, major complications were not more frequent. No case of life-threatening complication or the need for blood transfusion was reported. Conclusion. After urogynecological procedures, septuagenarians and older patients are more likely to develop mild postoperative complications but not more intraoperative or severe postoperative complications compared to younger patients. KW - gynecologic surgical procedures/methods KW - postoperative complications/epidemiology KW - vagina/surgery KW - pelvic organ prolapse/surgery KW - middle Aged KW - laparoscopy/methods KW - uterine prolapse/surgery KW - urinary incontinence/surgery KW - surgical Mesh KW - retrospective Studies KW - age factors KW - aged KW - aged 80 and over KW - female KW - reconstructive surgical procedures/methods Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161005 VL - 2016 IS - Article ID 5184595 ER - TY - JOUR A1 - Isaias, Ioannis U. A1 - Trujillo, Paula A1 - Summers, Paul A1 - Marotta, Giorgio A1 - Mainardi, Luca A1 - Pezzoli, Gianni A1 - Zecca, Luigi A1 - Costa, Antonella T1 - Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease JF - Frontiers in Aging Neuroscience N2 - Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease. KW - MRI KW - neuromelanin KW - dopamine KW - Parkinson's disease KW - FP-CIT SPECT Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164046 VL - 8 IS - 196 ER - TY - THES A1 - Lorenzin, Francesca T1 - Regulation of transcription by MYC - DNA binding and target genes T1 - Transkriptionelle Regulation durch MYC - DNA-Bindung und Zielgene N2 - MYC is a transcription factor, whose expression is elevated or deregulated in many human cancers (up to 70%) and is often associated with aggressive and poorly differentiated tumors. Although MYC is extensively studied, discrepancies have emerged about how this transcription factor works. In primary lymphocytes, MYC promotes transcriptional amplification of virtually all genes with an open promoter, whereas in tumor cells MYC regulates specific sets of genes that have significant prognostic value. Furthermore, the set of target genes that distinguish MYC’s physiological function from the pathological/oncogenic one, whether it exists or not, has not been fully understood yet. In this study, it could be shown that MYC protein levels within a cell and promoter affinity (determined by E-box presence or interaction with other proteins) of target genes toward MYC are important factors that influence MYC activity. At low levels, MYC can amplify a certain transcriptional program, which includes high affinity binding sites, whereas at high levels MYC leads to the specific up- and down regulation of genes with low affinity. Moreover, the promoter affinity characterizes different sets of target genes which can be distinguished in the physiological or oncogenic MYC signatures. MYC-mediated repression requires higher MYC levels than activation and formation of a complex with MIZ1 is necessary for inhibiting expression of a subset of MYC target genes. N2 - MYC ist ein Transkriptionsfaktor, dessen Expression in vielen humanen Tumoren (bis zu 70 %) erhöht oder dereguliert ist. Die Tumore, in denen viel MYC hergestellt wird, zeichnen sich durch einen geringen Differenzierungsgrad aus und verhalten sich sehr aggressiv. Obwohl das biologische Verhalten des MYC Proteins intensiv untersucht wurde, sind unterschiedliche Modelle, wie dieser Transkriptionsfaktor funktioniert, entwickelt worden. In primären Lymphozyten verstärkt MYC die Expression fast aller Gene mit offener Chromatinstruktur, während MYC in Tumorzellen spezifische Gengruppten reguliert, deren Expression mit der Prognose von Patienten korreliert. Es ist also unklar, ob sich die Zielgene der physiologischen Funktion von Myc von den oncogenen/pathophysiologischen Zielgenen unterscheidet und um welche Gene es sich bei letzteren handelt. In dieser Arbeit konnte gezeigt werden, dass Expressionsniveau von MYC und unterschiedliche Promotoraffinitäten zu MYC (charakterisiert durch den Ebox-Gehalt und Interaktionen zu anderen Proteinen) wichtig für die Aktivität des MYC Proteins sind. So kann Myc bei niedrigen Konzentrationen ein bestimmtes transkriptionelles Programm amplifizieren, das sich aus hochaffinen Promotoren zusammensetzt. Bei hohen Konzentrationen hingegen führt MYC zur transkriptionellen Aktivierung und Repression bestimmter Zielgengruppen, die sich durch niedrige Affinität zu MYC auszeichnen. Somit ist die Promotoraffinität ein Parameter, der physiologische von oncogenen MYC Signaturen trennen kann. Darüberhinaus konnte gezeigt werden, dass MYC-vermittelte Repression höhere MYC Mengen benötigt, als MYC-vermittelte Transaktivierung und die Komplexbildung mit MIZ1 für die Repression einer Gruppe an MYC Zielgenen nötig ist. KW - MYC KW - Transcription Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150766 ER - TY - CHAP A1 - Schmitz, Barbara T1 - Space, Borders and Boundaries in the Letter of Aristeas T2 - Borders : Terminologies, Ideologies, and Performances N2 - No abstract available. KW - Aristeas KW - Ad Philocratem KW - Aristeas-Brief KW - Letter of Aristeas KW - Aristeas, Epistolographus : Ad Philocratem Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151285 UR - https://www.mohr.de/en/book/borders-terminologies-ideologies-and-performances-9783161543760 SN - 978-3-16-154375-3 PB - Mohr Siebeck CY - Tübingen ER - TY - JOUR A1 - Tiede, Jennifer A1 - Grafe, Silke T1 - Media Pedagogy in German and US Teacher Education JF - Communicar N2 - Varios estudios de investigación y de práctica llegan a la conclusión de que la pedagogía de los medios debe integrarse en la formación de profesores para que estos futuros docentes puedan utilizar los medios de comunicación en sus clases con eficacia y éxito. Sin embargo, estos resultados no se reflejan en los programas universitarios vigentes, de manera que en algunas instituciones los profesores en formación pueden llegar al término de sus estudios sin haber abordado cuestiones de educación en medios. Para comprender, evaluar y más adelante mejorar la situación actual de la formación del profesorado en el ámbito de la pedagogía de los medios se necesitan extensas investigaciones. Teniendo en cuenta esta situación, el siguiente artículo presenta un resumen del «statu quo» de las competencias en pedagogía de los medios de los futuros profesores, centrándose en los ejemplos de Alemania y EEUU. Para crear una base presentamos diferentes modelos de competencias pedagógicas mediáticas de ambos países e intentaremos responder a la pregunta si estas competencias son promovidas por los programas de formación del profesorado. Después, se describirán el método y resultados seleccionados de un estudio que midió las competencias en pedagogía de los medios de estudiantes de ambos países, estudio basado en un modelo generalizador de competencias pedagógicas mediáticas que conectan la investigación alemana e internacional en este campo. La perspectiva internacional comparada ayuda a extender perspectivas y comprender diferencias y similitudes. Los datos de este estudio sirven para identificar diferentes formas de integrar la pedagogía de los medios de comunicación en la formación del profesorado. Además, se pueden sacar conclusiones sobre las consecuencias que implican estos procesos para profesores en formación y sus competencias mediáticas. N2 - Various research works and practitioners conclude that media pedagogy should be integrated in teacher education in order to enable future teachers to use media for their lessons effectively and successfully. However, this realization is not necessarily reflected in actual university curricula, as preservice teachers at some places can still finish their studies without ever dealing with media pedagogical issues. To understand, assess and eventually improve the status of media pedagogical teacher education, comprehensive research is required. Against this background, the following article seeks to present a theory-based and empirical overview of the status quo of preservice teachers’ pedagogical media competencies focusing Germany and the USA exemplarily. To form a basis, different models of pedagogical media competencies from both countries will be introduced and the extent to which these competencies have become part of teacher education programs and related studies will be summarised. Afterwards, method and selected results of a study will be described where the skills in question were measured with students from both countries, based on a comprehensive model of pedagogical media competencies that connects German and international research in this field. The international comparative perspective will help broaden the viewpoint and understand differences, but also similarities. These data serve to identify different ways of integrating media pedagogy into teacher training and draw conclusions on the consequences these processes entail for preservice teachers and their pedagogical media competencies. T2 - Pedagogía mediática en la formación de profesores de Alemania y EEUU KW - enseñanzapor por competencias KW - currículum KW - análisis transnacional KW - investigación de currículo universitario KW - currículo de la educación en medios KW - alfabetización mediática KW - educación en medios KW - pedagogía KW - formación de profesorado KW - investigación KW - media literacy KW - media education KW - pedagogy KW - preservice teacher education KW - competency based teaching KW - curricula KW - research KW - crossnational analysis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162600 VL - XXIV IS - 49 ER - TY - JOUR A1 - Kaluza, Benjamin F. A1 - Wallace, Helen A1 - Heard, Tim A. A1 - Klein, Aelxandra-Maria A1 - Leonhardt, Sara D. T1 - Urban gardens promote bee foraging over natural habitats and plantations JF - Ecology and Evolution N2 - Increasing human land use for agriculture and housing leads to the loss of natural habitat and to widespread declines in wild bees. Bee foraging dynamics and fitness depend on the availability of resources in the surrounding landscape, but how precisely landscape related resource differences affect bee foraging patterns remains unclear. To investigate how landscape and its interaction with season and weather drive foraging and resource intake in social bees, we experimentally compared foraging activity, the allocation of foragers to different resources (pollen, nectar, and resin) and overall resource intake in the Australian stingless bee Tetragonula carbonaria (Apidae, Meliponini). Bee colonies were monitored in different seasons over two years. We compared foraging patterns and resource intake between the bees' natural habitat (forests) and two landscapes differently altered by humans (suburban gardens and agricultural macadamia plantations). We found foraging activity as well as pollen and nectar forager numbers to be highest in suburban gardens, intermediate in forests and low in plantations. Foraging patterns further differed between seasons, but seasonal variations strongly differed between landscapes. Sugar and pollen intake was low in plantations, but contrary with our predictions, it was even higher in gardens than in forests. In contrast, resin intake was similar across landscapes. Consequently, differences in resource availability between natural and altered landscapes strongly affect foraging patterns and thus resource intake in social bees. While agricultural monocultures largely reduce foraging success, suburban gardens can increase resource intake well above rates found in natural habitats of bees, indicating that human activities can both decrease and increase the availability of resources in a landscape and thus reduce or enhance bee fitness. KW - urbanization KW - anthropogenic activities KW - climate factors KW - meliponines KW - resource availability Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162713 VL - 6 IS - 5 ER - TY - JOUR A1 - Seydelmann, Nora A1 - Liu, Dan A1 - Krämer, Johannes A1 - Drechsler, Christiane A1 - Hu, Kai A1 - Nordbeck, Peter A1 - Schneider, Andreas A1 - Störk, Stefan A1 - Bijnens, Bart A1 - Ertl, Georg A1 - Wanner, Christoph A1 - Weidemann, Frank T1 - High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease JF - Journal of the American Heart Association N2 - Background High‐sensitivity troponin (hs‐TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs‐TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow‐up study to assess longitudinal hs‐TNT changes relative to fibrosis and cardiomyopathy progression. Methods and Results For the prospective analysis, hs‐TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry‐associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs‐TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs‐TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56–302.59]; P=0.002); patients with elevated baseline hs‐TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1–3.3] %; follow‐up, 3.2 [2.3–4.9] %; P<0.001) and slightly elevated hs‐TNT (baseline, 44.7 [30.1–65.3] ng/L; follow‐up, 49.1 [27.6–69.5] ng/L; P=0.116) during follow‐up. Left ventricular wall thickness and EF of patients with elevated hs‐TNT were decreased during follow‐up, indicating potential cardiomyopathy progression. Conclusions hs‐TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs‐TNT could be helpful for staging and follow‐up of Fabry patients. KW - biomarker KW - cardiomyopathy KW - fabry disease KW - myocardial fibrosis KW - troponin T Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165682 VL - 5 IS - e002839 ER - TY - JOUR A1 - Albers, Gregory W. A1 - Bernstein, Richard A. A1 - Brachmann, Johannes A1 - Camm, John A1 - Easton, J. Donald A1 - Fromm, Peter A1 - Goto, Shinya A1 - Granger, Christopher B. A1 - Hohnloser, Stefan H. A1 - Hylek, Elaine A1 - Jaffer, Amir K. A1 - Krieger, Derk W. A1 - Passman, Rod A1 - Pines, Jesse M. A1 - Reed, Shelby D. A1 - Rothwell, Peter M. A1 - Kowey, Peter R. T1 - Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report JF - Journal of the American Heart Association N2 - No abstract available. KW - anticoagulants KW - atrial fibrillation KW - diagnosis KW - electrocardiography KW - insertable cardiac monitor KW - stroke prevention Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165709 VL - 5 IS - e00294 ER - TY - JOUR A1 - Wawra, Stephan A1 - Fesel, Philipp A1 - Widmer, Heidi A1 - Timm, Malte A1 - Seibel, Jürgen A1 - Leson, Lisa A1 - Kesseler, Leona A1 - Nostadt, Robin A1 - Hilbert, Magdalena A1 - Langen, Gregor A1 - Zuccaro, Alga T1 - The fungal-specific beta-glucan-binding lectin FGB1 alters cell-wall composition and suppresses glucan-triggered immunity in plants JF - Nature Communications N2 - β-glucans are well-known modulators of the immune system in mammals but little is known about β-glucan triggered immunity in planta. Here we show by isothermal titration calorimetry, circular dichroism spectroscopy and nuclear magnetic resonance spectroscopy that the FGB1 gene from the root endophyte Piriformospora indica encodes for a secreted fungal-specific β-glucan-binding lectin with dual function. This lectin has the potential to both alter fungal cell wall composition and properties, and to efficiently suppress β-glucan-triggered immunity in different plant hosts, such as Arabidopsis, barley and Nicotiana benthamiana. Our results hint at the existence of fungal effectors that deregulate innate sensing of β-glucan in plants. KW - Effectors in plant pathology KW - Fungal host response KW - Lectins Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165945 VL - 7 ER - TY - JOUR A1 - Knorr, Johannes A1 - Sokkar, Pandian A1 - Schott, Sebastian A1 - Costa, Paolo A1 - Thiel, Walter A1 - Sander, Wolfram A1 - Sanchez-Garcia, Elsa A1 - Nuernberger, Patrick T1 - Competitive solvent-molecule interactions govern primary processes of diphenylcarbene in solvent mixtures JF - Nature Communications N2 - Photochemical reactions in solution often proceed via competing reaction pathways comprising intermediates that capture a solvent molecule. A disclosure of the underlying reaction mechanisms is challenging due to the rapid nature of these processes and the intricate identification of how many solvent molecules are involved. Here combining broadband femtosecond transient absorption and quantum mechanics/molecular mechanics simulations, we show for one of the most reactive species, diphenylcarbene, that the decision-maker is not the nearest solvent molecule but its neighbour. The hydrogen bonding dynamics determine which reaction channels are accessible in binary solvent mixtures at room temperature. In-depth analysis of the amount of nascent intermediates corroborates the importance of a hydrogen-bonded complex with a protic solvent molecule, in striking analogy to complexes found at cryogenic temperatures. Our results show that adjacent solvent molecules take the role of key abettors rather than bystanders for the fate of the reactive intermediate. KW - Reaction kinetics and dynamics KW - Photochemistry Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165954 VL - 7 ER - TY - JOUR A1 - Mitchell, Jonathan S. A1 - Li, Ni A1 - Weinhold, Niels A1 - Försti, Asta A1 - Ali, Mina A1 - van Duin, Mark A1 - Thorleifsson, Gudmar A1 - Johnson, David C. A1 - Chen, Bowang A1 - Halvarsson, Britt-Marie A1 - Gudbjartsson, Daniel F. A1 - Kuiper, Rowan A1 - Stephens, Owen W. A1 - Bertsch, Uta A1 - Broderick, Peter A1 - Campo, Chiara A1 - Einsele, Hermann A1 - Gregory, Walter A. A1 - Gullberg, Urban A1 - Henrion, Marc A1 - Hillengass, Jens A1 - Hoffmann, Per A1 - Jackson, Graham H. A1 - Johnsson, Ellinor A1 - Jöud, Magnus A1 - Kristinsson, Sigurdur Y. A1 - Lenhoff, Stig A1 - Lenive, Oleg A1 - Mellqvist, Ulf-Henrik A1 - Migliorini, Gabriele A1 - Nahi, Hareth A1 - Nelander, Sven A1 - Nickel, Jolanta A1 - Nöthen, Markus M. A1 - Rafnar, Thorunn A1 - Ross, Fiona M. A1 - da Silva Filho, Miguel Inacio A1 - Swaminathan, Bhairavi A1 - Thomsen, Hauke A1 - Turesson, Ingemar A1 - Vangsted, Annette A1 - Vogel, Ulla A1 - Waage, Anders A1 - Walker, Brian A. A1 - Wihlborg, Anna-Karin A1 - Broyl, Annemiek A1 - Davies, Faith E. A1 - Thorsteinsdottir, Unnur A1 - Langer, Christian A1 - Hansson, Markus A1 - Kaiser, Martin A1 - Sonneveld, Pieter A1 - Stefansson, Kari A1 - Morgan, Gareth J. A1 - Goldschmidt, Hartmut A1 - Hemminki, Kari A1 - Nilsson, Björn A1 - Houlston, Richard S. T1 - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma JF - Nature Communications N2 - Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development. KW - Cancer genetics KW - Genome-wide association studies KW - Myeloma Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165983 VL - 7 ER - TY - JOUR A1 - Van Haute, Lindsey A1 - Dietmann, Sabine A1 - Kremer, Laura A1 - Hussain, Shobbir A1 - Pearce, Sarah F. A1 - Powell, Christopher A. A1 - Rorbach, Joanna A1 - Lantaff, Rebecca A1 - Blanco, Sandra A1 - Sauer, Sascha A1 - Kotzaeridou, Urania A1 - Hoffmann, Georg F. A1 - Memari, Yasin A1 - Kolb-Kokocinski, Anja A1 - Durbin, Richard A1 - Mayr, Johannes A. A1 - Frye, Michaela A1 - Prokisch, Holger A1 - Minczuk, Michal T1 - Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3 JF - Nature Communications N2 - Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m5C) methyltransferase NSun3 and link m5C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m5C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNAMet). Further, we demonstrate that m5C deficiency in mt-tRNAMet results in the lack of 5-formylcytosine (f5C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f5C in human mitochondrial RNA is generated by oxidative processing of m5C. KW - Methylation KW - RNA KW - Transferases Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165998 VL - 7 ER - TY - JOUR A1 - Kernreiter, T. A1 - Governale, M. A1 - Zülicke, U. A1 - Hankiewicz, E. M. T1 - Anomalous Spin Response and Virtual-Carrier-Mediated Magnetism in a Topological Insulator JF - Physical Review X N2 - We present a comprehensive theoretical study of the static spin response in HgTe quantum wells, revealing distinctive behavior for the topologically nontrivial inverted structure. Most strikingly, the q=0 (long-wavelength) spin susceptibility of the undoped topological-insulator system is constant and equal to the value found for the gapless Dirac-like structure, whereas the same quantity shows the typical decrease with increasing band gap in the normal-insulator regime. We discuss ramifications for the ordering of localized magnetic moments present in the quantum well, both in the insulating and electron-doped situations. The spin response of edge states is also considered, and we extract effective Landé g factors for the bulk and edge electrons. The variety of counterintuitive spin-response properties revealed in our study arises from the system’s versatility in accessing situations where the charge-carrier dynamics can be governed by ordinary Schrödinger-type physics; it mimics the behavior of chiral Dirac fermions or reflects the material’s symmetry-protected topological order. KW - spin response KW - magnetism KW - nanophysics KW - topological insulators Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166582 VL - 6 IS - 021010 ER - TY - JOUR A1 - Kim, Seonghoon A1 - Zhang, Bo A1 - Wang, Zhaorong A1 - Fischer, Julian A1 - Brodbeck, Sebastian A1 - Kamp, Martin A1 - Schneider, Christian A1 - Höfling, Sven A1 - Deng, Hui T1 - Coherent Polariton Laser JF - Physical Review X N2 - The semiconductor polariton laser promises a new source of coherent light, which, compared to conventional semiconductor photon lasers, has input-energy threshold orders of magnitude lower. However, intensity stability, a defining feature of a coherent state, has remained poor. Intensity noise many times the shot noise of a coherent state has persisted, attributed to multiple mechanisms that are difficult to separate in conventional polariton systems. The large intensity noise, in turn, limits the phase coherence. Thus, the capability of the polariton laser as a source of coherence light is limited. Here, we demonstrate a polariton laser with shot-noise-limited intensity stability, as expected from a fully coherent state. This stability is achieved by using an optical cavity with high mode selectivity to enforce single-mode lasing, suppress condensate depletion, and establish gain saturation. Moreover, the absence of spurious intensity fluctuations enables the measurement of a transition from exponential to Gaussian decay of the phase coherence of the polariton laser. It suggests large self-interaction energies in the polariton condensate, exceeding the laser bandwidth. Such strong interactions are unique to matter-wave lasers and important for nonlinear polariton devices. The results will guide future development of polariton lasers and nonlinear polariton devices. KW - polariton laser KW - condensed matter physics KW - photonics KW - quantum physics KW - coherent light Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166597 VL - 6 IS - 011026 ER -