TY - JOUR A1 - Bargul, Joel L. A1 - Jung, Jamin A1 - McOdimba, Francis A. A1 - Omogo, Collins O. A1 - Adung'a, Vincent O. A1 - Krüger, Timothy A1 - Masiga, Daniel K. A1 - Engstler, Markus T1 - Species-Specific Adaptations of Trypanosome Morphology and Motility to the Mammalian Host JF - PLoS Pathogens N2 - African trypanosomes thrive in the bloodstream and tissue spaces of a wide range of mammalian hosts. Infections of cattle cause an enormous socio-economic burden in sub-Saharan Africa. A hallmark of the trypanosome lifestyle is the flagellate’s incessant motion. This work details the cell motility behavior of the four livestock-parasites Trypanosoma vivax, T. brucei, T. evansi and T. congolense. The trypanosomes feature distinct swimming patterns, speeds and flagellar wave frequencies, although the basic mechanism of flagellar propulsion is conserved, as is shown by extended single flagellar beat analyses. Three-dimensional analyses of the trypanosomes expose a high degree of dynamic pleomorphism, typified by the ‘cellular waveform’. This is a product of the flagellar oscillation, the chirality of the flagellum attachment and the stiffness of the trypanosome cell body. The waveforms are characteristic for each trypanosome species and are influenced by changes of the microenvironment, such as differences in viscosity and the presence of confining obstacles. The distinct cellular waveforms may be reflective of the actual anatomical niches the parasites populate within their mammalian host. T. vivax displays waveforms optimally aligned to the topology of the bloodstream, while the two subspecies T. brucei and T. evansi feature distinct cellular waveforms, both additionally adapted to motion in more confined environments such as tissue spaces. T. congolense reveals a small and stiff waveform, which makes these parasites weak swimmers and destined for cell adherence in low flow areas of the circulation. Thus, our experiments show that the differential dissemination and annidation of trypanosomes in their mammalian hosts may depend on the distinct swimming capabilities of the parasites. KW - swimming KW - viscosity KW - flagella KW - host-pathogen interactions KW - cell motility KW - blood KW - parasitic diseases KW - trypanosoma brucei gambiense Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146513 VL - 12 IS - 2 ER - TY - THES A1 - König, Sebastian T1 - Spatially selective visual attention in Drosophila melanogaster T1 - Räumlich selektive visuelle Aufmerksamkeit in Drosophila melanogaster N2 - Finding the right behavior at the right time is one of the major tasks of brains. In a natural scenery there is often an abundance of stimuli present and the brain has to separate the relevant from the irrelevant ones. Selective visual attention (SVA) is a property of higher visual systems that achieves this separation, as it allows to ‘[…] focus on one source of sensory input to the exclusion of others’ (Luck and Mangun, 1996). There are probably several forms of SVA depending upon the criteria used for the separation, such as salience, color, location in space, novelty, or motion. Many studies have investigated SVA in humans and non-human primates. However, complex functions like attention were initially not expected to be already implemented in the brains of simple organisms like Drosophila. After a first demonstration of selective attention in the fly (Wolf and Heisenberg, 1980), it took some time until other studies included attentional mechanisms in their argumentation to explain certain behaviors of Drosophila. However, their definition and characterization of attention differed and often was ambiguous. Here, one particular form, spatially selective visual attention in the fly Drosophila is investigated. It has been shown earlier that the fly spontaneously may restrict its behavioral responses in stationary flight to the visual stimuli on one side of the visual field. On the basis of experiments of Sareen et al., (2011) it has been conjectured that the fly has a focus of attention (FoA) and that the fly responds to the visual stimuli within this area of the visual field. Whether the FoA is the adequate concept for this spatial property of SVA in the fly needs to be further discussed and is a subject also of the present study. At this stage, the concept will be used in the description of the new results expanding the characterization of SVA. This study continued the investigation of SVA during tethered flight with variable but controlled visual input and an automated primary data evaluation. This standardized paradigm allowed for analysis of wild-type behavior as well as for a comparison of several mutant and pharmacologically manipulated strains to the wild-type. Some properties of human SVA like the occurrence of externally as well as internally caused shifts of attention were found in Drosophila and it could be shown, that SVA in the fly can be externally guided and has an attention span. Additionally, a neurotransmitter and proteins, which play a significant role in SVA were discovered. Based on this, the genetic tools available for Drosophila provided the means to a first examination of cells and circuits involved in SVA. Finally, the free walk behavior of flies that had been shown to have compromised SVA was characterized. The results suggested that the observed phenotypes of SVA were not behavior specific. Covert shifts of the FoA were investigated. The FoA can be externally guided by visual cues to one or the other side of the visual field and even after the cue has disappeared it remains there for <4s. An intriguing finding of this study is the fact, that the quality of the cue determines whether it is attractive or repellent. For example a cue can be changed from being repellent (negative) to being attractive (positive) by changing its oscillation amplitude from 4° to 2°. Testing the effectiveness of cues in the upper and lower visual field separately, revealed that the perception of a cue by the fly is not exclusively based on a sum of its specifications. Because positive cueing did not have an after-effect in each of the two half-fields alone, but did so if the cue was shown in both, the fly seems to evaluate the cue for each combination of parameters specifically. Whether this evaluation of the cue changed on a trial-to-trial basis or if the cue in some cases failed to shift the FoA can at this point not be determined. Looking at the responses of the fly to the displacement of a black vertical stripe showed that they can be categorized as no responses, syn-directional responses (following the direction of motion of the stripe) and anti-directional responses (in the opposite direction of the motion of the stripe). The yaw-torque patterns of the latter bared similarities with spontaneous body saccades and they most likely represented escape attempts of the fly. Syn-directional responses, however, were genuine object responses, distinguishable by a longer latency until they were elicited and a larger amplitude. These properties as well as the distribution of response polarities were not influenced by the presence or absence of a cue. When two stripes were displaced simultaneously in opposite directions the rate of no responses increased in comparison to the displacement of a single stripe. If one of the stripes was cued, both, the responses towards and away from the side of cue resembled the syn-directional responses. Significant progress was made with the elucidation of the neuronal underpinnings of SVA. Ablation of the mushroom bodies (MB) demonstrated their requirement for SVA. Furthermore, it was shown that dopamine signaling has to be balanced between too much and too little. Either inhibiting the synthesis of dopamine or its re-uptake at the synapse via the dDAT impaired the flies’ susceptibility to cueing. Using the Gal4/UAS system, cell specific expression or knockdown of the dDAT was used to scrutinize the role of MB sub-compartments in SVA. The αβ-lobes turned out to be necessary and sufficient to maintain SVA. The Gal4-line c708a labels only a subset of Kenyon cells (KC) within the αβ-lobes, αβposterior. These cells stand out, because of (A) the mesh-like arrangement of their fibers within the lobes and (B) the fact that unlike the other KCs they bypass the calyx and thereby the main source of olfactory input to the MBs, forming connections only in the posterior accessory calyx (Tanaka et al., 2008). This structure receives no or only marginal olfactory input, suggesting for it a role in tasks other than olfaction. This study shows their requirement in a visual task by demonstrating that they are necessary to uphold SVA. Restoring dDAT function in these approximately only 90 cells was probably insufficient to lower the dopamine concentration at the relevant synapses and hence a rescue failed. Alternatively, the processes mediating SVA at the αβ-lobes might require an interplay between all of their KCs. In conclusion, the results provide an initial point for future research to fully understand the localization of and circuitry required for SVA in the brain. In the experiments described so far, attention has been externally guided. However, flies are also able to internally shift their FoA without any cues from the outside world. In a set of 60 consecutive simultaneous displacements of two stripes, they were more likely to produce a response with the same polarity as the preceding one than a random polarity selection predicted. This suggested a dwelling of the FoA on one side of the visual field. Assuming that each response was influenced by the previous one in a way that the probability to repeat the response polarity was increased by a certain factor (dwelling factor, df), a random selection of response type including a df was computed. Implementation of the df removed the difference between observed probability of polarity repetition and the one suggested by random selection. When the interval between displacements was iteratively increased to 5s, no significant df could be detected anymore for pauses longer than 4s. In conclusion, Drosophila has an attention span of approximately 4s. Flies with a mutation in the radish gene expressed no after-effect of cueing and had a shortened attention span of about 1s. The dDAT inhibitor methylphenidate is able to rescue the first, but does not affect the latter phenotype. Probably, radish is differently involved in the two mechanisms. This study showed, that endogenous (covert) shifts of spatially selective visual attention in the fly Drosophila can be internally and externally guided. The variables determining the quality of a cue turned out to be multifaceted and a more systematic approach is needed for a better understanding of what property or feature of the cue changes the way it is evaluated by the fly. A first step has been made to demonstrate that SVA is a fundamental process and compromising it can influence the characteristics of other behaviors like walking. The existence of an attention span, the dependence of SVA on dopamine as well as the susceptibility to pharmacological manipulations, which in humans are used to treat respective diseases, point towards striking similarities between SVA in humans and Drosophila. N2 - Eine der Hauptaufgaben eines Gehirns ist es, das richtige Verhalten zur richtigen Zeit zu finden. In einer natürlichen Umgebung gibt es eine Vielzahl visueller Reize, die das Gehirn unterteilen muss in solche, die irrelevant und solche, die bedeutsam sind. Selektive visuelle Aufmerksamkeit (SVA) ist eine Eigenschaft hoch entwickelter visueller Systeme, die diese Unterteilung erzielt, indem sie es erlaubt „[…] eine Quelle sensorischen Inputs zu fokussieren und dabei andere auszuschließen“ (Luck and Mangun, 1996). In Abhängigkeit der Kriterien (z.B. Salienz, Farbe, Lage im Raum, Neuartigkeit oder Bewegung), die für die Aufteilung herangezogen werden, existieren wahrscheinlich mehrere Formen von SVA. Viele Studien haben sich mit SVA in Menschen und in Primaten beschäftigt, ohne jedoch zu erwarten, dass eine komplexe Funktion wie Aufmerksamkeit bereits in den Gehirnen von einfachen Organismen wie Drosophila implementiert zu finden. Erst einige Zeit nachdem selektive Aufmerksamkeit ein erstes Mal in der Fliege gezeigt worden war (Wolf, Heisenberg, 1980) begannen auch andere Studien Aufmerksamkeit in ihrer Argumentation als Erklärung für bestimmte Verhaltensweisen von Drosophila heranzuziehen. Definition und Charakterisierung des Begriffes Aufmerksamkeit waren jedoch oft mehrdeutig und unterschieden sich von Studie zu Studie. In dieser Arbeit wird eine ganz bestimmte Form von Aufmerksamkeit – räumlich selektive visuelle Aufmerksamkeit - anhand der Fliege Drosophila untersucht. Es wurde bereits gezeigt, dass die Fliege im stationären Flug ihre Verhaltensantworten spontan auf visuelle Reize einer Seite des visuellen Feldes beschränken kann. Basierend auf Experimenten von Sareen et al. (2011) wurde vermutet, dass die Fliege einen Aufmerksamkeitsfokus (FoA) besitzt und auf Reize, die innerhalb dieses Teils des visuellen Feldes liegen antwortet. Ob der FoA ein angemessenes Konzept für diese räumliche Eigenschaft von SVA in der Fliege ist, steht zur Debatte und ist auch ein Thema dieser Studie. Vorerst soll dieses Konzept jedoch für die Beschreibung der Ergebnisse, die die Charakterisierung von SVA vorantreiben, genutzt werden. Die vorliegende Arbeit führt die Untersuchung von SVA mit variablem aber kontrolliertem visuellem Input im stationären Flug fort und nutzt dazu eine automatisierte Datenerfassung. Dieses standardisierte Paradigma ermöglicht eine Analyse von Verhalten im Wildtyp aber auch einen Vergleich mit verschiedenen mutanten und pharmakologisch manipulierten Fliegenstämmen. Einige im Menschen auftretende Eigenschaften von SVA wurden auch in Drosophila gefunden. Dazu zählt das Auftreten von extern und intern verursachten Aufmerksamkeitsverlagerungen. Es konnte gezeigt werden, dass SVA in der Fliege extern gelenkt werden kann und eine Aufmerksamkeitsspanne aufweist. Zusätzlich wurden ein Neurotransmitter und einige Proteine entdeckt, die eine wichtige Rolle in SVA einnehmen. Darauf basierend ermöglichten es die verfügbaren genetischen Werkzeuge mit einer ersten Untersuchung der an SVA beteiligten Zellen und Netzwerke zu beginnen. Des Weiteren wurde das Laufverhalten von Fliegen, die Einschränkungen in SVA aufwiesen charakterisiert. Die Ergebnisse lassen vermuten, dass die beobachteten Phänotypen von SVA nicht verhaltensspezifisch sind. Als nächstes wurden interne Bewegungen des Aufmerksamkeitskegels (FoA) betrachtet. Der FoA kann durch visuelle Reize von außerhalb zu der einen oder der anderen Seite des visuellen Feldes gelenkt werden. Er verweilt dort für >4s nachdem der lenkende Reiz verschwunden ist. Es ist ein spannender Befund dieser Arbeit, dass dieser Reiz in Abhängigkeit seiner Beschaffenheit abstoßend oder anziehend sein kann. So kann ein abstoßender (negativer) Reiz auf einmal anziehend (positiv) werden, wenn seine Oszillationsamplitude von 4° auf 2° reduziert wird. Eine Überprüfung der Wirksamkeit von Aufmerksamkeitslenkung durch Reize im oberen und unteren Teil des visuellen Feldes ergab, dass die Wahrnehmung eines Reizes durch die Fliege sich nicht ausschließlich aus der Summe seiner Spezifikationen ergibt. Da positive Aufmerksamkeitslenkung in keinem der beiden Halbfelder einen Nacheffekt hatte, ein solcher aber bei der Präsentation von Reizen in beiden Felder gleichzeitig auftrat, kann vermutet werden, dass die Fliege den Reiz für jede Kombination von Parametern spezifisch bewertet. Ob sich diese Bewertung in jedem einzelnen Durchgang änderte oder ob der Reiz in manchen Fällen den FoA nicht auf eine Seite lenkte kann mit dem jetzigen Kenntnisstand nicht bestimmt werden. Betrachtet man die Antworten der Fliege auf eine Versetzung eines schwarzen vertikalen Streifens, so zeigt sich eine mögliche Unterteilung in die Kategorien „keine Antwort“, „syn-direktionale Antwort“ (der Bewegungsrichtung des Streifens folgend) und „anti-direktionale Antwort“ (entgegengesetzt zur Bewegungsrichtung des Streifens). Die Drehmomentmuster der letzteren Kategorie wiesen starke Ähnlichkeit zu spontanen Körpersakkaden auf und es handelte sich bei ihnen sehr wahrscheinlich um Fluchtversuche der Fliege. Syn-direktionale Antworten waren hingegen reine Objekt-Bewegungsantworten, erkennbar an einer längeren Latenz bis zu ihrer Auslösung und einer größeren Amplitude. Diese Eigenschaften und auch die Verteilung der Antworten auf die beiden Kategorien wurden durch die An- oder Abwesenheit eines vorhergehenden Reizes nicht beeinflusst. Wurden zwei Streifen gleichzeitig gegenläufig versetzt, so blieben die Antworten im Vergleich zur Versetzung eines einzelnen Streifens häufiger aus. Wurde der FoA zuvor auf eine Seite gelenkt, so entsprachen die Drehmomentmuster der Antworten auf diese Seite und auch die der Antworten auf die andere Seite denen der syn-direktionalen Antworten. Die Aufklärung der SVA zu Grunde liegenden neuronalen Strukturen konnte bedeutend vorangetrieben werden. Eine Ablation der Pilzkörper (MB) zeigte, dass diese für SVA benötigt werden. Außerdem konnte gezeigt werden, dass die von Dopamin übermittelte Signalstärke weder zu stark, noch zu schwach sein darf. Wurde die Synthese von Dopamin inhibiert oder seine Wiederaufnahme aus dem synaptischen Spalt mittels dDAT blockiert, führte dies dazu, dass die Aufmerksamkeit dieser Fliegen nicht mehr extern gelenkt werden konnte. Mithilfe des Gal4/UAS-Systems und zellspezifischer Expression oder Unterdrückung der Bildung von dDAT wurde die Rolle einzelner Strukturen der Pilzkörper in SVA genauer untersucht. Es zeigte sich, dass die αβ-Loben sowohl ausreichend als auch notwendig sind, um SVA nachhaltig zu lenken. Die Gal4-Linie c708a markiert einen Teil der Kenyonzellen (KC) innerhalb der αβ-Loben, αβposterior. Diese Zellen sind besonders, da (A) ihre Fasern innerhalb der Loben eine netzartige Anordnung aufweisen und (B) da sie anders als die anderen KCs nicht mit der Kalyx, der größten Quelle olfaktorischen Inputs in die MBs, verknüpft sind, sondern nur in der posterioren akzessorischen Kalyx Verbindungen ausbilden (Tanaka et al., 2008). Diese Struktur erhält keinen oder zumindest nur marginalen olfaktorischen Input und es ist anzunehmen, dass sie eher an Aufgaben aus anderen sensorischen Modalitäten beteiligt ist. In dieser Arbeit wird die Beteiligung dieser Zellen an einem visuellen Task gezeigt, genauer ihre Notwendigkeit für einen Nacheffekt der Lenkung von SVA. Eine Wiederherstellung der Funktion von dDAT in diesen ca. 90 Zellen war erfolglos, da die geringe Anzahl möglicherweise nicht ausreichte, um die Konzentration von Dopamin an den relevanten Synapsen zu senken. Es ist jedoch auch möglich, dass die Prozesse, die SVA über die αβ-Loben vermitteln ein Zusammenspiel aller dortigen KCs erfordern. Zusammen bilden die gesammelten Ergebnisse einen Ausgangspunkt für zukünftige Bestrebungen, die für SVA erforderlichen neuronalen Strukturen und deren Verortung komplett zu verstehen. In den bisher beschriebenen Experimenten wurde die Aufmerksamkeit extern gelenkt. Fliegen können ihren FoA aber auch ganz ohne äußerliche Reize intern verlagern. In einer Reihe von 60 aufeinanderfolgenden gleichzeitigen Versetzungen zweier Streifen zeigte sich, dass die Fliegen häufiger Antworten mit der gleichen Polarität wie die vorausgegangene produzierten, als dies eine zufällige Auswahl der Polarität vorhersagte. Dies ließ vermuten, dass der FoA auf einer Seite des visuellen Feldes verweilt. Es wurde angenommen, dass jede Antwort von der vorhergehenden beeinflusst wird, sodass die Wahrscheinlichkeit die Polarität dieser Antwort zu wiederholen um einen gewissen Faktor erhöht wird (dwelling factor, df). Deswegen wurde eine zufällige Verteilung der Antwortpolaritäten unter Berücksichtigung des df berechnet. Dadurch verschwand der Unterschied zwischen der beobachteten Wiederholungswahrscheinlichkeit einer Antwortpolarität und derer einer rein zufälligen Wahl der Antwort. Als das Intervall zwischen den einzelnen Versetzungen schrittweise auf 5s erhöht wurde, konnte bereits bei Pausen über 4s kein signifikanter df mehr festgestellt werden. Als Schlussfolgerung ergibt sich, dass Drosophila eine Aufmerksamkeitsspanne von etwa 4s besitzt. Fliegen mit einer Mutation im radish Gen zeigten keine anhaltende Lenkung von SVA und hatten zudem eine verkürzte Aufmerksamkeitsspanne von ungefähr 1s. Der dDAT-Inhibitor Methylphenidat beseitigte den zuerst erwähnten Phänotyp, verlängerte jedoch nicht die Aufmerksamkeitsspanne. Es ist anzunehmen, dass radish auf unterschiedliche Art und Weise an beiden Mechanismen beteiligt ist. Im Zuge dieser Arbeit wurde gezeigt, dass endogene (covert) Verlagerungen von räumlich selektiver visueller Aufmerksamkeit in der Fliege Drosophila intern und extern gelenkt werden können. Vielfältige Variablen bestimmen die Beschaffenheit eines Reizes. Es bedarf eines systematischeren Ansatzes, um die Eigenschaften eines Reizes genauer zu verstehen, die dessen Wahrnehmung durch die Fliege verändern. Es konnte bereits grundlegend gezeigt werden, dass SVA ein fundamentaler Prozess ist, dessen Fehlfunktion auch die Eigenschaften anderer Verhaltensweisen wie z.B. Laufen beeinflusst. Die Existenz einer Aufmerksamkeitsspanne, die Abhängigkeit von SVA von Dopamin sowie deren Zugänglichkeit für pharmakologische Manipulationen, deren Nutzen für den Menschen in der Behandlung aufmerksamkeitsbezogener Erkrankungen liegt, deuten auf starke Ähnlichkeiten zwischen SVA in Menschen und in Drosophila hin. KW - Taufliege KW - Visueller Reiz KW - visuell KW - Selektive Wahrnehmung KW - Aufmerksamkeit KW - Drosophila Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134452 ER - TY - JOUR A1 - Nitsche, Wolfgang H. A1 - Kim, Na Young A1 - Roumpos, Georgios A1 - Schneider, Christian A1 - Höfling, Sven A1 - Forchel, Alfred A1 - Yamamoto, Yoshihisa T1 - Spatial correlation of two-dimensional bosonic multimode condensates JF - Physical Review A N2 - The Berezinskii-Kosterlitz-Thouless (BKT) theorem predicts that two-dimensional bosonic condensates exhibit quasi-long-range order which is characterized by a slow decay of the spatial coherence. However previous measurements on exciton-polariton condensates revealed that their spatial coherence can decay faster than allowed under the BKT theory, and different theoretical explanations have already been proposed. Through theoretical and experimental study of exciton-polariton condensates, we show that the fast decay of the coherence can be explained through the simultaneous presence of multiple modes in the condensate. KW - Exciton-polariton condensate KW - Long-range order KW - Microcavity KW - Vortices KW - Systems Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188897 VL - 93 IS - 5 ER - TY - JOUR A1 - Ben Ami, Tal A1 - Tong, Yuehong A1 - Bhuiyan, Alauddin A1 - Huisingh, Carrie A1 - Ablonczy, Zsolt A1 - Ach, Thomas A1 - Curcio, Christine A. A1 - Smith, R. Theodore T1 - Spatial and Spectral Characterization of Human Retinal Pigment Epithelium Fluorophore Families by Ex Vivo Hyperspectral Autofluorescence Imaging JF - Translational Vision Science & Technology N2 - Purpose: Discovery of candidate spectra for abundant fluorophore families in human retinal pigment epithelium (RPE) by ex vivo hyperspectral imaging. Methods: Hyperspectral autofluorescence emission images were captured between 420 and 720 nm (10-nm intervals), at two excitation bands (436–460, 480–510 nm), from three locations (fovea, perifovea, near-periphery) in 20 normal RPE/Bruch's membrane (BrM) flatmounts. Mathematical factorization extracted a BrM spectrum (S0) and abundant lipofuscin/melanolipofuscin (LF/ML) spectra of RPE origin (S1, S2, S3) from each tissue. Results: Smooth spectra S1 to S3, with perinuclear localization consistent with LF/ML at all three retinal locations and both excitations in 14 eyes (84 datasets), were included in the analysis. The mean peak emissions of S0, S1, and S2 at λ\(_{ex}\) 436 nm were, respectively, 495 ± 14, 535 ± 17, and 576 ± 20 nm. S3 was generally trimodal, with peaks at either 580, 620, or 650 nm (peak mode, 650 nm). At λ\(_{ex}\) 480 nm, S0, S1, and S2 were red-shifted to 526 ± 9, 553 ± 10, and 588 ± 23 nm, and S3 was again trimodal (peak mode, 620 nm). S1 often split into two spectra, S1A and S1B. S3 strongly colocalized with melanin. There were no significant differences across age, sex, or retinal location. Conclusions: There appear to be at least three families of abundant RPE fluorophores that are ubiquitous across age, retinal location, and sex in this sample of healthy eyes. Further molecular characterization by imaging mass spectrometry and localization via super-resolution microscopy should elucidate normal and abnormal RPE physiology involving fluorophores. Translational Relevance: Our results help establish hyperspectral autofluorescence imaging of the human retinal pigment epithelium as a useful tool for investigating retinal health and disease. KW - spectral characterization KW - human retinal pigment epithelium KW - fluorophores KW - hyperspectral autofluorescence imaging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168328 VL - 5 IS - 3 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 - Lapa, Constantin A1 - Reiter, Theresa A1 - Kircher, Malte A1 - Schirbel, Andreas A1 - Werner, Rudolf A. A1 - Pelzer, Theo A1 - Pizarro, Carmen A1 - Skowasch, Dirk A1 - Thomas, Lena A1 - Schlesinger-Irsch, Ulrike A1 - Thomas, Daniel A1 - Bundschuh, Ralph A. A1 - Bauer, Wolfgang R. A1 - Gartner, Florian C. T1 - Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI JF - Oncotarget N2 - Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series. KW - sarcoidosis KW - PET KW - SSTR KW - somatostatin receptor KW - DOTATOC Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-175423 VL - 7 IS - 47 ER - TY - JOUR A1 - Padberg, Inken A1 - Knispel, Petra A1 - Zöllner, Susanne A1 - Sieveking, Meike A1 - Schneider, Alice A1 - Steinbrink, Jens A1 - Heuschmann, Peter U. A1 - Wellwood, Ian A1 - Meisel, Andreas T1 - Social work after stroke: identifying demand for support by recording stroke patients' and carers' needs in different phases after stroke JF - BMC Neurology N2 - Background Previous studies examining social work interventions in stroke often lack information on content, methods and timing over different phases of care including acute hospital, rehabilitation and out-patient care. This limits our ability to evaluate the impact of social work in multidisciplinary stroke care. We aimed to quantify social-work-related support in stroke patients and their carers in terms of timing and content, depending on the different phases of stroke care. Methods We prospectively collected and evaluated data derived from a specialized “Stroke-Service-Point” (SSP); a “drop in” center and non-medical stroke assistance service, staffed by social workers and available to all stroke patients, their carers and members of the public in the metropolitan region of Berlin, Germany. Results Enquiries from 257 consenting participants consulting the SSP between March 2010 and April 2012 related to out-patient and in-patient services, therapeutic services, medical questions, medical rehabilitation, self-help groups and questions around obtaining benefits. Frequency of enquiries for different topics depended on whether patients were located in an in-patient or out-patient setting. The majority of contacts involved information provision. While the proportion of male and female patients with stroke was similar, about two thirds of the carers contacting the SSP were female. Conclusion The social-work-related services provided by a specialized center in a German metropolitan area were diverse in terms of topic and timing depending on the phase of stroke care. Targeting the timing of interventions might be important to increase the impact of social work on patient’s outcome. KW - Social support KW - Stroke KW - Rehabilitation KW - Social work KW - Patient-centered care Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164691 VL - 16 IS - 111 ER - TY - JOUR A1 - Üçeyler, Nurcan A1 - Schröter, Nils A1 - Kafke, Waldemar A1 - Kramer, Daniela A1 - Wanner, Christoph A1 - Weidemann, Frank A1 - Sommer, Claudia T1 - Skin Globotriaosylceramide 3 Load Is Increased in Men with Advanced Fabry Disease JF - PLoS ONE N2 - Background The X-chromosomally linked life-limiting Fabry disease (FD) is associated with deposits of the sphingolipid globotriaosylceramide 3 (Gb3) in various tissues. Skin is easily accessible and may be used as an additional diagnostic and follow-up medium. Our aims were to visualize skin Gb3 deposits in FD patients applying immunofluorescence and to determine if cutaneous Gb3 load correlates with disease severity. Methods At our Fabry Center for Interdisciplinary Therapy we enrolled 84 patients with FD and 27 healthy controls. All subjects underwent 5-mm skin punch biopsy at the lateral lower leg and the back. Skin samples were processed for immunohistochemistry using antibodies against CD77 (i.e. Gb3). Cutaneous Gb3 deposition was quantified in a blinded manner and correlated to clinical data. Results We found that Gb3 load was higher in distal skin of male FD patients compared to healthy controls (p<0.05). Men (p<0.01) and women (p<0.05) with a classic FD phenotype had higher distal skin Gb3 load than healthy controls. Men with advanced disease as reflected by impaired renal function, and men and women with small fiber neuropathy had more Gb3 deposits in distal skin samples than males with normal renal function (p<0.05) and without small fiber neuropathy. Gb3 deposits were not different between patients with and without enzyme replacement therapy. Conclusions Immunofluorescence on minimally invasive skin punch biopsies may be useful as a tool for assessment and follow-up in FD patients. KW - biopsy KW - neuropathy KW - Fabry disease KW - renal system KW - immunofluorescence KW - enzyme replacement therapy KW - skin diseases KW - nerve fibers Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-178856 VL - 11 IS - 11 ER - TY - JOUR A1 - Kramer, Susanne T1 - Simultaneous detection of mRNA transcription and decay intermediates by dual colour single mRNA FISH on subcellular resolution JF - Nucleic Acids Research N2 - The detection of mRNAs undergoing transcription or decay is challenging, because both processes are fast. However, the relative proportion of an mRNA in synthesis or decay increases with mRNA size and decreases with mRNA half-life. Based on this rationale, I have exploited a 22 200 nucleotide-long, short-lived endogenous mRNA as a reporter for mRNA metabolism in trypanosomes. The extreme 5΄ and 3΄ ends were labeled with red- and green-fluorescent Affymetrix® single mRNA FISH probes, respectively. In the resulting fluorescence images, yellow spots represent intact mRNAs; red spots are mRNAs in transcription or 3΄-5΄ decay, and green spots are mRNAs in 5΄-3΄ degradation. Most red spots were nuclear and insensitive to transcriptional inhibition and thus likely transcription intermediates. Most green spots were cytoplasmic, confirming that the majority of cytoplasmic decay in trypanosomes is 5΄-3΄. The system showed the expected changes at inhibition of transcription or translation and RNAi depletion of the trypanosome homologue to the 5΄-3΄ exoribonuclease Xrn1. The method allows to monitor changes in mRNA metabolism both on cellular and on population/tissue wide levels, but also to study the subcellular localization of mRNA transcription and decay pathways. I show that the system is applicable to mammalian cells. KW - mRNA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148002 ER - TY - JOUR A1 - Baier, Pablo A. A1 - Baier-Saip, Jürgen A. A1 - Schilling, Klaus A1 - Oliveira, Jauvane C. T1 - Simulator for Minimally Invasive Vascular Interventions: Hardware and Software JF - Presence N2 - In the present work, a simulation system is proposed that can be used as an educational tool by physicians in training basic skills of minimally invasive vascular interventions. In order to accomplish this objective, initially the physical model of the wire proposed by Konings has been improved. As a result, a simpler and more stable method was obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. Then a recipe is given to merge the physical and the geometrical methods, resulting in efficient relaxations. Moreover, tests have shown that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions, and furthermore, the hardware to assemble the simulator has a low cost. KW - simulation system KW - educational tool KW - invasive vascular interventions Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-140580 SN - 1531-3263 VL - 25 IS - 2 ER - TY - THES A1 - Weber, Stefan T1 - Simulation Studies on the New Small Wheel Shielding of the ATLAS Experiment and Design and Construction of a Test Facility for Gaseous Detectors T1 - Simulationsstudien zur New Small Wheel Abschirmung des ATLAS Experiments und Entwurf und Konstruktion eines Teststandes für Gasdetektoren N2 - In this thesis two main projects are presented, both aiming at the overall goal of particle detector development. In the first part of the thesis detailed shielding studies are discussed, focused on the shielding section of the planned New Small Wheel as part of the ATLAS detector upgrade. Those studies supported the discussions within the upgrade community and decisions made on the final design of the New Small Wheel. The second part of the thesis covers the design, construction and functional demonstration of a test facility for gaseous detectors at the University of Würzburg. Additional studies on the trigger system of the facility are presented. Especially the precision and reliability of reference timing signals were investigated. N2 - In dieser Arbeit werden zwei Projekte vorgestellt, welche beide das gemeinsame Ziel der Entwicklung von Teilchendetektoren verfolgen. Im ersten Teil der Arbeit werden ausführliche Simulationsstudien zur Abschirmung behandelt, die sich auf die Abschirmungsbereiche des geplanten New Small Wheels als Teil der ATLAS-Detektor Verbesserungen konzentrieren. Diese Studien unterstützten die Diskussionen innerhalb der Upgrade-Gemeinschaft und Entscheidungen, welche für die endgültige Kostruktionsplanung des New Small Wheels getroffen wurden. Der zweite Teil der Arbeit umfasst die Konstruktion, den Aufbau sowie den Funktionsnachweis eines Teststandes für Gasdetektoren an der Universität Würzburg. Ebenfalls werden Studien über das Triggersystems des Teststandes dargestellt. Insbesondere wurden die Präzision und Verlässlichkeit von Referenzzeitsignalen untersucht. KW - Teilchendetektor KW - Abschirmung KW - Simulation KW - test facility KW - New Small Wheel KW - Teststand KW - Gasionisationsdetektor KW - European Organization for Nuclear Research. ATLAS Collaboration KW - Computersimulation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133084 ER - TY - JOUR A1 - Jahn, Martin T. A1 - Markert, Sebastian M. A1 - Ryu, Taewoo A1 - Ravasi, Timothy A1 - Stigloher, Christian A1 - Hentschel, Ute A1 - Moitinho-Silva, Lucas T1 - Shedding light on cell compartmentation in the candidate phylum Poribacteria by high resolution visualisation and transcriptional profiling JF - Scientific Reports N2 - Assigning functions to uncultivated environmental microorganisms continues to be a challenging endeavour. Here, we present a new microscopy protocol for fluorescence in situ hybridisation-correlative light and electron microscopy (FISH-CLEM) that enabled, to our knowledge for the first time, the identification of single cells within their complex microenvironment at electron microscopy resolution. Members of the candidate phylum Poribacteria, common and uncultivated symbionts of marine sponges, were used towards this goal. Cellular 3D reconstructions revealed bipolar, spherical granules of low electron density, which likely represent carbon reserves. Poribacterial activity profiles were retrieved from prokaryotic enriched sponge metatranscriptomes using simulation-based optimised mapping. We observed high transcriptional activity for proteins related to bacterial microcompartments (BMC) and we resolved their subcellular localisation by combining FISH-CLEM with immunohistochemistry (IHC) on ultra-thin sponge tissue sections. In terms of functional relevance, we propose that the BMC-A region may be involved in 1,2-propanediol degradation. The FISH-IHC-CLEM approach was proven an effective toolkit to combine -omics approaches with functional studies and it should be widely applicable in environmental microbiology. KW - high resolution visualisation KW - transcriptional profiling KW - FISH-CLEM KW - cell compartmentation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167513 VL - 6 IS - 35860 ER - TY - JOUR A1 - Bening, C. A1 - Hamouda, K. A1 - Leyh, R. T1 - Sex differences in volume overload in skinned fibers JF - BMC Cardiovascular Disorders N2 - Background The impact of sex on cardiac morphology and function in chronic volume overload has been described in detail. However, the relation between sex and contractile properties at the actin-myosin level has not been well defined. Therefore, we evaluated the influence of sex on the contractile capacities of patients with chronic volume overload. Methods In 36 patients (18 males, 65 ± 9 years; 18 females, 65 ± 13 years) scheduled for elective mitral valve surgery due to severe mitral regurgitation (MR) with preserved left ventricular function, right auricle samples were obtained prior to extracorporal circulation. The fibers were prepared and skinned and exposed to a gradual increase in the calcium concentration (from pCa of 6.5–4.0) for calcium-induced force-developing measurements. Calcium sensitivity was also measured and recorded. Results The pCa-force relationship of the fibers obtained from males and females was significantly different, with the force values of the female fibers greater than those of male fibers at maximum calcium concentrations (pCa of 4.0: 3.6 ± 0.3 mN versus 3.2 ± 0.4 mN, p 0.02) and pCa of 4.5 2.6 ± 0.6 versus 2.0 ± 0.5, p 0.002). In contrast, the force values of female fibers were lower at mean calcium concentrations compared to those of male fibers (at 5.5 and pCa of 6.0: 1.0 ± 0.3 mN versus 1.2 ± 0.5 mN, p 0.04; 0.61 ± 0.05 versus 0.88 ± 0.09, p 0.04). Calcium sensitivity was observed at pCa of 5.0 in females and pCa of 4.5 in males. Conclusion This study demonstrated that female fibers from patients exposed to chronic volume overload developed higher force values at a given calcium concentration compared to fibers from male patients. We assume that female patients might tap the full force potential, which is required when exposed to the highest calcium concentrations in our experimental cycle. The calcium sensitivity among genders was significantly different, with the results suggesting that males have higher calcium sensitivity and might compensate for lower force values at maximal calcium concentrations by a higher affinity for calcium. Hence, female patients with MR seem to work more “energy efficient”. KW - calcium sensitivity KW - pCa KW - force relationship KW - skinned fibers Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147896 VL - 16 IS - 197 ER - TY - JOUR A1 - Neufang, S. A1 - Akhrif, A. A1 - Herrmann, C.G. A1 - Drepper, C. A1 - Homola, G.A. A1 - Nowak, J. A1 - Waider, J. A1 - Schmitt, A.G. A1 - Lesch, K.-P. A1 - Romanos, M. T1 - Serotonergic modulation of 'waiting impulsivity' is mediated by the impulsivity phenotype in humans JF - Translational Psychiatry N2 - In rodents, the five-choice serial reaction time task (5-CSRTT) has been established as a reliable measure of waiting impulsivity being defined as the ability to regulate a response in anticipation of reinforcement. Key brain structures are the nucleus accumbens (NAcc) and prefrontal regions (for example, pre- and infralimbic cortex), which are, together with other transmitters, modulated by serotonin. In this functional magnetic resonance imaging study, we examined 103 healthy males while performing the 5-CSRTT measuring brain activation in humans by means of a paradigm that has been widely applied in rodents. Subjects were genotyped for the tryptophan hydroxylase-2 (TPH2; G-703T; rs4570625) variant, an enzyme specific for brain serotonin synthesis. We addressed neural activation patterns of waiting impulsivity and the interaction between the NAcc and the ventromedial prefrontal cortex (vmPFC) using dynamic causal modeling. Genetic influence was examined via interaction analyses between the TPH2 genotype (GG homozygotes vs T allele carriers) and the degree of impulsivity as measured by the 5-CSRTT. We found that the driving input of the vmPFC was reduced in highly impulsive T allele carriers (reflecting a reduced top-down control) in combination with an enhanced response in the NAcc after correct target processing (reflecting an augmented response to monetary reward). Taken together, we found a high overlap of our findings with reports from animal studies in regard to the underlying cognitive processes, the brain regions associated with waiting impulsivity and the neural interplay between the NAcc and vmPFC. Therefore, we conclude that the 5-CSRTT is a promising tool for translational studies. KW - Clinical Genetics Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164418 IS - 6 ER - TY - JOUR A1 - Conrad, Thomas A1 - Albrecht, Anne-Susann A1 - Rodrigues de Melo Costa, Veronica A1 - Sauer, Sascha A1 - Meierhofer, David A1 - Andersson Ørom, Ulf T1 - Serial interactome capture of the human cell nucleus JF - Nature Communications N2 - Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present ‘serial RNA interactome capture’ (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)–RNA–protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA–RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs. KW - human cell nucleus KW - serial RNA interactome capture KW - RNA-binding proteins Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166172 VL - 7 IS - 11212 ER - TY - JOUR A1 - Singh, Krishna P. A1 - Verma, Neeraj A1 - Akhoon, Bashir A . A1 - Bhatt, Vishal A1 - Gupta, Shishir K. A1 - Gupta, Shailendra K. A1 - Smita, Suchi T1 - Sequence-based approach for rapid identification of cross-clade CD8+ T-cell vaccine candidates from all high-risk HPV strains JF - 3 Biotech N2 - Human papilloma virus (HPV) is the primary etiological agent responsible for cervical cancer in women. Although in total 16 high-risk HPV strains have been identified so far. Currently available commercial vaccines are designed by targeting mainly HPV16 and HPV18 viral strains as these are the most common strains associated with cervical cancer. Because of the high level of antigenic specificity of HPV capsid antigens, the currently available vaccines are not suitable to provide cross-protection from all other high-risk HPV strains. Due to increasing reports of cervical cancer cases from other HPV high-risk strains other than HPV16 and 18, it is crucial to design vaccine that generate reasonable CD8+ T-cell responses for possibly all the high-risk strains. With this aim, we have developed a computational workflow to identify conserved cross-clade CD8+ T-cell HPV vaccine candidates by considering E1, E2, E6 and E7 proteins from all the high-risk HPV strains. We have identified a set of 14 immunogenic conserved peptide fragments that are supposed to provide protection against infection from any of the high-risk HPV strains across globe. KW - HPV KW - Epitope KW - Cytotoxic KW - T lymphocytes KW - Cervical cancer KW - Vaccine Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191056 VL - 6 ER - TY - JOUR A1 - Ullmann, Tobias A1 - Büdel, Christian A1 - Baumhauer, Roland A1 - Padashi, Majid T1 - Sentinel-1 SAR Data Revealing Fluvial Morphodynamics in Damghan (Iran): Amplitude and Coherence Change Detection JF - International Journal of Earth Science and Geophysics N2 - The Sentinel-1 Satellite (S-1) of ESA's Copernicus Mission delivers freely available C-Band Synthetic Aperture Radar (SAR) data that are suited for interferometric applications (InSAR). The high geometric resolution of less than fifteen meter and the large coverage offered by the Interferometric Wide Swath mode (IW) point to new perspectives on the comprehension and understanding of surface changes, the quantification and monitoring of dynamic processes, especially in arid regions. The contribution shows the application of S-1 intensities and InSAR coherences in time series analysis for the delineation of changes related to fluvial morphodynamics in Damghan, Iran. The investigations were carried out for the period from April to October 2015 and exhibit the potential of the S-1 data for the identification of surface disturbances, mass movements and fluvial channel activity in the surroundings of the Damghan Playa. The Amplitude Change Detection highlighted extensive material movement and accumulation - up to sizes of more than 4,000 m in width - in the east of the Playa via changes in intensity. Further, the Coherence Change Detection technique was capable to indicate small-scale channel activity of the drainage system that was neither recognizable in the S-1 intensity nor the multispectral Landsat-8 data. The run off caused a decorrelation of the SAR signals and a drop in coherence. Seen from a morphodynamic point of view, the results indicated a highly dynamic system and complex tempo-spatial patterns were observed that will be subject of future analysis. Additionally, the study revealed the necessity to collect independent reference data on fluvial activity in order to train and adjust the change detector. KW - SAR KW - InSAR KW - coherence KW - Iran KW - Sentinel-1 KW - radar KW - geomorphology KW - change detection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147863 VL - 2 IS - 1 ER - TY - JOUR A1 - Fetsch, Corinna A1 - Gaitzsch, Jens A1 - Messager, Lea A1 - Battaglia, Giuseppe A1 - Luxenhofer, Roberts T1 - Self-Assembly of Amphiphilic Block Copolypeptoids – Micelles, Worms and Polymersomes JF - Scientific Reports N2 - Polypeptoids are an old but recently rediscovered polymer class with interesting synthetic, physico-chemical and biological characteristics. Here, we introduce new aromatic monomers, N-benzyl glycine N-carboxyanhydride and N-phenethyl glycine N-carboxyanhydride and their block copolymers with the hydrophilic polysarcosine. We compare their self-assembly in water and aqueous buffer with the self-assembly of amphiphilic block copolypeptoids with aliphatic side chains. The aggregates in water were investigated by dynamic light scattering and electron microscopy. We found a variety of morphologies, which were influenced by the polymer structure as well as by the preparation method. Overall, we found polymersomes, worm-like micelles and oligo-lamellar morphologies as well as some less defined aggregates of interconnected worms and vesicles. Such, this contribution may serve as a starting point for a more detailed investigation of the self-assembly behavior of the rich class of polypeptoids and for a better understanding between the differences in the aggregation behavior of non-uniform polypeptoids and uniform peptoids. KW - bioinspired materials KW - polymer characterization KW - polymer synthesis KW - polymers KW - self-assembly Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147855 VL - 6 ER - TY - THES A1 - Gershberg, Jana T1 - Self-assembled Perylene Bisimide Dimers and their Interaction with Double-stranded DNA T1 - Selbst-assemblierte Perylenbisimid-Dimere und ihre Wechselwirkung mit DNA N2 - The self-assembly of molecules based on π-π-interactions and hydrogen bonding is of significant importance in nature. These processes enable the formation of complex supramolecular structures with diverse functions. For the transfer of the concepts from nature to artificial supramolecular structures, a basic understanding of those processes is needed. For this purpose, π-conjugated aromatic molecules with an easy synthetic access are suitable as their functionalities can be changed effortless. Perylene bisimide (PBIs) dyes are attractive candidates since they fulfill these requirements owing to their tendency to self-assemble in solution due to their large aromatic π-surfaces. Furthermore, the changes of the optical properties (for instance absorption, emission or circular dichroism) of PBI dyes, caused by their self-assembly, are easy to study experimentally. Structural variations of PBI dyes including additional non-covalent interactions, such as hydro-gen bonding, enable to direct their self-assembly process. Thus, the formation of interesting su-pramolecular structures of PBI dyes could be realized, although, often of undefined size. The aim of this thesis was to develop strategies to restrict the aggregate size of PBI dyes. Therefore, de-fined structural features of PBI molecules were combined and a variation of external influences such as solvent and concentration included. Furthermore, DNA was utilized as a template for the limitation of the aggregate size of PBI dyes. Chapters 1 and 2 provide general information and describe examples from literature which are necessary to understand the following experimental work. The first chapter is based on the inter-actions of various molecules with DNA. Therefore, DNA is considered as a supramolecular biom-acromolecule containing specific structural and functional features to interact with small mole-cules. Afterwards, the main interaction modes of small molecules with DNA such as electrostatic interaction, intercalation and groove binding with corresponding examples are discussed. Among all techniques applied to study the interaction of ligands with DNA, UV/Vis absorption, fluores-cence and circular dichroism spectroscopy were described in detail. At the end of this chapter, examples of already pre-associated systems showing interactions with DNA are presented. The second chapter is focused on the determination and mathematic evaluation of the self-assembly processes. The simplest models such as monomer-dimer and isodesmic model are de-scribed and supplemented by examples. Furthermore, the simplest modification of the isodesmic model, the K2-K model, is presented. Additionally, experimental problems, which may arise dur-ing the investigations of the self-assembly processes, are addressed. For the description of the entire self-assembly process, a sufficiently large concentration range and an appropriate measure-ment method that is sensitive in this concentration range is necessary. Furthermore, the full transi-tion from the monomeric to the aggregated species has to be spectroscopically ascertainable. This enables an accurate mathematic evaluation of the self-assembly process and provides meaningful binding constants. The self-assembly pathway can be controlled by the variation of solvent, con-centration or temperature. However, this pathway can also be directed by a rational design of the molecular structure of the considered system. For example, a specific interplay of π-π-interactions and hydrogen bonding may promote isodesmic as well as cooperative growth into large struc-tures. The main focus of this thesis is to develop strategies to control the aggregate size of PBI dyes (Chapter 3). For this purpose, a PBI scaffold was designed which contains hydrogen bonding amide functions at the imide positions derived from the amino acid L-alanine and solubilizing side groups in the periphery (Figure 81). The variations of the residues R/R’ range from didodecylox-yphenyl, didodecylphenyl, dioligo(ethylene glycol)phenyl to branched and linear alkyl chains. The most extensive study of the aggregation behavior was performed for the PBI dye 5. Concen-tration-dependent 1H NMR and UV/Vis absorption measurements clearly revealed the formation of dimers in chloroform. Further investigations by means of 2D NMR, VPO and ITC confirmed the exclusive presence of dimer aggregates of PBI 5 in the investigated concentration range. Mo-lecular modelling studies, supported by NMR and FT-IR experiments, provided structural reasons for the absence of further growth into larger aggregates. The specific combination of π-π interac-tions and hydrogen bonds between the NH groups of the amide groups and the carbonyl oxygen atoms of the PBI core are decisive for the formation of the discrete dimer stack (see Figure 82). The investigations of the aggregation behavior of PBIs 6-9 were less extensive but consistent with the results obtained for PBI 5. However, the determined binding constants vary over a considera-ble range of 1.1 x 102 M-1 (PBI 8) to 1.4 x 104 M-1 (PBI 5). These differences could be attributed to structural variations of the dyes. The electron-rich phenyl substituent promoted the aggregation tendency of PBIs 5-7 compared with 8 and 9 that carry only alkyl side chains. Thus, the π-π in-teractions of bay-unsubstituted PBI cores in combination with hydrogen bonding of the amide functions control the formation of discrete dimers of these PBI dyes. The variation of conditions, such as solvent, change the aggregation behavior of PBI dyes. In the solvents toluene and/or methylcyclohexane, anti-cooperative growth into larger aggregates of PBI 5 was observed (Chapter 4). The important feature of this self-assembly process is the absence of isosbestic points over the whole concentration range in the UV/Vis absorption measurements. The preference for the dimeric species of PBI 5 remained in both solvents as well as in mixtures of them, but upon increasing the concentration these dimers self-assemble into larger aggregates. An important feature of the self-assembly process is the preferred formation of even-numbered aggregates compared to the odd-numbered ones (see Figure 83). Although, the conventional K2-K model provides plausible binding constants, it is not capable to describe the aggregation behavior adequately, since it considers a continuous size distribution. The gradual aggregation process over dimers, tetramers, hexamers, etc. was therefore analyzed with a newly developed K2-K model for anti-cooperative supramolecular polymerization. By the global analysis of the UV/Vis absorption spectra a very good agreement between the experimental and simulated spectra, which were based on the new K2-K model, was obtained. Furthermore, the calculated UV/Vis absorption spectra of a dimer and an aggregate highlighted the most important structural differences. The absorption spectrum of the dimer still has a pronounced vibronic structure which gets lost in the spectrum of the aggregate. In another part of this work, a series of water soluble PBI dyes were described which contain similar PBI scaffolds as PBIs 5-8 (Chapter 5). These PBI dyes self-assemble into similar dimer aggregates in water due to their positively charged side chains causing electrostatic repulsion be-tween the molecules (see Figure 84). Here, however, the self-assembly behavior has not been studied thoroughly in water due to the similarities of already reported PBI dyes. Instead, the focus here is on the characterization of the interactions of these dyes with DNA/RNA. The comprehensive studies using thermal denaturation experiments showed the high stability of these PBI/polynucleotide complexes. The spermine-functionalized PBI dyes having six positive charges showed strong interactions with DNA/RNA which was expressed in a signif-icant increase of the melting temperatures of DNA/RNA (ΔTm values between 7 and > 35 ° C). The dioxa analogues containing only two positive charges had lower enhancement of the melting temperature of DNA/RNA (ΔTm values between 3 and 30 ° C). A similar trend has been observed in the fluorimetric titrations. The spermine-functionalized PBI dyes showed high binding con-stants (log Ks = 9.2 - 9.8), independently of the used polynucleotides. In contrast, the dioxa ana-logues displayed smaller binding constants (log Ks = 6.5 - 7.9) without any correlation between binding affinity and binding strength of the PBI dyes and the applied polynucleotides. The CD-spectroscopic measurements revealed significant differences in the binding properties of the dyes with DNA/RNA. They were dependent on the steric hindrance of the amino acid residues at the imide position and their configuration on one side and the grooves properties of ds-DNA/RNA on the other side. The spectroscopic results confirmed the formation of excitonically coupled PBI dimers in the minor groove of ds-DNA and the major groove of ds-RNA. Depending on the se-quence, the grooves of the polynucleotides provide different amount of space for embedding molecules. The guanine amino groups protrude into the minor groove of the polynucleotide poly(dG-dC)2 increasing the steric hindrance, which is not the case for poly(dA-dT)2. Molecular modeling studies showed that the PBI dimers penetrate deeper into the groove of poly(dA-dT)2 due to the absence of the steric hindrance, in comparison to the groove of poly(dG-dC)2 (see Figure 85). N2 - Die Selbstassemblierung von Molekülen, die auf π-π-Wechselwirkungen und Wasenstoffbrücken-bindungen basiert, ist von entscheidender Bedeutung in der Natur. Selbstassemblierungsprozesse ermöglichen den Aufbau von komplexen supramolekularen Strukturen mit vielfältigen Funktio-nen. Um Konzepte aus der Natur für künstliche supramolekulare Systeme nutzen zu können, müs-sen die wesentlichen Abläufe der Selbstassemblierungsprozesse verstanden werden. Dazu eignen sich π-konjugierte aromatische Moleküle, die einen relativ einfachen synthetischen Zugang bieten und vielfältig funktionalisiert werden können. Perylenbisimid-Farbstoffe (PBI) stellen für diesen Zweck eine attraktive Substanzklasse dar, da sie aufgrund von großen aromatischen π-Flächen zur Selbstassemblierung tendieren. Zusätzlich können durch die Selbstassemblierung einhergehenden Änderungen der optischen Eigenschaften (beispielsweise Absorption, Emission oder Circulardich-roismus) von PBI-Farbstoffen einfach experimentell studiert werden. Die vielen strukturellen Va-riationsmöglichkeiten von PBI-Farbstoffen erlauben das Einbeziehen von weiteren nichtkovalen-ten Wechselwirkungen zwischen den Molekülen, beispielsweise Wasserstoffbrückenbindungen, sodass der Selbstassemblierungsprozess dirigiert werden kann. Mit diesem Ansatz gelang es bis-her interessante supramolekulare Strukturen von PBI-Farbstoffen aufzubauen, allerdings waren diese oft von undefinierter Größe. Daher war das Ziel dieser Arbeit die Entwicklung von Kon-zepten um die Aggregatgröße von PBI-Farbstoffen zu begrenzen. Hierzu wurden definierte Strukturmerkmale von PBI Molekülen kombiniert, der äußere Einfluss wie Lösungsmittel und Konzentration variiert und DNA als Templat für die größenlimitierte Aggregatstruktur der PBI-Farbstoffe eingesetzt. Die Kapitel 1 und 2 geben allgemeine Informationen und diskutieren Beispiele aus der Literatur, die nötig sind, um die nachfolgend diskutierten experimentellen Arbeiten zu verstehen. Das erste Kapitel diskutiert die Wechselwirkungen verschiedener Molekülen mit DNA. Hierbei wird DNA als ein supramolekulares Biomakromolekül betrachtet und seine spezifischen strukturellen und funktionalen Eigenschaften beschrieben, die für die Interaktionen mit kleinen Molekülen aus-schlaggebend sind. Die wichtigsten Interaktionsformen wie elektrostatische Wechselwirkungen mit dem Phosphatrückgrat, Interkalation durch π-π-Wechselwirkungen mit den Basenpaaren und Furchenbindung durch Wasserstoffbrückenbindungen und van der Waals-Wechselwirkungen werden anhand ausgewählter Beispiele diskutiert. Von der Vielzahl möglicher Techniken, die angewendet werden, um Wechselwirkungen zwischen Liganden und DNA zu untersuchen, wer-den UV/Vis-, Fluoreszenz- und Circulardichroismus-Spektroskopie in Detail erläutert. Am Ende des Kapitels werden Beispiele von Wechselwirkungen von bereits prä-assoziierten supramolekula-ren Systemen mit DNA vorgestellt. Das zweite Kapitel beschäftigt sich mit der Bestimmung und mathematischen Beschreibung von Selbstassemblierungsprozessen. Die einfachsten Modelle, wie das Monomer-Dimer und das iso-desmische Modell, werden beschrieben und mit Beispielen ergänzt. Des Weiteren wird die ein-fachste Modifikation des isodesmischen Modells, das K2-K Modell vorgestellt. Anschließend wird auf experimentelle Probleme eingegangen, die bei der Untersuchung von Selbstassemblie-rungsprozessen auftreten können. Um den Assemblierungsprozess vollständig beschreiben zu können, wird ein ausreichend großer Konzentrationsbereich und eine entsprechende Messtechnik, die für diesen Konzentrationsbereich empfindlich genug ist, benötigt. Des Weiteren sollte der vollständige Übergang vom Monomer zum assemblierten System spektroskopisch erfassbar sein. Dies ermöglicht eine akkurate mathematische Auswertung des Selbstassemblierungsprozesses und liefert sinnvolle Bindungskonstanten. Der Selbstassemblierungspfad kann oft durch Variation des Lösungsmittels, Konzentration und Temperatur kontrolliert werden. Darüber hinaus besteht die Möglichkeit, den Selbstassemblierungspfad mit Hilfe eines spezifischen Designs der molekularen Struktur von dem untersuchten System zu dirigieren. Es konnte gezeigt werden, dass ein beson-deres Zusammenspiel von π-π-Wechselwirkungen und Wasserstoffbrückenbindungen sowohl zum isodesmischen als auch kooperativen Wachstum von großen Strukturen führen kann. Der Hauptfokus dieser Arbeit liegt in der Entwicklung von Strategien für die Kontrolle der Aggregatgröße von PBI Farbstoffen. (Kapitel 3). Um dieses Ziel zu erreichen, wurde ein PBI Gerüst entworfen, das Amidfunktionen in den Imidpositionen für die Ausbildung von Wasser-stoffbrückenbindungen enthält, die von der Aminosäure L-Alanin abgeleitet wurden. Zusätzlich wurden in der Peripherie des Farbstoffgerüsts jeweils löslichkeitsfördernde Seitengruppen R/R‘ wie Didodecyloxyphenyl, Didodecylphenyl, Dioligo(ethyleneglykol)phenyl sowie verzweigte oder lineare Alkylketten eingeführt (siehe Abbildung 81). Der PBI-Farbstoff 5 wurde ausführlich im Hinblick auf sein Aggregationsverhalten untersucht. Konzentrationsabhängige 1H NMR- und UV/Vis Absorptionsmessungen haben klar gezeigt, dass im Lösungsmittel Chloroform dimere Strukturen ausgebildet werden. Begleitende Untersuchungen (2D NMR, VPO und ITC) bestätigten die ausschließliche Präsenz von Dimeren von 5 im experimentell zugänglichen Konzentrationsbereich. Molekulare Modellie-rungs-Studien, die durch NMR und FT-IR Untersuchungen unterstützt werden, illustrieren sehr gut die Ursachen für das Ausbleiben einer weiteren Aggregation zu größeren Strukturen. Die be-sondere Kombination aus den π-π-Wechselwirkungen und den Wasserstoffbrückenbindungen zwischen den NH-Gruppen der Amidfunktionen und den Carbonylsauerstoffen des PBI-Kerns sind demzufolge entscheidend für die Bildung des diskreten Dimer-Stapels (siehe Abbildung 82). Die Untersuchungen zum Aggregationsverhalten der PBI-Farbstoffe 6-9 waren weniger ausführ-lich, stehen aber im Einklang mit den für PBI 5 gefundenen Ergebnissen. Die ermittelten Bin-dungskonstanten variieren jedoch über einen beachtlichen Bereich von 1.1 x 102 M-1 (PBI 8) bis 1.4 x 104 M-1 (PBI 5). Diese Unterschiede konnten auf strukturelle Variationen der Farbstoffe zurückgeführt werden. Der elektronenreiche Phenylsubstituent förderte die Assemblierungsten-denz von PBIs 5-7 im Vergleich zu 8 und 9, die nur Alkylseitenkennten tragen. Die π-π-Wechselwirkungen der in den Buchpositionen unsubstituierten PBI-Kerne in Kombination mit wasserstoffbrückenbildenden Amidfunktionen steuern somit die Ausbildung diskreter Dimere dieser PBI-Farbstoffe. Durch die Variation der Bedingungen, beispielsweise des Lösungsmittels, ändert sich das Aggre-gationsverhalten der PBI-Farbstoffe. In den Lösungsmitteln Toluol und/oder Methylcyclohexan wurde für das PBI 5 anti-kooperatives Wachstum zu größeren Aggregaten beobachtet (Kapitel 4). Das entscheidende Merkmal dieses Selbstassemblierungsprozesses ist das Fehlen von isosbesti-schen Punkten über den kompletten Konzentrationsbereich in den UV/Vis Absorptionsmessun-gen. Die Bevorzugung der dimeren Struktur von PBI 5 blieb in beiden Lösungsmitteln bzw. de-ren Mischungen erhalten, allerdings assemblierten diese Dimere durch den Anstieg der Konzent-ration in größere Aggregate. Ein wichtiger Schritt im Selbstassemblierungsprozesses ist die bevor-zugte Bildung von geradzahligen Aggregaten gegenüber den ungeradzahligen Aggregaten (siehe Abbildung 83). Das konventionelle K2-K Modell liefert zwar plausible Bindungskonstanten, kann dieses Aggre-gationsverhalten aber nur ungenügend beschreiben, da hier von kontinuierlicher Größenverteilung ausgegangen wird. Der schrittweise Aggregationsprozess über Dimere, Tetramere, Hexamere usw. wurde daher im Folgenden mit einem neu entwickelten K2-K-Modell für anti-kooperatives supra-molekulares Wachstum analysiert. Durch die globale Analyse von UV/Vis Absorptionsspektren konnte eine sehr gute Übereinstimmung zwischen den experimentellen und den auf das neue K2-K Modell basierenden, simulierten Spektren erhalten werden. Des Weiteren zeigten berechnete UV/Vis Absorptionsspektren eines Dimer- und Aggregatspektrums die wichtigsten strukturellen Unterschiede. Das Absorptionsspektrum des Dimers weist immer noch eine ausgeprägte vibroni-sche Struktur auf, welche im Spektrum des Aggregats verloren geht. In einem weiteren Teil dieser Arbeit wird eine Serie von wasserlöslichen PBI-Farbstoffen be-schrieben, die ein ähnliches durch Aminosäuren funktionalisiertes PBI-Gerüst wie PBIs 5-8 auf-weisen (Kapitel 5). Aufgrund der positiv geladenen Seitenketten, die für die elektrostatische Ab-stoßung zwischen den Molekülen sorgen, aggregieren diese Farbstoffe in Wasser zu ähnlichen Dimerstrukturen (siehe Abbildung 84). Hier wurde allerdings das Selbstassemblierungsverhalten in Wasser aufgrund der strukturellen Ähnlichkeit zu bereits publizierten PBI-Farbstoffen nicht eingehend untersucht. Stattdessen lag der Fokus hier auf der Charakterisierung der Wechselwirkungen dieser Farbstoffe mit DNA/RNA. Die umfassenden Studien mit Hilfe von thermischen Denaturierungsstudien zeigten eine hohe Stabilität der PBI/Polynukleotid-Komplexe. Die Spermin-funktionalisierten PBI-Farbstoffe, welche sechs positive Ladungen aufweisen, zeigten starke Wechselwirkungen mit DNA/RNA, was sich durch deutliche Schmelzpunkterhöhung der DNA/RNA (ΔTm-Werte zwischen 7 und > 35 °C) äußerte. Die analogen Dioxa-Verbindungen mit nur zwei positiven La-dungen wiesen geringere Schmelztemperaturerhöhungen der jeweiligen DNA/RNA (ΔTm-Werte zwischen 3 und 30 °C) auf. Dieser Trend wurde auch in den fluorimetrischen Titrationsstudien beobachtet. Die Spermin-funktionalisierten PBI-Farbstoffe zeigten hohe Bindungskostanten (log Ks = 9.2 – 9.8), unabhängig von den verwendeten Polynukleotiden. Im Gegensatz dazu wie-sen die Dioxa-Analoge kleinere Bindungskonstanten (log Ks = 6.5 – 7.9) auf, wobei kein Zusam-menhang zwischen Bindungsaffinität und Bindungsstärke zwischen den PBI-Molekülen und den verwendeten Polynukleotiden hergestellt werden konnte. Die CD-spektroskopischen Messungen verdeutlichten die signifikanten Unterschiede in den Bindungseigenschaften der Farbstoffe mit DNA/RNA. Entscheidend waren die sterische Hinderung der Aminosäurereste in den Imidposi-tion und deren Konfiguration auf der einen Seite und die Furcheneigenschaften von ds-DNA/RNA auf der anderen Seite. Die spektroskopischen Ergebnisse belegten die Bildung von exzitonisch gekoppelten PBI-Dimeren in der kleinen Furche von ds-DNA und der großen Furche von ds-RNA. Die Furchen der Polynukleotide bieten unterschiedlich viel Raum für das Einbetten von Molekülen, was von der jeweiligen Sequenz abhängt. Die Guanin-Aminogruppen ragen in die kleine Furche des Polynukleotids poly(dG-dC)2, wodurch die sterische Hinderung im Vergleich mit dem Polynukleotid poly(dA-dT)2 zunimmt. Molekulare Modellierungsstudien belegten, dass die PBI-Dimere tiefer in die Furche von poly(dA-dT)2, als in die Furche von poly(dG-dC)2 einge-schlossen werden, was auf die eben genannte sterische Hinderung zurückgeführt werden kann (siehe Abbildung 85). KW - Perylentetracarbonsäurederivate KW - Perylene bisimide KW - Aggregat KW - Dimer-Konfiguration KW - DNS KW - aggregation KW - dimer KW - DNA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136725 ER - TY - JOUR A1 - Heurich, Marco A1 - Zeis, Klara A1 - Küchenhoff, Helmut A1 - Müller, Jörg A1 - Belotti, Elisa A1 - Bufka, Luděk A1 - Woelfing, Benno T1 - Selective Predation of a Stalking Predator on Ungulate Prey JF - PLoS ONE N2 - Prey selection is a key factor shaping animal populations and evolutionary dynamics. An optimal forager should target prey that offers the highest benefits in terms of energy content at the lowest costs. Predators are therefore expected to select for prey of optimal size. Stalking predators do not pursue their prey long, which may lead to a more random choice of prey individuals. Due to difficulties in assessing the composition of available prey populations, data on prey selection of stalking carnivores are still scarce. We show how the stalking predator Eurasian lynx (Lynx lynx) selects prey individuals based on species identity, age, sex and individual behaviour. To address the difficulties in assessing prey population structure, we confirm inferred selection patterns by using two independent data sets: (1) data of 387 documented kills of radio-collared lynx were compared to the prey population structure retrieved from systematic camera trapping using Manly’s standardized selection ratio alpha and (2) data on 120 radio-collared roe deer were analysed using a Cox proportional hazards model. Among the larger red deer prey, lynx selected against adult males—the largest and potentially most dangerous prey individuals. In roe deer lynx preyed selectively on males and did not select for a specific age class. Activity during high risk periods reduced the risk of falling victim to a lynx attack. Our results suggest that the stalking predator lynx actively selects for size, while prey behaviour induces selection by encounter and stalking success rates. KW - stalking predators KW - prey selection KW - Lynx lynx Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166827 VL - 11 IS - 8 ER - TY - JOUR A1 - Weigand, Annika A1 - Boos, Anja M. A1 - Tasbihi, Kereshmeh A1 - Beier, Justus P. A1 - Dalton, Paul D. A1 - Schrauder, Michael A1 - Horch, Raymund E. A1 - Beckmann, Matthias W. A1 - Strissel, Pamela L. A1 - Strick, Reiner T1 - Selective isolation and characterization of primary cells from normal breast and tumors reveal plasticity of adipose derived stem cells JF - Breast Cancer Research N2 - Background There is a need to establish more cell lines from breast tumors in contrast to immortalized cell lines from metastatic effusions in order to represent the primary tumor and not principally metastatic biology of breast cancer. This investigation describes the simultaneous isolation, characterization, growth and function of primary mammary epithelial cells (MEC), mesenchymal cells (MES) and adipose derived stem cells (ADSC) from four normal breasts, one inflammatory and one triple-negative ductal breast tumors. Methods A total of 17 cell lines were established and gene expression was analyzed for MEC and MES (n = 42) and ADSC (n = 48) and MUC1, pan-KRT, CD90 and GATA-3 by immunofluorescence. DNA fingerprinting to track cell line identity was performed between original primary tissues and isolates. Functional studies included ADSC differentiation, tumor MES and MEC invasion co-cultured with ADSC-conditioned media (CM) and MES adhesion and growth on 3D-printed scaffolds. Results Comparative analysis showed higher gene expression of EPCAM, CD49f, CDH1 and KRTs for normal MEC lines; MES lines e.g. Vimentin, CD10, ACTA2 and MMP9; and ADSC lines e.g. CD105, CD90, CDH2 and CDH11. Compared to the mean of all four normal breast cell lines, both breast tumor cell lines demonstrated significantly lower ADSC marker gene expression, but higher expression of mesenchymal and invasion gene markers like SNAI1 and MMP2. When compared with four normal ADSC differentiated lineages, both tumor ADSC showed impaired osteogenic and chondrogenic but enhanced adipogenic differentiation and endothelial-like structures, possibly due to high PDGFRB and CD34. Addressing a functional role for overproduction of adipocytes, we initiated 3D-invasion studies including different cell types from the same patient. CM from ADSC differentiating into adipocytes induced tumor MEC 3D-invasion via EMT and amoeboid phenotypes. Normal MES breast cells adhered and proliferated on 3D-printed scaffolds containing 20 fibers, but not on 2.5D-printed scaffolds with single fiber layers, important for tissue engineering. Conclusion Expression analyses confirmed successful simultaneous cell isolations of three different phenotypes from normal and tumor primary breast tissues. Our cell culture studies support that breast-tumor environment differentially regulates tumor ADSC plasticity as well as cell invasion and demonstrates applications for regenerative medicine. KW - Normal breast KW - Breast cancer KW - Stem cells plasticity KW - Primary cell lines KW - Tissue engineering Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164759 VL - 18 IS - 32 ER - TY - JOUR A1 - Walper, Elisabeth A1 - Weiste, Christoph A1 - Mueller, Martin J. A1 - Hamberg, Mats A1 - Dröge-Laser, Wolfgang T1 - Screen Identifying Arabidopsis Transcription Factors Involved in the Response to 9-Lipoxygenase-Derived Oxylipins JF - PLoS One N2 - 13-Lipoxygenase-derived oxylipins, such as jasmonates act as potent signaling molecules in plants. Although experimental evidence supports the impact of oxylipins generated by the 9-Lipoxygenase (9-LOX) pathway in root development and pathogen defense, their signaling function in plants remains largely elusive. Based on the root growth inhibiting properties of the 9-LOX-oxylipin 9-HOT (9-hydroxy-10,12,15-octadecatrienoic acid), we established a screening approach aiming at identifying transcription factors (TFs) involved in signaling and/or metabolism of this oxylipin. Making use of the AtTORF-Ex (Arabidopsis thaliana Transcription Factor Open Reading Frame Expression) collection of plant lines overexpressing TF genes, we screened for those TFs which restore root growth on 9-HOT. Out of 6,000 lines, eight TFs were recovered at least three times and were therefore selected for detailed analysis. Overexpression of the basic leucine Zipper (bZIP) TF TGA5 and its target, the monoxygenase CYP81D11 reduced the effect of added 9-HOT, presumably due to activation of a detoxification pathway. The highly related ETHYLENE RESPONSE FACTORs ERF106 and ERF107 induce a broad detoxification response towards 9-LOX-oxylipins and xenobiotic compounds. From a set of 18 related group S-bZIP factors isolated in the screen, bZIP11 is known to participate in auxin-mediated root growth and may connect oxylipins to root meristem function. The TF candidates isolated in this screen provide starting points for further attempts to dissect putative signaling pathways involving 9-LOX-derived oxylipins. KW - Jasmonic acid KW - root growth KW - arabidopsis thaliana KW - detoxification KW - seedlings KW - stress signaling cascade KW - hyperexpression techniques KW - ranscription factors Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146857 VL - 11 IS - 4 ER - TY - JOUR A1 - Bousquet, J. A1 - Farrell, J. A1 - Crooks, G. A1 - Hellings, P. A1 - Bel, E. H. A1 - Bewick, M. A1 - Chavannes, N. H. A1 - Correia de Sousa, J. A1 - Cruz, A. A. A1 - Haahtela, T. A1 - Joos, G. A1 - Khaltaev, N. A1 - Malva, J. A1 - Muraro, A. A1 - Nogues, M. A1 - Palkonen, S. A1 - Pedersen, S. A1 - Robalo-Cordeiro, C. A1 - Samolinski, B. A1 - Strandberg, T. A1 - Valiulis, A. A1 - Yorgancioglu, A. A1 - Zuberbier, T. A1 - Bedbrook, A. A1 - Aberer, W. A1 - Adachi, M. A1 - Agusti, A. A1 - Akdis, C. A. A1 - Akdis, M. A1 - Ankri, J. A1 - Alonso, A. A1 - Annesi-Maesano, I. A1 - Ansotegui, I. J. A1 - Anto, J. M. A1 - Arnavielhe, S. A1 - Arshad, H. A1 - Bai, C. A1 - Baiardini, I. A1 - Bachert, C. A1 - Baigenzhin, A. K. A1 - Barbara, C. A1 - Bateman, E. D. A1 - Beghé, B. A1 - Ben Kheder, A. A1 - Bennoor, K. S. A1 - Benson, M. A1 - Bergmann, K. C. A1 - Bieber, T. A1 - Bindslev-Jensen, C. A1 - Bjermer, L. A1 - Blain, H. A1 - Blasi, F. A1 - Boner, A. L. A1 - Bonini, M. A1 - Bonini, S. A1 - Bosnic-Anticevitch, S. A1 - Boulet, L. P. A1 - Bourret, R. A1 - Bousquet, P. J. A1 - Braido, F. A1 - Briggs, A. H. A1 - Brightling, C. E. A1 - Brozek, J. A1 - Buhl, R. A1 - Burney, P. G. A1 - Bush, A. A1 - Caballero-Fonseca, F. A1 - Caimmi, D. A1 - Calderon, M. A. A1 - Calverley, P. M. A1 - Camargos, P. A. M. A1 - Canonica, G. W. A1 - Camuzat, T. A1 - Carlsen, K. H. A1 - Carr, W. A1 - Carriazo, A. A1 - Casale, T. A1 - Cepeda Sarabia, A. M. A1 - Chatzi, L. A1 - Chen, Y. Z. A1 - Chiron, R. A1 - Chkhartishvili, E. A1 - Chuchalin, A. G. A1 - Chung, K. F. A1 - Ciprandi, G. A1 - Cirule, I. A1 - Cox, L. A1 - Costa, D. J. A1 - Custovic, A. A1 - Dahl, R. A1 - Dahlen, S. E. A1 - Darsow, U. A1 - De Carlo, G. A1 - De Blay, F. A1 - Dedeu, T. A1 - Deleanu, D. A1 - De Manuel Keenoy, E. A1 - Demoly, P. A1 - Denburg, J. A. A1 - Devillier, P. A1 - Didier, A. A1 - Dinh-Xuan, A. T. A1 - Djukanovic, R. A1 - Dokic, D. A1 - Douagui, H. A1 - Dray, G. A1 - Dubakiene, R. A1 - Durham, S. R. A1 - Dykewicz, M. S. A1 - El-Gamal, Y. A1 - Emuzyte, R. A1 - Fabbri, L. M. A1 - Fletcher, M. A1 - Fiocchi, A. A1 - Fink Wagner, A. A1 - Fonseca, J. A1 - Fokkens, W. J. A1 - Forastiere, F. A1 - Frith, P. A1 - Gaga, M. A1 - Gamkrelidze, A. A1 - Garces, J. A1 - Garcia-Aymerich, J. A1 - Gemicioğlu, B. A1 - Gereda, J. E. A1 - González Diaz, S. A1 - Gotua, M. A1 - Grisle, I. A1 - Grouse, L. A1 - Gutter, Z. A1 - Guzmán, M. A. A1 - Heaney, L. G. A1 - Hellquist-Dahl, B. A1 - Henderson, D. A1 - Hendry, A. A1 - Heinrich, J. A1 - Heve, D. A1 - Horak, F. A1 - Hourihane, J. O’. B. A1 - Howarth, P. A1 - Humbert, M. A1 - Hyland, M. E. A1 - Illario, M. A1 - Ivancevich, J. C. A1 - Jardim, J. R. A1 - Jares, E. J. A1 - Jeandel, C. A1 - Jenkins, C. A1 - Johnston, S. L. A1 - Jonquet, O. A1 - Julge, K. A1 - Jung, K. S. A1 - Just, J. A1 - Kaidashev, I. A1 - Kaitov, M. R. A1 - Kalayci, O. A1 - Kalyoncu, A. F. A1 - Keil, T. A1 - Keith, P. K. A1 - Klimek, L. A1 - Koffi N’Goran, B. A1 - Kolek, V. A1 - Koppelman, G. H. A1 - Kowalski, M. L. A1 - Kull, I. A1 - Kuna, P. A1 - Kvedariene, V. A1 - Lambrecht, B. A1 - Lau, S. A1 - Larenas‑Linnemann, D. A1 - Laune, D. A1 - Le, L. T. T. A1 - Lieberman, P. A1 - Lipworth, B. A1 - Li, J. A1 - Lodrup Carlsen, K. A1 - Louis, R. A1 - MacNee, W. A1 - Magard, Y. A1 - Magnan, A. A1 - Mahboub, B. A1 - Mair, A. A1 - Majer, I. A1 - Makela, M. J. A1 - Manning, P. A1 - Mara, S. A1 - Marshall, G. D. A1 - Masjedi, M. R. A1 - Matignon, P. A1 - Maurer, M. A1 - Mavale‑Manuel, S. A1 - Melén, E. A1 - Melo‑Gomes, E. A1 - Meltzer, E. O. A1 - Menzies‑Gow, A. A1 - Merk, H. A1 - Michel, J. P. A1 - Miculinic, N. A1 - Mihaltan, F. A1 - Milenkovic, B. A1 - Mohammad, G. M. Y. A1 - Molimard, M. A1 - Momas, I. A1 - Montilla‑Santana, A. A1 - Morais‑Almeida, M. A1 - Morgan, M. A1 - Mösges, R. A1 - Mullol, J. A1 - Nafti, S. A1 - Namazova‑Baranova, L. A1 - Naclerio, R. A1 - Neou, A. A1 - Neffen, H. A1 - Nekam, K. A1 - Niggemann, B. A1 - Ninot, G. A1 - Nyembue, T. D. A1 - O’Hehir, R. E. A1 - Ohta, K. A1 - Okamoto, Y. A1 - Okubo, K. A1 - Ouedraogo, S. A1 - Paggiaro, P. A1 - Pali‑Schöll, I. A1 - Panzner, P. A1 - Papadopoulos, N. A1 - Papi, A. A1 - Park, H. S. A1 - Passalacqua, G. A1 - Pavord, I. A1 - Pawankar, R. A1 - Pengelly, R. A1 - Pfaar, O. A1 - Picard, R. A1 - Pigearias, B. A1 - Pin, I. A1 - Plavec, D. A1 - Poethig, D. A1 - Pohl, W. A1 - Popov, T. A. A1 - Portejoie, F. A1 - Potter, P. A1 - Postma, D. A1 - Price, D. A1 - Rabe, K. F. A1 - Raciborski, F. A1 - Radier Pontal, F. A1 - Repka‑Ramirez, S. A1 - Reitamo, S. A1 - Rennard, S. A1 - Rodenas, F. A1 - Roberts, J. A1 - Roca, J. A1 - Rodriguez Mañas, L. A1 - et al, T1 - Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5) JF - Clinical and Translational Allergy N2 - Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) focuses on the integrated care of chronic diseases. Area 5 (Care Pathways) was initiated using chronic respiratory diseases as a model. The chronic respiratory disease action plan includes (1) AIRWAYS integrated care pathways (ICPs), (2) the joint initiative between the Reference site MACVIA-LR (Contre les MAladies Chroniques pour un VIeillissement Actif) and ARIA (Allergic Rhinitis and its Impact on Asthma), (3) Commitments for Action to the European Innovation Partnership on Active and Healthy Ageing and the AIRWAYS ICPs network. It is deployed in collaboration with the World Health Organization Global Alliance against Chronic Respiratory Diseases (GARD). The European Innovation Partnership on Active and Healthy Ageing has proposed a 5-step framework for developing an individual scaling up strategy: (1) what to scale up: (1-a) databases of good practices, (1-b) assessment of viability of the scaling up of good practices, (1-c) classification of good practices for local replication and (2) how to scale up: (2-a) facilitating partnerships for scaling up, (2-b) implementation of key success factors and lessons learnt, including emerging technologies for individualised and predictive medicine. This strategy has already been applied to the chronic respiratory disease action plan of the European Innovation Partnership on Active and Healthy Ageing. KW - EIP on AHA KW - European Innovation Partnership on Active and Healthy Ageing KW - AIRWAYS ICPs KW - MACVIA KW - Scaling up KW - Chronic respiratory diseases KW - ARIA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166874 VL - 6 IS - 29 ER - TY - JOUR A1 - Roesch, J. A1 - Panje, C. A1 - Sterzing, F. A1 - Mantel, F. A1 - Nestle, U. A1 - Andratschke, N. A1 - Guckenberger, M. T1 - SBRT for centrally localized NSCLC - What is too central? JF - Radiation Oncology N2 - Purpose Current guidelines recommend stereotactic body radiotherapy (SBRT) for stage I non-small-cell lung cancer (NSCLC) in medically inoperable patients. There are excellent outcome and toxicity data for SBRT of peripheral lung tumors. However, the discussion on SBRT for centrally located tumors is controversial. This study evaluated current clinical practice regarding SBRT of centrally located lung tumors, to identify common fractionation schedules and commonly accepted contraindications for SBRT. Methods A questionnaire consisting of two parts was introduced at the annual meeting of the DEGRO working group on stereotactic radiotherapy, representing centers in Germany and Switzerland. The first part of the questionnaire covered general information about the centers, whereas the second part specifically addressed SBRT of centrally located lung tumors, using case examples of nine primary NSCLC patients. Reconstructions of a contrast enhanced CT, as well as PET-Imaging for each case were demonstrated to the participants. Results Twenty-six centers participated in the meeting. The majority was academic (73%), participated in interdisciplinary thoracic oncology tumorboards (88%) and offered SBRT for lung tumors (96%). Two centers questioned the indication of SBRT for central lung tumors because of lack of evidence. The majority of centers had experience in SBRT for central lung tumors (88%) and half of the centers reported more than ten cases treated during a median period of five years. Most fractionation schedules used PTV encompassing doses of 48–60 Gy in eight fractions with maximum doses of 125–150%. A clear indication for SBRT treatment was seen by more than 85% of centers in three of the nine patients in whom tumors were small and not closer than 2 cm to the main bronchus. Prior pneumonectomy or immediate adjacency to hilar/mediastinal structures were not considered as contraindications for SBRT. In cases where the tumor exceeded 4 cm in diameter or was located closer than 4 cm to the carina 50–80% of centers saw an indication for SBRT. One case, with a 7 cm tumor reaching to the carina would have been treated with SBRT only by one center. Conclusion Within DEGRO working group on stereotactic radiotherapy, SBRT for small (<4 cm) early stage NSCLC is a common indication, if the minimal distance to the main bronchi is at least 2 cm. The controversy on the treatment of larger and more central tumors will hopefully be solved by ongoing prospective clinical trials. KW - SBRT KW - SABR KW - NSCLC KW - central lung KW - pulmonary toxicity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167459 VL - 11 IS - 157 ER - TY - THES A1 - Schulze, Marcus T1 - Ruthenium Complexes as Water Oxidation Catalysts and Photosensitizers T1 - Rutheniumkomplexe als Wasseroxidationskatalysatoren und Photosensibilisatoren N2 - In der vorliegenden Arbeit werden Aspekte der photokatalytischen Wasseroxidationsreaktion behandelt. Der erste Themenschwerpunkt der Dissertation beschäftigt sich mit einem supramolekularen Makrozyklus, der drei Rutheniummetallzentren enthält. Dieser neuartige Katalysator zeigt eine sehr hohe katalytische Aktivität und gewährt neue Einblicke in den Mechanismus der Wasseroxidationsreaktion. Des Weiteren wird auf die mit Licht interagierenden Komponenten der photokatalytischen Wasseroxidation eingegangen. Hierbei haben sich azabenz-anellierte Perylenderivate als vielseitige Farbstoffklasse herausgestellt. Die Kombination dieser Farbstoffe mit Metallkomplexen liefert metallorganische Verbindungen, die als Photosensibilisatoren eingesetzt werden können. N2 - The thesis discusses aspects of the photocatalytic water oxidation reaction. The first chapter deals with a supramolecular macrocycle which contains three ruthenium metal centers. This novel catalyst shows promising catalytic activity and provides insides into the mechanism of the water oxidation reaction. After this part, the focus lies on the light interacting components of the photocatalytic water oxidation. In this regard, the azabenz-annulated perylene derivatives appeared to be a promising dye class. The combination of these chromophores and metal complexes result in metal organic compounds, which have photosensitizer potential. KW - Farbstoff KW - Ruthenium KW - Fotokatalyse KW - Photosensibilisator KW - Makrozyklus KW - macrocycle KW - Wasseroxidationsreaktion KW - water oxidation reation KW - Perylen-Farbstoffe KW - perylene dyes KW - Katalyse KW - Wasserspaltung Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142454 ER - TY - JOUR A1 - Trudzinski, Franziska C. A1 - Minko, Peter A1 - Rapp, Daniel A1 - Fähndrich, Sebastian A1 - Haake, Hendrik A1 - Haab, Myriam A1 - Bohle, Rainer M. A1 - Flaig, Monika A1 - Kaestner, Franziska A1 - Bals, Robert A1 - Wilkens, Heinrike A1 - Muellenbach, Ralf M. A1 - Link, Andreas A1 - Groesdonk, Heinrich V. A1 - Lensch, Christian A1 - Langer, Frank A1 - Lepper, Philipp M. T1 - Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis JF - Annals of Intensive Care N2 - Background Even though bleeding and thromboembolic events are major complications of extracorporeal membrane oxygenation (ECMO), data on the incidence of venous thrombosis (VT) and thromboembolism (VTE) under ECMO are scarce. This study analyzes the incidence and predictors of VTE in patients treated with ECMO due to respiratory failure. Methods Retrospective analysis of patients treated on ECMO in our center from 04/2010 to 11/2015. Patients with thromboembolic events prior to admission were excluded. Diagnosis was made by imaging in survivors and postmortem examination in deceased patients. Results Out of 102 screened cases, 42 survivors and 21 autopsy cases [mean age 46.0 ± 14.4 years; 37 (58.7 %) males] fulfilling the above-mentioned criteria were included. Thirty-four patients (54.0 %) underwent ECMO therapy due to ARDS, and 29 patients (46.0 %) with chronic organ failure were bridged to lung transplantation. Despite systemic anticoagulation at a mean PTT of 50.6 ± 12.8 s, [VT/VTE 47.0 ± 12.3 s and no VT/VTE 53.63 ± 12.51 s (p = 0.037)], VT and/or VTE was observed in 29 cases (46.1 %). The rate of V. cava thrombosis was 15/29 (51.7 %). Diagnosis of pulmonary embolism prevailed in deceased patients [5/21 (23.8 %) vs. 2/42 (4.8 %) (p = 0.036)]. In a multivariable analysis, only aPTT and time on ECMO predicted VT/VTE. There was no difference in the incidence of clinically diagnosed VT in ECMO survivors and autopsy findings. Conclusions Venous thrombosis and thromboembolism following ECMO therapy are frequent. Quality of anticoagulation and ECMO runtime predicted thromboembolic events. " KW - Pulmonary Embolism KW - Inferior Vena Cava KW - Venous Thrombosis KW - Fresh Freeze Plasma KW - Extracorporeal Membrane Oxygenation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164455 VL - 6 ER - TY - JOUR A1 - Lundt, Nils A1 - Klembt, Sebastian A1 - Cherotchenko, Evgeniia A1 - Betzold, Simon A1 - Iff, Oliver A1 - Nalitov, Anton V. A1 - Klaas, Martin A1 - Dietrich, Christof P. A1 - Kavokin, Alexey V. A1 - Höfling, Sven A1 - Schneider, Christian T1 - Room-temperature Tamm-plasmon exciton-polaritons with a WSe\(_{2}\) monolayer JF - Nature Communications N2 - Solid-state cavity quantum electrodynamics is a rapidly advancing field, which explores the frontiers of light–matter coupling. Metal-based approaches are of particular interest in this field, as they carry the potential to squeeze optical modes to spaces significantly below the diffraction limit. Transition metal dichalcogenides are ideally suited as the active material in cavity quantum electrodynamics, as they interact strongly with light at the ultimate monolayer limit. Here, we implement a Tamm-plasmon-polariton structure and study the coupling to a monolayer of WSe\(_{2}\), hosting highly stable excitons. Exciton-polariton formation at room temperature is manifested in the characteristic energy–momentum dispersion relation studied in photoluminescence, featuring an anti-crossing between the exciton and photon modes with a Rabi-splitting of 23.5 meV. Creating polaritonic quasiparticles in monolithic, compact architectures with atomic monolayers under ambient conditions is a crucial step towards the exploration of nonlinearities, macroscopic coherence and advanced spinor physics with novel, low-mass bosons. KW - optics and photonics KW - two-dimensional materials KW - electronic properties and materials Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169470 VL - 7 ER - TY - JOUR A1 - Koessler, Juergen A1 - Hermann, Stephanie A1 - Weber, Katja A1 - Koessler, Angela A1 - Kuhn, Sabine A1 - Boeck, Markus A1 - Kobsar, Anna T1 - Role of Purinergic Receptor Expression and Function for Reduced Responsiveness to Adenosine Diphosphate in Washed Human Platelets JF - PLoS One N2 - Background Washing of platelets is an important procedure commonly used for experimental studies, e.g. in cardiovascular research. As a known phenomenon, responsiveness to adenosine diphosphate (ADP) is reduced in washed platelets, although underlying molecular mechanisms—potentially interfering with experimental results—have not been thoroughly studied. Objectives Since ADP mediates its effects via three purinergic receptors P2Y1, P2X1 and P2Y12, their surface expression and function were investigated in washed platelets and, for comparison, in platelet-rich-plasma (PRP) at different time points for up to 2 hours after preparation. Results In contrast to PRP, flow cytometric analysis of surface expression in washed platelets revealed an increase of all receptors during the first 60 minutes after preparation followed by a significant reduction, which points to an initial preactivation of platelets and consecutive degeneration. The activity of the P2X1 receptor (measured by selectively induced calcium flux) was substantially maintained in both PRP and washed platelets. P2Y12 function (determined by flow cytometry as platelet reactivity index) was partially reduced after platelet washing compared to PRP, but remained stable in course of ongoing storage. However, the function of the P2Y1 receptor (measured by selectively induced calcium flux) continuously declined after preparation of washed platelets. Conclusion In conclusion, decreasing ADP responsiveness in washed platelets is particularly caused by impaired activity of the P2Y1 receptor associated with disturbed calcium regulation, which has to be considered in the design of experimental studies addressing ADP mediated platelet function. KW - platelets KW - flow cytometry KW - adenosine KW - statistical data KW - platelet activation KW - platelet aggregation KW - phosphorylation KW - blood plasma Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146400 VL - 11 IS - 1 ER - TY - JOUR A1 - Bankoglu, Ezgi Eyluel A1 - Tschopp, Oliver A1 - Schmitt, Johannes A1 - Burkard, Philipp A1 - Jahn, Daniel A1 - Geier, Andreas A1 - Stopper, Helga T1 - Role of PTEN in Oxidative Stress and DNA Damage in the Liver of Whole-Body Pten Haplodeficient Mice JF - PLoS One N2 - Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction. In the molecular events from insulin receptor binding to genomic damage, some signaling steps have been identified, pointing at the PI3K/AKT pathway. For further elucidation Phosphatase and Tensin homolog (Pten), a tumour suppressor phosphatase that plays a role in insulin signaling by negative regulation of PI3K/AKT and its downstream targets, was investigated here. Dihydroethidium (DHE) staining was used to detect ROS formation in immortalized human hepatocytes. Comet assay and micronucleus test were performed to investigate genomic damage in vitro. In liver samples, DHE staining and western blot detection of HSP70 and HO-1 were performed to evaluate oxidative stress response. DNA double strand breaks (DSBs) were detected by immunohistostaining. Inhibition of PTEN with the pharmacologic inhibitor VO-OHpic resulted in increased ROS production and genomic damage in a liver cell line. Knockdown of Pten in a mouse model yielded increased oxidative stress levels, detected by ROS levels and expression of the two stress-proteins HSP70 and HO-1 and elevated genomic damage in the liver, which was significant in mice fed with a high fat diet. We conclude that PTEN is involved in oxidative stress and genomic damage induction in vitro and that this may also explain the in vivo observations. This further supports the hypothesis that the PI3K/AKT pathway is responsible for damaging effects of high levels of insulin. KW - insulin KW - mouse models DNA damage KW - oxidative stress KW - mammalian genomics KW - fatty liver KW - micronuclei KW - insulin signaling Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146970 VL - 11 IS - 11 ER - 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 - 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 - Biogenic KW - volatile KW - organic KW - compounds Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198547 VL - 16 ER - TY - JOUR A1 - Arimany-Nardi, Cristina A1 - Minuesa, Gerard A1 - Pastor-Anglada, Marçal A1 - Keller, Thorsten A1 - Erkizia, Itziar A1 - Koepsell, Hermann A1 - Martinez-Picado, Javier T1 - Role of Human Organic Cation Transporter 1 (hOCT1) Polymorphisms in Lamivudine (3TC) Uptake and Drug-Drug Interactions JF - Frontiers in Pharmacology N2 - Lamivudine (3TC), a drug used in the treatment of HIV infection, needs to cross the plasma membrane to exert its therapeutic action. Human Organic cation transporter 1 (hOCT1), encoded by the SLC22A1 gene, is the transporter responsible for its uptake into target cells. As SLC22A1 is a highly polymorphic gene, the aim of this study was to determine how SNPs in the OCT1-encoding gene affected 3TC internalization and its interaction with other co-administered drugs. HEK293 cells stably transfected with either the wild type form or the polymorphic variants of hOCT1 were used to perform kinetic and drug-drug interaction studies. Protein co-immunoprecipitation was used to assess the impact of selected polymorphic cysteines on the oligomerization of the transporter. Results showed that 3TC transport efficiency was reduced in all polymorphic variants tested (R61C, C88R, S189L, M420del, and G465R). This was not caused by lack of oligomerization in case of variants located at the transporter extracellular loop (R61C and C88R). Drug-drug interaction measurements showed that co-administered drugs [abacavir (ABC), zidovudine (AZT), emtricitabine (FTC), tenofovir diproxil fumarate (TDF), efavirenz (EFV) and raltegravir (RAL)], differently inhibited 3TC uptake depending upon the polymorphic variant analyzed. These data highlight the need for accurate analysis of drug transporter polymorphic variants of clinical relevance, because polymorphisms can impact on substrate (3TC) translocation but even more importantly they can differentially affect drug-drug interactions at the transporter level. KW - hOCT1 KW - pharmacogenetics KW - lamivudine KW - HIV infection KW - therapy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165236 VL - 7 IS - 175 ER - TY - THES A1 - Busch, Stephan T1 - Robust, Flexible and Efficient Design for Miniature Satellite Systems T1 - Moderne Kleinstsatelliten - Zwischen Robustheit, Flexibilität und Effizienz N2 - Small satellites contribute significantly in the rapidly evolving innovation in space engineering, in particular in distributed space systems for global Earth observation and communication services. Significant mass reduction by miniaturization, increased utilization of commercial high-tech components, and in particular standardization are the key drivers for modern miniature space technology. This thesis addresses key fields in research and development on miniature satellite technology regarding efficiency, flexibility, and robustness. Here, these challenges are addressed by the University of Wuerzburg’s advanced pico-satellite bus, realizing a generic modular satellite architecture and standardized interfaces for all subsystems. The modular platform ensures reusability, scalability, and increased testability due to its flexible subsystem interface which allows efficient and compact integration of the entire satellite in a plug-and-play manner. Beside systematic design for testability, a high degree of operational robustness is achieved by the consequent implementation of redundancy of crucial subsystems. This is combined with efficient fault detection, isolation and recovery mechanisms. Thus, the UWE-3 platform, and in particular the on-board data handling system and the electrical power system, offers one of the most efficient pico-satellite architectures launched in recent years and provides a solid basis for future extensions. The in-orbit performance results of the pico-satellite UWE-3 are presented and summarize successful operations since its launch in 2013. Several software extensions and adaptations have been uploaded to UWE-3 increasing its capabilities. Thus, a very flexible platform for in-orbit software experiments and for evaluations of innovative concepts was provided and tested. N2 - Miniaturisierte Satellitensysteme übernehmen zunehmend eine entscheidende Rolle in der fortschreitenden Globalisierung und Demokratisierung der Raumfahrt. Großes Innovationspotential und neue Kommerzialisierungschancen verspricht der effektive Einsatz von Kleinstsatelliten in zukünftigen fraktionierten Missionen für Erdbeobachtungs- und Kommunikationsanwendungen. Basierend auf vielen kleinen kooperierenden Systemen können diese Systeme zukünftig große multifunktionale Satelliten ergänzen oder ersetzen. Die Herausforderung bei der Entwicklung miniaturisierter Satellitensysteme ist die Gratwanderung zwischen der im Rahmen der Miniaturisierung notwendigen Effizienz, der für die Erfüllung der Mission geforderten Zuverlässigkeit und der wünschenswerten Wiederverwendbarkeit und Erweiterbarkeit zur Realisierung agiler Kleinstsatellitenserien. Diese Arbeit adressiert verschiedene Aspekte für den optimalen Entwurf robuster, flexibler und effizienter Kleinstsatelliten am Beispiel des UWE Pico-Satelliten Bus der Universität Würzburg. Mit dem Ziel der Entwicklung einer soliden Basisplattform für zukünftige Kleinstsatelliten-Formationen wurden entsprechende Designansätze im Rahmen des UWE-3 Projektes in einem integralen Designansatz konsistent umgesetzt. Neben der Entwicklung von effizienten Redundanzkonzepten mit minimalem Overhead für den optimalen Betrieb auf Ressourcen-limitierten Kleinstsatelliten wurde ein modularer Satellitenbus entworfen, der als eine robuste und erweiterbare Basis für zukünftige Missionen dienen soll. Damit realisiert UWE-3 eine der effizientesten Kleinstsatelliten-Architekturen die in den letzten Jahren in den Orbit gebracht wurde. Dargestellte Missionsergebnisse fassen den erfolgreichen Betrieb des Satelliten seit seinem Launch in Jahr 2013 zusammen. T3 - Forschungsberichte in der Robotik = Research Notes in Robotics - 11 KW - Kleinsatellit KW - Fehlertoleranz KW - Miniaturisierung KW - Modularität KW - Picosatellite KW - Satellit Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136523 SN - 978-3-945459-10-2 ER - TY - JOUR A1 - Hellenbrand, Wiebke A1 - Claus, Heike A1 - Schink, Susanne A1 - Marcus, Ulrich A1 - Wichmann, Ole A1 - Vogel, Ulrich T1 - Risk of Invasive Meningococcal Disease in Men Who Have Sex with Men: Lessons Learned from an Outbreak in Germany, 2012-2013 JF - PLoS ONE N2 - Background We undertook investigations in response to an invasive meningococcal disease (IMD) outbreak in men who have sex with men (MSM) in Berlin 2012–2013 to better understand meningococcal transmission and IMD risk in MSM. Methods We retrospectively searched for further IMD cases in MSM in Germany through local health departments and undertook exploratory interviews. We performed antigen sequence typing, characterized fHbp and aniA genes of strains with the outbreak finetype and reviewed epidemiologically or spatiotemporally linked cases from 2002–2014. Results Among the 148 IMD-cases notified from 01.01.2012–30.09.2013 in 18–59 year-old men we identified 13 MSM in 6 federal states: 11 serogroup C (MenC, all finetype C:P1.5–1,10–8:F3-6), 2 MenB. Interviews with 7 MSM revealed frequent meeting of multiple partners online or via mobile apps and illicit drug use as potential risk factors. MenC incidence was 13-fold higher in MSM than non-MSM. MenC isolates from 9/11 MSM had a novel fHbp allele 766. All C:P1.5–1,10–8:F3-6 strains from MSM versus 16/23 from non-MSM had intact aniA genes (p = 0.04). Although definitive evidence for transmission among MSM in epidemiological or spatiotemporal clusters in 2002–2014 was lacking, clusters were more frequent in men aged 20–49 years. Molecular analysis of C:P1.5–1,10–8:F3-6 strains revealed cases with intact aniA since 2007, mainly associated with fHbp361, fHbp766 and fHbp813, all involving one or more MSM. Conclusions MenC incidence was elevated in MSM during the study period. Multiple casual sexual contacts and illicit drug use were common in affected MSM. In all strains from MSM we detected an intact aniA gene coding for a nitrite reductase, which permits survival in microanaerobic environments and could play a role in meningococcal transmission in MSM through urogenital colonization. Furthermore, meningococcal transmission among MSM may be sustained over large areas and thus require modified spatiotemporal scanning algorithms for timely detection and control. KW - invasive meningococcal disease KW - men who have sex with men KW - Germany Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166842 VL - 11 IS - 8 ER - TY - JOUR A1 - Senthilan, Pingkalai R. A1 - Helfrich-Förster, Charlotte T1 - Rhodopsin 7-The unusual Rhodopsin in Drosophila JF - PeerJ N2 - Rhodopsins are the major photopigments in the fruit fly Drosophila melanogaster. Drosophila express six well-characterized Rhodopsins (Rh1–Rh6) with distinct absorption maxima and expression pattern. In 2000, when the Drosophila genome was published, a novel Rhodopsin gene was discovered: Rhodopsin 7 (Rh7). Rh7 is highly conserved among the Drosophila genus and is also found in other arthropods. Phylogenetic trees based on protein sequences suggest that the seven Drosophila Rhodopsins cluster in three different groups. While Rh1, Rh2 and Rh6 form a “vertebrate-melanopsin-type”–cluster, and Rh3, Rh4 and Rh5 form an “insect-type”-Rhodopsin cluster, Rh7 seem to form its own cluster. Although Rh7 has nearly all important features of a functional Rhodopsin, it differs from other Rhodopsins in its genomic and structural properties, suggesting it might have an overall different role than other known Rhodopsins. KW - vision KW - Drosophila KW - Opsins KW - Rhodopsins KW - phototransduction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177998 VL - 4 ER - TY - JOUR A1 - Hassouna, I. A1 - Ott, C. A1 - Wüstefeld, L. A1 - Offen, N. A1 - Neher, R. A. A1 - Mitkovski, M. A1 - Winkler, D. A1 - Sperling, S. A1 - Fries, L. A1 - Goebbels, S. A1 - Vreja, I. C. A1 - Hagemeyer, N. A1 - Dittrich, M. A1 - Rossetti, M. F. A1 - Kröhnert, K. A1 - Hannke, K. A1 - Boretius, S. A1 - Zeug, A. A1 - Höschen, C. A1 - Dandekar, T. A1 - Dere, E. A1 - Neher, E. A1 - Rizzoli, S. O. A1 - Nave, K.-A. A1 - Sirén, A.-L. A1 - Ehrenreich, H. T1 - Revisiting adult neurogenesis and the role of erythropoietin for neuronal and oligodendroglial differentiation in the hippocampus JF - Molecular Psychiatry N2 - Recombinant human erythropoietin (EPO) improves cognitive performance in neuropsychiatric diseases ranging from schizophrenia and multiple sclerosis to major depression and bipolar disease. This consistent EPO effect on cognition is independent of its role in hematopoiesis. The cellular mechanisms of action in brain, however, have remained unclear. Here we studied healthy young mice and observed that 3-week EPO administration was associated with an increased number of pyramidal neurons and oligodendrocytes in the hippocampus of similar to 20%. Under constant cognitive challenge, neuron numbers remained elevated until >6 months of age. Surprisingly, this increase occurred in absence of altered cell proliferation or apoptosis. After feeding a \(^{15}\)N-leucine diet, we used nanoscopic secondary ion mass spectrometry, and found that in EPO-treated mice, an equivalent number of neurons was defined by elevated \(^{15}\)N-leucine incorporation. In EPO-treated NG2-Cre-ERT2 mice, we confirmed enhanced differentiation of preexisting oligodendrocyte precursors in the absence of elevated DNA synthesis. A corresponding analysis of the neuronal lineage awaits the identification of suitable neuronal markers. In cultured neurospheres, EPO reduced Sox9 and stimulated miR124, associated with advanced neuronal differentiation. We are discussing a resulting working model in which EPO drives the differentiation of non-dividing precursors in both (NG2+) oligodendroglial and neuronal lineages. As endogenous EPO expression is induced by brain injury, such a mechanism of adult neurogenesis may be relevant for central nervous system regeneration. KW - neural stem-cells KW - recombinat-human-erythropoietin KW - cognitive functions KW - pyramidal neurons KW - nervous-sytem KW - brain-injury KW - mouse-brain KW - progenitors KW - mice KW - memory Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186669 VL - 21 IS - 12 ER - TY - JOUR A1 - Ritter, Cathrin A1 - Fan, Kaiji A1 - Paulson, Kelly G. A1 - Nghiem, Paul A1 - Schrama, David A1 - Becker, Jürgen C. T1 - Reversal of epigenetic silencing of MHC class I chain-related protein A and B improves immune recognition of Merkel cell carcinoma JF - Scientific Reports N2 - Merkel cell carcinoma (MCC) is a virally associated cancer characterized by its aggressive behavior and strong immunogenicity. Both viral infection and malignant transformation induce expression of MHC class I chain-related protein (MIC) A and B, which signal stress to cells of the immune system via Natural Killer group 2D (NKG2D) resulting in elimination of target cells. However, despite transformation and the continued presence of virally-encoded proteins, MICs are only expressed in a minority of MCC tumors in situ and are completely absent on MCC cell lines in vitro. This lack of MIC expression was due to epigenetic silencing via MIC promoter hypo-acetylation; indeed, MIC expression was re-induced by pharmacological inhibition of histone deacetylases (HDACs) both in vitro and in vivo. This re-induction of MICs rendered MCC cells more sensitive to immune-mediated lysis. Thus, epigenetic silencing of MICs is an important immune escape mechanism of MCCs. KW - epigenetic silencing KW - Merkel cell carcinoma KW - MHC class I chain-related protein KW - skin cancer Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167992 IS - 21678 ET - 6 ER - TY - THES A1 - Wiebusch, Dennis T1 - Reusability for Intelligent Realtime Interactive Systems T1 - Wiederverwendbarkeit für Intelligente Echtzeit-interaktive Systeme N2 - Software frameworks for Realtime Interactive Systems (RIS), e.g., in the areas of Virtual, Augmented, and Mixed Reality (VR, AR, and MR) or computer games, facilitate a multitude of functionalities by coupling diverse software modules. In this context, no uniform methodology for coupling these modules does exist; instead various purpose-built solutions have been proposed. As a consequence, important software qualities, such as maintainability, reusability, and adaptability, are impeded. Many modern systems provide additional support for the integration of Artificial Intelligence (AI) methods to create so called intelligent virtual environments. These methods exacerbate the above-mentioned problem of coupling software modules in the thus created Intelligent Realtime Interactive Systems (IRIS) even more. This, on the one hand, is due to the commonly applied specialized data structures and asynchronous execution schemes, and the requirement for high consistency regarding content-wise coupled but functionally decoupled forms of data representation on the other. This work proposes an approach to decoupling software modules in IRIS, which is based on the abstraction of architecture elements using a semantic Knowledge Representation Layer (KRL). The layer facilitates decoupling the required modules, provides a means for ensuring interface compatibility and consistency, and in the end constitutes an interface for symbolic AI methods. N2 - Software Frameworks zur Entwicklung Echtzeit-interaktiver Systeme (engl. Realtime Interactive Systems, RIS), z.B. mit Anwendungen in der Virtual, Augmented und Mixed Reality (VR, AR und MR) sowie in Computerspielen, integrieren vielfältige Funktionalitäten durch die Kopplung verschiedener Softwaremodule. Eine einheitliche Methodik einer Kopplung in diesen Systemen besteht dabei nicht, stattdessen existieren mannigfaltige individuelle Lösungen. Als Resultat sinken wichtige Softwarequalitätsfaktoren wie Wartbarkeit, Wiederverwendbarkeit und Anpassbarkeit. Viele moderne Systeme setzen zusätzlich unterschiedliche Methoden der Künstlichen Intelligenz (KI) ein, um so intelligente virtuelle Umgebungen zu generieren. Diese KI-Methoden verschärfen in solchen Intelligenten Echtzeit-interaktiven Systemen (engl. Intelligent Realtime Interactive Systems, IRIS) das eingangs genannte Kopplungsproblem signifikant durch ihre spezialisierten Datenstrukturen und häufig asynchronen Prozessflüssen bei gleichzeitig hohen Konsistenzanforderungen bzgl. inhaltlich assoziierter, aber funktional entkoppelter Datenrepräsentationen in anderen Modulen. Die vorliegende Arbeit beschreibt einen Lösungsansatz für das Entkopplungsproblem mittels Abstraktion maßgeblicher Softwarearchitekturelemente basierend auf einer erweiterbaren semantischen Wissensrepräsentationsschicht. Diese semantische Abstraktionsschicht erlaubt die Entkopplung benötigter Module, ermöglicht eine automatische Überprüfung von Schnittstellenkompatibiltät und Konsistenz und stellt darüber hinaus eine generische Schnittstelle zu symbolischen KI-Methoden bereit. KW - Virtuelle Realität KW - Ontologie KW - Wissensrepräsentation KW - Echtzeitsystem KW - Framework KW - Intelligent Realtime Interactive System KW - Virtual Reality KW - Knowledge Representation Layer KW - Intelligent Virtual Environment KW - Semantic Entity Model KW - Erweiterte Realität KW - Softwarewiederverwendung KW - Modul KW - Software Engineering Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121869 SN - 978-3-95826-040-5 (print) SN - 978-3-95826-041-2 (online) N1 - Parallel erschienen als Druckausg. in Würzburg University Press, ISBN 978-3-95826-040-5, 34,90 EUR PB - Würzburg University Press CY - Würzburg ER - TY - JOUR A1 - Adolfi, Mateus C. A1 - Herpin, Amaury A1 - Regensburger, Martina A1 - Sacquegno, Jacopo A1 - Waxman, Joshua S. A1 - Schartl, Manfred T1 - Retinoic acid and meiosis induction in adult versus embryonic gonads of medaka JF - Scientific Reports N2 - In vertebrates, one of the first recognizable sex differences in embryos is the onset of meiosis, known to be regulated by retinoic acid (RA) in mammals. We investigated in medaka a possible meiotic function of RA during the embryonic sex determination (SD) period and in mature gonads. We found RA mediated transcriptional activation in germ cells of both sexes much earlier than the SD stage, however, no such activity during the critical stages of SD. In adults, expression of the RA metabolizing enzymes indicates sexually dimorphic RA levels. In testis, RA acts directly in Sertoli, Leydig and pre-meiotic germ cells. In ovaries, RA transcriptional activity is highest in meiotic oocytes. Our results show that RA plays an important role in meiosis induction and gametogenesis in adult medaka but contrary to common expectations, not for initiating the first meiosis in female germ cells at the SD stage. KW - developmental biology KW - molecular biology Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147843 VL - 6 ER - TY - JOUR A1 - Peperkorn, Henrik M. A1 - Diemer, Julia E. A1 - Alpers, Georg W. A1 - Mühlberger, Andreas T1 - Representation of Patients' Hand Modulates Fear Reactions of Patients with Spider Phobia in Virtual Reality JF - frontiers in Psychology N2 - Embodiment (i.e., the involvement of a bodily representation) is thought to be relevant in emotional experiences. Virtual reality (VR) is a capable means of activating phobic fear in patients. The representation of the patient’s body (e.g., the right hand) in VR enhances immersion and increases presence, but its effect on phobic fear is still unknown. We analyzed the influence of the presentation of the participant’s hand in VR on presence and fear responses in 32 women with spider phobia and 32 matched controls. Participants sat in front of a table with an acrylic glass container within reaching distance. During the experiment this setup was concealed by a head-mounted display (HMD). The VR scenario presented via HMD showed the same setup, i.e., a table with an acrylic glass container. Participants were randomly assigned to one of two experimental groups. In one group, fear responses were triggered by fear-relevant visual input in VR (virtual spider in the virtual acrylic glass container), while information about a real but unseen neutral control animal (living snake in the acrylic glass container) was given. The second group received fear-relevant information of the real but unseen situation (living spider in the acrylic glass container), but visual input was kept neutral VR (virtual snake in the virtual acrylic glass container). Participants were instructed to touch the acrylic glass container with their right hand in 20 consecutive trials. Visibility of the hand was varied randomly in a within-subjects design. We found for all participants that visibility of the participant’s hand increased presence independently of the fear trigger. However, in patients, the influence of the virtual hand on fear depended on the fear trigger. When fear was triggered perceptually, i.e., by a virtual spider, the virtual hand increased fear. When fear was triggered by information about a real spider, the virtual hand had no effect on fear. Our results shed light on the significance of different fear triggers (visual, conceptual) in interaction with body representations. KW - virtual reality KW - presence KW - immersion KW - perception KW - fear KW - specific phobia Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165307 VL - 7 IS - 268 ER - TY - JOUR A1 - Ehnert, Ina A1 - Parsa, Sepideh A1 - Roper, Ian A1 - Wagner, Marcus A1 - Muller-Camen, Michael T1 - Reporting on sustainability and HRM: a comparative study of sustainability reporting practices by the world's largest companies JF - International Journal of Human Resource Management N2 - As a response to the growing public awareness on the importance of organisational contributions to sustainable development, there is an increased incentive for corporations to report on their sustainability activities. In parallel with this has been the development of Sustainable HRM' which embraces a growing body of practitioner and academic literature connecting the notions of corporate sustainability to HRM. The aim of this article is to analyse corporate sustainability reporting amongst the world's largest companies and to assess the HRM aspects of sustainability within these reports in comparison to environmental aspects of sustainable management and whether organisational attributes - principally country-of-origin - influences the reporting of such practices. A focus in this article is the extent to which the reporting of various aspects of sustainability may reflect dominant models of corporate governance in the country in which a company is headquartered. The findings suggest, first and against expectations, that the overall disclosure on HRM-related performance is not lower than that on environmental performance. Second, companies report more on their internal workforce compared to their external workforce. Finally, international differences, in particular those between companies headquartered in liberal market economies and coordinated market economies, are not as apparent as expected. KW - Human Resource Management KW - comparative HRM KW - global reporting initiative KW - sustainability reporting KW - Sustainable HRM Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191141 VL - 27 IS - 1 ER - TY - JOUR A1 - Korn, Thomas A1 - Kleinschnitz, Christoph A1 - Magnus, Tim A1 - Meuth, Sven G. A1 - Linker, Ralf A. T1 - Report on the 7th scientific meeting of the Association for the Advancement of Young Academics in Neurology (NEUROWIND e.V.) held in Motzen, Germany, October 30–November 1, 2015 JF - Experimental and Translational Stroke Medicine N2 - From October 30–November 1, 2015, the 7th NEUROWIND e.V. meeting was held in Motzen, Brandenburg, Germany. Seventy doctoral students and postdocs from over 25 different groups working in German and Swiss University Hospitals or Research Institutes attended the meeting to discuss their latest experiments and findings in the fields of neuroimmunology, neurodegeneration and neurovascular research. This meeting report summarizes the many diverse presentations and the new preclinical to clinical neurology research data that were shared by the participants at the meeting. KW - NEUROWIND Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146595 VL - 8 IS - 3 ER - TY - JOUR A1 - Maass, Anne A1 - Düzel, Sandra A1 - Brigadski, Tanja A1 - Goerke, Monique A1 - Becke, Andreas A1 - Sobieray, Uwe A1 - Neumann, Katja A1 - Lövdén, Martin A1 - Lindenberger, Ulman A1 - Bäckman, Lars A1 - Braun-Dullaeus, Rüdiger A1 - Ahrens, Dörte A1 - Heinze, Hans-Jochen A1 - Müller, Notger G. A1 - Lessmann, Volkmar A1 - Sendtner, Michael A1 - Düzel, Emrah T1 - Relationships of peripheral IGF-1, VEGF and BDNF levels to exercise-related changes in memory, hippocampal perfusion and volumes in older adults JF - NeuroImage N2 - Animal models point towards a key role of brain-derived neurotrophic factor (BDNF), insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in mediating exercise-induced structural and functional changes in the hippocampus. Recently, also platelet derived growth factor-C (PDGF-C) has been shown to promote blood vessel growth and neuronal survival. Moreover, reductions of these neurotrophic and angiogenic factors in old age have been related to hippocampal atrophy, decreased vascularization and cognitive decline. In a 3-month aerobic exercise study, forty healthy older humans (60 to 77 years) were pseudo-randomly assigned to either an aerobic exercise group (indoor treadmill, n = 21) or to a control group (indoor progressive-muscle relaxation/stretching, n = 19). As reported recently, we found evidence for fitness-related perfusion changes of the aged human hippocampus that were closely linked to changes in episodic memory function. Here, we test whether peripheral levels of BDNF, IGF-I, VEGF or PDGF-C are related to changes in hippocampal blood flow, volume and memory performance. Growth factor levels were not significantly affected by exercise, and their changes were not related to changes in fitness or perfusion. However, changes in IGF-I levels were positively correlated with hippocampal volume changes (derived by manual volumetry and voxel-based morphometry) and late verbal recall performance, a relationship that seemed to be independent of fitness, perfusion or their changes over time. These preliminary findings link IGF-I levels to hippocampal volume changes and putatively hippocampus-dependent memory changes that seem to occur over time independently of exercise. We discuss methodological shortcomings of our study and potential differences in the temporal dynamics of how IGF-1, VEGF and BDNF may be affected by exercise and to what extent these differences may have led to the negative findings reported here. KW - Exercise KW - Neurotrophic factors KW - Hippocampus KW - Vascular plasticity KW - Aging Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189219 VL - 131 ER - TY - JOUR A1 - Sabel, Magnus A1 - Fleischhack, Gudrun A1 - Tippelt, Stephan A1 - Gustafsson, Göran A1 - Doz, François A1 - Kortmann, Rolf A1 - Massimino, Maura A1 - Navajas, Aurora A1 - von Hoff, Katja A1 - Rutkowski, Stefan A1 - Warmuth-Metz, Monika A1 - Clifford, Steven C. A1 - Pietsch, Torsten A1 - Pizer, Barry A1 - Linnering, Birgitta T1 - Relapse patterns and outcome after relapse in standard risk medulloblastoma: a report from the HIT-SIOP-PNET4 study JF - Journal of Neurooncology N2 - The HIT-SIOP-PNET4 randomised trial for standard risk medulloblastoma (MB) (2001-2006) included 338 patients and compared hyperfractionated and conventional radiotherapy. We here report the long-term outcome after a median follow up of 7.8 years, including detailed information on relapse and the treatment of relapse. Data were extracted from the HIT Group Relapsed MB database and by way of a specific case report form. The event-free and overall (OS) survival at 10 years were 76 +/- 2 % and 78 +/- 2 % respectively with no significant difference between the treatment arms. Seventy-two relapses and three second malignant neoplasms were reported. Thirteen relapses (18 %) were isolated local relapses in the posterior fossa (PF) and 59 (82 %) were craniospinal, metastatic relapses (isolated or multiple) with or without concurrent PF disease. Isolated PF relapse vs all other relapses occurred at mean/median of 38/35 and 28/26 months respectively (p = 0.24). Late relapse, i.e. > 5 years from diagnosis, occurred in six patients (8 %). Relapse treatment consisted of combinations of surgery (25 %), focal radiotherapy (RT 22 %), high dose chemotherapy with stem cell rescue (HDSCR 21 %) and conventional chemotherapy (90 %). OS at 5 years after relapse was 6.0 +/- 4 %. In multivariate analysis; isolated relapse in PF, and surgery were significantly associated with prolonged survival whereas RT and HDSCR were not. Survival after relapse was not related to biological factors and was very poor despite several patients receiving intensive treatments. Exploration of new drugs is warranted, preferably based on tumour biology from biopsy of the relapsed tumour. KW - High-dose chemotherapy KW - Childhood medulloblastoma KW - Adolescents KW - Primitive neuroectodermal KW - Tumors KW - Recurrent medulloblastoma KW - Childrens-cancer KW - Phase-II KW - Trial KW - Therapy KW - Reirradiation KW - Medulloblastoma KW - Relapse KW - Survival KW - Treatment KW - Clinical trial KW - Chemotherapy KW - Radiotherapy KW - Paediatric KW - Secondary tumours Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187498 VL - 129 IS - 3 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 - JOUR A1 - Endres, Marcel A1 - Kneitz, Susanne A1 - Orth, Martin F. A1 - Perera, Ruwan K. A1 - Zernecke, Alma A1 - Butt, Elke T1 - Regulation of matrix metalloproteinases (MMPs) expression and secretion in MDA-MB-231 breast cancer cells by LIM and SH3 protein 1 (LASP1) JF - Oncotarget N2 - The process of tumor invasion requires degradation of extracellular matrix by proteolytic enzymes. Cancer cells form protrusive invadopodia, which produce and release matrix metalloproteinases (MMPs) to degrade the basement membrane thereby enabling metastasis. We investigated the effect of LASP1, a newly identified protein in invadopodia, on expression, secretion and activation of MMPs in invasive breast tumor cell lines. By analyzing microarray data of in-house generated control and LASP1-depleted MDA-MB-231 breast cancer cells, we observed downregulation of MMP1, -3 and -9 upon LASP1 depletion. This was confirmed by Western blot analysis. Conversely, rescue experiments restored in part MMP expression and secretion. The regulatory effect of LASP1 on MMP expression was also observed in BT-20 breast cancer cells as well as in prostate and bladder cancer cell lines. In line with bioinformatic FunRich analysis of our data, which mapped a high regulation of transcription factors by LASP1, public microarray data analysis detected a correlation between high LASP1 expression and enhanced c-Fos levels, a protein that is part of the transcription factor AP-1 and known to regulate MMP expression. Compatibly, in luciferase reporter assays, AP-1 showed a decreased transcriptional activity after LASP1 knockdown. Zymography assays and Western blot analysis revealed an additional promotion of MMP secretion into the extracellular matrix by LASP1, thus, most likely, altering the microenvironment during cancer progression. The newly identified role of LASP1 in regulating matrix degradation by affecting MMP transcription and secretion elucidated the migratory potential of LASP1 overexpressing aggressive tumor cells in earlier studies. KW - LASP1 KW - c-Fos KW - extracellular matrix KW - AP-1 KW - matrix metalloproteinases KW - breast cancer Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176920 VL - 7 IS - 39 ER - TY - JOUR A1 - Schlagenhauf, Ulrich A1 - Jakob, Lena A1 - Eigenthaler, Martin A1 - Segerer, Sabine A1 - Jockel-Schneider, Yvonne A1 - Rehn, Monika T1 - Regular consumption of Lactobacillus reuteri-containing lozenges reduces pregnancy gingivitis: an RCT JF - Journal of Clinical Periodontology N2 - Aim: This randomized controlled trial assessed the impact of Lactobacillus reuteri on pregnancy gingivitis in healthy women. Materials and Methods: Forty-five healthy women (24 test/21 placebo) with pregnancy gingivitis in the third trimester of pregnancy were enrolled. At baseline Gingival Index (GI) and Plaque Index (PlI) were assessed at the Ramfjord teeth and venous blood taken for TNF-alpha analysis. Subsequently participants were randomly provided with lozenges to be consumed 2 9 daily until birth (approx. 7 weeks) containing >= 10(8) CFU L. reuteri ATCC PTA 5289 and >= 10(8) CFU L. reuteri DSM 17938 (test) or being devoid of L. reuteri (placebo). Within 2 days after birth recording of GI, PlI and blood sampling were repeated. Results: At baseline, mean GI and mean PlI did not differ significantly between both groups. In the test group mean TNF-alpha serum level was significantly (p < 0.02) lower than in the placebo group. At reevaluation, mean GI and mean PlI of the test group were both significantly (p < 0.0001) lower than in the placebo group. Mean TNF-alpha serum level did no longer differ significantly between the groups. Conclusions: The consumption of L. reuteri lozenges may be a useful adjunct in the control of pregnancy gingivitis. KW - chronic periodontitis KW - probiotic lozenges KW - subgingival KW - bacteria KW - postpartum KW - microbiota KW - disease KW - L. reuteri KW - plaque KW - pregnancy KW - pregnancy gingivitis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186783 VL - 43 IS - 11 ER - TY - JOUR A1 - Song, Ning-Ning A1 - Jia, Yun-Fang A1 - Zhang, Lei A1 - Zhang, Qiong A1 - Huang, Ying A1 - Liu, Xiao-Zhen A1 - Hu, Ling A1 - Lan, Wei A1 - Chen, Ling A1 - Lesch, Klaus-Peter A1 - Chen, Xiaoyan A1 - Xu, Lin A1 - Ding, Yu-Qiang T1 - Reducing central serotonin in adulthood promotes hippocampal neurogenesis JF - Scientific Reports N2 - Chronic administration of selective serotonin reuptake inhibitors (SSRIs), which up-regulates central serotonin (5-HT) system function, enhances adult hippocampal neurogenesis. However, the relationship between central 5-HT system and adult neurogenesis has not fully been understood. Here, we report that lowering 5-HT level in adulthood is also able to enhance adult hippocampal neurogenesis. We used tamoxifen (TM)-induced Cre in Pet1-CreER\(^{T2}\) mice to either deplete central serotonergic (5-HTergic) neurons or inactivate 5-HT synthesis in adulthood and explore the role of central 5-HT in adult hippocampal neurogenesis. A dramatic increase in hippocampal neurogenesis is present in these two central 5-HT-deficient mice and it is largely prevented by administration of agonist for 5-HTR2c receptor. In addition, the survival of new-born neurons in the hippocampus is enhanced. Furthermore, the adult 5-HT-deficient mice showed reduced depression-like behaviors but enhanced contextual fear memory. These findings demonstrate that lowering central 5-HT function in adulthood can also enhance adult hippocampal neurogenesis, thus revealing a new aspect of central 5-HT in regulating adult neurogenesis. KW - serotonin KW - SSRI KW - hippocampal neurogenesis KW - adulthood Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168004 VL - 6 IS - 20338 ER - TY - JOUR A1 - Dreschers, Stephan A1 - Saupp, Peter A1 - Hornef, Mathias A1 - Prehn, Andrea A1 - Platen, Christopher A1 - Morschhäuser, Joachim A1 - Orlikowsky, Thorsten W. T1 - Reduced PICD in Monocytes Mounts Altered Neonate Immune Response to Candida albicans JF - PLoS ONE N2 - Background Invasive fungal infections with Candida albicans (C. albicans) occur frequently in extremely low birthweight (ELBW) infants and are associated with poor outcome. Phagocytosis of C.albicans initializes apoptosis in monocytes (phagocytosis induced cell death, PICD). PICD is reduced in neonatal cord blood monocytes (CBMO). Hypothesis Phagocytosis of C. albicans causes PICD which differs between neonatal monocytes (CBMO) and adult peripheral blood monocytes (PBMO) due to lower stimulation of TLR-mediated immune responses. Methods The ability to phagocytose C. albicans, expression of TLRs, the induction of apoptosis (assessment of sub-G1 and nick-strand breaks) were analyzed by FACS. TLR signalling was induced by agonists such as lipopolysaccharide (LPS), Pam3Cys, FSL-1 and Zymosan and blocked (neutralizing TLR2 antibodies and MYD88 inhibitor). Results Phagocytic indices of PBMO and CBMO were similar. Following stimulation with agonists and C. albicans induced up-regulation of TLR2 and consecutive phosphorylation of MAP kinase P38 and expression of TNF-α, which were stronger on PBMO compared to CBMO (p < 0.005). Downstream, TLR2 signalling initiated caspase-3-dependent PICD which was found reduced in CBMO (p < 0.05 vs PBMO). Conclusion Our data suggest direct involvement of TLR2-signalling in C. albicans-induced PICD in monocytes and an alteration of this pathway in CBMO. KW - Candida albicans KW - monocytes KW - immune response KW - PICD Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166778 VL - 11 IS - 11 ER - TY - JOUR A1 - Konte, Tilen A1 - Terpitz, Ulrich A1 - Plemenitaš, Ana T1 - Reconstruction of the High-Osmolarity Glycerol (HOG) Signaling Pathway from the Halophilic Fungus Wallemia ichthyophaga in Saccharomyces cerevisiae JF - Frontiers in Microbiology N2 - The basidiomycetous fungus Wallemia ichthyophaga grows between 1.7 and 5.1 M NaCl and is the most halophilic eukaryote described to date. Like other fungi, W. ichthyophaga detects changes in environmental salinity mainly by the evolutionarily conserved high-osmolarity glycerol (HOG) signaling pathway. In Saccharomyces cerevisiae, the HOG pathway has been extensively studied in connection to osmotic regulation, with a valuable knock-out strain collection established. In the present study, we reconstructed the architecture of the HOG pathway of W. ichthyophaga in suitable S. cerevisiae knock-out strains, through heterologous expression of the W. ichthyophaga HOG pathway proteins. Compared to S. cerevisiae, where the Pbs2 (ScPbs2) kinase of the HOG pathway is activated via the SHO1 and SLN1 branches, the interactions between the W. ichthyophaga Pbs2 (WiPbs2) kinase and the W. ichthyophaga SHO1 branch orthologs are not conserved: as well as evidence of poor interactions between the WiSho1 Src-homology 3 (SH3) domain and the WiPbs2 proline-rich motif, the absence of a considerable part of the osmosensing apparatus in the genome of W. ichthyophaga suggests that the SHO1 branch components are not involved in HOG signaling in this halophilic fungus. In contrast, the conserved activation of WiPbs2 by the S. cerevisiae ScSsk2/ScSsk22 kinase and the sensitivity of W. ichthyophaga cells to fludioxonil, emphasize the significance of two-component (SLN1-like) signaling via Group III histidine kinase. Combined with protein modeling data, our study reveals conserved and non-conserved protein interactions in the HOG signaling pathway of W. ichthyophaga and therefore significantly improves the knowledge of hyperosmotic signal processing in this halophilic fungus. KW - signaling KW - protein-protein interaction KW - protein phosphorylation KW - mitogen activated protein kinase (MAPK) KW - high-osmolarity glycerol (HOG) KW - signaling pathway KW - Saccharomyces cerevisiae KW - halophilic fungus KW - Wallemia ichthyophaga Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165214 ER - TY - JOUR A1 - Grundgeiger, T. A1 - Albert, M. A1 - Reinhardt, D. A1 - Happel, O. A1 - Steinisch, A. A1 - Wurmb, T. T1 - Real-time tablet-based resuscitation documentation by the team leader: evaluating documentation quality and clinical performance JF - Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine N2 - Background Precise and complete documentation of in-hospital cardiopulmonary resuscitations is important but data quality can be poor. In the present study, we investigated the effect of a tablet-based application for real-time resuscitation documentation used by the emergency team leader on documentation quality and clinical performance of the emergency team. Methods Senior anaesthesiologists either used the tablet-based application during the simulated resuscitation for documentation and also used the application for the final documentation or conducted the full documentation at the end of the scenario using the local hospital information system. The latter procedure represents the current local documentation method. All scenarios were video recorded. To assess the documentation, we compared the precision of intervention delivery times, documentation completeness, and final documentation time. To assess clinical performance, we compared adherence to guidelines for defibrillation and adrenaline administration, the no-flow fraction, and the time to first defibrillation. Results The results showed significant benefits for the tablet-based application compared to the hospital information system for precision of the intervention delivery times, the final documentation time, and the no-flow fraction. We observed no differences between the groups for documentation completeness, adherence to guidelines for defibrillation and adrenaline administration, and the time to first defibrillation. Discussion In the presented study, we observed that a tablet-based application can improve documentation data quality. Furthermore, we demonstrated that a well-designed application can be used in real-time by a member of the emergency team with possible beneficial effects on clinical performance. Conclusion The present evaluation confirms the advantage of tablet-based documentation tools and also shows that the application can be used by an active member of an emergency team without compromising clinical performance. KW - cardiac arrest documentation KW - cardiopulmonary resuscitation KW - simulation KW - no-flow fraction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146582 VL - 24 IS - 51 ER - TY - JOUR A1 - Münch, Miriam A1 - Hsin, Chih-Hsuan A1 - Ferber, Elena A1 - Berger, Susanne A1 - Müller, Martin J. T1 - Reactive electrophilic oxylipins trigger a heat stress-like response through HSFA1 transcription factors JF - Journal of Experimental Botany N2 - Electrophilic oxylipins trigger a heat-shock-like response in the absence of heat through the canonical heat-shock transcription factor A1, thereby helping to cope with stresses associated with protein damage.Abiotic and biotic stresses are often characterized by an induction of reactive electrophile species (RES) such as the jasmonate 12-oxo-phytodienoic acid (OPDA) or the structurally related phytoprostanes. Previously, RES oxylipins have been shown massively to induce heat-shock-response (HSR) genes including HSP101 chaperones. Moreover, jasmonates have been reported to play a role in basal thermotolerance. We show that representative HSR marker genes are strongly induced by RES oxylipins through the four master regulator transcription factors HSFA1a, b, d, and e essential for short-term adaptation to heat stress in Arabidopsis. When compared with Arabidopsis seedlings treated at the optimal acclimation temperature of 37 A degrees C, the exogenous application of RES oxylipins at 20 A degrees C induced a much weaker induction of HSP101 at both the gene and protein expression levels which, however, was not sufficient to confer short-term acquired thermotolerance. Moreover, jasmonate-deficient mutant lines displayed a wild-type-like HSR and were not compromised in acquiring thermotolerance. Hence, the OPDA- and RES oxylipin-induced HSR is not sufficient to protect seedlings from severe heat stress but may help plants to cope better with stresses associated with protein unfolding by inducing a battery of chaperones in the absence of heat. KW - arabidopsis-thaliana KW - shock response KW - gene-expression KW - model KW - acquired thermotolerance KW - 12-oxo-phytodienoic acid KW - thermotolerance KW - plants KW - detoxification KW - acquisition KW - activation KW - heat stress KW - jasmonates KW - phytoprostanes KW - reactive electrophilic species KW - unfolded protein response Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186766 VL - 67 IS - 21 ER - TY - JOUR A1 - Hesbacher, Sonja A1 - Pfitzer, Lisa A1 - Wiedorfer, Katharina A1 - Angermeyer, Sabrina A1 - Borst, Andreas A1 - Haferkamp, Sebastian A1 - Scholz, Claus-Jürgen A1 - Wobser, Marion A1 - Schrama, David A1 - Houben, Roland T1 - RB1 is the crucial target of the Merkel cell polyomavirus Large T antigen in Merkel cell carcinoma cells JF - Oncotarget N2 - The pocket protein (PP) family consists of the three members RB1, p107 and p130 all possessing tumor suppressive properties. Indeed, the PPs jointly control the G1/S transition mainly by inhibiting E2F transcription factors. Notably, several viral oncoproteins are capable of binding and inhibiting PPs. Merkel cell polyomavirus (MCPyV) is considered as etiological factor for Merkel cell carcinoma (MCC) with expression of the viral Large T antigen (LT) harboring an intact PP binding domain being required for proliferation of most MCC cells. Therefore, we analyzed the interaction of MCPyV-LT with the PPs. Co-IP experiments indicate that MCPyV-LT binds potently only to RB1. Moreover, MCPyV-LT knockdown-induced growth arrest in MCC cells can be rescued by knockdown of RB1, but not by p107 or p130 knockdown. Accordingly, cell cycle arrest and E2F target gene repression mediated by the single PPs can only in the case of RB1 be significantly reverted by MCPyV-LT expression. Moreover, data from an MCC patient indicate that loss of RB1 rendered the MCPyV-positive MCC cells LT independent. Thus, our results suggest that RB1 is the dominant tumor suppressor PP in MCC, and that inactivation of RB1 by MCPyV-LT is largely sufficient for its growth supporting function in established MCPyV-positive MCC cells. KW - Merkel cell carcinoma KW - polyomavirus KW - Large T antigen KW - retinoblastoma protein KW - viral carcinogenesis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177858 VL - 7 IS - 22 ER - TY - JOUR A1 - Keppler, Sarah A1 - Weißbach, Susann A1 - Langer, Christian A1 - Knop, Stefan A1 - Pischimarov, Jordan A1 - Kull, Miriam A1 - Stühmer, Thorsten A1 - Steinbrunn, Torsten A1 - Bargou, Ralf A1 - Einsele, Hermann A1 - Rosenwald, Andreas A1 - Leich, Ellen T1 - Rare SNPs in receptor tyrosine kinases are negative outcome predictors in multiple myeloma JF - Oncotarget N2 - Multiple myeloma (MM) is a plasma cell disorder that is characterized by a great genetic heterogeneity. Recent next generation sequencing studies revealed an accumulation of tumor-associated mutations in receptor tyrosine kinases (RTKs) which may also contribute to the activation of survival pathways in MM. To investigate the clinical role of RTK-mutations in MM, we deep-sequenced the coding DNA-sequence of EGFR, EPHA2, ERBB3, IGF1R, NTRK1 and NTRK2 which were previously found to be mutated in MM, in 75 uniformly treated MM patients of the “Deutsche Studiengruppe Multiples Myelom”. Subsequently, we correlated the detected mutations with common cytogenetic alterations and clinical parameters. We identified 11 novel non-synonymous SNVs or rare patient-specific SNPs, not listed in the SNP databases 1000 genomes and dbSNP, in 10 primary MM cases. The mutations predominantly affected the tyrosine-kinase and ligand-binding domains and no correlation with cytogenetic parameters was found. Interestingly, however, patients with RTK-mutations, specifically those with rare patient-specific SNPs, showed a significantly lower overall, event-free and progression-free survival. This indicates that RTK SNVs and rare patient-specific RTK SNPs are of prognostic relevance and suggests that MM patients with RTK-mutations could potentially profit from treatment with RTK-inhibitors. KW - multiple myeloma KW - rare SNP KW - amplicon sequencing KW - receptor tyrosine kinases Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177840 VL - 7 IS - 25 ER - TY - JOUR A1 - Hölldobler, Bert T1 - Queen Specific Exocrine Glands in Legionary Ants and Their Possible Function in Sexual Selection JF - PLoS ONE N2 - The colonies of army ants and some other legionary ant species have single, permanently wingless queens with massive post petioles and large gasters. Such highly modified queens are called dichthadiigynes. This paper presents the unusually rich exocrine gland endowment of dichthadiigynes, which is not found in queens of other ant species. It has been suggested these kinds of glands produce secretions that attract and maintain worker retinues around queens, especially during migration. However, large worker retinues also occur in non-legionary species whose queens do not have such an exuberance of exocrine glands. We argue and present evidence in support of our previously proposed hypothesis that the enormous outfit of exocrine glands found in dichthadiigynes is due to sexual selection mediated by workers as the main selecting agents KW - exocrine glands KW - dichthadiigynes KW - legionary ants KW - queens KW - sexual selection KW - army ants Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167057 VL - 11 IS - 3 ER - TY - JOUR A1 - Diao, Wenwen A1 - Mousset, Mathilde A1 - Horsburgh, Gavin J. A1 - Vermeulen, Cornelis J. A1 - Johannes, Frank A1 - van de Zande, Louis A1 - Ritchie, Michael G. A1 - Schmitt, Thomas A1 - Beukeboom, Leo W. T1 - Quantitative Trait Locus Analysis of Mating Behavior and Male Sex Pheromones in Nasonia Wasps JF - G3: Genes Genomes Genetics N2 - A major focus in speciation genetics is to identify the chromosomal regions and genes that reduce hybridization and gene flow. We investigated the genetic architecture of mating behavior in the parasitoid wasp species pair Nasonia giraulti and Nasonia oneida that exhibit strong prezygotic isolation. Behavioral analysis showed that N. oneida females had consistently higher latency times, and broke off the mating sequence more often in the mounting stage when confronted with N. giraulti males compared with males of their own species. N. oneida males produce a lower quantity of the long-range male sex pheromone (4R,5S)-5-hydroxy-4-decanolide (RS-HDL). Crosses between the two species yielded hybrid males with various pheromone quantities, and these males were used in mating trials with females of either species to measure female mate discrimination rates. A quantitative trait locus (QTL) analysis involving 475 recombinant hybrid males (F2), 2148 reciprocally backcrossed females (F3), and a linkage map of 52 equally spaced neutral single nucleotide polymorphism (SNP) markers plus SNPs in 40 candidate mating behavior genes revealed four QTL for male pheromone amount, depending on partner species. Our results demonstrate that the RS-HDL pheromone plays a role in the mating system of N. giraulti and N. oneida, but also that additional communication cues are involved in mate choice. No QTL were found for female mate discrimination, which points at a polygenic architecture of female choice with strong environmental influences. KW - Nasonia courtship KW - female choice KW - sex pheromone KW - QTL analysis KW - speciation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165412 VL - 6 IS - 6 ER - TY - JOUR A1 - Dejung, Mario A1 - Subota, Ines A1 - Bucerius, Ferdinand A1 - Dindar, Gülcin A1 - Freiwald, Anja A1 - Engstler, Markus A1 - Boshart, Michael A1 - Butter, Falk A1 - Janzen, Chistian J. T1 - Quantitative proteomics uncovers novel factors involved in developmental differentiation of Trypanosoma brucei JF - PLoS Pathogens N2 - Developmental differentiation is a universal biological process that allows cells to adapt to different environments to perform specific functions. African trypanosomes progress through a tightly regulated life cycle in order to survive in different host environments when they shuttle between an insect vector and a vertebrate host. Transcriptomics has been useful to gain insight into RNA changes during stage transitions; however, RNA levels are only a moderate proxy for protein abundance in trypanosomes. We quantified 4270 protein groups during stage differentiation from the mammalian-infective to the insect form and provide classification for their expression profiles during development. Our label-free quantitative proteomics study revealed previously unknown components of the differentiation machinery that are involved in essential biological processes such as signaling, posttranslational protein modifications, trafficking and nuclear transport. Furthermore, guided by our proteomic survey, we identified the cause of the previously observed differentiation impairment in the histone methyltransferase DOT1B knock-out strain as it is required for accurate karyokinesis in the first cell division during differentiation. This epigenetic regulator is likely involved in essential chromatin restructuring during developmental differentiation, which might also be important for differentiation in higher eukaryotic cells. Our proteome dataset will serve as a resource for detailed investigations of cell differentiation to shed more light on the molecular mechanisms of this process in trypanosomes and other eukaryotes. KW - cell differentiation KW - cell cycle and cell division KW - parasitic cell cycles KW - proteomes KW - chromatin KW - parasitic life cycles KW - transcriptome analysis KW - host-pathogen interactions Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146362 VL - 12 IS - 2 ER - TY - JOUR A1 - Nukarinen, Ella A1 - Nägele, Thomas A1 - Pedrotti, Lorenzo A1 - Wurzinger, Bernhard A1 - Mair, Andrea A1 - Landgraf, Ramona A1 - Börnke, Frederik A1 - Hanson, Johannes A1 - Teige, Markus A1 - Baena-Gonzalez, Elena A1 - Dröge-Laser, Wolfgang A1 - Weckwerth, Wolfram T1 - Quantitative phosphoproteomics reveals the role of the AMPK plant ortholog SnRK1 as a metabolic master regulator under energy deprivation JF - Scientific Reports N2 - Since years, research on SnRK1, the major cellular energy sensor in plants, has tried to define its role in energy signalling. However, these attempts were notoriously hampered by the lethality of a complete knockout of SnRK1. Therefore, we generated an inducible amiRNA::SnRK1α2 in a snrk1α1 knock out background (snrk1α1/α2) to abolish SnRK1 activity to understand major systemic functions of SnRK1 signalling under energy deprivation triggered by extended night treatment. We analysed the in vivo phosphoproteome, proteome and metabolome and found that activation of SnRK1 is essential for repression of high energy demanding cell processes such as protein synthesis. The most abundant effect was the constitutively high phosphorylation of ribosomal protein S6 (RPS6) in the snrk1α1/α2 mutant. RPS6 is a major target of TOR signalling and its phosphorylation correlates with translation. Further evidence for an antagonistic SnRK1 and TOR crosstalk comparable to the animal system was demonstrated by the in vivo interaction of SnRK1α1 and RAPTOR1B in the cytosol and by phosphorylation of RAPTOR1B by SnRK1α1 in kinase assays. Moreover, changed levels of phosphorylation states of several chloroplastic proteins in the snrk1α1/α2 mutant indicated an unexpected link to regulation of photosynthesis, the main energy source in plants. KW - phosphoproteomics KW - SnRK1 KW - energy deprivation KW - plants Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167638 VL - 6 IS - 31697 ER - TY - JOUR A1 - Litts, Katie M. A1 - Ach, Thomas A1 - Hammack, Kristen M. A1 - Sloan, Kenneth R. A1 - Zhang, Yuhua A1 - Freund, K. Bailey A1 - Curcio, Christine A. T1 - Quantitative Analysis of Outer Retinal Tubulation in Age-Related Macular Degeneration From Spectral-Domain Optical Coherence Tomography and Histology JF - Investigative Ophthalmology & Visual Science N2 - Purpose: To assess outer retinal tubulation (ORT) morphology from spectral-domain optical coherence tomography (SD-OCT) volumes and donor eye histology, analyze ORT reflectivity, and estimate the number of cones surviving in ORT. Methods: In SD-OCT volumes from nine patients with advanced AMD, ORT was analyzed en face and in B-scans. The hyperreflective ORT border in cross-section was delineated and surface area calculated. Reflectivity was compared between ORT types (Closed, Open, Forming, and Branching). A flatmount retina from a donor with neovascular AMD was labeled to visualize the external limiting membrane that delimits ORT and allow measurements of cross-sectional cone area, center-to-center cone spacing, and cone density. The number of cones surviving in ORT was estimated. Results: By en face SD-OCT, ORT varies in complexity and shape. Outer retinal tubulation networks almost always contain Closed cross-sections. Spectral-domain OCT volumes containing almost exclusively Closed ORTs showed no significant direction-dependent differences in hyperreflective ORT border intensity. The surface areas of partial ORT assessed by SD-OCT volumes ranged from 0.16 to 1.76 mm2. From the flatmount retina, the average cross-sectional area of cone inner segments was 49.1 ± 7.9 μm2. The average cone spacing was 7.5 ± 0.6 μm. Outer retinal tubulation cone density was 20,351 cones/mm2. The estimated number of cones in ORT in a macula ranged from 26,399 to 186,833 cones, which is 6% to 44% of the cones present in a healthy macula. Conclusions: These first estimates for cone density and number of cones surviving in ORT suggest that ORT formation considerably distorts the photoreceptor mosaic. Results provide additional insight into the reflectivity characteristics and number of ORT cones observable in living patients by SD-OCT, as cones persist and disease progresses. KW - spectral-domain optical coherence tomography KW - photoreceptors KW - cones KW - Müller cells KW - age-related macular degeneration KW - outer retinal tubulation KW - ellipsoid KW - histology Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165532 VL - 57 ER - TY - THES A1 - Pasold, Christian T1 - QCD and electroweak NLO corrections to W + Photon and Z + Photon production including leptonic decays T1 - QCD und elektroschwache NLO Korrekturen zu W + Photon und Z + Photon Produktion inklusive leptonischer Zerfälle N2 - At a hadron collider as the LHC or the Tevatron the production of a photon in association with a leptonically decaying vector boson represents an important class of processes. These processes stand out due to a very clean signal of a photon and two leptons. Furthermore they provide direct access to the photon–vector-boson couplings and thus an easy opportunity to test the gauge sector of the Standard Model. Within the scope of this work we present a full calculation of the next-to-leading-order corrections which include the O (αs) corrections of the strong interaction as well as the electroweak corrections of O (α) including all photon-induced contributions. For the creation of matrix elements we use methods based on Feynman diagrams. The IR singularities are treated with the dipole subtraction technique. In order to separate photons from jets, a quark-to-photon fragmentation function ´a la Glover / Morgan or Frixione’s cone isolation is employed. Moreover, two different scenarios for charged leptons in the fi state were considered. The fi scenario for dressed leptons assumes that a charged lepton and a photon will be recombined if they are collinear. In the second scenario for bare muons it is assumed that leptons and photon can be separated in a detector also if they are collinear. For our calculation we implemented all corrections into a fl Monte Carlo program. Be- sides the computation of the total cross section this program is also able to generate diff tial distributions of several experimentally motivated observables. Apart from the expected large electroweak corrections in the high transverse-momentum regions and sizeable corrections in the resonance regions of the transverse or the invariant masses we found photon-induced corrections up to several 10% for high transverse momenta. Within run I at the LHC for 7/8 TeV the experimental accuracy for Vγ production was roughly 10%. Due to the higher luminosity at run II this accuracy will be reduced to the level of a few percent so that corrections of the same order within the theoretical predictions might become relevant. In this work we present results for the total cross section at the LHC for 7, 8 and 14 TeV and the corresponding distributions for 14 TeV. N2 - An einem Hadron Beschleuniger wie dem LHC oder dem Tevatron spielt die Prozessklasse der Produktion eines Photons in Kombination mit einem leptonisch zerfallenden massiven Eichbosons eine wichtige Rolle. Die Gründe für die große Bedeutung sind zum einen die klare Signatur aus einem Photon und zwei Leptonen als auch der direkte Zugang zu den Kopplungen des Photons an die massiven Eichbosonen und damit die Möglichkeit den Eichsektor des Standard-Modells der Elementarteilchenphysik zu testen. Um die Präzision der theoretischen Vorhersagen weiter zu erhöhen wurde im Rahmen dieser Arbeit eine vollständige Berechnung der Korrekturen in nächstführender Ordnung durchgeführt. Diese umfassen alle Korrekturen der starken Wechselwirkung von O (αs) sowie die elektroschwachen Korrekturen von O (α) inklusive aller photon-induzierten Beiträge. Zur Erzeugung von Matrixelementen wurde dabei auf Feynman-Diagramm basierte Methoden zurückgegriffen. Für die Behandlung der IR-Divergenzen wurde die Dipolesubtraktion verwendet wobei die Separation von kollinearen Photon–Jet-Konfigurationen mithilfe der Quark-Photon-Fragmentationsfunktion a´ la Glover / Morgan oder des Frixione-Kriteriums erfolgte. Außerdem wurden zwei experimentell motivierte Szenarien für die Behandlung von geladenen Leptonen im Endzustand berücksichtigt. In einem Fall werden kollineare Photon–Lepton-Paare zu einem Quasiteilchen zusammengefasst. Dieses Szenario entspricht der experimentellen Behandlung von Elektronen, die im Falle eines kollinearen Photons im elektromagnetischen Kalorimeter nicht von diesem getrennt werden können. Im zweiten Szenario werden Myonen und Photonen als experimentell separierbar angenommen, sodass Myon und Photon getrennt von einander im Detektor rekonstruiert werden können. Für die Berechnung der Korrekturen wurden alle Beiträge in einem fl Monte Carlo Programm implementiert, das neben der Berechnung des totalen Wirkungsquerschnittes auch die Erzeugung von Histogrammen für verschiedenste experimentell motivierte Observablen ermöglicht. Neben den typischen großen elektroschwachen Korrekturen bei hohen Transversalimpulsen sowie in Bereichen der Resonanzregion von transversaler beziehungsweise invarianter Masse zeigt sich, dass auch die photon-induzierten Korrekturen in der Größenordnung von einigen 10% bei hohen Transversalimpulsen beitragen. Die experimentelle Genauigkeit für Vγ Produktion in Run I mit 7/8 TeV am LHC lag bei etwa 10%. Aufgrund der gesteigerten Luminosität in Run II wird diese Genauigkeit noch weiter verbessert werden, sodass Korrekturen von ∼ 5% innerhalb der theoretischen Vorhersagen nicht mehr vernachlässigt werden können. In dieser Arbeit zeigen wir Ergebnisse für den totalen Wirkungsquerschnitt am LHC für 7, 8 und 14 TeV sowie die dazugehörigen Verteilungen für 14 TeV. KW - Quantenchromodynamik KW - particle physics Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137456 ER - TY - JOUR A1 - Szczerba, Wojciech A1 - Zukrowski, Jan A1 - Przybylski, Marek A1 - Sikora, Marcin A1 - Safonova, Olga A1 - Shmeliov, Aleksey A1 - Nicolosi, Valeria A1 - Schneider, Michael A1 - Granath, Tim A1 - Oppmann, Maximilian A1 - Straßer, Marion A1 - Mandel, Karl T1 - Pushing up the magnetisation values for iron oxide nanoparticles via zinc doping: X-ray studies on the particle's sub-nano structure of different synthesis routes JF - Physical Chemistry Chemical Physics N2 - The maximum magnetisation (saturation magnetisation) obtainable for iron oxide nanoparticles can be increased by doping the nanocrystals with non-magnetic elements such as zinc. Herein, we closely study how only slightly different synthesis approaches towards such doped nanoparticles strongly influence the resulting sub-nano/atomic structure. We compare two co-precipitation approaches, where we only vary the base (NaOH versus NH\(_3\)), and a thermal decomposition route. These methods are the most commonly applied ones for synthesising doped iron oxide nanoparticles. The measurable magnetisation change upon zinc doping is about the same for all systems. However, the sub-nano structure, which we studied with Mossbauer and X-ray absorption near edge spectroscopy, differs tremendously. We found evidence that a much more complex picture has to be drawn regarding what happens upon Zn doping compared to what textbooks tell us about the mechanism. Our work demonstrates that it is crucial to study the obtained structures very precisely when "playing'' with the atomic order in iron oxide nanocrystals. KW - Ferrite KW - FE Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187390 VL - 18 IS - 36 ER - TY - JOUR A1 - Subramanian, Hariharan A1 - Döring, Frank A1 - Kollert, Sina A1 - Rukoyatkina, Natalia A1 - Sturm, Julia A1 - Gambaryan, Stepan A1 - Stellzig-Eisenhauer, Angelika A1 - Meyer-Marcotty, Philipp A1 - Eigenthaler, Martin A1 - Wischmeyer, Erhard T1 - PTH1R Mutants Found in Patients with Primary Failure of Tooth Eruption Disrupt G-Protein Signaling JF - PLoS One N2 - Aim Primary failure of tooth eruption (PFE) is causally linked to heterozygous mutations of the parathyroid hormone receptor (PTH1R) gene. The mutants described so far lead to exchange of amino acids or truncation of the protein that may result in structural changes of the expressed PTH1R. However, functional effects of these mutations have not been investigated yet. Materials and Methods In HEK293 cells, PTH1R wild type was co-transfected with selected PTH1R mutants identified in patients with PFE. The effects on activation of PTH-regulated intracellular signaling pathways were analyzed by ELISA and Western immunoblotting. Differential effects of wild type and mutated PTH1R on TRESK ion channel regulation were analyzed by electrophysiological recordings in Xenopus laevis oocytes. Results In HEK293 cells, activation of PTH1R wild type increases cAMP and in response activates cAMP-stimulated protein kinase as detected by phosphorylation of the vasodilator stimulated phosphoprotein (VASP). In contrast, the PTH1R mutants are functionally inactive and mutant PTH1R/Gly452Glu has a dominant negative effect on the signaling of PTH1R wild type. Confocal imaging revealed that wild type PTH1R is expressed on the cell surface, whereas PTH1R/Gly452Glu mutant is mostly retained inside the cell. Furthermore, in contrast to wild type PTH1R which substantially augmented K+ currents of TRESK channels, coupling of mutated PTH1R to TRESK channels was completely abolished. Conclusions PTH1R mutations affect intracellular PTH-regulated signaling in vitro. In patients with primary failure of tooth eruption defective signaling of PTH1R mutations is suggested to occur in dento-alveolar cells and thus may lead to impaired tooth movement. KW - phosphorylation KW - xenopus oocytes KW - calcium signaling KW - intracellular receptors KW - mutation KW - teeth KW - tooth eruption KW - transfection Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-147967 VL - 11 IS - 11 ER - TY - JOUR A1 - Reicherts, Philipp A1 - Gerdes, Antje B. M. A1 - Pauli, Paul A1 - Wieser, Matthias J. T1 - Psychological placebo and nocebo effects on pain rely on expectation and previous experience JF - Journal of Pain N2 - Expectation and previous experience are both well established key mediators of placebo and nocebo effects. However, the investigation of their respective contribution to placebo and nocebo responses is rather difficult because most placebo and nocebo manipulations are contaminated by pre-existing treatment expectancies resulting from a learning history of previous medical interventions. To circumvent any resemblance to classical treatments, a purely psychological placebonocebo manipulation was established, namely, the "visual stripe pattern induced modulation of pain." To this end, experience and expectation regarding the effects of different visual cues (stripe patterns) on pain were varied across 3 different groups, with either only placebo instruction (expectation), placebo conditioning (experience), or both (expectation + experience) applied. Only the combined manipulation (expectation + experience) revealed significant behavioral and physiological placebo nocebo effects on pain. Two subsequent experiments, which, in addition to placebo and nocebo cues, included a neutral control condition further showed that especially nocebo responses were more easily induced by this psychological placebo and nocebo manipulation. The results emphasize the great effect of psychological processes on placebo and nocebo effects. Particularly, nocebo effects should be addressed more thoroughly and carefully considered in clinical practice to prevent the accidental induction of side effects. KW - psychological placebo intervention KW - placebo hypoalgesia KW - nocebo hyperalgesia KW - experience KW - expectation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190962 VL - 17 IS - 2 ER - TY - THES A1 - Schindele, Andreas T1 - Proximal methods in medical image reconstruction and in nonsmooth optimal control of partial differential equations T1 - Proximale Methoden in der medizinischen Bildrekonstruktion und in der nicht-glatten optimalen Steuerung von partiellen Differenzialgleichungen N2 - Proximal methods are iterative optimization techniques for functionals, J = J1 + J2, consisting of a differentiable part J2 and a possibly nondifferentiable part J1. In this thesis proximal methods for finite- and infinite-dimensional optimization problems are discussed. In finite dimensions, they solve l1- and TV-minimization problems that are effectively applied to image reconstruction in magnetic resonance imaging (MRI). Convergence of these methods in this setting is proved. The proposed proximal scheme is compared to a split proximal scheme and it achieves a better signal-to-noise ratio. In addition, an application that uses parallel imaging is presented. In infinite dimensions, these methods are discussed to solve nonsmooth linear and bilinear elliptic and parabolic optimal control problems. In particular, fast convergence of these methods is proved. Furthermore, for benchmarking purposes, truncated proximal schemes are compared to an inexact semismooth Newton method. Results of numerical experiments are presented to demonstrate the computational effectiveness of our proximal schemes that need less computation time than the semismooth Newton method in most cases. Results of numerical experiments are presented that successfully validate the theoretical estimates. N2 - Proximale Methoden sind iterative Optimierungsverfahren für Funktionale J = J1 +J2, die aus einem differenzierbaren Teil J2 und einem möglicherweise nichtdifferenzierbaren Teil bestehen. In dieser Arbeit werden proximale Methoden für endlich- und unendlichdimensionale Optimierungsprobleme diskutiert. In endlichen Dimensionen lösen diese `1- und TV-Minimierungsprobleme welche erfolgreich in der Bildrekonstruktion der Magnetresonanztomographie (MRT) angewendet wurden. Die Konvergenz dieser Methoden wurde in diesem Zusammenhang bewiesen. Die vorgestellten proximalen Methoden wurden mit einer geteilten proximalen Methode verglichen und konnten ein besseres Signal-Rausch-Verhältnis erzielen. Zusätzlich wurde eine Anwendung präsentiert, die parallele Bildgebung verwendet. Diese Methoden werden auch für unendlichdimensionale Probleme zur Lösung von nichtglatten linearen und bilinearen elliptischen und parabolischen optimalen Steuerungsproblemen diskutiert. Insbesondere wird die schnelle Konvergenz dieser Methoden bewiesen. Außerdem werden abgeschnittene proximale Methoden mit einem inexakten halbglatten Newtonverfahren verglichen. Die numerischen Ergebnisse demonstrieren die Effektivität der proximalen Methoden, welche im Vergleich zu den halbglatten Newtonverfahren in den meisten Fällen weniger Rechenzeit benötigen. Zusätzlich werden die theoretischen Abschätzungen bestätigt. KW - Optimale Kontrolle KW - Proximal-Punkt-Verfahren KW - Bildrekonstruktion KW - Komprimierte Abtastung KW - Optimal Control KW - Elliptic equations KW - Parabolic equations KW - Proximal Method KW - Semismooth Newton Method KW - Medical image reconstruction KW - Sparsity KW - Total Variation KW - Compressed Sensing KW - Magnetic Resonance Imaging KW - Partielle Differentialgleichung Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136569 ER - TY - JOUR A1 - Schindele, Andreas A1 - Borzì, Alfio T1 - Proximal Methods for Elliptic Optimal Control Problems with Sparsity Cost Functional JF - Applied Mathematics N2 - First-order proximal methods that solve linear and bilinear elliptic optimal control problems with a sparsity cost functional are discussed. In particular, fast convergence of these methods is proved. For benchmarking purposes, inexact proximal schemes are compared to an inexact semismooth Newton method. Results of numerical experiments are presented to demonstrate the computational effectiveness of proximal schemes applied to infinite-dimensional elliptic optimal control problems and to validate the theoretical estimates. KW - semismooth Newton method KW - optimal control KW - elliptic PDE KW - nonsmooth optimization KW - proximal method Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145850 VL - 7 IS - 9 ER - TY - JOUR A1 - Plum, Sarah A1 - Steinbach, Simone A1 - Attems, Johannes A1 - Keers, Sharon A1 - Riederer, Peter A1 - Gerlach, Manfred A1 - May, Caroline A1 - Marcus, Katrin T1 - Proteomic characterization of neuromelanin granules isolated from human substantia nigra by laser-microdissection JF - Scientific Reports N2 - Neuromelanin is a complex polymer pigment found primarily in the dopaminergic neurons of human substantia nigra. Neuromelanin pigment is stored in granules including a protein matrix and lipid droplets. Neuromelanin granules are yet only partially characterised regarding their structure and function. To clarify the exact function of neuromelanin granules in humans, their enrichment and in-depth characterization from human substantia nigra is necessary. Previously published global proteome studies of neuromelanin granules in human substantia nigra required high tissue amounts. Due to the limited availability of human brain tissue we established a new method based on laser microdissection combined with mass spectrometry for the isolation and analysis of neuromelanin granules. With this method it is possible for the first time to isolate a sufficient amount of neuromelanin granules for global proteomics analysis from ten 10 μm tissue sections. In total 1,000 proteins were identified associated with neuromelanin granules. More than 68% of those proteins were also identified in previously performed studies. Our results confirm and further extend previously described findings, supporting the connection of neuromelanin granules to iron homeostasis and lysosomes or endosomes. Hence, this method is suitable for the donor specific enrichment and proteomic analysis of neuromelanin granules. KW - neuromelanin KW - substantia nigra KW - pigment KW - granules Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167507 VL - 6 IS - 37139 ER - TY - JOUR A1 - Vendelova, Emilia A1 - de Lima, Jeferson Camargo A1 - Lorenzatto, Karina Rodrigues A1 - Monteiro, Karina Mariante A1 - Mueller, Thomas A1 - Veepaschit, Jyotishman A1 - Grimm, Clemens A1 - Brehm, Klaus A1 - Hrčková, Gabriela A1 - Lutz, Manfred B. A1 - Ferreira, Henrique B. A1 - Nono, Justin Komguep T1 - Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions JF - PLoS Neglected Tropical Diseases N2 - Accumulating evidences have assigned a central role to parasite-derived proteins in immunomodulation. Here, we report on the proteomic identification and characterization of immunomodulatory excretory-secretory (ES) products from the metacestode larva (tetrathyridium) of the tapeworm Mesocestoides corti (syn. M. vogae). We demonstrate that ES products but not larval homogenates inhibit the stimuli-driven release of the pro-inflammatory, Th1-inducing cytokine IL-12p70 by murine bone marrow-derived dendritic cells (BMDCs). Within the ES fraction, we biochemically narrowed down the immunosuppressive activity to glycoproteins since active components were lipid-free, but sensitive to heat- and carbohydrate-treatment. Finally, using bioassay-guided chromatographic analyses assisted by comparative proteomics of active and inactive fractions of the ES products, we defined a comprehensive list of candidate proteins released by M. corti tetrathyridia as potential suppressors of DC functions. Our study provides a comprehensive library of somatic and ES products and highlight some candidate parasite factors that might drive the subversion of DC functions to facilitate the persistence of M. corti tetrathyridia in their hosts. KW - proteomic analysis KW - excretory-secretory KW - Mesocestoides corti Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166742 VL - 10 IS - 10 ER - TY - JOUR A1 - Dueñas-Espín, Ivan A1 - Vela, Emili A1 - Pauws, Steffen A1 - Bescos, Cristina A1 - Cano, Isaac A1 - Cleries, Montserrat A1 - Contel, Joan Carles A1 - Keenoy, Esteban de Manuel A1 - Garcia-Aymerich, Judith A1 - Gomez-Cabrero, David A1 - Kaye, Rachelle A1 - Lahr, Maarten M. H. A1 - Lluch-Ariet, Magí A1 - Moharra, Montserrat A1 - Monterde, David A1 - Mora, Joana A1 - Nalin, Marco A1 - Pavlickova, Andrea A1 - Piera, Jordi A1 - Ponce, Sara A1 - Santaeugenia, Sebastià A1 - Schonenberg, Helen A1 - Störk, Stefan A1 - Tegner, Jesper A1 - Velickovski, Filip A1 - Westerteicher, Christoph A1 - Roca, Josep T1 - Proposals for enhanced health risk assessment and stratification in an integrated care scenario JF - BMJ Open N2 - Objectives Population-based health risk assessment and stratification are considered highly relevant for large-scale implementation of integrated care by facilitating services design and case identification. The principal objective of the study was to analyse five health-risk assessment strategies and health indicators used in the five regions participating in the Advancing Care Coordination and Telehealth Deployment (ACT) programme (http://www.act-programme.eu). The second purpose was to elaborate on strategies toward enhanced health risk predictive modelling in the clinical scenario. Settings The five ACT regions: Scotland (UK), Basque Country (ES), Catalonia (ES), Lombardy (I) and Groningen (NL). Participants Responsible teams for regional data management in the five ACT regions. Primary and secondary outcome measures We characterised and compared risk assessment strategies among ACT regions by analysing operational health risk predictive modelling tools for population-based stratification, as well as available health indicators at regional level. The analysis of the risk assessment tool deployed in Catalonia in 2015 (GMAs, Adjusted Morbidity Groups) was used as a basis to propose how population-based analytics could contribute to clinical risk prediction. Results There was consensus on the need for a population health approach to generate health risk predictive modelling. However, this strategy was fully in place only in two ACT regions: Basque Country and Catalonia. We found marked differences among regions in health risk predictive modelling tools and health indicators, and identified key factors constraining their comparability. The research proposes means to overcome current limitations and the use of population-based health risk prediction for enhanced clinical risk assessment. Conclusions The results indicate the need for further efforts to improve both comparability and flexibility of current population-based health risk predictive modelling approaches. Applicability and impact of the proposals for enhanced clinical risk assessment require prospective evaluation. KW - health risk assessment Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164743 VL - 6 IS - e010301 ER - TY - THES A1 - Ulrich, Natalie T1 - Processing of Near Outcomes and Outcome Sequences in Gambling: Implications for the Biopsychological Basis of Problem Gambling T1 - Verarbeitung von knappen Ergebnissen und Ergebnissequenzen im Glücksspiel : Implikationen für die biopsychologische Basis von problematischem Glücksspielverhalten N2 - Gambling is a popular activity in Germany, with 40% of a representative sample reporting having gambled at least once in the past year (Bundeszentrale für gesundheitliche Aufklärung, 2014). While the majority of gamblers show harmless gambling behavior, a subset develops serious problems due to their gambling, affecting their psychological well-being, social life and work. According to recent estimates, up to 0.8% of the German population are affected by such pathological gambling. People in general and pathological gamblers in particular show several cognitive distortions, that is, misconceptions about the chances of winning and skill involvement, in gambling. The current work aimed at elucidating the biopsychological basis of two such kinds of cognitive distortions, the illusion of control and the gambler’s and hot hand fallacies, and their modulation by gambling problems. Therefore, four studies were conducted assessing the processing of near outcomes (used as a proxy for the illusion of control) and outcome sequences (used as a proxy for the gambler’s and hot hand fallacies) in samples of varying degrees of gambling problems, using a multimethod approach. The first study analyzed the processing and evaluation of near outcomes as well as choice behavior in a wheel of fortune paradigm using electroencephalography (EEG). To assess the influence of gambling problems, a group of problem gamblers was compared to a group of controls. The results showed that there were no differences in the processing of near outcomes between the two groups. Near compared to full outcomes elicited smaller P300 amplitudes. Furthermore, at a trend level, the choice behavior of participants showed signs of a pattern opposite to the gambler’s fallacy, with longer runs of an outcome color leading to increased probabilities of choosing this color again on the subsequent trial. Finally, problem gamblers showed smaller feedback-related negativity (FRN) amplitudes relative to controls. The second study also targeted the processing of near outcomes in a wheel of fortune paradigm, this time using functional magnetic resonance imaging and a group of participants with varying degrees of gambling problems. The results showed increased activity in the bilateral superior parietal cortex following near compared to full outcomes. The third study examined the peripheral physiology reactions to near outcomes in the wheel of fortune. Heart period and skin conductance were measured while participants with varying degrees of gambling problems played on the wheel of fortune. Near compared to full outcomes led to increased heart period duration shortly after the outcome. Furthermore, heart period reactions and skin conductance responses (SCRs) were modulated by gambling problems. Participants with high relative to low levels of gambling problems showed increased SCRs to near outcomes and similar heart period reactions to near outcomes and full wins. The fourth study analyzed choice behavior and sequence effects in the processing of outcomes in a coin toss paradigm using EEG in a group of problem gamblers and controls. Again, problem gamblers showed generally smaller FRN amplitudes compared to controls. There were no differences between groups in the processing of outcome sequences. The break of an outcome streak led to increased power in the theta frequency band. Furthermore, the P300 amplitude was increased after a sequence of previous wins. Finally, problem gamblers compared to controls showed a trend of switching the outcome symbol relative to the previous outcome symbol more often. In sum, the results point towards differences in the processing of near compared to full outcomes in brain areas and measures implicated in attentional and salience processes. The processing of outcome sequences involves processes of salience attribution and violation of expectations. Furthermore, problem gamblers seem to process near outcomes as more win-like compared to controls. The results and their implications for problem gambling as well as further possible lines of research are discussed. N2 - Glücksspiel ist eine verbreitete Aktivität in Deutschland. 40% einer repräsentativen Stichprobe gaben an mindestens einmal im vergangenen Jahr um Geld gespielt zu haben (Bundeszentrale für gesundheitliche Aufklärung, 2014). Während die Mehrheit der Glücksspieler unbedenkliches Spielverhalten zeigt, entwickelt ein Teil der Spieler ernsthafte Probleme durch das Spielen, die das psychische Wohlergehen, sowie das soziale und Arbeitsleben beeinträchtigen. Nach aktuellen Schätzungen sind bis zu 0,8% der deutschen Bevölkerung von solch pathologischem Glücksspielen betroffen. Generell zeigen Menschen verschiedene kognitive Verzerrungen im Sinne falscher Einschätzungen der Gewinnwahrscheinlichkeit und der Beteiligung von Fähigkeiten in Bezug auf Glücksspiel. Dies trifft insbesondere für pathologische Glücksspieler zu. Das Ziel der vorliegenden Arbeit ist die Untersuchung der biopsychologischen Grundlagen zweier solcher kognitiver Verzerrungen, der Kontrollillusion sowie der Gambler’s Fallacy (bisweilen auch Spielerfehlschluss genannt) und Hot-Hand-Phänomene, sowie deren Modulation durch Glücksspielprobleme. Zu diesem Zweck wurden vier Studien durchgeführt, die die Verarbeitung knapper Ergebnisse (stellvertretend für die Kontrollillusion) und Ergebnissequenzen (stellvertretend für die Phänomene der Gambler’s Fallacy und Hot Hand) untersuchten. Dazu wurden Stichproben mit unterschiedlichem Schweregrad der Glücksspielproblematik sowie ein Multi-Methoden Ansatz verwendet. Die erste Studie untersuchte die Verarbeitung und Bewertung knapper Ergebnisse sowie das Wahlverhalten in einem Glücksrad Paradigma mittels Elektroenzephalographie (EEG). Um den Einfluss der Glücksspielproblematik zu erfassen, wurde eine Gruppe von Problemspielern mit einer Kontrollgruppe verglichen. Es zeigten sich keine Unterschiede in der Verarbeitung knapper Ergebnisse zwischen den beiden Gruppen. Im Vergleich zu vollen Ergebnissen führten knappe Ergebnisse zu kleineren Amplituden in der P300. Des Weiteren zeigte sich auf Trendniveau im Wahlverhalten der Probanden Anzeichen für ein der Gambler’s Fallacy entgegengesetztes Muster. Längere Sequenzen einer Ergebnisfarbe führten zu einer höheren Wahrscheinlichkeit diese Farbe im folgenden Durchgang erneut zu wählen. Schließlich zeigten Problemspieler relativ zur Kontrollgruppe kleinere Amplituden in der Feedbacknegativierung (FRN). Die zweite Studie zielte ebenfalls auf die Verarbeitung knapper Ergebnisse im Glücksrad Paradigma ab, allerdings unter Verwendung funktioneller Magnetresonanztomographie sowie einer Probandengruppe mit variierendem Ausmaß der Glücksspielproblematik. Es zeigte sich eine verstärkte Aktivierung im bilateralen superioren parietalen Cortex nach knappen im Vergleich zu vollen Ergebnissen. Die dritte Studie untersuchte peripherphysiologische Reaktionen auf knappe Ergebnisse im Glücksrad. Hierzu wurden Herzperiode und Hautleitfähigkeit erfasst während eine Probandengruppe mit unterschiedlichem Ausmaß an Glücksspielproblemen am Glücksrad spielte. Knappe Ergebnisse führten im Vergleich zu vollen Ergebnissen zu verlängerten Herzperioden kurz nach dem Ergebnis. Des Weiteren wurden die Herzperiodenreaktion und Hautleitfähigkeitsreaktion durch Glücksspielprobleme moduliert. Probanden mit einem hohem im Vergleich zu einem niedrigen Ausmaß an Glücksspielproblemen zeigten gesteigerte Hautleitfähigkeitsreaktionen auf knappe im Vergleich zu vollen Ergebnissen, sowie ähnliche Herzperiodenreaktionen auf knappe Ergebnisse und volle Gewinne. Die vierte Studie untersuchte das Wahlverhalten sowie Einflüsse vorheriger Sequenzen auf die Verarbeitung von Ergebnissen in einem Münzwurf Paradigma. Hierzu wurde ein EEG bei einer Gruppe von Problemspielern und Kontrollprobanden abgeleitet. Problemspieler zeigten wiederum generell kleinere FRN Amplituden als Kontrollen. Es zeigten sich keine Unterschiede in der Verarbeitung der Ergebnissequenzen zwischen den Gruppen. Die Unterbrechung einer Sequenz gleicher Ergebnisse führte zu verstärkter Power im Theta Frequenzband. Zusätzlich war die Amplitude der P300 nach zwei vorangegangenen Gewinnen erhöht. Schließlich zeigten Problemspieler im Vergleich zu Kontrollen die Tendenz das gewählte Symbol relativ zum vorangegangenen Ergebnissymbol häufiger zu wechseln. Zusammenfassend deuten die Ergebnisse auf Unterschiede in der Verarbeitung knapper und voller Ergebnisse hin, die vor allem Gehirnareale und Prozesse umfassen, die mit Aufmerksamkeit und Salienz assoziiert sind. Die Verarbeitung von Ergebnissequenzen umfasst Prozesse der Salienzzuschreibung und Erwartungsverletzung. Außerdem scheinen Problemspieler im Vergleich zu Kontrollen knappe Ergebnisse als gewinnähnlicher zu verarbeiten. Die Ergebnisse und deren Implikationen für problematisches Glücksspielverhalten sowie weitere mögliche Forschungsfragen werden diskutiert. KW - Spielsucht KW - Psychobiologie KW - Near Miss KW - Problem Gambling KW - Heart Period KW - EEG KW - fMRI KW - Gambler's Fallacy KW - Hot Hand Fallacy KW - Cognitive Distortions KW - Glücksspiel KW - Electroencephalographie KW - Funktionelle Kernspintomografie Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139612 ER - TY - THES A1 - Bahník, Štěpán T1 - Processing fluency and judgment T1 - Verarbeitungsflüssigkeit und Urteilsbildung N2 - To simplify a judgment, people often base it on easily accessible information. One cue that is usually readily available is processing fluency – a metacognitive feeling of ease of cognitive processing. Consequently, processing fluency is used as a cue for many different types of judgment, such as judgment of truth, confidence, and novelty. The present work describes results of three studies investigating various aspects of processing fluency effects on judgment. Processing fluency has been sometimes equated with speed of a cognitive process. Therefore, response times have been used for evaluation of processing fluency. However, response times in experimental tasks often do not encompass only the time needed for a given process, but also the time needed for a decision based on the resulting information. The study described in Chapter II uses a novel experimental method that enables separation of reading and decision times. The results show that people make a decision about liking of pseudowords faster when the pseudowords are hard-to-pronounce (i.e., disfluent) than when they are moderate in pronounceability. This suggests that response times cannot be used as a proxy for processing fluency when they include the time needed to make a decision. One of the studies of judgmental effects of processing fluency showed that food additives with easier pronounceable names are judged to be less harmful than those with hard-to-pronounce names. While people encounter food additives that are safe more often, this environmental association may be in the opposite direction for some categories of objects. For example, people are more likely to see names of especially dangerous criminals in the news. Chapter III describes a study which initially tested whether the fluency-safety association may be in the opposite direction for some categories of objects as a consequence of this selective exposure to especially dangerous exemplars. The results did not show support for this hypothesis. Furthermore, subsequent studies suggest that the previously found association between fluency and safety is replicable with the original stimuli used in the previous research, but not with newly constructed stimuli. Chapter IV describes a study which applied a finding from the processing fluency literature to a positive psychology exercise in order to increase its effectiveness. Namely, the experiment manipulated the number of good things that participants listed daily for two weeks as part of the exercise. While listing more things was considered harder, the number of things listed each day had no effect on effectiveness of the exercise. N2 - Um Urteilsprozesse zu vereinfachen, basieren Menschen diese oft auf leicht zugänglichen Informationen. Eine hierfür immer und jederzeit verfügbare Information ist die Verarbeitungsflüssigkeit – ein metakognitives Gefühl von Leichtigkeit bei der kognitiven Verarbeitung. Verarbeitungsflüssigkeit wird als Information bei vielen verschiedenen Arten von Urteilen genutzt, so beispielsweise bei Urteilen hinsichtlich Wahrheit, Vertrauenswürdigkeit und Neuheit. Die vorliegende Arbeit beschreibt die Ergebnisse von drei Studien, die verschiedene Aspekte des Einflusses von Verarbeitungsflüssigkeit auf Urteilsprozesse untersuchen. Verarbeitungsflüssigkeit wurde in der Literatur manchmal mit der Geschwindigkeit eines kognitiven Prozesses gleichgesetzt. Daher wurden Reaktionszeiten zur Schätzung der Verarbeitungsflüssigkeit herangezogen. In experimentellen Paradigmen umfassen Reaktionszeiten allerdings oft nicht nur die Zeit, die für den Prozess von Interesse benötigt wird, sondern auch die Zeit, die für eine Entscheidung benötigt wird, die auf der aus dem Prozess resultierenden Information basiert. Die Studie, die in Kapitel II beschrieben wird, verwendet daher eine neue experimentelle Methode, die eine Differenzierung zwischen der Zeit, die zum Lesen, und der Zeit, die für die Entscheidung benötigt wurde, ermöglicht. In den Ergebnissen zeigt sich, dass Menschen schneller eine Entscheidung darüber fällen, wie sehr sie bestimmte Pseudowörter mögen, wenn die Pseudowörter schwer aussprechbar sind (also nicht flüssig verarbeitbar sind) als wenn sie moderat aussprechbar sind. Dieser Befund legt nahe, dass Reaktionszeiten nicht zur Schätzung von Verarbeitungsflüssigkeit herangezogen werden können, da sie auch die Zeit beinhalten, die gebraucht wird, um eine Entscheidung zu treffen. Eine Studie zum Einfluss von Verarbeitungsflüssigkeit auf Urteilsbildung zeigte, dass Lebensmittelzusatzstoffe mit leicht aussprechbaren Namen im Vergleich zu solchen mit schwer aussprechbaren Namen als weniger gefährlich beurteilt wurden. Während Menschen ungefährlichen Lebensmittelzusatzstoffen öfter begegnen als gefährlichen, könnte dieser Umweltzusammenhang bei anderen Objektkategorien in entgegengesetzter Richtung verlaufen. Zum Beispiel sehen Menschen die Namen von besonders gefährlichen Verbrechern mit einer höheren Wahrscheinlichkeit in den Nachrichten. In Kapitel III wird daher eine Studie beschrieben, die ursprünglich testen sollte, ob der Verarbeitungsflüssigkeit-Sicherheit-Zusammenhang bei manchen Objektkategorien, bei denen man selektiv besonders gefährlichen Exemplaren ausgesetzt ist, in die entgegengesetzte Richtung verläuft. Die Ergebnisse unterstützten diese Hypothese jedoch nicht. Zudem lassen die Ergebnisse weiterer Studien darauf schließen, dass der zuvor gezeigte Zusammenhang zwischen Verarbeitungsflüssigkeit und Sicherheit nur mit den Originalstimuli aus früheren Studien, nicht aber mit neu konstruierten Studien repliziert werden kann. In Kapitel IV wird eine Studie beschrieben, die einen Befund der Verarbeitungsflüssigkeitsliteratur auf eine Übung aus dem Bereich der Positiven Psychologie anwendet, um deren Effektivität zu steigern. Konkret manipulierte das Experiment die Anzahl an guten Erlebnissen, die die Teilnehmer zwei Wochen lang täglich als Teil der Übung auflisten sollten. Obwohl das Auflisten einer größeren Anzahl an Erlebnissen als schwieriger bewertet wurde, hatte die Anzahl an Erlebnissen, die jeden Tag aufgelistet wurde, keinen Einfluss auf die Effektivität der Übung. KW - Urteilen KW - Judgment KW - Processing fluency KW - Informationsverarbeitung KW - Psychologie Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144656 ER - TY - JOUR A1 - Deeb, Wissam A1 - Giordano, James J. A1 - Rossi, Peter J. A1 - Mogilner, Alon Y. A1 - Gunduz, Aysegul A1 - Judy, Jack W. A1 - Klassen, Bryan T. A1 - Butson, Christopher R. A1 - Van Horne, Craig A1 - Deny, Damiaan A1 - Dougherty, Darin D. A1 - Rowell, David A1 - Gerhardt, Greg A. A1 - Smith, Gwenn S. A1 - Ponce, Francisco A. A1 - Walker, Harrison C. A1 - Bronte-Stewart, Helen M. A1 - Mayberg, Helen S. A1 - Chizeck, Howard J. A1 - Langevin, Jean-Philippe A1 - Volkmann, Jens A1 - Ostrem, Jill L. A1 - Shute, Jonathan B. A1 - Jimenez-Shahed, Joohi A1 - Foote, Kelly D. A1 - Wagle Shukla, Aparna A1 - Rossi, Marvin A. A1 - Oh, Michael A1 - Pourfar, Michael A1 - Rosenberg, Paul B. A1 - Silburn, Peter A. A1 - de Hemptine, Coralie A1 - Starr, Philip A. A1 - Denison, Timothy A1 - Akbar, Umer A1 - Grill, Warren M. A1 - Okun, Michael S. T1 - Proceedings of the Fourth Annual Deep Brain Stimulation Think Tank: A Review of Emerging Issues and Technologies JF - Frontiers in Integrative Neuroscience N2 - This paper provides an overview of current progress in the technological advances and the use of deep brain stimulation (DBS) to treat neurological and neuropsychiatric disorders, as presented by participants of the Fourth Annual DBS Think Tank, which was convened in March 2016 in conjunction with the Center for Movement Disorders and Neurorestoration at the University of Florida, Gainesveille FL, USA. The Think Tank discussions first focused on policy and advocacy in DBS research and clinical practice, formation of registries, and issues involving the use of DBS in the treatment of Tourette Syndrome. Next, advances in the use of neuroimaging and electrochemical markers to enhance DBS specificity were addressed. Updates on ongoing use and developments of DBS for the treatment of Parkinson's disease, essential tremor, Alzheimer's disease, depression, post-traumatic stress disorder, obesity, addiction were presented, and progress toward innovation(s) in closed-loop applications were discussed. Each section of these proceedings provides updates and highlights of new information as presented at this year's international Think Tank, with a view toward current and near future advancement of the field. KW - deep brain stimulation KW - Parkinson’s disease KW - Alzheimer’s disease KW - closed-loop KW - depression KW - post-traumatic stress disorder KW - Tourette syndrome KW - DARPA Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168493 VL - 10 IS - 38 ER - TY - JOUR A1 - Wandrey, Georg A1 - Wurzel, Joel A1 - Hoffmann, Kyra A1 - Ladner, Tobias A1 - Büchs, Jochen A1 - Meinel, Lorenz A1 - Lühmann, Tessa T1 - Probing unnatural amino acid integration into enhanced green fluorescent protein by genetic code expansion with a high-throughput screening platform JF - Journal of Biological Engineering N2 - Background Genetic code expansion has developed into an elegant tool to incorporate unnatural amino acids (uAA) at predefined sites in the protein backbone in response to an amber codon. However, recombinant production and yield of uAA comprising proteins are challenged due to the additional translation machinery required for uAA incorporation. Results We developed a microtiter plate-based high-throughput monitoring system (HTMS) to study and optimize uAA integration in the model protein enhanced green fluorescence protein (eGFP). Two uAA, propargyl-L-lysine (Plk) and (S)-2-amino-6-((2-azidoethoxy) carbonylamino) hexanoic acid (Alk), were incorporated at the same site into eGFP co-expressing the native PylRS/tRNAPyl CUA pair originating from Methanosarcina barkeri in E. coli. The site-specific uAA functionalization was confirmed by LC-MS/MS analysis. uAA-eGFP production and biomass growth in parallelized E. coli cultivations was correlated to (i) uAA concentration and the (ii) time of uAA addition to the expression medium as well as to induction parameters including the (iii) time and (iv) amount of IPTG supplementation. The online measurements of the HTMS were consolidated by end point-detection using standard enzyme-linked immunosorbent procedures. Conclusion The developed HTMS is powerful tool for parallelized and rapid screening. In light of uAA integration, future applications may include parallelized screening of different PylRS/tRNAPyl CUA pairs as well as further optimization of culture conditions. KW - protein engineering KW - amber codon suppression KW - online monitoring system KW - high-throughput screening KW - unnatural amino acid KW - bio-orthogonal chemistry Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166304 VL - 10 IS - 11 ER - TY - JOUR A1 - Hargart, F A1 - Roy-Choudhury, K A1 - John, T A1 - Portalupi, S L A1 - Schneider, C A1 - Höfling, S A1 - Kamp, M A1 - Hughes, S A1 - Michler, P T1 - Probing different regimes of strong field light-matter interaction with semiconductor quantum dots and few cavity photons JF - New Journal of Physics N2 - In this work we present an extensive experimental and theoretical investigation of different regimes of strong field light–matter interaction for cavity-driven quantum dot (QD) cavity systems. The electric field enhancement inside a high-Q micropillar cavity facilitates exceptionally strong interaction with few cavity photons, enabling the simultaneous investigation for a wide range of QD-laser detuning. In case of a resonant drive, the formation of dressed states and a Mollow triplet sideband splitting of up to 45 μeV is measured for amean cavity photon number \(\leq\) 1. In the asymptotic limit of the linear ACStark effect we systematically investigate the power and detuning dependence of more than 400 QDs. Some QD-cavity systems exhibit an unexpected anomalous Stark shift, which can be explained by an extended dressed 4-levelQDmodel.Weprovide a detailed analysis of the QD-cavity systems properties enabling this novel effect. The experimental results are successfully reproduced using a polaron master equation approach for the QD-cavity system, which includes the driving laser field, exciton-cavity and exciton-phonon interactions KW - light–matter interaction KW - quantum dots KW - AC Stark effect KW - dressed states Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166278 VL - 18 ER - TY - JOUR A1 - Asthana, Manish Kumar A1 - Brunhuber, Bettina A1 - Mühlberger, Andreas A1 - Reif, Andreas A1 - Schneider, Simone A1 - Herrmann, Martin J. T1 - Preventing the Return of Fear Using Reconsolidation Update Mechanisms Depends on the Met-Allele of the Brain Derived Neurotrophic Factor Val66Met Polymorphism JF - International Journal of Neuropsychopharmacology N2 - Background: Memory reconsolidation is the direct effect of memory reactivation followed by stabilization of newly synthesized proteins. It has been well proven that neural encoding of both newly and reactivated memories requires synaptic plasticity. Brain derived neurotrophic factor (BDNF) has been extensively investigated regarding its role in the formation of synaptic plasticity and in the alteration of fear memories. However, its role in fear reconsolidation is still unclear; hence, the current study has been designed to investigate the role of the BDNF val66met polymorphism (rs6265) in fear memory reconsolidation in humans. Methods: An auditory fear-conditioning paradigm was conducted, which comprised of three stages (acquisition, reactivation, and spontaneous recovery). One day after fear acquisition, the experimental group underwent reactivation of fear memory followed by the extinction training (reminder group), whereas the control group (non-reminder group) underwent only extinction training. On day 3, both groups were subjected to spontaneous recovery of earlier learned fearful memories. The treat-elicited defensive response due to conditioned threat was measured by assessing the skin conductance response to the conditioned stimulus. All participants were genotyped for rs6265. Results: The results indicate a diminishing effect of reminder on the persistence of fear memory only in the Met-allele carriers, suggesting a moderating effect of the BDNF polymorphism in fear memory reconsolidation. Conclusions: Our findings suggest a new role for BDNF gene variation in fear memory reconsolidation in humans. KW - BDNF KW - brain derived neurotrophic factor KW - fear conditioning KW - genetics memory KW - reconsolidation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166217 VL - 19 IS - 6 ER - TY - JOUR A1 - Fornari, C. I. A1 - Rappl, P. H. O. A1 - Morelhao, S. L. A1 - Peixoto, T. R. F. A1 - Bentmann, H. A1 - Reinert, F. A1 - Abramof, E. T1 - Preservation of pristine Bi\(_2\)Te\(_3\) thin film topological insulator surface after ex situ mechanical removal of Te capping layer JF - APL Materials N2 - Ex situ analyses on topological insulator films require protection against surface contamination during air exposure. This work reports on a technique that combines deposition of protective capping just after epitaxial growth and its mechanical removal inside ultra-high vacuum systems. This method was applied to Bi2Te3 films with thickness varying from 8 to 170 nm. Contrarily to other methods, this technique does not require any sputtering or thermal annealing setups installed inside the analyzing system and preserves both film thickness and surface characteristics. These results suggest that the technique presented here can be expanded to other topological insulator materials. KW - Insulator surfaces KW - Atomic force microscopy KW - Insulating thin films KW - Molecular beam epitaxy KW - Surface states KW - Vacuum chambers KW - Thin film growth KW - Sputter deposition KW - Epitaxy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164468 VL - 4 ER - TY - JOUR A1 - Peters, Marcell K. A1 - Hemp, Andreas A1 - Appelhans, Tim A1 - Behler, Christina A1 - Classen, Alice A1 - Detsch, Florian A1 - Ensslin, Andreas A1 - Ferger, Stefan W. A1 - Frederiksen, Sara B. A1 - Gebert, Frederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Claudia A1 - Kindeketa, William J. A1 - Mwangomo, Ephraim A1 - Ngereza, Christine A1 - Otte, Insa A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Costa, David Schellenberger A1 - Tardanico, Joseph A1 - Zancolli, Giulia A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Peters, Ralph S. A1 - Rödel, Mark-Oliver A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Kakengi, Victor A1 - Zhang, Jie A1 - Böhning-Gaese, Katrin A1 - Brandl, Roland A1 - Kalko, Elisabeth K.V. A1 - Kleyer, Michael A1 - Nauss, Thomas A1 - Tschapka, Marco A1 - Fischer, Markus A1 - Steffan-Dewenter, Ingolf T1 - Predictors of elevational biodiversity gradients change from single taxa to the multi-taxa community level JF - Nature Communications N2 - The factors determining gradients of biodiversity are a fundamental yet unresolved topic in ecology. While diversity gradients have been analysed for numerous single taxa, progress towards general explanatory models has been hampered by limitations in the phylogenetic coverage of past studies. By parallel sampling of 25 major plant and animal taxa along a 3.7 km elevational gradient on Mt. Kilimanjaro, we quantify cross-taxon consensus in diversity gradients and evaluate predictors of diversity from single taxa to a multi-taxa community level. While single taxa show complex distribution patterns and respond to different environmental factors, scaling up diversity to the community level leads to an unambiguous support for temperature as the main predictor of species richness in both plants and animals. Our findings illuminate the influence of taxonomic coverage for models of diversity gradients and point to the importance of temperature for diversification and species coexistence in plant and animal communities. KW - community ecology KW - macroecology KW - tropical ecology KW - biodiversity Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169374 VL - 7 ER - TY - JOUR A1 - Rech, Juergen A1 - Hueber, Axel J. A1 - Finzel, Stephanie A1 - Englbrecht, Matthias A1 - Haschka, Judith A1 - Manger, Bernhard A1 - Kleyer, Arnd A1 - Reiser, Michaela A1 - Cobra, Jayme Fogagnolo A1 - Figueiredo, Camille A1 - Tony, Hans-Peter A1 - Kleinert, Stefan A1 - Wendler, Joerg A1 - Schuch, Florian A1 - Ronneberger, Monika A1 - Feuchtenberger, Martin A1 - Fleck, Martin A1 - Manger, Karin A1 - Ochs, Wolfgang A1 - Schmitt-Haendle, Matthias A1 - Lorenz, Hanns-Martin A1 - Nuesslein, Hubert A1 - Alten, Rieke A1 - Henes, Joerg A1 - Krueger, Klaus A1 - Schett, Georg T1 - Prediction of disease relapses by multibiomarker disease activity and autoantibody status in patients with rheumatoid arthritis on tapering DMARD treatment JF - Annals of the Rheumatic Diseases N2 - Objective To analyse the role of multibiomarker disease activity (MBDA) score in predicting disease relapses in patients with rheumatoid arthritis (RA) in sustained remission who tapered disease modifying antirheumatic drug (DMARD) therapy in RETRO, a prospective randomised controlled trial. Methods MBDA scores (scale 1-100) were determined based on 12 inflammation markers in baseline serum samples from 94 patients of the RETRO study. MBDA scores were compared between patients relapsing or remaining in remission when tapering DMARDs. Demographic and disease-specific parameters were included in multivariate logistic regression analysis for defining predictors of relapse. Results Moderate-to-high MBDA scores were found in 33% of patients with RA overall. Twice as many patients who relapsed (58%) had moderate/high MBDA compared with patients who remained in remission (21%). Baseline MBDA scores were significantly higher in patients with RA who were relapsing than those remaining in stable remission (N=94; p=0.0001) and those tapering/stopping (N=59; p=0.0001). Multivariate regression analysis identified MBDA scores as independent predictor for relapses in addition to anticitrullinated protein antibody (ACPA) status. Relapse rates were low (13%) in patients who were MBDA-/ACPA-, moderate in patients who were MBDA+/ACPA- (33.3%) and MBDA-ACPA+ (31.8%) and high in patients who were MBDA+/ACPA+ (76.4%). Conclusions MBDA improved the prediction of relapses in patients with RA in stable remission undergoing DMARD tapering. If combined with ACPA testing, MBDA allowed prediction of relapse in more than 80% of the patients. Trial registration number EudraCT 2009-015740-42. KW - Drug-free remission KW - Clinical remission KW - Validation KW - Synovitis Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187519 VL - 75 IS - 9 ER - TY - JOUR A1 - De Palma, Adriana A1 - Abrahamczyk, Stefan A1 - Aizen, Marcelo A. A1 - Albrecht, Matthias A1 - Basset, Yves A1 - Bates, Adam A1 - Blake, Robin J. A1 - Boutin, Céline A1 - Bugter, Rob A1 - Connop, Stuart A1 - Cruz-López, Leopoldo A1 - Cunningham, Saul A. A1 - Darvill, Ben A1 - Diekötter, Tim A1 - Dorn, Silvia A1 - Downing, Nicola A1 - Entling, Martin H. A1 - Farwig, Nina A1 - Felicioli, Antonio A1 - Fonte, Steven J. A1 - Fowler, Robert A1 - Franzen, Markus Franzén A1 - Goulson, Dave A1 - Grass, Ingo A1 - Hanley, Mick E. A1 - Hendrix, Stephen D. A1 - Herrmann, Farina A1 - Herzog, Felix A1 - Holzschuh, Andrea A1 - Jauker, Birgit A1 - Kessler, Michael A1 - Knight, M. E. A1 - Kruess, Andreas A1 - Lavelle, Patrick A1 - Le Féon, Violette A1 - Lentini, Pia A1 - Malone, Louise A. A1 - Marshall, Jon A1 - Martínez Pachón, Eliana A1 - McFrederick, Quinn S. A1 - Morales, Carolina L. A1 - Mudri-Stojnic, Sonja A1 - Nates-Parra, Guiomar A1 - Nilsson, Sven G. A1 - Öckinger, Erik A1 - Osgathorpe, Lynne A1 - Parra-H, Alejandro A1 - Peres, Carlos A. A1 - Persson, Anna S. A1 - Petanidou, Theodora A1 - Poveda, Katja A1 - Power, Eileen F. A1 - Quaranta, Marino A1 - Quintero, Carolina A1 - Rader, Romina A1 - Richards, Miriam H. A1 - Roulston, T’ai A1 - Rousseau, Laurent A1 - Sadler, Jonathan P. A1 - Samnegård, Ulrika A1 - Schellhorn, Nancy A. A1 - Schüepp, Christof A1 - Schweiger, Oliver A1 - Smith-Pardo, Allan H. A1 - Steffan-Dewenter, Ingolf A1 - Stout, Jane C. A1 - Tonietto, Rebecca K. A1 - Tscharntke, Teja A1 - Tylianakis, Jason M. A1 - Verboven, Hans A. F. A1 - Vergara, Carlos H. A1 - Verhulst, Jort A1 - Westphal, Catrin A1 - Yoon, Hyung Joo A1 - Purvis, Andy T1 - Predicting bee community responses to land-use changes: Effects of geographic and taxonomic biases JF - Scientific Reports N2 - Land-use change and intensification threaten bee populations worldwide, imperilling pollination services. Global models are needed to better characterise, project, and mitigate bees' responses to these human impacts. The available data are, however, geographically and taxonomically unrepresentative; most data are from North America and Western Europe, overrepresenting bumblebees and raising concerns that model results may not be generalizable to other regions and taxa. To assess whether the geographic and taxonomic biases of data could undermine effectiveness of models for conservation policy, we have collated from the published literature a global dataset of bee diversity at sites facing land-use change and intensification, and assess whether bee responses to these pressures vary across 11 regions (Western, Northern, Eastern and Southern Europe; North, Central and South America; Australia and New Zealand; South East Asia; Middle and Southern Africa) and between bumblebees and other bees. Our analyses highlight strong regionally-based responses of total abundance, species richness and Simpson's diversity to land use, caused by variation in the sensitivity of species and potentially in the nature of threats. These results suggest that global extrapolation of models based on geographically and taxonomically restricted data may underestimate the true uncertainty, increasing the risk of ecological surprises. KW - bee community KW - land-use change KW - intensification KW - geographic biases KW - taxonomic biases KW - global dataset Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167642 VL - 6 ER - TY - JOUR A1 - Rücker, Viktoria A1 - Keil, Ulrich A1 - Fitzgerald, Anthony P A1 - Malzahn, Uwe A1 - Prugger, Christof A1 - Ertl, Georg A1 - Heuschmann, Peter U A1 - Neuhauser, Hannelore T1 - Predicting 10-Year Risk of Fatal Cardiovascular Disease in Germany: An Update Based on the SCORE-Deutschland Risk Charts JF - PLoS ONE N2 - Estimation of absolute risk of cardiovascular disease (CVD), preferably with population-specific risk charts, has become a cornerstone of CVD primary prevention. Regular recalibration of risk charts may be necessary due to decreasing CVD rates and CVD risk factor levels. The SCORE risk charts for fatal CVD risk assessment were first calibrated for Germany with 1998 risk factor level data and 1999 mortality statistics. We present an update of these risk charts based on the SCORE methodology including estimates of relative risks from SCORE, risk factor levels from the German Health Interview and Examination Survey for Adults 2008–11 (DEGS1) and official mortality statistics from 2012. Competing risks methods were applied and estimates were independently validated. Updated risk charts were calculated based on cholesterol, smoking, systolic blood pressure risk factor levels, sex and 5-year age-groups. The absolute 10-year risk estimates of fatal CVD were lower according to the updated risk charts compared to the first calibration for Germany. In a nationwide sample of 3062 adults aged 40–65 years free of major CVD from DEGS1, the mean 10-year risk of fatal CVD estimated by the updated charts was lower by 29% and the estimated proportion of high risk people (10-year risk > = 5%) by 50% compared to the older risk charts. This recalibration shows a need for regular updates of risk charts according to changes in mortality and risk factor levels in order to sustain the identification of people with a high CVD risk. KW - fatal cardiovascular disease KW - SCORE KW - Germany Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166804 VL - 11 IS - 9 ER - TY - JOUR A1 - Drakulić, Sanja A1 - Feldhaar, Heike A1 - Lisičić, Duje A1 - Mioč, Mia A1 - Cizelj, Ivan A1 - Seiler, Michael A1 - Spatz, Theresa A1 - Rödel, Mark-Oliver T1 - Population-specific effects of developmental temperature on body condition and jumping performance of a widespread European frog JF - Ecology and Evolution N2 - All physiological processes of ectotherms depend on environmental temperature. Thus, adaptation of physiological mechanisms to the thermal environments is important for achieving optimal performance and fitness. The European Common Frog, Rana temporaria, is widely distributed across different thermal habitats. This makes it an exceptional model for studying the adaptations to different thermal conditions. We raised tadpoles from Germany and Croatia at two constant temperature treatments (15°C, 20°C), and under natural temperature fluctuations (in outdoor treatments), and tested how different developmental temperatures affected developmental traits, that is, length of larval development, morphometrics, and body condition, as well as jumping performance of metamorphs. Our results revealed population‐specific differences in developmental time, body condition, and jumping performance. Croatian frogs developed faster in all treatments, were heavier, in better body condition, and had longer hind limbs and better jumping abilities than German metamorphs. The populations further differed in thermal sensitivity of jumping performance. While metamorphs from Croatia increased their jumping performance with higher temperatures, German metamorphs reached their performance maximum at lower temperatures. These population‐specific differences in common environments indicate local genetic adaptation, with southern populations being better adapted to higher temperatures than those from north of the Alps. KW - Amphibians KW - ectotherms KW - physiological traits KW - plasticity KW - thermal adaptation Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164960 VL - 6 IS - 10 ER - TY - JOUR A1 - Kramer, Susanne A1 - Piper, Sophie A1 - Estevez, Antonio A1 - Carrington, Mark T1 - Polycistronic trypanosome mRNAs are a target for the exosome JF - Molecular and Biochemical Parasitology N2 - Eukaryotic cells have several mRNA quality control checkpoints to avoid the production of aberrant proteins. Intron-containing mRNAs are actively degraded by the nuclear exosome, prevented from nuclear exit and, if these systems fail, degraded by the cytoplasmic NMD machinery. Trypanosomes have only two introns. However, they process mRNA5 from long polycistronic precursors by trans-splicing and polycistronic mRNA molecules frequently arise from any missed splice site. Here, we show that RNAi depletion of the trypanosome exosome, but not of the cytoplasmic 5'-3' exoribonuclease XRNA or the NMD helicase UPF1, causes accumulation of oligocistronic mRNA5. We have also revisited the localization of the trypanosome exosome by expressing eYFP-fusion proteins of the exosome subunits RRP44 and RRP6. Both proteins are significantly enriched in the nucleus. Together with published data, our data suggest a major nuclear function of the trypanosome exosome in rRNA, snoRNA and mRNA quality control. KW - Trypanosoma brucei KW - Exosome KW - NMD KW - Polycistronic mRNA KW - trans-splicing KW - Trypanosomes Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191350 VL - 205 IS - 1-2 ER - TY - JOUR A1 - Mildner, Stephanie A1 - Roces, Flavio T1 - Plasticity of Daily Behavioral Rhythms in Foragers and Nurses of the Ant Camponotus rufipes: Influence of Social Context and Feeding Times JF - PLoS One N2 - Daily activities within an ant colony need precise temporal organization, and an endogenous clock appears to be essential for such timing processes. A clock drives locomotor rhythms in isolated workers in a number of ant species, but its involvement in activities displayed in the social context is unknown. We compared locomotor rhythms in isolated individuals and behavioral rhythms in the social context of workers of the ant Camponotus rufipes. Both forager and nurse workers exhibited circadian rhythms in locomotor activity under constant conditions, indicating the involvement of an endogenous clock. Activity was mostly nocturnal and synchronized with the 12:12h light-dark-cycle. To evaluate whether rhythmicity was maintained in the social context and could be synchronized with non-photic zeitgebers such as feeding times, daily behavioral activities of single workers inside and outside the nest were quantified continuously over 24 hours in 1656 hours of video recordings. Food availability was limited to a short time window either at day or at night, thus mimicking natural conditions of temporally restricted food access. Most foragers showed circadian foraging behavior synchronized with food availability, either at day or nighttime. When isolated thereafter in single locomotor activity monitors, foragers mainly displayed arrhythmicity. Here, high mortality suggested potential stressful effects of the former restriction of food availability. In contrast, nurse workers showed high overall activity levels in the social context and performed their tasks all around the clock with no circadian pattern, likely to meet the needs of the brood. In isolation, the same individuals exhibited in turn strong rhythmic activity and nocturnality. Thus, endogenous activity rhythms were inhibited in the social context, and timing of daily behaviors was flexibly adapted to cope with task demands. As a similar socially-mediated plasticity in circadian rhythms was already shown in honey bees, the temporal organization in C. rufipes and honey bees appear to share similar basic features. KW - honey bees KW - biological locomotion KW - foraging KW - circadian rhythms KW - chronobiology KW - insects KW - nurses KW - ants Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148010 VL - 12 IS - 1 ER - TY - JOUR A1 - Audehm, P. A1 - Schmidt, M. A1 - Brück, S. A1 - Tietze, T. A1 - Gräfe, J. A1 - Macke, S. A1 - Schütz, G. A1 - Goering, E. T1 - Pinned orbital moments - A new contribution to magnetic anisotropy JF - Scientific Reports N2 - Reduced dimensionality and symmetry breaking at interfaces lead to unusual local magnetic configurations, such as glassy behavior, frustration or increased anisotropy. The interface between a ferromagnet and an antiferromagnet is such an example for enhanced symmetry breaking. Here we present detailed X-ray magnetic circular dichroism and X-ray resonant magnetic reflectometry investigations on the spectroscopic nature of uncompensated pinned magnetic moments in the antiferromagnetic layer of a typical exchange bias system. Unexpectedly, the pinned moments exhibit nearly pure orbital moment character. This strong orbital pinning mechanism has not been observed so far and is not discussed in literature regarding any theory for local magnetocrystalline anisotropy energies in magnetic systems. To verify this new phenomenon we investigated the effect at different temperatures. We provide a simple model discussing the observed pure orbital moments, based on rotatable spin magnetic moments and pinned orbital moments on the same atom. This unexpected observation leads to a concept for a new type of anisotropy energy. KW - pinned orbital moments KW - ferromagnet KW - antiferromagnet KW - anisotropy energy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167727 VL - 6 IS - 25517 ER - TY - JOUR A1 - Dyksik, M. A1 - Motyka, M. A1 - Kurka, M. A1 - Ryczo, K. A1 - Dallner, M. A1 - Höfling, S. A1 - Kamp, M. A1 - Sęk, G. A1 - Misiwicz, J. T1 - Photoluminescence quenching mechanisms in type IIInAs/GaInSb QWs on InAs substrates JF - Optical and Quantum Electronics N2 - Optical properties of AlSb/InAs/GaInSb/InAs/AlSb quantum wells (QWs) grown on an InAs substrate were investigated from the point of view of room temperature emission in the mid- and long-wavelength infrared ranges. By means of two independent techniques of optical spectroscopy, photoreflectance and temperature-dependent photoluminescence, it was proven that the main process limiting the performance of such InAs substrate-based type II structures is related to the escape of carriers from the hole ground state of the QW. Two nonradiative recombination channels were identified. The main process was attributed to holes tunneling to the valence band of the GaAsSb spacing layer and the second one with trapping of holes by native defects located in the same layer. KW - Interband cascade lasers KW - Quantum wells KW - MU-M KW - Fourier-transform spectroscopy KW - Mid-infrared photoluminescence KW - Type II quantum wells KW - Localized states Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204672 VL - 48 IS - 401 ER - TY - JOUR A1 - Wohlgemuth, Matthias A1 - Mitric, Roland T1 - Photochemical Chiral Symmetry Breaking in Alanine JF - Journal of Physical Chemistry A N2 - We introduce a general theoretical approach for the simulation of photochemical dynamics under the influence of circularly polarized light to explore the possibility of generating enantiomeric enrichment through polarized-light-selective photochemistry. The method is applied to the simulation of the photolysis of alanine, a prototype chiral amino acid. We show that a systematic enantiomeric enrichment can be obtained depending on the helicity of the circularly polarized light that induces the excited-state photochemistry of alanine. By analyzing the patterns of the photoinduced fragmentation of alanine we find an inducible enantiomeric enrichment up to 1.7%, which is also in good correspondence to the experimental findings. Our method is generally applicable to complex systems and might serve to systematically explore the photochemical origin of homochirality. KW - circularly-polarized light KW - amino-acids KW - homochirality KW - molecular dynamics KW - dichroism Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158557 UR - https://pubs.acs.org/doi/10.1021/acs.jpca.6b07611 N1 - This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Physical Chemistry A, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.jpca.6b07611 VL - 45 IS - 120 ER - TY - JOUR A1 - Cui, Huanhuan A1 - Schlesinger, Jenny A1 - Schoenhals, Sophia A1 - Tonjes, Martje A1 - Dunkel, Ilona A1 - Meierhofer, David A1 - Cano, Elena A1 - Schulz, Kerstin A1 - Berger, Michael F. A1 - Haack, Timm A1 - Abdelilah-Seyfried, Salim A1 - Bulyk, Martha L. A1 - Sauer, Sascha A1 - Sperling, Silke R. T1 - Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA JF - Nucleic Acids Research N2 - DPF3 (BAF45c) is a member of the BAF chromatin remodeling complex. Two isoforms have been described, namely DPF3a and DPF3b. The latter binds to acetylated and methylated lysine residues of histones. Here, we elaborate on the role of DPF3a and describe a novel pathway of cardiac gene transcription leading to pathological cardiac hypertrophy. Upon hypertrophic stimuli, casein kinase 2 phosphorylates DPF3a at serine 348. This initiates the interaction of DPF3a with the transcriptional repressors HEY, followed by the release of HEY from the DNA. Moreover, BRG1 is bound by DPF3a, and is thus recruited to HEY genomic targets upon interaction of the two components. Consequently, the transcription of downstream targets such as NPPA and GATA4 is initiated and pathological cardiac hypertrophy is established. In human, DPF3a is significantly up-regulated in hypertrophic hearts of patients with hypertrophic cardiomyopathy or aortic stenosis. Taken together, we show that activation of DPF3a upon hypertrophic stimuli switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure. KW - phosphorylation KW - DPF3a KW - HEY repressors KW - DNA KW - cardiac hypertrophy Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166391 VL - 44 IS - 6 ER - TY - JOUR A1 - Viera, Jonathan Trujillo A1 - El-Merahbi, Rabih A1 - Nieswandt, Bernhard A1 - Stegner, David A1 - Sumara, Grzegorz T1 - Phospholipases D1 and D2 Suppress Appetite and Protect against Overweight JF - PLoS ONE N2 - Obesity is a major risk factor predisposing to the development of peripheral insulin resistance and type 2 diabetes (T2D). Elevated food intake and/or decreased energy expenditure promotes body weight gain and acquisition of adipose tissue. Number of studies implicated phospholipase D (PLD) enzymes and their product, phosphatidic acid (PA), in regulation of signaling cascades controlling energy intake, energy dissipation and metabolic homeostasis. However, the impact of PLD enzymes on regulation of metabolism has not been directly determined so far. In this study we utilized mice deficient for two major PLD isoforms, PLD1 and PLD2, to assess the impact of these enzymes on regulation of metabolic homeostasis. We showed that mice lacking PLD1 or PLD2 consume more food than corresponding control animals. Moreover, mice deficient for PLD2, but not PLD1, present reduced energy expenditure. In addition, deletion of either of the PLD enzymes resulted in development of elevated body weight and increased adipose tissue content in aged animals. Consistent with the fact that elevated content of adipose tissue predisposes to the development of hyperlipidemia and insulin resistance, characteristic for the pre-diabetic state, we observed that Pld1\(^{-/-}\) and Pld2\(^{-/-}\) mice present elevated free fatty acids (FFA) levels and are insulin as well as glucose intolerant. In conclusion, our data suggest that deficiency of PLD1 or PLD2 activity promotes development of overweight and diabetes. KW - enzyme regulation KW - insulin resistance KW - body weight KW - mouse models KW - bioenergetics KW - insulin KW - hypothalamus KW - adipose tissue Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-179729 VL - 11 IS - 6 ER - TY - JOUR A1 - Richter, K. A1 - Mathes, V. A1 - Fronius, M. A1 - Althaus, M. A1 - Hecker, A. A1 - Krasteva-Christ, G. A1 - Padberg, W. A1 - Hone, A. J. A1 - McIntosh, J. M. A1 - Zakrzewicz, A. A1 - Grau, V. T1 - Phosphocholine - an agonist of metabotropic but not of ionotropic functions of α9-containing nicotinic acetylcholine receptors JF - Scientific Reports N2 - We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1β release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing α9 and α10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of α9 subunits or heteromeric receptors containing α9 and α10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions. KW - phosphocholine KW - interleukin-1β KW - nicotinic acetylcholine receptors Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167655 VL - 6 IS - 28660 ER - TY - JOUR A1 - Eisenhardt, Anja E. A1 - Sprenger, Adrian A1 - Röring, Michael A1 - Herr, Ricarda A1 - Weinberg, Florian A1 - Köhler, Martin A1 - Braun, Sandra A1 - Orth, Joachim A1 - Diedrich, Britta A1 - Lanner, Ulrike A1 - Tscherwinski, Natalja A1 - Schuster, Simon A1 - Dumaz, Nicolas A1 - Schmidt, Enrico A1 - Baumeister, Ralf A1 - Schlosser, Andreas A1 - Dengjel, Jörn A1 - Brummer, Tilman T1 - Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles JF - Oncotarget N2 - B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1 double deficient DT40 lymphoma cells complemented with wildtype or mutant B-Raf expression vectors. Using a multi-protease digestion approach, we identified a novel ubiquitination site and provide a detailed B-Raf phospho-map. Importantly, we identify two evolutionary conserved phosphorylation clusters around T401 and S419 in the B-Raf hinge region. SILAC labelling and genetic/biochemical follow-up revealed that these clusters are phosphorylated in the contexts of oncogenic Ras, sorafenib induced Raf dimerization and in the background of the V600E mutation. We further show that the vemurafenib sensitive phosphorylation of the T401 cluster occurs in trans within a Raf dimer. Substitution of the Ser/Thr-residues of this cluster by alanine residues enhances the transforming potential of B-Raf, indicating that these phosphorylation sites suppress its signaling output. Moreover, several B-Raf phosphorylation sites, including T401 and S419, are somatically mutated in tumors, further illustrating the importance of phosphorylation for the regulation of this kinase. KW - BRAF KW - proteomics KW - phosphorylation KW - sorafenib KW - protein-protein interaction Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166529 VL - 7 IS - 18 ER - TY - JOUR A1 - Ene, Iuliana V. A1 - Lohse, Matthew B. A1 - Vladu, Adrian V. A1 - Morschhäuser, Joachim A1 - Johnson, Alexander D. A1 - Bennett, Richard J. T1 - Phenotypic Profiling Reveals that Candida albicans Opaque Cells Represent a Metabolically Specialized Cell State Compared to Default White Cells JF - mBio N2 - The white-opaque switch is a bistable, epigenetic transition affecting multiple traits in Candida albicans including mating, immunogenicity, and niche specificity. To compare how the two cell states respond to external cues, we examined the fitness, phenotypic switching, and filamentation properties of white cells and opaque cells under 1,440 different conditions at 25°C and 37°C. We demonstrate that white and opaque cells display striking differences in their integration of metabolic and thermal cues, so that the two states exhibit optimal fitness under distinct conditions. White cells were fitter than opaque cells under a wide range of environmental conditions, including growth at various pHs and in the presence of chemical stresses or antifungal drugs. This difference was exacerbated at 37°C, consistent with white cells being the default state of C. albicans in the mammalian host. In contrast, opaque cells showed greater fitness than white cells under select nutritional conditions, including growth on diverse peptides at 25°C. We further demonstrate that filamentation is significantly rewired between the two states, with white and opaque cells undergoing filamentous growth in response to distinct external cues. Genetic analysis was used to identify signaling pathways impacting the white-opaque transition both in vitro and in a murine model of commensal colonization, and three sugar sensing pathways are revealed as regulators of the switch. Together, these findings establish that white and opaque cells are programmed for differential integration of metabolic and thermal cues and that opaque cells represent a more metabolically specialized cell state than the default white state. KW - biology Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165818 VL - 7 IS - 6 ER - TY - JOUR A1 - Görl, Daniel A1 - Soberats, Bartolome A1 - Herbst, Stefanie A1 - Stepanenko, Vladimir A1 - Würthner, Frank T1 - Perylene bisimide hydrogels and lyotropic liquid crystals with temperature-responsive color change JF - Chemical Science N2 - The self-assembly of perylene bisimide (PBI) dyes bearing oligo ethylene glycol (OEG) units in water affords responsive functional nanostructures characterized by their lower critical solution temperature (LCST). Tuning of the LCST is realized by a supramolecular approach that relies on two structurally closely related PBI–OEG molecules. The two PBIs socially co-assemble in water and the resulting nanostructures exhibit a single LCST in between the transition temperatures of the aggregates formed by single components. This permits to precisely tune the transition from a hydrogel to a lyotropic liquid crystal state at temperatures between 26 and 51 °C by adjusting the molar fraction of the two PBIs. Owing to concomitant changes in PBI–PBI interactions this phase transition affords a pronounced color change with “fluorescence-on” response that can be utilized as a smart temperature sensory system. KW - perylene bisimide hydrogels Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162459 VL - 7 IS - 11 ER - TY - JOUR A1 - Chillo, Omary A1 - Kleinert, Eike Christian A1 - Lautz, Thomas A1 - Lasch, Manuel A1 - Pagel, Judith-Irina A1 - Heun, Yvonn A1 - Troidl, Kerstin A1 - Fischer, Silvia A1 - Caballero-Martinez, Amelia A1 - Mauer, Annika A1 - Kurz, Angela R. M. A1 - Assmann, Gerald A1 - Rehberg, Markus A1 - Kanse, Sandip M. A1 - Nieswandt, Bernhard A1 - Walzog, Barbara A1 - Reichel, Christoph A. A1 - Mannell, Hanna A1 - Preissner, Klaus T. A1 - Deindl, Elisabeth T1 - Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function JF - Cell Reports N2 - The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases. KW - Mast cells Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164800 VL - 16 IS - 8 ER - TY - JOUR A1 - Regn, Michael A1 - Laggerbauer, Bernhard A1 - Jentzsch, Claudia A1 - Ramanujam, Deepak A1 - Ahles, Andrea A1 - Sichler, Sonja A1 - Calzada-Wack, Julia A1 - Koenen, Rory R. A1 - Braun, Attila A1 - Nieswandt, Bernhard A1 - Engelhardt, Stefan T1 - Peptidase inhibitor 16 is a membrane-tethered regulator of chemerin processing in the myocardium JF - Journal of Molecular and Cellular Cardiology N2 - A key response of the myocardium to stress is the secretion of factors with paracrine or endocrine function. Intriguing in this respect is peptidase inhibitor 16 (PI16), a member of the CAP family of proteins which we found to be highly upregulated in cardiac disease. Up to this point, the mechanism of action and physiological function of PI16 remained elusive. Here, we show that PI16 is predominantly expressed by cardiac fibroblasts, which expose PI16 to the interstitium via a glycophosphatidylinositol (-GPI) membrane anchor. Based on a reported genetic association of PI16 and plasma levels of the chemokine chemerin, we investigated whether PI16 regulates post-translational processing of its precursor pro-chemerin. PI16-deficient mice were engineered and found to generate higher levels of processed chemerin than wildtype mice. Purified recombinant PI16 efficiently inhibited cathepsin K, a chemerin-activating protease, in vitro. Moreover, we show that conditioned medium from PI16-overexpressing cells impaired the activation of pro-chemerin. Together, our data indicate that PI16 suppresses chemerin activation in the myocardium and suggest that this circuit may be part of the cardiac stress response. KW - Cells KW - Activation KW - Purification KW - Protein KW - Peptidase inhibitor 16 (PI16) KW - Identification KW - Inflammation KW - Adipokine KW - Metabolism KW - Heart KW - Mice KW - Chemerin KW - RARRES2 KW - TIG2 KW - Protease inhibition KW - Chemerin processing Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-187039 VL - 99 ER - TY - JOUR A1 - Joschinski, Jens A1 - Beer, Katharina A1 - Helfrich-Förster, Charlotte A1 - Krauss, Jochen T1 - Pea Aphids (Hemiptera: Aphididae) Have Diurnal Rhythms When Raised Independently of a Host Plant JF - Journal of Insect Science N2 - Seasonal timing is assumed to involve the circadian clock, an endogenous mechanism to track time and measure day length. Some debate persists, however, and aphids were among the first organisms for which circadian clock involvement was questioned. Inferences about links to phenology are problematic, as the clock itself is little investigated in aphids. For instance, it is unknown whether aphids possess diurnal rhythms at all. Possibly, the close interaction with host plants prevents independent measurements of rhythmicity. We reared the pea aphid Acyrthosiphon pisum (Harris) on an artificial diet, and recorded survival, moulting, and honeydew excretion. Despite their plant-dependent life style, aphids were independently rhythmic under light–dark conditions. This first demonstration of diurnal aphid rhythms shows that aphids do not simply track the host plant’s rhythmicity. KW - artificial diet KW - circadian clock KW - hourglass clock KW - Acyrthosiphon pisum KW - photoperiodism Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168783 VL - 16 IS - 1 ER - TY - JOUR A1 - Bousquet, J. A1 - Anto, J. M. A1 - Akdis, M. A1 - Auffray, C. A1 - Keil, T. A1 - Momas, I. A1 - Postma, D. S. A1 - Valenta, R. A1 - Wickman, M. A1 - Cambon-Thomsen, A. A1 - Haahtela, T. A1 - Lambrecht, B. N. A1 - Lodrup Carlsen, K. C. A1 - Koppelman, G. H. A1 - Sunyer, J. A1 - Zuberbier, T. A1 - Annesi-Maesano, I. A1 - Arno, A. A1 - Bindslev-Jensen, C. A1 - De Carlo, G. A1 - Forastiere, F. A1 - Heinrich, J. A1 - Kowalski, M. L. A1 - Maier, D. A1 - Melen, E. A1 - Palkonen, S. A1 - Smit, H. A. A1 - Standl, M. A1 - Wright, J. A1 - Asarnoj, A. A1 - Benet, M. A1 - Ballardini, N. A1 - Garcia-Aymerich, J. A1 - Gehring, U. A1 - Guerra, S. A1 - Hohman, C. A1 - Kull, I. A1 - Lupinek, C. A1 - Pinart, M. A1 - Skrindo, I. A1 - Westman, M. A1 - Smagghe, D. A1 - Akdis, C. A1 - Albang, R. A1 - Anastasova, V. A1 - Anderson, N. A1 - Bachert, C. A1 - Ballereau, S. A1 - Ballester, F. A1 - Basagana, X. A1 - Bedbrook, A. A1 - Bergstrom, A. A1 - von Berg, A. A1 - Brunekreef, B. A1 - Burte, E. A1 - Carlsen, K.H. A1 - Chatzi, L. A1 - Coquet, J.M. A1 - Curin, M. A1 - Demoly, P. A1 - Eller, E. A1 - Fantini, M.P. A1 - Gerhard, B. A1 - Hammad, H. A1 - von Hertzen, L. A1 - Hovland, V. A1 - Jacquemin, B. A1 - Just, J. A1 - Keller, T. A1 - Kerkhof, M. A1 - Kiss, R. A1 - Kogevinas, M. A1 - Koletzko, S. A1 - Lau, S. A1 - Lehmann, I. A1 - Lemonnier, N. A1 - McEachan, R. A1 - Makela, M. A1 - Mestres, J. A1 - Minina, E. A1 - Mowinckel, P. A1 - Nadif, R. A1 - Nawijn, M. A1 - Oddie, S. A1 - Pellet, J. A1 - Pin, I. A1 - Porta, D. A1 - Rancière, F. A1 - Rial-Sebbag, A. A1 - Schuijs, M.J. A1 - Siroux, V. A1 - Tischer, C.G. A1 - Torrent, M. A1 - Varraso, R. A1 - De Vocht, J. A1 - Wenger, K. A1 - Wieser, S. A1 - Xu, C. T1 - Paving the way of systems biology and precision medicine in allergic diseases: the MeDALL success story Mechanisms of the Development of ALLergy; EUFP7-CP-IP; Project No: 261357; 2010-2015 JF - Allergy N2 - MeDALL (Mechanisms of the Development of ALLergy; EU FP7-CP-IP; Project No: 261357; 2010-2015) has proposed an innovative approach to develop early indicators for the prediction, diagnosis, prevention and targets for therapy. MeDALL has linked epidemiological, clinical and basic research using a stepwise, large-scale and integrative approach: MeDALL data of precisely phenotyped children followed in 14 birth cohorts spread across Europe were combined with systems biology (omics, IgE measurement using microarrays) and environmental data. Multimorbidity in the same child is more common than expected by chance alone, suggesting that these diseases share causal mechanisms irrespective of IgE sensitization. IgE sensitization should be considered differently in monosensitized and polysensitized individuals. Allergic multimorbidities and IgE polysensitization are often associated with the persistence or severity of allergic diseases. Environmental exposures are relevant for the development of allergy-related diseases. To complement the population-based studies in children, MeDALL included mechanistic experimental animal studies and in vitro studies in humans. The integration of multimorbidities and polysensitization has resulted in a new classification framework of allergic diseases that could help to improve the understanding of genetic and epigenetic mechanisms of allergy as well as to better manage allergic diseases. Ethics and gender were considered. MeDALL has deployed translational activities within the EU agenda. KW - asthma KW - birth cohort KW - atopic-dermatitis KW - immune-responses KW - IgE KW - multimorbidity KW - polysensitization KW - rhinitis KW - chronic respiratory-diseases KW - childhood asthma KW - immunological reactivity KW - IgE sensitazion KW - immunoglobulin-e KW - integraed care Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186858 VL - 71 IS - 11 ER - TY - JOUR A1 - Mussel, Patrick A1 - Ulrich, Nathalie A1 - Allen, John J. B. A1 - Osinsky, Roman A1 - Hewig, Johannes T1 - Patterns of theta oscillation reflect the neural basis of individual differences in epistemic motivation JF - Scientific Reports N2 - Theta oscillations in the EEG have been shown to reflect ongoing cognitive processes related to mental effort. Here, we show that the pattern of theta oscillation in response to varying cognitive demands reflects stable individual differences in the personality trait epistemic motivation: Individuals with high levels of epistemic motivation recruit relatively more cognitive resources in response to situations possessing high, compared to low, cognitive demand; individuals with low levels do not show such a specific response. Our results provide direct evidence for the theory of the construct need for cognition and add to our understanding of the neural processes underlying theta oscillations. More generally, we provide an explanation how individual differences in personality traits might be represented on a neural level. KW - Motivation KW - Personality Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146957 VL - 6 ER - TY - JOUR A1 - Wolf, Karen A1 - Braun, Attila A1 - Haining, Elizabeth J. A1 - Tseng, Yu-Lun A1 - Kraft, Peter A1 - Schuhmann, Michael K. A1 - Gotru, Sanjeev K. A1 - Chen, Wenchun A1 - Hermanns, Heike M. A1 - Stoll, Guido A1 - Lesch, Klaus-Peter A1 - Nieswandt, Bernhard T1 - Partially Defective Store Operated Calcium Entry and Hem(ITAM) Signaling in Platelets of Serotonin Transporter Deficient Mice JF - PLoS One N2 - Background Serotonin (5-hydroxytryptamin, 5-HT) is an indolamine platelet agonist, biochemically derived from tryptophan. 5-HT is secreted from the enterochromaffin cells into the gastrointestinal tract and blood. Blood 5-HT has been proposed to regulate hemostasis by acting as a vasoconstrictor and by triggering platelet signaling through 5-HT receptor 2A (5HTR2A). Although platelets do not synthetize 5-HT, they take 5-HT up from the blood and store it in their dense granules which are secreted upon platelet activation. Objective To identify the molecular composite of the 5-HT uptake system in platelets and elucidate the role of platelet released 5-HT in thrombosis and ischemic stroke. Methods: 5-HT transporter knockout mice (5Htt\(^{-/-}\)) were analyzed in different in vitro and in vivo assays and in a model of ischemic stroke. Results In 5Htt\(^{-/-}\) platelets, 5-HT uptake from the blood was completely abolished and agonist-induced Ca2+ influx through store operated Ca\(^{2+}\) entry (SOCE), integrin activation, degranulation and aggregation responses to glycoprotein VI (GPVI) and C-type lectin-like receptor 2 (CLEC-2) were reduced. These observed in vitro defects in 5Htt\(^{-/-}\) platelets could be normalized by the addition of exogenous 5-HT. Moreover, reduced 5-HT levels in the plasma, an increased bleeding time and the formation of unstable thrombi were observed ex vivo under flow and in vivo in the abdominal aorta and carotid artery of 5Htt\(^{-/-}\) mice. Surprisingly, in the transient middle cerebral artery occlusion (tMCAO) model of ischemic stroke 5Htt\(^{-/-}\) mice showed nearly normal infarct volume and the neurological outcome was comparable to control mice. Conclusion Although secreted platelet 5-HT does not appear to play a crucial role in the development of reperfusion injury after stroke, it is essential to amplify the second phase of platelet activation through SOCE and plays an important role in thrombus stabilization. KW - platelets KW - serotonin KW - integrins KW - blood flow KW - collagens KW - platelet activation KW - platelet aggregation KW - ischemic stroke Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146399 VL - 11 IS - 1 ER - TY - JOUR A1 - Schuberth, Florian A1 - Henseler, Jörg A1 - Dijkstra, Theo K. T1 - Partial least squares path modeling using ordinal categorical indicators JF - Quality & Quantity N2 - This article introduces a new consistent variance-based estimator called ordinal consistent partial least squares (OrdPLSc). OrdPLSc completes the family of variance-based estimators consisting of PLS, PLSc, and OrdPLS and permits to estimate structural equation models of composites and common factors if some or all indicators are measured on an ordinal categorical scale. A Monte Carlo simulation (N =500) with different population models shows that OrdPLSc provides almost unbiased estimates. If all constructs are modeled as common factors, OrdPLSc yields estimates close to those of its covariance-based counterpart, WLSMV, but is less efficient. If some constructs are modeled as composites, OrdPLSc is virtually without competition. KW - polychoric correlation KW - composites KW - common factors KW - ordinal categorical indicators KW - consistent partial least squares KW - structural equation models Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144016 ER - TY - JOUR A1 - Isles, Anthony R. A1 - Ingason, Andrés A1 - Lowther, Chelsea A1 - Walters, James A1 - Gawlick, Micha A1 - Stöber, Gerald A1 - Rees, Elliott A1 - Martin, Joanna A1 - Little, Rosie B. A1 - Potter, Harry A1 - Georgieva, Lyudmila A1 - Pizzo, Lucilla A1 - Ozaki, Norio A1 - Aleksic, Branko A1 - Kushima, Itaru A1 - Ikeda, Masashi A1 - Iwata, Nakao A1 - Levinson, Douglas F. A1 - Gejman, Pablo V. A1 - Shi, Jianxin A1 - Sanders, Alan R. A1 - Duan, Jubao A1 - Willis, Joseph A1 - Sisodiya, Sanjay A1 - Costain, Gregory A1 - Werge, Thomas M. A1 - Degenhardt, Franziska A1 - Giegling, Ina A1 - Rujescu, Dan A1 - Hreidarsson, Stefan J. A1 - Saemundsen, Evald A1 - Ahn, Joo Wook A1 - Ogilvie, Caroline A1 - Girirajan, Santhosh D. A1 - Stefansson, Hreinn A1 - Stefansson, Kari A1 - O'Donovan, Michael C. A1 - Owen, Michael J. A1 - Bassett, Anne A1 - Kirov, George T1 - Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders JF - PLoS Genetics N2 - Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally expressed imprinted genes in the contribution of Copy Number Variants (CNVs) at this interval to the incidence of psychotic illness. This work will have tangible benefits for patients with 15q11.2-q13.3 duplications by aiding genetic counseling. KW - interstitial duplications KW - schizophrenia KW - developmental delay KW - autism spectrum disorder KW - parental origin KW - genetics Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166706 VL - 12 IS - 5 ER - TY - JOUR A1 - Politei, Juan M. A1 - Bouhassira, Didier A1 - Germain, Dominique P. A1 - Goizet, Cyril A1 - Guerrero-Sola, Antonio A1 - Hilz, Max J. A1 - Hutton, Elspeth J. A1 - Karaa, Amel A1 - Liuori, Rocco A1 - Üceyler, Nurcan A1 - Zeltzer, Lonnie K. A1 - Burlina, Alessandro T1 - Pain in fabry disease: practical recommendations for diagnosis and treatment JF - CNS Neuroscience & Therapeutics N2 - Aims: Patients with Fabry disease (FD) characteristically develop peripheral neuropathy at an early age, with pain being a crucial symptom of underlying pathology. However, the diagnosis of pain is challenging due to the heterogeneous and nonspecific symptoms. Practical guidance on the diagnosis and management of pain in FD is needed. Methods: In 2014, experts met to discuss recent advances on this topic and update clinical guidance. Results: Emerging disease-specific tools, including FabryScan, Fabry-specific Pediatric Health and Pain Questionnaire, and Wurzburg Fabry Pain Questionnaire, and more general tools like the Total Symptom Score can aid diagnosis, characterization, and monitoring of pain in patients with FD. These tools can be complemented by more objective and quantifiable sensory testing. In male and female patients of any age, pain related to FD can be an early indication to start disease-specific enzyme replacement therapy before potentially irreversible organ damage to the kidneys, heart, or brain occurs. Conclusion: To improve treatment outcomes, pain should be diagnosed early in unrecognized or newly identified FD patients. Treatment should include: (a) enzyme replacement therapy controlling the progression of underlying pathology; (b) adjunctive, symptomatic pain management with analgesics for chronic neuropathic and acute nociceptive, and inflammatory or mixed pain; and (c) lifestyle modifications. KW - Enzyme replacement therapy KW - Small fiber dysfunction KW - System involvement KW - Outcome survey KW - Fabry disease KW - Randomized controlled-trial KW - Chronic neuropathic pain KW - Agalsidase beta KW - Screening questionnaire KW - Dose reduction KW - Adult patients KW - Diagnosis KW - Pain KW - Peripheral nervous system Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188127 VL - 22 IS - 7 ER -