TY - JOUR A1 - Abdali, Narges A1 - Barth, Enrico A1 - Norouzy, Amir A1 - Schulz, Robert A1 - Nau, Werner M. A1 - Kleinekathofer, Ulrich A1 - Tauch, Andreas A1 - Benz, Roland T1 - Corynebacterium jeikeium jk0268 Constitutes for the 40 Amino Acid Long PorACj, Which Forms a Homooligomeric and Anion- Selective Cell Wall Channel JF - PLoS ONE N2 - Corynebacterium jeikeium, a resident of human skin, is often associated with multidrug resistant nosocomial infections in immunodepressed patients. C. jeikeium K411 belongs to mycolic acid-containing actinomycetes, the mycolata and contains a channel-forming protein as judged from reconstitution experiments with artificial lipid bilayer experiments. The channel-forming protein was present in detergent treated cell walls and in extracts of whole cells using organic solvents. A gene coding for a 40 amino acid long polypeptide possibly responsible for the pore-forming activity was identified in the known genome of C. jeikeium by its similar chromosomal localization to known porH and porA genes of other Corynebacterium strains. The gene jk0268 was expressed in a porin deficient Corynebacterium glutamicum strain. For purification temporarily histidine-tailed or with a GST-tag at the N-terminus, the homogeneous protein caused channel-forming activity with an average conductance of 1.25 nS in 1M KCl identical to the channels formed by the detergent extracts. Zero-current membrane potential measurements of the voltage dependent channel implied selectivity for anions. This preference is according to single-channel analysis caused by some excess of cationic charges located in the channel lumen formed by oligomeric alpha-helical wheels. The channel has a suggested diameter of 1.4 nm as judged from the permeability of different sized hydrated anions using the Renkin correction factor. Surprisingly, the genome of C. jeikeium contained only one gene coding for a cell wall channel of the PorA/PorH type found in other Corynebacterium species. The possible evolutionary relationship between the heterooligomeric channels formed by certain Corynebacterium strains and the homooligomeric pore of C. jeikeium is discussed. KW - antibiotics KW - detergents KW - anions KW - corynebacterium diphtheriae KW - membrane potential KW - corynebacteria KW - cell walls KW - permeability Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129989 VL - 8 IS - 10 ER - TY - JOUR A1 - Ablin, Jacob A1 - Fitzcharles, Mary-Ann A1 - Buskila, Dan A1 - Shir, Yoram A1 - Sommer, Claudia A1 - Häuser, Winfried T1 - Treatment of Fibromyalgia Syndrome: Recommendations of Recent Evidence-Based Interdisciplinary Guidelines with Special Emphasis on Complementary and Alternative Therapies JF - Evidence-Bayed Complementary and Alternative Medicine N2 - Objective. Current evidence indicates that there is no single ideal treatment for fibromyalgia syndrome (FMS). First choice treatment options remain debatable, especially concerning the importance of complementary and alternative medicine (CAM) treatments. Methods. Three evidence-based interdisciplinary guidelines on FMS in Canada, Germany, and Israel were compared for their first choice and CAM-recommendations. Results. All three guidelines emphasized a patient-tailored approach according to the key symptoms. Aerobic exercise, cognitive behavioral therapy, and multicomponent therapy were first choice treatments. The guidelines differed in the grade of recommendation for drug treatment. Anticonvulsants (gabapentin, pregabalin) and serotonin noradrenaline reuptake inhibitors (duloxetine, milnacipran) were strongly recommended by the Canadian and the Israeli guidelines. These drugs received only a weak recommendation by the German guideline. In consideration of CAM-treatments, acupuncture, hypnosis/guided imagery, and Tai Chi were recommended by the German and Israeli guidelines. The Canadian guidelines did not recommend any CAM therapy. Discussion. Recent evidence-based interdisciplinary guidelines concur on the importance of treatment tailored to the individual patient and further emphasize the need of self-management strategies (exercise, and psychological techniques). KW - metaanalysis KW - management KW - care Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122235 SN - 1741-427X ER - TY - JOUR A1 - Aistleitner, Karin A1 - Heinz, Christian A1 - Hoermann, Alexandra A1 - Heinz, Eva A1 - Montanaro, Jacqueline A1 - Schulz, Frederik A1 - Maier, Elke A1 - Pichler, Peter A1 - Benz, Roland A1 - Horn, Matthias T1 - Identification and Characterization of a Novel Porin Family Highlights a Major Difference in the Outer Membrane of Chlamydial Symbionts and Pathogens JF - PLoS ONE N2 - The Chlamydiae constitute an evolutionary well separated group of intracellular bacteria comprising important pathogens of humans as well as symbionts of protozoa. The amoeba symbiont Protochlamydia amoebophila lacks a homologue of the most abundant outer membrane protein of the Chlamydiaceae, the major outer membrane protein MOMP, highlighting a major difference between environmental chlamydiae and their pathogenic counterparts. We recently identified a novel family of putative porins encoded in the genome of P. amoebophila by in silico analysis. Two of these Protochlamydia outer membrane proteins, PomS (pc1489) and PomT (pc1077), are highly abundant in outer membrane preparations of this organism. Here we show that all four members of this putative porin family are toxic when expressed in the heterologous host Escherichia coli. Immunofluorescence analysis using antibodies against heterologously expressed PomT and PomS purified directly from elementary bodies, respectively, demonstrated the location of both proteins in the outer membrane of P. amoebophila. The location of the most abundant protein PomS was further confirmed by immuno-transmission electron microscopy. We could show that pomS is transcribed, and the corresponding protein is present in the outer membrane throughout the complete developmental cycle, suggesting an essential role for P. amoebophila. Lipid bilayer measurements demonstrated that PomS functions as a porin with anion-selectivity and a pore size similar to the Chlamydiaceae MOMP. Taken together, our results suggest that PomS, possibly in concert with PomT and other members of this porin family, is the functional equivalent of MOMP in P. amoebophila. This work contributes to our understanding of the adaptations of symbiotic and pathogenic chlamydiae to their different eukaryotic hosts. KW - cell wall KW - protochlamydia amoebophila KW - escherichia coli KW - matrix protein porin KW - gram negative bacteria KW - single channel analysis KW - developmental cycle KW - mycobacterium smegmatis KW - monoclonal antibodies KW - signal peptides Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131176 VL - 8 IS - 1 ER - TY - JOUR A1 - Al-Kassab, Jasser A1 - Thiesse, Frederic A1 - Buckel, Thomas T1 - RFID Data Analytics in Retail Logistics: A Case Example JF - Journal of Theoretical and Applied E-Commerce Research N2 - The growing interest in Radio Frequency Identification (RFID) technology in recent years has sparked an intensive debate on the benefits to be expected. With the growth of RFID implementations in size and scope comes a shift away from infrastructural aspects to the question of how to draw value from the large amounts of collected data. However, the necessary procedures for the handling of massive RFID data sets are still an under-researched issue. Against this background, the study presents results from a real-world trial conducted by a large apparel retailer. The objective of the trial was to explore the opportunities for generating novel performance indicators and reports on the reality of store processes and customer behavior on the sales floor. We give an overview of the algorithms used for RFID data processing and the interpretation of the resulting insights from a practitioner’s point of view. The case example thus provides an overview of the potential of RFID as a powerful tool for assortment optimization, customer research, store layout design, and other management tasks in retail. KW - RFID KW - apparel retail KW - store logistics KW - data management KW - business analytics Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129500 VL - 8 IS - 2 ER - TY - JOUR A1 - Almanzar, Giovanni A1 - Zlamy, Manuela A1 - Koppelstaetter, Christian A1 - Brunner, Andrea A1 - Jeller, Verena A1 - Duftner, Christina A1 - Dejaco, Christian A1 - Brunner, Juergen A1 - Prelog, Martina T1 - Increased replication of CD4+ naive T cells and changes in T cell homeostasis in a case of acute exacerbation of juvenile idiopathic arthritis: a case comparison study JF - Journal of Medical Case Reports N2 - Introduction Juvenile idiopathic arthritis is a heterogeneous T cell-mediated autoimmune disease with symptoms of premature aging of the immune system (immunosenescence). The present work is an investigation of immunosenescence parameters, such as quantity of naive and CD28- T cells, T cell receptor excision circles, relative telomere length and alterations of peripheral T cell replication, and was performed via comparison of a case of acute exacerbation of juvenile idiopathic arthritis against six patients with juvenile idiopathic arthritis with disease remission and six age-matched healthy donors over a follow-up course of 12 months. Case presentation Phenotypical T cell characterization and intracellular interferon γ, tumor necrosis factor α, and interleukin 2 production were studied in peripheral blood mononuclear cells from seven patients with juvenile idiopathic arthritis and six healthy control donors, with findings determined by flow cytometry. T cell receptor excision circles and relative telomere length quantification were performed on deoxyribonucleic acid isolated from naive (CD4+CD28+CD45RA+) T cells and investigated via reverse transcription polymerase chain reaction. Ki67 expression was studied by immunohistochemistry on naive T cells. The non-parametric Mann-Whitney U test and Wilcoxon test for two independent groups of variables were used to compare healthy donors with patients with juvenile idiopathic arthritis. During follow-up, patients with juvenile idiopathic arthritis showed lower total counts of naive and CD28-expressing T cells compared to healthy donors. Acute exacerbation led to low naive and CD28+ T cell populations and elevated proportions of Ki67-expressing CD4+ naive T cells. In conditions of exacerbation, T cell receptor excision circle numbers were in the lower range in patients with juvenile idiopathic arthritis and increased after follow-up. Healthy donors showed significantly higher relative telomere lengths compared to patients with juvenile idiopathic arthritis. Conclusions This investigation illustrates that the changes in T cell homeostasis in patients with juvenile idiopathic arthritis may be the result of several mechanisms, such as diminished thymus function and peripheral exertions to maintain the peripheral T cell pool. The results also demonstrate that hallmarks of immunosenescence such as decreased naive T cell levels and lower T cell receptor excision circle numbers can only be interpreted together with replication markers such as relative telomere length or Ki67 expression. KW - Exacerbation KW - Juvenile idiopathic arthritis KW - Naive T cells KW - T cell receptor excision circles Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96325 UR - http://www.jmedicalcasereports.com/content/7/1/135 ER - TY - JOUR A1 - Alsheimer, Manfred A1 - Link, Jana A1 - Jahn, Daniel A1 - Schmitt, Johannes A1 - Göb, Eva A1 - Baar, Johannes A1 - Ortega, Sagrario A1 - Benavente, Ricardo T1 - The Meiotic Nuclear Lamina Regulates Chromosome Dynamics and Promotes Efficient Homologous Recombination in the Mouse JF - PLoS Genetics N2 - The nuclear lamina is the structural scaffold of the nuclear envelope and is well known for its central role in nuclear organization and maintaining nuclear stability and shape. In the past, a number of severe human disorders have been identified to be associated with mutations in lamins. Extensive research on this topic has provided novel important clues about nuclear lamina function. These studies have contributed to the knowledge that the lamina constitutes a complex multifunctional platform combining both structural and regulatory functions. Here, we report that, in addition to the previously demonstrated significance for somatic cell differentiation and maintenance, the nuclear lamina is also an essential determinant for germ cell development. Both male and female mice lacking the short meiosis-specific A-type lamin C2 have a severely defective meiosis, which at least in the male results in infertility. Detailed analysis revealed that lamin C2 is required for telomere-driven dynamic repositioning of meiotic chromosomes. Loss of lamin C2 affects precise synapsis of the homologs and interferes with meiotic double-strand break repair. Taken together, our data explain how the nuclear lamina contributes to meiotic chromosome behaviour and accurate genome haploidization on a mechanistic level. KW - homologous chromosomes KW - homologous recombination KW - lamins KW - Oocytes KW - spermatocytes KW - synapsis KW - telomeres KW - testes Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96285 ER - TY - JOUR A1 - Amich, Jorge A1 - Schafferer, Lukas A1 - Haas, Hubertus A1 - Krappmann, Sven T1 - Regulation of Sulphur Assimilation Is Essential for Virulence and Affects Iron Homeostasis of the Human-Pathogenic Mould Aspergillus fumigatus JF - PLoS Pathogens N2 - Abstract Sulphur is an essential element that all pathogens have to absorb from their surroundings in order to grow inside their infected host. Despite its importance, the relevance of sulphur assimilation in fungal virulence is largely unexplored. Here we report a role of the bZIP transcription factor MetR in sulphur assimilation and virulence of the human pathogen Aspergillus fumigatus. The MetR regulator is essential for growth on a variety of sulphur sources; remarkably, it is fundamental for assimilation of inorganic S-sources but dispensable for utilization of methionine. Accordingly, it strongly supports expression of genes directly related to inorganic sulphur assimilation but not of genes connected to methionine metabolism. On a broader scale, MetR orchestrates the comprehensive transcriptional adaptation to sulphur-starving conditions as demonstrated by digital gene expression analysis. Surprisingly, A. fumigatus is able to utilize volatile sulphur compounds produced by its methionine catabolism, a process that has not been described before and that is MetR-dependent. The A. fumigatus MetR transcriptional activator is important for virulence in both leukopenic mice and an alternative mini-host model of aspergillosis, as it was essential for the development of pulmonary aspergillosis and supported the systemic dissemination of the fungus. MetR action under sulphur-starving conditions is further required for proper iron regulation, which links regulation of sulphur metabolism to iron homeostasis and demonstrates an unprecedented regulatory crosstalk. Taken together, this study provides evidence that regulation of sulphur assimilation is not only crucial for A. fumigatus virulence but also affects the balance of iron in this prime opportunistic pathogen. Author Summary Invasive pulmonary aspergillosis (IPA) is a life-threatening disease that affects primarily immunosuppressed patients. During the last decades the incidence of this disease that is accompanied by high mortality rates has increased. Since opportunistic pathogenic fungi, unlike other pathogens, do not express specific virulence factors, it is becoming more and more clear that the elucidation of fungal metabolism is an essential task to understand fungal pathogenicity and to identify novel antifungal targets. In this work we report genetic inactivation of the sulphur transcription regulator MetR in Aspergillus fumigatus and subsequent study of the resulting phenotypes and transcriptional deregulation of the mutant. Here we show that regulation of sulphur assimilation is an essential process for the manifestation of IPA. Moreover, a regulatory connection between sulphur metabolism and iron homeostasis, a further essential virulence determinant of A. fumigatus, is demonstrated in this study for the first time. A deeper knowledge of sulphur metabolism holds the promise of increasing our understanding of fungal virulence and might lead to improved antifungal therapy. KW - gene regulation KW - transcription factors KW - DNA transcription KW - aspergillus fumigatus KW - methionine KW - sulfur KW - fungal pathogens KW - sulfates Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130372 VL - 9 IS - 8 ER - TY - JOUR A1 - Anders, Diana A1 - Trautmann, Axel T1 - Allergic anaphylaxis due to subcutaneously injected heparin JF - Allergy, Asthma & Clinical Immunology N2 - Heparins are one of the most used class of anticoagulants in daily clinical practice. Despite their widespread application immune-mediated hypersensitivity reactions to heparins are rare. Among these, the delayed-type reactions to s.c. injected heparins are well-known usually presenting as circumscribed eczematous plaques at the injection sites. In contrast, potentially life-threatening systemic immediate-type anaphylactic reactions to heparins are extremely rare. Recently, some cases of non-allergic anaphylaxis could be attributed to undesirable heparin contaminants. A 43-year-old patient developed severe anaphylaxis symptoms within 5–10 minutes after s.c. injection of enoxaparin. Titrated skin prick testing with wheal and flare responses up to an enoxaparin dilution of 1:10.000 indicated a probable allergic mechanism of the enoxaparin-induced anaphylaxis. The basophil activation test as an additional in-vitro test method was negative. Furthermore, skin prick testing showed rather broad cross-reactivity among different heparin preparations tested. In the presented case, history, symptoms, and results of skin testing strongly suggested an IgE-mediated allergic hypersensitivity against different heparins. Therefore, as safe alternative anticoagulants the patient could receive beneath coumarins the hirudins or direct thrombin inhibitors. Because these compounds have a completely different molecular structure compared with the heparin-polysaccharides. KW - Anaphylaxis KW - Allergy KW - Basophil activation test KW - Enoxaparin KW - Heparin KW - Hypersensitivity KW - Immunoglobulin E KW - Immediate-type Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96214 UR - http://www.aacijournal.com/content/9/1/1 ER - TY - JOUR A1 - Andreatta, Marta A1 - Mühlberger, Andreas A1 - Glotzbach-Schoon, Evelyn A1 - Pauli, Paul T1 - Pain predictability reverses valence ratings of a relief-associated stimulus JF - Front in Systems Neuroscience N2 - Relief from pain is positively valenced and entails reward-like properties. Notably, stimuli that became associated with pain relief elicit reward-like implicit responses too, but are explicitly evaluated by humans as aversive. Since the unpredictability of pain makes pain more aversive, this study examined the hypotheses that the predictability of pain also modulates the valence of relief-associated stimuli. In two studies, we presented one conditioned stimulus \((_{FORWARD}CS+)\) before a painful unconditioned stimulus (US), another stimulus \((_{BACKWARD}CS+)\) after the painful US, and a third stimulus (CS−) was never associated with the US. In Study 1, \(_{FORWARD}CS+\) predicted half of the USs while the other half was delivered unwarned and followed by \(_{BACKWARD}CS+\). In Study 2, all USs were predicted by \(_{FORWARD}CS+\) and followed by \(_{BACKWARD}CS+\). In Study 1 both \(_{FORWARD}CS+\) and \(_{BACKWARD}CS+\) were rated as negatively valenced and high arousing after conditioning, while \(_{BACKWARD}CS+\) in Study 2 acquired positive valence and low arousal. Startle amplitude was significantly attenuated to \(_{BACKWARD}CS+\) compared to \(_{FORWARD}CS+\) in Study 2, but did not differ among CSs in Study 1. In summary, predictability of aversive events reverses the explicit valence of a relief-associated stimulus. KW - threat unpredictability KW - implicit and explicit responses KW - forward conditioning KW - backward conditioning KW - pain relief Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129275 VL - 7 IS - 53 ER - TY - JOUR A1 - Andres, Katharina T1 - 'Fashion's Final Frontier': The Correlation of Gender Roles and Fashion in Star Trek JF - Culture Unbound N2 - Since its creation in 1966, Star Trek has been a dominant part of popular culture and as thus served as the source for many cultural references. Star Trek’s creator Gene Roddenberry wanted to realize his vision of a utopia but at the same time, he used the futuristic setting of the show to comment on the present time, on actual social and political circumstances. This means that each series can be regarded as a mirror image of the time in which it was created. The clothing of the characters in the different series is one part of that image. The uniforms of The Original Se-ries show influences of the 1960s pop art movement as well as the mini-skirt trend that experienced its peak in that decade. In the course of almost 40 years, howev-er, many things changed. In the 1990s, in Deep Space Nine and Voyager, a unisex uniform replaced the mini-dresses, with few exceptions; the colorful shirts gave way to ones that were mostly black. This trend continues into the new century. This essay interprets the evolution of the female officers’ uniforms from femi-nized dresses to androgynous clothing over the development of the series as a reflection of the change of gender roles in contemporary American society. The general functions of the female characters’ uniforms are the central object of its analysis while the few, but noteworthy exceptions to this pattern are given specif-ic attention. Finally, one of the most intriguing lines of enquiry is, how the pre-quel series Enterprise, supposed to be set before The Original Series, but pro-duced and aired from 2001 to 2005, fits in the picture. KW - Star Trek KW - science fiction KW - fashion KW - women KW - 1960s KW - backlash Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128827 VL - 5 ER - TY - JOUR A1 - Araragi, Naozumi A1 - Mlinar, Boris A1 - Baccini, Gilda A1 - Gutknecht, Lise A1 - Lesch, Klaus-Peter A1 - Corradetti, Renato T1 - Conservation of 5-HT1A receptor-mediated autoinhibition of serotonin (5-HT) neurons in mice with altered 5-HT homeostasis JF - Frontiers in Neuropharmacology N2 - Firing activity of serotonin (5-HT) neurons in the dorsal raphe nucleus (DRN) is controlled by inhibitory somatodendritic 5-HT1A autoreceptors. This autoinhibitory mechanism is implicated in the etiology of disorders of emotion regulation, such as anxiety disorders and depression, as well as in the mechanism of antidepressant action. Here, we investigated how persistent alterations in brain 5-HT availability affect autoinhibition in two genetically modified mouse models lacking critical mediators of serotonergic transmission: 5-HT transporter knockout (Sert-/-) and tryptophan hydroxylase-2 knockout (Tph2-/-) mice. The degree of autoinhibition was assessed by loose-seal cell-attached recording in DRN slices. First, application of the 5-HT1A-selective agonist R(+)-8-hydroxy-2-(di-n-propylamino)tetralin showed mild sensitization and marked desensitization of 5-HT1A receptors in Tph2-/- mice and Sert-/- mice, respectively. While 5-HT neurons from Tph2-/- mice did not display autoinhibition in response to L-tryptophan, autoinhibition of these neurons was unaltered in Sert-/- mice despite marked desensitization of their 5-HT1A autoreceptors. When the Tph2-dependent 5-HT synthesis step was bypassed by application of 5-hydroxy-L-tryptophan (5-HTP), neurons from both Tph2-/- and Sert-/- mice decreased their firing rates at significantly lower concentrations of 5-HTP compared to wildtype controls. Our findings demonstrate that, as opposed to the prevalent view, sensitivity of somatodendritic 5-HT1A receptors does not predict the magnitude of 5-HT neuron autoinhibition. Changes in 5-HT1A receptor sensitivity may rather be seen as an adaptive mechanism to keep autoinhibition functioning in response to extremely altered levels of extracellular 5-HT resulting from targeted inactivation of mediators of serotonergic signaling. KW - serotonin transporter KW - tryptophan hydroxylase-2 KW - knockout KW - dorsal raphe nucleus KW - autoinhibition KW - 5-HT1A receptor Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97098 ER - TY - JOUR A1 - Arca, Francesco A1 - Tedde, Sandro F. A1 - Sramek, Maria A1 - Rauh, Julia A1 - Lugli, Paolo A1 - Hayden, Oliver T1 - Interface Trap States in Organic Photodiodes JF - Scientific Reports N2 - Organic semiconductors are attractive for optical sensing applications due to the effortless processing on large active area of several \(cm^2\), which is difficult to achieve with solid-state devices. However, compared to silicon photodiodes, sensitivity and dynamic behavior remain a major challenge with organic sensors. Here, we show that charge trapping phenomena deteriorate the bandwidth of organic photodiodes (OPDs) to a few Hz at low-light levels. We demonstrate that, despite the large OPD capacitances of similar to 10 nF \(cm^{-2}\), a frequency response in the kHz regime can be achieved at light levels as low as 20 nW \(cm^{-2}\) by appropriate interface engineering, which corresponds to a 1000-fold increase compared to state-of-the-art OPDs. Such device characteristics indicate that large active area OPDs are suitable for industrial sensing and even match medical requirements for single X-ray pulse detection in the millisecond range. KW - ultrafast photonics KW - materials for optics KW - electrical and electronic engineering KW - polymers Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131507 VL - 3 ER - TY - JOUR A1 - Assaad, F. F. A1 - Bercx, M. A1 - Hohenadler, M. T1 - Topological Invariant and Quantum Spin Models from Magnetic pi Fluxes in Correlated Topological Insulators JF - Physical Review X N2 - The adiabatic insertion of a \(\pi\) flux into a quantum spin Hall insulator gives rise to localized spin and charge fluxon states. We demonstrate that \(\pi\) fluxes can be used in exact quantum Monte Carlo simulations to identify a correlated \(Z_2\) topological insulator using the example of the Kane-Mele-Hubbard model. In the presence of repulsive interactions, a \(\pi\) flux gives rise to a Kramers doublet of spin-fluxon states with a Curie-law signature in the magnetic susceptibility. Electronic correlations also provide a bosonic mode of magnetic excitons with tunable energy that act as exchange particles and mediate a dynamical interaction of adjustable range and strength between spin fluxons. \(\pi\) fluxes can therefore be used to build models of interacting spins. This idea is applied to a three-spin ring and to one-dimensional spin chains. Because of the freedom to create almost arbitrary spin lattices, correlated topological insulators with \(\pi\) fluxes represent a novel kind of quantum simulator, potentially useful for numerical simulations and experiments. KW - topological insulators KW - strongly correlated materials Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129849 VL - 3 IS - 1 ER - TY - JOUR A1 - Assaad, Fakher F. A1 - Herbut, Igor F. T1 - Pinning the Order: The Nature of Quantum Criticality in the Hubbard Model on Honeycomb Lattice JF - Physical Review X N2 - In numerical simulations, spontaneously broken symmetry is often detected by computing two-point correlation functions of the appropriate local order parameter. This approach, however, computes the square of the local order parameter, and so when it is small, very large system sizes at high precisions are required to obtain reliable results. Alternatively, one can pin the order by introducing a local symmetrybreaking field and then measure the induced local order parameter infinitely far from the pinning center. The method is tested here at length for the Hubbard model on honeycomb lattice, within the realm of the projective auxiliary-field quantum Monte Carlo algorithm. With our enhanced resolution, we find a direct and continuous quantum phase transition between the semimetallic and the insulating antiferromagnetic states with increase of the interaction. The single-particle gap, measured in units of Hubbard U, tracks the staggered magnetization. An excellent data collapse is obtained by finite-size scaling, with the values of the critical exponents in accord with the Gross-Neveu universality class of the transition. KW - strongly correlated materials KW - mesoscopics KW - computational physics Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129829 VL - 3 IS - 031010 ER - TY - JOUR A1 - Astakhov, Georgy V. A1 - Fuchs, F. A1 - Soltamov, V. A. A1 - Väth, S. A1 - Baranov, P. G. A1 - Mokhov, E. N. A1 - Dyakonov, V. T1 - Silicon carbide light-emitting diode as a prospective room temperature source for single photons JF - Scientific Reports N2 - Generation of single photons has been demonstrated in several systems. However, none of them satisfies all the conditions, e.g. room temperature functionality, telecom wavelength operation, high efficiency, as required for practical applications. Here, we report the fabrication of light-emitting diodes (LEDs) based on intrinsic defects in silicon carbide (SiC). To fabricate our devices we used a standard semiconductor manufacturing technology in combination with high-energy electron irradiation. The room temperature electroluminescence (EL) of our LEDs reveals two strong emission bands in the visible and near infrared (NIR) spectral ranges, associated with two different intrinsic defects. As these defects can potentially be generated at a low or even single defect level, our approach can be used to realize electrically driven single photon source for quantum telecommunication and information processing. KW - semiconductors KW - inorganic LEDs KW - quantum optics KW - nanophotonics KW - plasmonics Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96308 ER - TY - JOUR A1 - Atanasov, Georgi A1 - Benkert, Christoph A1 - Thelen, Armin A1 - Tappe, Dennis A1 - Frosch, Matthias A1 - Teichmann, Dieter A1 - Barth, Thomas F. E. A1 - Wittekind, Christian A1 - Schubert, Stefan A1 - Jonas, Sven T1 - Alveolar echinococcosis-spreading disease challenging clinicians: A case report and literature review JF - World Journal of Gastroenterology N2 - Human alveolar echinococcosis (AE) is a potentially deadly disease; recent studies have shown that the endemic area of Echinococcus multilocularis, its causative agent, is larger than previously known. This disease has low prevalence and remains underreported in Europe. Emerging clinical data show that diagnostic difficulties are still common. We report on a 76-year old patient suffering from AE lesions restricted to the left lobe of the liver who underwent a curative extended left hemihepatectomy. Prior to the resection a liver biopsy under the suspicion of an atypical malignancy was performed. After the intervention he developed a pseudoaneurysm of the hepatic artery that was successfully coiled. Surprisingly, during surgery, the macroscopic appearance of the tumour revealed a growth pattern that was rather typical for cystic echinococcosis (CE), i.e., a gross tumour composed of multiple large vesicles with several centimeters in diameter. In addition, there were neither extensive adhesions nor infiltrations of the neighboring pancreas and diaphragm as was expected from previous imaging results. The unexpected diagnosis of AE was confirmed by definite histopathology, specific polymerase chain reaction and serology results. This is a rare case of unusual macroscopic presentation of AE that posed immense diagnostic challenges and had an eventful course. To our knowledge this is the first case of an autochthonous infection in this particular geographic area of Germany, the federal state of Saxony. This report may provide new hints for an expanding area of risk for AE and emphasizes the risk of complications in the scope of diagnostic procedures and the limitations of modern radiological imaging. KW - hemihepatectomy KW - multilocularis KW - Germany KW - Europe KW - liver KW - alveolar echinococcosis KW - echinococcus multilocularis KW - autochthonous infection KW - liver resection Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131525 VL - 19 IS - 26 ER - TY - JOUR A1 - Attia, Mohamed I. A1 - Herdeis, Claus A1 - Bräuner-Osborne, Hans T1 - GABA(B)-Agonistic Activity of Certain Baclofen Homologues JF - Molecules N2 - Baclofen (1) is a potent and selective agonist for bicuculline-insensitive GABAB receptors and is used clinically as an antispastic and muscle relaxant agent. In the search for new bioactive chemical entities that bind specifically to GABAB receptors, we report here the synthesis of certain baclofen homologues, namely (R,S)-5-amino-3-arylpentanoic acid hydrochlorides (R,S)-1a–h as well as (R,S)-5-amino-3-methylpentanoic acid [(RS)-1i] to be evaluated as GABABR agonists. Compound 1a is an agonist to GABAB receptors with an EC50 value of 46 μM on tsA201 cells transfected with GABAB1b/GABAB2/Gqz5, being the most active congener among all the synthesized compounds. KW - pharmacological evaluation KW - synthesis KW - GABA KW - baclofen homologues KW - GABAB receptor agonists Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129690 VL - 18 IS - 9 ER - TY - JOUR A1 - Bajda, Marek A1 - Wieckowska, Anna A1 - Hebda, Michalina A1 - Guzior, Natalia A1 - Sotriffer, Christoph A. A1 - Malawska, Barbara T1 - Structure-Based Search for New Inhibitors of Cholinesterases JF - International Journal of Molecular Sciences N2 - Cholinesterases are important biological targets responsible for regulation of cholinergic transmission, and their inhibitors are used for the treatment of Alzheimer’s disease. To design new cholinesterase inhibitors, of different structure-based design strategies was followed, including the modification of compounds from a previously developed library and a fragment-based design approach. This led to the selection of heterodimeric structures as potential inhibitors. Synthesis and biological evaluation of selected candidates confirmed that the designed compounds were acetylcholinesterase inhibitors with \(IC_{50}\) values in the mid-nanomolar to low micromolar range, and some of them were also butyrylcholinesterase inhibitors. KW - fragment-based design KW - cholinesterases inhibitors KW - butyrylcholinesterase KW - acetylcholinesterase KW - drug design Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129423 VL - 14 IS - 3 ER - TY - JOUR A1 - Becker, Martin A1 - Caminiti, Saverio A1 - Fiorella, Donato A1 - Francis, Louise A1 - Gravino, Pietro A1 - Haklay, Mordechai (Muki) A1 - Hotho, Andreas A1 - Loreto, Virrorio A1 - Mueller, Juergen A1 - Ricchiuti, Ferdinando A1 - Servedio, Vito D. P. A1 - Sirbu, Alina A1 - Tria, Franesca T1 - Awareness and Learning in Participatory Noise Sensing JF - PLOS ONE N2 - The development of ICT infrastructures has facilitated the emergence of new paradigms for looking at society and the environment over the last few years. Participatory environmental sensing, i.e. directly involving citizens in environmental monitoring, is one example, which is hoped to encourage learning and enhance awareness of environmental issues. In this paper, an analysis of the behaviour of individuals involved in noise sensing is presented. Citizens have been involved in noise measuring activities through the WideNoise smartphone application. This application has been designed to record both objective (noise samples) and subjective (opinions, feelings) data. The application has been open to be used freely by anyone and has been widely employed worldwide. In addition, several test cases have been organised in European countries. Based on the information submitted by users, an analysis of emerging awareness and learning is performed. The data show that changes in the way the environment is perceived after repeated usage of the application do appear. Specifically, users learn how to recognise different noise levels they are exposed to. Additionally, the subjective data collected indicate an increased user involvement in time and a categorisation effect between pleasant and less pleasant environments. KW - exposure Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127675 SN - 1932-6203 VL - 8 IS - 12 ER - TY - JOUR A1 - Becker, Svetlana A1 - Oelschlaeger, Tobias A. A1 - Wullaert, Andy A1 - Pasparakis, Manolis A1 - Wehkamp, Jan A1 - Stange, Eduard F. A1 - Gersemann, Michael T1 - Bacteria Regulate Intestinal Epithelial Cell Differentiation Factors Both In Vitro and In Vivo JF - PLoS ONE N2 - Background: The human colon harbours a plethora of bacteria known to broadly impact on mucosal metabolism and function and thought to be involved in inflammatory bowel disease pathogenesis and colon cancer development. In this report, we investigated the effect of colonic bacteria on epithelial cell differentiation factors in vitro and in vivo. As key transcription factors we focused on Hes1, known to direct towards an absorptive cell fate, Hath1 and KLF4, which govern goblet cell. Methods: Expression of the transcription factors Hes1, Hath1 and KLF4, the mucins Muc1 and Muc2 and the defensin HBD2 were measured by real-time PCR in LS174T cells following incubation with several heat-inactivated E. coli strains, including the probiotic E. coli Nissle 1917+/- flagellin, Lactobacilli and Bifidobacteria. For protein detection Western blot experiments and chamber-slide immunostaining were performed. Finally, mRNA and protein expression of these factors was evaluated in the colon of germfree vs. specific pathogen free vs. conventionalized mice and colonic goblet cells were counted. Results: Expression of Hes1 and Hath1, and to a minor degree also of KLF4, was reduced by E. coli K-12 and E. coli Nissle 1917. In contrast, Muc1 and HBD2 expression were significantly enhanced, independent of the Notch signalling pathway. Probiotic E. coli Nissle 1917 regulated Hes1, Hath1, Muc1 and HBD2 through flagellin. In vivo experiments confirmed the observed in vitro effects of bacteria by a diminished colonic expression of Hath1 and KLF4 in specific pathogen free and conventionalized mice as compared to germ free mice whereas the number of goblet cells was unchanged in these mice. Conclusions: Intestinal bacteria influence the intestinal epithelial differentiation factors Hes1, Hath1 and KLF4, as well as Muc1 and HBD2, in vitro and in vivo. The induction of Muc1 and HBD2 seems to be triggered directly by bacteria and not by Notch. KW - stem cells KW - inflammatory-bowel-disease KW - Ileal Crohns-disease KW - coli nissel 1917 KW - ulcreative colitis KW - escherichia coli KW - porphyromonas gingivalis KW - antimicrobial peptides KW - colorectal cancer KW - alpha defensins Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131168 VL - 8 IS - 2 ER - TY - JOUR A1 - Beier, Hildburg A1 - Gätschenberger, Heike A1 - Azzami, Klara A1 - Tautz, Jürgen T1 - Antibacterial Immune Competence of Honey Bees (Apis mellifera) Is Adapted to Different Life Stages and Environmental Risks JF - PLoS ONE N2 - The development of all honey bee castes proceeds through three different life stages all of which encounter microbial infections to a various extent. We have examined the immune strength of honey bees across all developmental stages with emphasis on the temporal expression of cellular and humoral immune responses upon artificial challenge with viable Escherichia coli bacteria. We employed a broad array of methods to investigate defence strategies of infected individuals: (a) fate of bacteria in the haemocoel; (b) nodule formation and (c) induction of antimicrobial peptides (AMPs). Newly emerged adult worker bees and drones were able to activate efficiently all examined immune reactions. The number of viable bacteria circulating in the haemocoel of infected bees declined rapidly by more than two orders of magnitude within the first 4–6 h post-injection (p.i.), coinciding with the occurrence of melanised nodules. Antimicrobial activity, on the other hand, became detectable only after the initial bacterial clearance. These two temporal patterns of defence reactions very likely represent the constitutive cellular and the induced humoral immune response. A unique feature of honey bees is that a fraction of worker bees survives the winter season in a cluster mostly engaged in thermoregulation. We show here that the overall immune strength of winter bees matches that of young summer bees although nodulation reactions are not initiated at all. As expected, high doses of injected viable E.coli bacteria caused no mortality in larvae or adults of each age. However, drone and worker pupae succumbed to challenge with E.coli even at low doses, accompanied by a premature darkening of the pupal body. In contrast to larvae and adults, we observed no fast clearance of viable bacteria and no induction of AMPs but a rapid proliferation of E.coli bacteria in the haemocoel of bee pupae ultimately leading to their death. KW - escherichia coli infections KW - honey bees KW - bees KW - antimicrobials KW - bacterial pathogens KW - larvae KW - pupae KW - winter Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96895 ER - TY - JOUR A1 - Beilhack, Andreas A1 - Chopra, Martin A1 - Kraus, Sabrina A1 - Schwinn, Stefanie A1 - Ritz, Miriam A1 - Mattenheimer, Katharina A1 - Mottok, Anja A1 - Rosenwald, Andreas A1 - Einsele, Hermann T1 - Non-Invasive Bioluminescence Imaging to Monitor the Immunological Control of a Plasmablastic Lymphoma-Like B Cell Neoplasia after Hematopoietic Cell Transplantation N2 - To promote cancer research and to develop innovative therapies, refined pre-clinical mouse tumor models that mimic the actual disease in humans are of dire need. A number of neoplasms along the B cell lineage are commonly initiated by a translocation recombining c-myc with the immunoglobulin heavy-chain gene locus. The translocation is modeled in the C.129S1-Ighatm1(Myc)Janz/J mouse which has been previously engineered to express c-myc under the control of the endogenous IgH promoter. This transgenic mouse exhibits B cell hyperplasia and develops diverse B cell tumors. We have isolated tumor cells from the spleen of a C.129S1-Ighatm1(Myc)Janz/J mouse that spontaneously developed a plasmablastic lymphoma-like disease. These cells were cultured, transduced to express eGFP and firefly luciferase, and gave rise to a highly aggressive, transplantable B cell lymphoma cell line, termed IM380. This model bears several advantages over other models as it is genetically induced and mimics the translocation that is detectable in a number of human B cell lymphomas. The growth of the tumor cells, their dissemination, and response to treatment within immunocompetent hosts can be imaged non-invasively in vivo due to their expression of firefly luciferase. IM380 cells are radioresistant in vivo and mice with established tumors can be allogeneically transplanted to analyze graft-versus-tumor effects of transplanted T cells. Allogeneic hematopoietic stem cell transplantation of tumor-bearing mice results in prolonged survival. These traits make the IM380 model very valuable for the study of B cell lymphoma pathophysiology and for the development of innovative cancer therapies. KW - B cells KW - T cells KW - Bioluminescence imaging KW - Bone marrow cells KW - Bone marrow transplantation KW - Cancer treatment KW - Spleen KW - Lymphomas Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111341 ER - TY - JOUR A1 - Beitzinger, Christoph A1 - Bronnhuber, Annika A1 - Duscha, Kerstin A1 - Riedl, Zsuzsanna A1 - Huber-Lang, Markus A1 - Benz, Roland A1 - Hajos, György A1 - Barth, Holger T1 - Designed Azolopyridinium Salts Block Protective Antigen Pores In Vitro and Protect Cells from Anthrax Toxin JF - PLoS ONE N2 - Background Several intracellular acting bacterial protein toxins of the AB-type, which are known to enter cells by endocytosis, are shown to produce channels. This holds true for protective antigen (PA), the binding component of the tripartite anthrax-toxin of Bacillus anthracis. Evidence has been presented that translocation of the enzymatic components of anthrax-toxin across the endosomal membrane of target cells and channel formation by the heptameric/octameric \(PA_{63}\) binding/translocation component are related phenomena. Chloroquine and some 4-aminoquinolones, known as potent drugs against Plasmodium falciparium infection of humans, block efficiently the \(PA_{63}\)-channel in a dose dependent way. Methodology/Principal Findings Here we demonstrate that related positively charged heterocyclic azolopyridinium salts block the \(PA_{63}\)-channel in the µM range, when both, inhibitor and \(PA_{63}\) are added to the same side of the membrane, the cis-side, which corresponds to the lumen of acidified endosomal vesicles of target cells. Noise-analysis allowed the study of the kinetics of the plug formation by the heterocycles. In vivo experiments using J774A.1 macrophages demonstrated that the inhibitors of \(PA_{63}\)-channel function also efficiently block intoxication of the cells by the combination lethal factor and \(PA_{63}\) in the same concentration range as they block the channels in vitro. Conclusions/Significance These results strongly argue in favor of a transport of lethal factor through the \(PA_{63}\)-channel and suggest that the heterocycles used in this study could represent attractive candidates for development of novel therapeutic strategies against anthrax. KW - intoxication KW - chloroquine KW - toxins KW - anthrax KW - cell membranes KW - lipid bilayer KW - macrophages KW - membrane potential Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130097 VL - 8 IS - 6 ER - TY - JOUR A1 - Bentmann, Hendrik A1 - Reinert, Friedrich T1 - Enhancing and reducing the Rashba-splitting at surfaces by adsorbates: Na and Xe on Bi/Cu(111) JF - New Journal of Physics N2 - The surface alloy Bi/Cu(111) shows a paradigmatic free-electron-like surface state with a very large Rashba-type spin–orbit splitting. Using angle-resolved photoemission we investigate how adsorbates of different chemical nature influence the size of the spin splitting in this system. We find that the adsorption of small amounts of monovalent Na atoms leads to an enhancement of the spin splitting while an overlayer of the closed-shell rare gas Xe causes a reduction. The latter result is in contrast to the Au(111) surface for which an increased splitting size after Xe-adsorption was observed. We discuss these experimental findings in terms of the characteristic differences of the surface state wave functions and their spatial deformation in the presence of different types of adsorbates. Our results provide insight into the complex interplay of atomic and interface potential gradients governing the Rashba effect. KW - Rashba-Splitting Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129722 VL - 15 IS - 115011 ER - TY - JOUR A1 - Benz, Peter M. A1 - Merkel, Carla J. A1 - Offner, Kristin A1 - Abeßer, Marco A1 - Ullrich, Melanie A1 - Fischer, Tobias A1 - Bayer, Barbara A1 - Wagner, Helga A1 - Gambaryan, Stepan A1 - Ursitti, Jeanine A. A1 - Adham, Ibrahim M. A1 - Linke, Wolfgang A. A1 - Feller, Stephan M. A1 - Fleming, Ingrid A1 - Renné, Thomas A1 - Frantz, Stefan A1 - Unger, Andreas A1 - Schuh, Kai T1 - Mena/VASP and alphaII-Spectrin complexes regulate cytoplasmic actin networks in cardiomyocytes and protect from conduction abnormalities and dilated cardiomyopathy JF - Cell Communication and Signaling N2 - Background: In the heart, cytoplasmic actin networks are thought to have important roles in mechanical support, myofibrillogenesis, and ion channel function. However, subcellular localization of cytoplasmic actin isoforms and proteins involved in the modulation of the cytoplasmic actin networks are elusive. Mena and VASP are important regulators of actin dynamics. Due to the lethal phenotype of mice with combined deficiency in Mena and VASP, however, distinct cardiac roles of the proteins remain speculative. In the present study, we analyzed the physiological functions of Mena and VASP in the heart and also investigated the role of the proteins in the organization of cytoplasmic actin networks. Results: We generated a mouse model, which simultaneously lacks Mena and VASP in the heart. Mena/VASP double-deficiency induced dilated cardiomyopathy and conduction abnormalities. In wild-type mice, Mena and VASP specifically interacted with a distinct αII-Spectrin splice variant (SH3i), which is in cardiomyocytes exclusively localized at Z- and intercalated discs. At Z- and intercalated discs, Mena and β-actin localized to the edges of the sarcomeres, where the thin filaments are anchored. In Mena/VASP double-deficient mice, β-actin networks were disrupted and the integrity of Z- and intercalated discs was markedly impaired. Conclusions: Together, our data suggest that Mena, VASP, and αII-Spectrin assemble cardiac multi-protein complexes, which regulate cytoplasmic actin networks. Conversely, Mena/VASP deficiency results in disrupted β-actin assembly, Z- and intercalated disc malformation, and induces dilated cardiomyopathy and conduction abnormalities. KW - Mena/VASP KW - dilated cardiomyopathy KW - actin KW - heart KW - spectrin Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128760 VL - 11 IS - 56 ER - TY - JOUR A1 - Berghoff, Bork A. A1 - Konzer, Anne A1 - Mank, Nils N. A1 - Looso, Mario A1 - Rische, Tom A1 - Förstner, Konrad U. A1 - Krüger, Marcus A1 - Klug, Gabriele T1 - Integrative "Omics"-Approach Discovers Dynamic and Regulatory Features of Bacterial Stress Responses JF - PLOS Genetics N2 - Bacteria constantly face stress conditions and therefore mount specific responses to ensure adaptation and survival. Stress responses were believed to be predominantly regulated at the transcriptional level. In the phototrophic bacterium Rhodobacter sphaeroides the response to singlet oxygen is initiated by alternative sigma factors. Further adaptive mechanisms include post-transcriptional and post-translational events, which have to be considered to gain a deeper understanding of how sophisticated regulation networks operate. To address this issue, we integrated three layers of regulation: (1) total mRNA levels at different time-points revealed dynamics of the transcriptome, (2) mRNAs in polysome fractions reported on translational regulation (translatome), and (3) SILAC-based mass spectrometry was used to quantify protein abundances (proteome). The singlet oxygen stress response exhibited highly dynamic features regarding short-term effects and late adaptation, which could in part be assigned to the sigma factors RpoE and RpoH2 generating distinct expression kinetics of corresponding regulons. The occurrence of polar expression patterns of genes within stress-inducible operons pointed to an alternative of dynamic fine-tuning upon stress. In addition to transcriptional activation, we observed significant induction of genes at the post-transcriptional level (translatome), which identified new putative regulators and assigned genes of quorum sensing to the singlet oxygen stress response. Intriguingly, the SILAC approach explored the stress-dependent decline of photosynthetic proteins, but also identified 19 new open reading frames, which were partly validated by RNA-seq. We propose that comparative approaches as presented here will help to create multi-layered expression maps on the system level ("expressome"). Finally, intense mass spectrometry combined with RNA-seq might be the future tool of choice to re-annotate genomes in various organisms and will help to understand how they adapt to alternating conditions. KW - singlet oxygen stress KW - genome-wide analysis KW - anti-sigma factor KW - rhodobacter sphaeroides KW - gene expression KW - quanititative proteomics KW - photooxidative stress KW - in-vivo KW - photosynthesis genes KW - mass spectrometry Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127587 SN - 1553-7404 VL - 9 IS - 6 ER - TY - JOUR A1 - Biehl, Stefanie C. A1 - Ehlis, Ann-Christine A1 - Müller, Laura D. A1 - Niklaus, Andrea A1 - Pauli, Paul A1 - Herrmann, Martin J. T1 - The impact of task relevance and degree of distraction on stimulus processing JF - BMC Neuroscience N2 - Background The impact of task relevance on event-related potential amplitudes of early visual processing was previously demonstrated. Study designs, however, differ greatly, not allowing simultaneous investigation of how both degree of distraction and task relevance influence processing variations. In our study, we combined different features of previous tasks. We used a modified 1-back task in which task relevant and task irrelevant stimuli were alternately presented. The task irrelevant stimuli could be from the same or from a different category as the task relevant stimuli, thereby producing high and low distracting task irrelevant stimuli. In addition, the paradigm comprised a passive viewing condition. Thus, our paradigm enabled us to compare the processing of task relevant stimuli, task irrelevant stimuli with differing degrees of distraction, and passively viewed stimuli. EEG data from twenty participants was collected and mean P100 and N170 amplitudes were analyzed. Furthermore, a potential connection of stimulus processing and symptoms of attention deficit hyperactivity disorder (ADHD) was investigated. Results Our results show a modulation of peak N170 amplitudes by task relevance. N170 amplitudes to task relevant stimuli were significantly higher than to high distracting task irrelevant or passively viewed stimuli. In addition, amplitudes to low distracting task irrelevant stimuli were significantly higher than to high distracting stimuli. N170 amplitudes to passively viewed stimuli were not significantly different from either kind of task irrelevant stimuli. Participants with more symptoms of hyperactivity and impulsivity showed decreased N170 amplitudes across all task conditions. On a behavioral level, lower N170 enhancement efficiency was significantly correlated with false alarm responses. Conclusions Our results point to a processing enhancement of task relevant stimuli. Unlike P100 amplitudes, N170 amplitudes were strongly influenced by enhancement and enhancement efficiency seemed to have direct behavioral consequences. These findings have potential implications for models of clinical disorders affecting selective attention, especially ADHD. KW - Selective attention KW - Working memory KW - Cognitive control KW - P100 KW - N170 KW - ADHD Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97271 UR - http://www.biomedcentral.com/1471-2202/14/107 ER - TY - JOUR A1 - Bing-Shi Tan, Ariel A1 - Kress, Sebastian A1 - Castro, Leticia A1 - Sheppard, Allan A1 - Raghunath, Michael T1 - Cellular re- and de-programming by microenvironmental memory: why short TGF-β1 pulses can have long effects JF - Fibrogenesis Tissue Repair N2 - Background Fibrosis poses a substantial setback in regenerative medicine. Histopathologically, fibrosis is an excessive accumulation of collagen affected by myofibroblasts and this can occur in any tissue that is exposed to chronic injury or insult. Transforming growth factor (TGF)-β1, a crucial mediator of fibrosis, drives differentiation of fibroblasts into myofibroblasts. These cells exhibit α-smooth muscle actin (α-SMA) and synthesize high amounts of collagen I, the major extracellular matrix (ECM) component of fibrosis. While hormones stimulate cells in a pulsatile manner, little is known about cellular response kinetics upon growth factor impact. We therefore studied the effects of short TGF-β1 pulses in terms of the induction and maintenance of the myofibroblast phenotype. Results Twenty-four hours after a single 30 min TGF-β1 pulse, transcription of fibrogenic genes was upregulated, but subsided 7 days later. In parallel, collagen I secretion rate and α-SMA presence were elevated for 7 days. A second pulse 24 h later extended the duration of effects to 14 days. We could not establish epigenetic changes on fibrogenic target genes to explain the long-lasting effects. However, ECM deposited under singly pulsed TGF-β1 was able to induce myofibroblast features in previously untreated fibroblasts. Dependent on the age of the ECM (1 day versus 7 days’ formation time), this property was diminished. Vice versa, myofibroblasts were cultured on fibroblast ECM and cells observed to express reduced (in comparison with myofibroblasts) levels of collagen I. Conclusions We demonstrated that short TGF-β1 pulses can exert long-lasting effects on fibroblasts by changing their microenvironment, thus leaving an imprint and creating a reciprocal feed-back loop. Therefore, the ECM might act as mid-term memory for pathobiochemical events. We would expect this microenvironmental memory to be dependent on matrix turnover and, as such, to be erasable. Our findings contribute to the current understanding of fibroblast induction and maintenance, and have bearing on the development of antifibrotic drugs. KW - cytokine KW - fibrosis KW - transforming growth factor-beta 1 KW - extracellular matrix KW - memory KW - pulses KW - phenotype KW - kinetics Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131898 VL - 6 IS - 12 ER - TY - JOUR A1 - Blömer, Nadja A1 - Pachel, Christina A1 - Hofmann, Urlich A1 - Nordbeck, Peter A1 - Bauer, Wolfgang A1 - Mathes, Denise A1 - Frey, Anna A1 - Bayer, Barbara A1 - Vogel, Benjamin A1 - Ertl, Georg T1 - 5-Lipoxygenase facilitates healing after myocardial infarction JF - Basic Research in Cardiology N2 - Early healing after myocardial infarction (MI) is characterized by a strong inflammatory reaction. Most leukotrienes are pro-inflammatory and are therefore potential mediators of healing and remodeling after myocardial ischemia. The enzyme 5-lipoxygenase (5-LOX) has a key role in the transformation of arachidonic acid in leukotrienes. Thus, we tested the effect of 5-LOX on healing after MI. After chronic coronary artery ligation, early mortality was significantly increased in 5-LOX\(^{−/−}\) when compared to matching wildtype (WT) mice due to left ventricular rupture. This effect could be reproduced in mice treated with the 5-LOX inhibitor Zileuton. A perfusion mismatch due to the vasoactive potential of leukotrienes is not responsible for left ventricular rupture since local blood flow assessed by magnetic resonance perfusion measurements was not different. However, after MI, there was an accentuation of the inflammatory reaction with an increase of pro-inflammatory macrophages. Yet, mortality was not changed in chimeric mice (WT vs. 5-LOX\(^{−/−}\) bone marrow in 5-LOX\(^{−/−}\) animals), indicating that an altered function of 5-LOX\(^{−/−}\) inflammatory cells is not responsible for the phenotype. Collagen production and accumulation of fibroblasts were significantly reduced in 5-LOX\(^{−/−}\) mice in vivo after MI. This might be due to an impaired migration of 5-LOX\(^{−/−}\) fibroblasts, as shown in vitro to serum. In conclusion, a lack or inhibition of 5-LOX increases mortality after MI because of healing defects. This is not mediated by a change in local blood flow, but through an altered inflammation and/or fibroblast function. KW - lipoxygenase KW - myocardial infarction KW - extracellular matrix remodeling KW - inflammation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132602 VL - 108 IS - 4 ER - TY - JOUR A1 - Bodem, Jochen A1 - Rethwilm, Axel T1 - Evolution of Foamy Viruses: The Most Ancient of All Retroviruses JF - Viruses N2 - Recent evidence indicates that foamy viruses (FVs) are the oldest retroviruses (RVs) that we know and coevolved with their hosts for several hundred million years. This coevolution may have contributed to the non-pathogenicity of FVs, an important factor in development of foamy viral vectors in gene therapy. However, various questions on the molecular evolution of FVs remain still unanswered. The analysis of the spectrum of animal species infected by exogenous FVs or harboring endogenous FV elements in their genome is pivotal. Furthermore, animal studies might reveal important issues, such as the identification of the FV in vivo target cells, which than require a detailed characterization, to resolve the molecular basis of the accuracy with which FVs copy their genome. The issues of the extent of FV viremia and of the nature of the virion genome (RNA vs. DNA) also need to be experimentally addressed. KW - foamy viruses KW - retroviruses KW - hepadnaviruses KW - evolution KW - genetic conservation KW - recombination Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97312 ER - TY - JOUR A1 - Bodem, Jochen A1 - Schrom, Eva-Maria A1 - Moschall, Rebecca A1 - Hartl, Maximilian J. A1 - Weitner, Helena A1 - Fecher, David A1 - Langemeier, Jörg A1 - Wöhrl, Brigitta M. T1 - U1snRNP-mediated suppression of polyadenylation in conjunction with the RNA structure controls poly (A) site selection in foamy viruses JF - Retrovirology N2 - Background During reverse transcription, retroviruses duplicate the long terminal repeats (LTRs). These identical LTRs carry both promoter regions and functional polyadenylation sites. To express full-length transcripts, retroviruses have to suppress polyadenylation in the 5′LTR and activate polyadenylation in the 3′LTR. Foamy viruses have a unique LTR structure with respect to the location of the major splice donor (MSD), which is located upstream of the polyadenylation signal. Results Here, we describe the mechanisms of foamy viruses regulating polyadenylation. We show that binding of the U1 small nuclear ribonucleoprotein (U1snRNP) to the MSD suppresses polyadenylation at the 5′LTR. In contrast, polyadenylation at the 3′LTR is achieved by adoption of a different RNA structure at the MSD region, which blocks U1snRNP binding and furthers RNA cleavage and subsequent polyadenylation. Conclusion Recently, it was shown that U1snRNP is able to suppress the usage of intronic cryptic polyadenylation sites in the cellular genome. Foamy viruses take advantage of this surveillance mechanism to suppress premature polyadenylation at the 5’end of their RNA. At the 3’end, Foamy viruses use a secondary structure to presumably block access of U1snRNP and thereby activate polyadenylation at the end of the genome. Our data reveal a contribution of U1snRNP to cellular polyadenylation site selection and to the regulation of gene expression. KW - Polyadenylation KW - foamy virus KW - RNA structure KW - Major splice donor KW - Polyadenylierung KW - RNS Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96085 UR - http://www.retrovirology.com/content/10/1/55 ER - TY - JOUR A1 - Bogdan, Sven A1 - Schultz, Jörg A1 - Grosshans, Jörg T1 - Formin’ cellular structures: Physiological roles of Diaphanous (Dia) in actin dynamics JF - Communicative & Integrative Biology N2 - Members of the Diaphanous (Dia) protein family are key regulators of fundamental actin driven cellular processes, which are conserved from yeast to humans. Researchers have uncovered diverse physiological roles in cell morphology, cell motility, cell polarity, and cell division, which are involved in shaping cells into tissues and organs. The identification of numerous binding partners led to substantial progress in our understanding of the differential functions of Dia proteins. Genetic approaches and new microscopy techniques allow important new insights into their localization, activity, and molecular principles of regulation. KW - Drosophila KW - cytoskeleton KW - actin KW - nucleator KW - development KW - formin Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121305 VL - 6 IS - e27634 ER - TY - JOUR A1 - Bonn, M. A1 - Schmitt, A. A1 - Lesch, K.-P. A1 - Van Bockstaele, E. J. A1 - Asan, E. T1 - Serotonergic innervation and serotonin receptor expression of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei JF - Brain Structure and Function N2 - Pharmacobehavioral studies in experimental animals, and imaging studies in humans, indicate that serotonergic transmission in the amygdala plays a key role in emotional processing, especially for anxiety-related stimuli. The lateral and basolateral amygdaloid nuclei receive a dense serotonergic innervation in all species studied to date. We investigated interrelations between serotonergic afferents and neuropeptide Y (NPY)-producing neurons, which are a subpopulation of inhibitory interneurons in the rat lateral and basolateral nuclei with particularly strong anxiolytic properties. Dual light microscopic immunolabeling showed numerous appositions of serotonergic afferents on NPY-immunoreactive somata. Using electron microscopy, direct membrane appositions and synaptic contacts between serotonin-containing axon terminals and NPY-immunoreactive cellular profiles were unequivocally established. Double in situ hybridization documented that more than 50 %, and about 30–40 % of NPY mRNA-producing neurons, co-expressed inhibitory 5-HT1A and excitatory 5-HT2C mRNA receptor subtype mRNA, respectively, in both nuclei with no gender differences. Triple in situ hybridization showed that individual NPY mRNA-producing interneurons co-express both 5-HT1A and 5-HT2C mRNAs. Co-expression of NPY and 5-HT3 mRNA was not observed. The results demonstrate that serotonergic afferents provide substantial innervation of NPY-producing neurons in the rat lateral and basolateral amygdaloid nuclei. Studies of serotonin receptor subtype co-expression indicate a differential impact of the serotonergic innervation on this small, but important, population of anxiolytic interneurons, and provide the basis for future studies of the circuitry underlying serotonergic modulation of emotional stimulus processing in the amygdala. KW - NPY KW - serotonergic system KW - amygdala KW - anxiety Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132591 VL - 218 IS - 2 ER - TY - JOUR A1 - Borchers, Svenja A1 - Müller, Laura A1 - Synofzik, Matthis A1 - Himmelbach, Marc T1 - Guidelines and quality measures for the diagnosis of optic ataxia JF - Frontiers in Human Neuroscience N2 - Since the first description of a systematic mis-reaching by Balint in 1909, a reasonable number of patients showing a similar phenomenology, later termed optic ataxia (OA), has been described. However, there is surprising inconsistency regarding the behavioral measures that are used to detect OA in experimental and clinical reports, if the respective measures are reported at all. A typical screening method that was presumably used by most researchers and clinicians, reaching for a target object in the peripheral visual space, has never been evaluated. We developed a set of instructions and evaluation criteria for the scoring of a semi-standardized version of this reaching task. We tested 36 healthy participants, a group of 52 acute and chronic stroke patients, and 24 patients suffering from cerebellar ataxia. We found a high interrater reliability and a moderate test-retest reliability comparable to other clinical instruments in the stroke sample. The calculation of cut-off thresholds based on healthy control and cerebellar patient data showed an unexpected high number of false positives in these samples due to individual outliers that made a considerable number of errors in peripheral reaching. This study provides first empirical data from large control and patient groups for a screening procedure that seems to be widely used but rarely explicitly reported and prepares the grounds for its use as a standard tool for the description of patients who are included in single case or group studies addressing optic ataxia similar to the use of neglect, extinction, or apraxia screening tools. KW - systems KW - deficit KW - target KW - damage KW - delay KW - posterior cortical atrophy KW - Balints-Syndrome KW - hand KW - impairments KW - reliability KW - cerebellar atrophy KW - cerebellar ataxia KW - cerebellum KW - parietal lobe KW - optic ataxia KW - beside test Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122439 SN - 1662-5161 VL - 7 IS - 324 ER - TY - JOUR A1 - Boschert, Verena A1 - van Dinther, Maarten A1 - Weidauer, Stella A1 - van Pee, Katharina A1 - Muth, Eva-Maria A1 - ten Dijke, Peter A1 - Mueller, Thomas D. T1 - Mutational Analysis of Sclerostin Shows Importance of the Flexible Loop and the Cystine-Knot for Wnt-Signaling Inhibition JF - PLoS ONE N2 - The cystine-knot containing protein Sclerostin is an important negative regulator of bone growth and therefore represents a promising therapeutic target. It exerts its biological task by inhibiting the Wnt (wingless and int1) signaling pathway, which participates in bone formation by promoting the differentiation of mesenchymal stem cells to osteoblasts. The core structure of Sclerostin consists of three loops with the first and third loop (Finger 1 and Finger 2) forming a structured \(\beta\)-sheet and the second loop being unstructured and highly flexible. Biochemical data showed that the flexible loop is important for binding of Sclerostin to Wnt co-receptors of the low-density lipoprotein related-protein family (LRP), by interacting with the Wnt co-receptors LRP5 or -6 it inhibits Wnt signaling. To further examine the structural requirements for Wnt inhibition, we performed an extensive mutational study within all three loops of the Sclerostin core domain involving single and multiple mutations as well as truncation of important regions. By this approach we could confirm the importance of the second loop and especially of amino acids Asn92 and Ile94 for binding to LRP6. Based on a Sclerostin variant found in a Turkish family suffering from Sclerosteosis we generated a Sclerostin mutant with cysteines 84 and 142 exchanged thereby removing the third disulfide bond of the cystine-knot. This mutant binds to LRP6 with reduced binding affinity and also exhibits a strongly reduced inhibitory activity against Wnt1 thereby showing that also elements outside the flexible loop are important for inhibition of Wnt by Sclerostin. Additionally, we examined the effect of the mutations on the inhibition of two different Wnt proteins, Wnt3a and Wnt1. We could detect clear differences in the inhibition of these proteins, suggesting that the mechanism by which Sclerostin antagonizes Wnt1 and Wnt3a is fundamentally different. KW - Wnt signaling cascade KW - binding analysis KW - osteoblasts KW - sequence motif analysis KW - biological locomotion KW - signal inhibition KW - cell binding assay KW - luciferase Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129862 VL - 8 IS - 11 ER - TY - JOUR A1 - Brandenburg, Vincent M. A1 - Kramann, Rafael A1 - Koos, Ralf A1 - Krueger, Thilo A1 - Schurgers, Leon A1 - Mühlenbruch, Georg A1 - Hübner, Sinah A1 - Gladziwa, Ulrich A1 - Drechler, Christiane A1 - Ketteler, Markus T1 - Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study JF - BMC Nephrology N2 - Background: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. Methods: We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 +/- 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR). Results: CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 +/- 0.81 vs 0.76 +/- 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 +/- 0.84 vs 1.35 +/- 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves. Conclusion: We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification. KW - coronary calcification KW - cardiovascular disease KW - aortic valve disease KW - calcium KW - mortality KW - sclerostin KW - aortic valve KW - bone formation KW - computed tomography KW - fetuin A KW - risk factors KW - GLA protein UCMGP KW - kidney-disease CKD KW - coronary-artery calcification KW - hemodialysis KW - mineral metabolism KW - vascular calcification KW - renal osteodystrophy Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122070 SN - 1471-2369 VL - 14 IS - 219 ER - TY - JOUR A1 - Brehm, Klaus A1 - Koziol, Uriel A1 - Krohne, Georg T1 - Anatomy and development of the larval nervous system in Echinococcus multilocularis JF - Frontiers in Zoology N2 - Background The metacestode larva of Echinococcus multilocularis (Cestoda: Taeniidae) develops in the liver of intermediate hosts (typically rodents, or accidentally in humans) as a labyrinth of interconnected cysts that infiltrate the host tissue, causing the disease alveolar echinococcosis. Within the cysts, protoscoleces (the infective stage for the definitive canid host) arise by asexual multiplication. These consist of a scolex similar to that of the adult, invaginated within a small posterior body. Despite the importance of alveolar echinococcosis for human health, relatively little is known about the basic biology, anatomy and development of E. multilocularis larvae, particularly with regard to their nervous system. Results We describe the existence of a subtegumental nerve net in the metacestode cysts, which is immunoreactive for acetylated tubulin-α and contains small populations of nerve cells that are labeled by antibodies raised against several invertebrate neuropeptides. However, no evidence was found for the existence of cholinergic or serotoninergic elements in the cyst wall. Muscle fibers occur without any specific arrangement in the subtegumental layer, and accumulate during the invaginations of the cyst wall that form brood capsules, where protoscoleces develop. The nervous system of the protoscolex develops independently of that of the metacestode cyst, with an antero-posterior developmental gradient. The combination of antibodies against several nervous system markers resulted in a detailed description of the protoscolex nervous system, which is remarkably complex and already similar to that of the adult worm. Conclusions We provide evidence for the first time of the existence of a nervous system in the metacestode cyst wall, which is remarkable given the lack of motility of this larval stage, and the lack of serotoninergic and cholinergic elements. We propose that it could function as a neuroendocrine system, derived from the nervous system present in the bladder tissue of other taeniids. The detailed description of the development and anatomy of the protoscolex neuromuscular system is a necessary first step toward the understanding of the developmental mechanisms operating in these peculiar larval stages. KW - Echinococcus KW - Metacestode KW - Protoscolex KW - Nervous system KW - Neuropeptide KW - Serotonin KW - Acetylated tubulin Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96504 UR - http://www.frontiersinzoology.com/content/10/1/24 ER - TY - JOUR A1 - Brixner, T. A1 - Aeschlimann, M. A1 - Fischer, A. A1 - Geisler, P. A1 - Goetz, S. A1 - Hecht, B. A1 - Huang, J. S. A1 - Keitzl, T. A1 - Kramer, C. A1 - Melchior, P. A1 - Pfeiffer, W. A1 - Razinskas, G. A1 - Rewitz, C. A1 - Schneider, C. A1 - Strüber, C. A1 - Tuchscherer, P. A1 - Voronine, D. V. T1 - Coherent spectroscopies on ultrashort time and length scales JF - EPJ Web of Conferences N2 - Three spectroscopic techniques are presented that provide simultaneous spatial and temporal resolution: modified confocal microscopy with heterodyne detection, space-time-resolved spectroscopy using coherent control concepts, and coherent two-dimensional nano-spectroscopy. Latest experimental results are discussed. KW - coherent spectroscopy KW - ultrashort time KW - length scale Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129073 VL - 41 ER - TY - JOUR A1 - Brixner, Tobias A1 - Koch, Federico A1 - Kullmann, Martin A1 - Selig, Ulrike A1 - Nuernberger, Patrick A1 - Götz, Daniel C. G. A1 - Bringmann, Gerhard T1 - Coherent two-dimensional electronic spectroscopy in the Soret band of a chiral porphyrin dimer JF - New Journal of Physics N2 - Using coherent two-dimensional (2D) electronic spectroscopy in fully noncollinear geometry, we observe the excitonic coupling of β,β'-linked bis[tetraphenylporphyrinato-zinc(II)] on an ultrafast timescale in the excited state. The results for two states in the Soret band originating from an excitonic splitting are explained by population transfer with approximately 100 fs from the energetically higher to the lower excitonic state. This interpretation is consistent with exemplary calculations of 2D spectra for a model four-level system with coupling. KW - optics KW - quantum optics KW - laser Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96139 ER - TY - JOUR A1 - Buchberger, Alexander A1 - Böhm, Stephanie T1 - The Budding Yeast Cdc48Shp1 Complex Promotes Cell Cycle Progression by Positive Regulation of Protein Phosphatase 1 (Glc7) JF - PLoS One N2 - The conserved, ubiquitin-selective AAA ATPase Cdc48 regulates numerous cellular processes including protein quality control, DNA repair and the cell cycle. Cdc48 function is tightly controlled by a multitude of cofactors mediating substrate specificity and processing. The UBX domain protein Shp1 is a bona fide substrate-recruiting cofactor of Cdc48 in the budding yeast S. cerevisiae. Even though Shp1 has been proposed to be a positive regulator of Glc7, the catalytic subunit of protein phosphatase 1 in S. cerevisiae, its cellular functions in complex with Cdc48 remain largely unknown. Here we show that deletion of the SHP1 gene results in severe growth defects and a cell cycle delay at the metaphase to anaphase transition caused by reduced Glc7 activity. Using an engineered Cdc48 binding-deficient variant of Shp1, we establish the Cdc48Shp1 complex as a critical regulator of mitotic Glc7 activity. We demonstrate that shp1 mutants possess a perturbed balance of Glc7 phosphatase and Ipl1 (Aurora B) kinase activities and show that hyper-phosphorylation of the kinetochore protein Dam1, a key mitotic substrate of Glc7 and Ipl1, is a critical defect in shp1. We also show for the first time a physical interaction between Glc7 and Shp1 in vivo. Whereas loss of Shp1 does not significantly affect Glc7 protein levels or localization, it causes reduced binding of the activator protein Glc8 to Glc7. Our data suggest that the Cdc48Shp1 complex controls Glc7 activity by regulating its interaction with Glc8 and possibly further regulatory subunits. KW - alleles KW - cell cycle KW - immunoprecipitation KW - phosphatases KW - genetic interactions Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96073 ER - TY - JOUR A1 - Buchner, Erich A1 - Blanco Redondo, Beatriz A1 - Bunz, Melanie A1 - Halder, Partho A1 - Sadanandappa, Madhumala K. A1 - Mühlbauer, Barbara A1 - Erwin, Felix A1 - Hofbauer, Alois A1 - Rodrigues, Veronica A1 - VijayRaghavan, K. A1 - Ramaswami, Mani A1 - Rieger, Dirk A1 - Wegener, Christian A1 - Förster, Charlotte T1 - Identification and Structural Characterization of Interneurons of the Drosophila Brain by Monoclonal Antibodies of the Würzburg Hybridoma Library JF - PLoS ONE N2 - Several novel synaptic proteins have been identified by monoclonal antibodies (mAbs) of the Würzburg hybridoma library generated against homogenized Drosophila brains, e.g. cysteine string protein, synapse-associated protein of 47 kDa, and Bruchpilot. However, at present no routine technique exists to identify the antigens of mAbs of our library that label only a small number of cells in the brain. Yet these antibodies can be used to reproducibly label and thereby identify these cells by immunohistochemical staining. Here we describe the staining patterns in the Drosophila brain for ten mAbs of the Würzburg hybridoma library. Besides revealing the neuroanatomical structure and distribution of ten different sets of cells we compare the staining patterns with those of antibodies against known antigens and GFP expression patterns driven by selected Gal4 lines employing regulatory sequences of neuronal genes. We present examples where our antibodies apparently stain the same cells in different Gal4 lines suggesting that the corresponding regulatory sequences can be exploited by the split-Gal4 technique for transgene expression exclusively in these cells. The detection of Gal4 expression in cells labeled by mAbs may also help in the identification of the antigens recognized by the antibodies which then in addition to their value for neuroanatomy will represent important tools for the characterization of the antigens. Implications and future strategies for the identification of the antigens are discussed. KW - cell staining KW - drosophila melanogaster KW - gene expression KW - hybridomas KW - immune serum KW - library screening KW - monoclonal antibodies KW - neurons Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97109 ER - TY - JOUR A1 - Buder, Kristina A1 - Gesierich, Anja A1 - Gelbrich, Götz A1 - Goebeler, Matthias T1 - Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives JF - Cancer Medicine N2 - Up to 50% of patients with uveal melanoma develop metastatic disease with poor prognosis. Regional, mainly liver-directed, therapies may induce limited tumor responses but do not improve overall survival. Response rates of metastatic uveal melanoma (MUM) to systemic chemotherapy are poor. Insights into the molecular biology of MUM recently led to investigation of new drugs. In this study, to compare response rates of systemic treatment for MUM we searched Pubmed/Web of Knowledge databases and ASCO website (1980–2013) for “metastatic/uveal/melanoma” and “melanoma/eye.” Forty studies (one case series, three phase I, five pilot, 22 nonrandomized, and two randomized phase II, one randomized phase III study, data of three expanded access programs, three retrospective studies) with 841 evaluable patients were included in the numeric outcome analysis. Complete or partial remissions were observed in 39/841 patients (overall response rate [ORR] 4.6%; 95% confidence intervals [CI] 3.3–6.3%), no responses were observed in 22/40 studies. Progression-free survival ranged from 1.8 to 7.2, median overall survival from 5.2 to 19.0 months as reported in 21/40 and 26/40 studies, respectively. Best responses were seen for chemoimmunotherapy (ORR 10.3%; 95% CI 4.8–18.7%) though mainly in first-line patients. Immunotherapy with ipilimumab, antiangiogenetic approaches, and kinase inhibitors have not yet proven to be superior to chemotherapy. MEK inhibitors are currently investigated in a phase II trial with promising preliminary data. Despite new insights into genetic and molecular background of MUM, satisfying systemic treatment approaches are currently lacking. Study results of innovative treatment strategies are urgently awaited. KW - Clinical trials KW - drug therapy KW - metastatic KW - review KW - uveal melanoma Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97175 VL - 2 IS - 5 ER - TY - JOUR A1 - Budich, Jan Carl A1 - Trauzettel, Björn T1 - Z(2) Green's function topology of Majorana wires JF - New Journal of Physics N2 - We represent the Z2 topological invariant characterizing a one-dimensional topological superconductor using a Wess–Zumino–Witten dimensional extension. The invariant is formulated in terms of the single-particle Green’s function which allows us to classify interacting systems. Employing a recently proposed generalized Berry curvature method, the topological invariant is represented independent of the extra dimension requiring only the single-particle Green’s function at zero frequency of the interacting system. Furthermore, a modified twisted boundary conditions approach is used to rigorously define the topological invariant for disordered interacting systems. KW - Green's function Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129751 VL - 15 IS - 065006 ER - TY - JOUR A1 - Busch, Albert A1 - Lorenz, Udo A1 - Tiurbe, George Christian A1 - Bühler, Christoph A1 - Kellersmann, Richard T1 - Femoral vein obturator bypass revascularization in groin infectious bleeding: two case reports and review of the literature JF - Journal of Medical Case Reports N2 - Introduction Groin infections resulting in arterial bleeding due to bacterial vessel destruction are a severe challenge in vascular surgery. Patients with them most often present as emergencies and therefore need individualized reconstruction solutions. Case presentation Case 1 is a 67-year-old man with infectious bleeding after an autologous reconstruction of the femoral bifurcation with greater saphenous vein due to infection of a bovine pericard patch after thrombendarterectomy. Case 2 is a 35-year-old male drug addict and had severe femoral bleeding and infection after repeated intravenous and intra-arterial substance abuse. Both patients were treated with an autologous obturator bypass of the superficial femoral vein. We review the current literature and highlight our therapeutic concept of this clinical entity. Conclusions Treatment should include systemic antibiotic medication, surgical control of the infectious site, revascularization and soft tissue repair. An extra-anatomical obturator bypass with autologous superficial femoral vein should be considered as the safest revascularization procedure in infections caused by highly pathogenic bacteria. KW - Obturator bypass KW - Groin infection KW - Autologous KW - Extra-anatomical KW - Femoral vein Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95901 UR - http://www.jmedicalcasereports.com/content/7/1/75 ER - TY - JOUR A1 - Busch, Albert A1 - Tschernitz, Sebastian A1 - Thurner, Anette A1 - Kellersmann, Richard A1 - Lorenz, Udo T1 - Fatal Paraneoplastic Embolisms in Both Circulations in a Patient with Poorly Differentiated Neuroendocrine Tumour JF - Case Reports in Vascular Medicine N2 - Arterial embolism with lower limb ischemia is a rare manifestation of paraneoplastic hypercoagulability in cancer patients. We report a unique case of fatal thromboembolism involving both circulations associated with a poorly differentiated neuroendocrine tumor of the lung with rapid progress despite high doses of unfractioned heparin and review the current literature on anticoagulative regimen in tumour patients. KW - Medizin Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97335 ER - TY - JOUR A1 - Bárcena-Uribarri, Iván A1 - Thein, Marcus A1 - Maier, Elke A1 - Bonde, Mari A1 - Bergström, Sven A1 - Benz, Roland T1 - Use of Nonelectrolytes Reveals the Channel Size and Oligomeric Constitution of the Borrelia burgdorferi P66 Porin JF - PLoS ONE N2 - In the Lyme disease spirochete Borrelia burgdorferi, the outer membrane protein P66 is capable of pore formation with an atypical high single-channel conductance of 11 nS in 1 M KCl, which suggested that it could have a larger diameter than ‘normal’ Gram-negative bacterial porins. We studied the diameter of the P66 channel by analyzing its single-channel conductance in black lipid bilayers in the presence of different nonelectrolytes with known hydrodynamic radii. We calculated the filling of the channel with these nonelectrolytes and the results suggested that nonelectrolytes (NEs) with hydrodynamic radii of 0.34 nm or smaller pass through the pore, whereas neutral molecules with greater radii only partially filled the channel or were not able to enter it at all. The diameter of the entrance of the P66 channel was determined to be \(\leq\)1.9 nm and the channel has a central constriction of about 0.8 nm. The size of the channel appeared to be symmetrical as judged from one-sidedness of addition of NEs. Furthermore, the P66-induced membrane conductance could be blocked by 80–90% by the addition of the nonelectrolytes PEG 400, PEG 600 and maltohexaose to the aqueous phase in the low millimolar range. The analysis of the power density spectra of ion current through P66 after blockage with these NEs revealed no chemical reaction responsible for channel block. Interestingly, the blockage of the single-channel conductance of P66 by these NEs occurred in about eight subconductance states, indicating that the P66 channel could be an oligomer of about eight individual channels. The organization of P66 as a possible octamer was confirmed by Blue Native PAGE and immunoblot analysis, which both demonstrated that P66 forms a complex with a mass of approximately 460 kDa. Two dimension SDS PAGE revealed that P66 is the only polypeptide in the complex. KW - radii KW - hydrodynamics KW - SDS polyacrylamide gel electrophoresis KW - molecular mass KW - outer membrane proteins KW - single channel recording KW - blue native polyacrylamide gel electrophoresis KW - borrelia burgdorferi Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129965 VL - 8 IS - 11 ER - TY - JOUR A1 - Bäuerlein, Carina A. A1 - Riedel, Simone S. A1 - Baker, Jeanette A1 - Brede, Christian A1 - Jordán Garrote, Ana-Laura A1 - Chopra, Martin A1 - Ritz, Miriam A1 - Beilhack, Georg F. A1 - Schulz, Stephan A1 - Zeiser, Robert A1 - Schlegel, Paul G. A1 - Einsele, Hermann A1 - Negrin, Robert S. A1 - Beilhack, Andreas T1 - A diagnostic window for the treatment of acute graft-versus-host disease prior to visible clinical symptoms in a murine model JF - BMC Medicine N2 - Background Acute graft-versus-host disease (aGVHD) poses a major limitation for broader therapeutic application of allogeneic hematopoietic cell transplantation (allo-HCT). Early diagnosis of aGVHD remains difficult and is based on clinical symptoms and histopathological evaluation of tissue biopsies. Thus, current aGVHD diagnosis is limited to patients with established disease manifestation. Therefore, for improved disease prevention it is important to develop predictive assays to identify patients at risk of developing aGVHD. Here we address whether insights into the timing of the aGVHD initiation and effector phases could allow for the detection of migrating alloreactive T cells before clinical aGVHD onset to permit for efficient therapeutic intervention. Methods Murine major histocompatibility complex (MHC) mismatched and minor histocompatibility antigen (miHAg) mismatched allo-HCT models were employed to assess the spatiotemporal distribution of donor T cells with flow cytometry and in vivo bioluminescence imaging (BLI). Daily flow cytometry analysis of peripheral blood mononuclear cells allowed us to identify migrating alloreactive T cells based on homing receptor expression profiles. Results We identified a time period of 2 weeks of massive alloreactive donor T cell migration in the blood after miHAg mismatch allo-HCT before clinical aGVHD symptoms appeared. Alloreactive T cells upregulated α4β7 integrin and P-selectin ligand during this migration phase. Consequently, targeted preemptive treatment with rapamycin, starting at the earliest detection time of alloreactive donor T cells in the peripheral blood, prevented lethal aGVHD. Conclusions Based on this data we propose a critical time frame prior to the onset of aGVHD symptoms to identify alloreactive T cells in the peripheral blood for timely and effective therapeutic intervention. KW - Allogeneic stem cell transplantation KW - Graft-versus-host disease KW - Minor histocompatibility antigen mismatch transplantation Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96797 UR - http://www.biomedcentral.com/1741-7015/11/134 ER - TY - JOUR A1 - Böhm, Johann A1 - Vasli, Nasim A1 - Maurer, Marie A1 - Cowling, Belinda A1 - Shelton, G. Diane A1 - Kress, Wolfram A1 - Toussaint, Anne A1 - Prokic, Ivana A1 - Schara, Ulrike A1 - Anderson, Thomas James A1 - Weis, Joachim A1 - Tiret, Laurent A1 - Laporte, Jocelyn T1 - Altered Splicing of the BIN1 Muscle-Specific Exon in Humans and Dogs with Highly Progressive Centronuclear Myopathy JF - PLOS Genetics N2 - Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies. KW - linked myotubular myopathy KW - skeletal muscle KW - inherited myopathy KW - SH3 domain KW - amphiphysin-2 BIN1 KW - membrane curvature KW - tumor-suppressor KW - great dane KW - mutation KW - gene Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127590 SN - 1553-7404 VL - 9 IS - 6 ER - TY - JOUR A1 - Büdel, Burkhard A1 - Vivas, Mercedes A1 - Lange, Otto L. T1 - Lichen species dominance and the resulting photosynthetic behavior of sonoran desert soil crust types (Baja California, Mexico) JF - Ecological Processes N2 - Introduction: Lichen dominated biological soil crusts (BSCs) occur over large areas in the Sonoran Desert of the southwestern USA and northwest Mexico. In Baja California BSCs show a distinct patchiness and several types can be distinguished. Two chlorolichen- and two cyanolichen-dominated BSCs were selected. We hypothesize that patchiness and the resulting domination of certain functional lichen groups will result in patchiness of photosynthetic CO2-uptake related to environmental factors as well. Methods: Four different soil crust samples were placed in cuvettes and their CO2 exchange was recorded in an open system with an infrared gas analyzer. Air blown over the BSCs had a controlled CO2 content of 350 ppm. Four cuvettes were operated in parallel. Photosynthetic CO2 exchange was continually recorded throughout the experiment. Results: Besides the dominating chlorolichens Psora decipiens and Placidium squamulosum and the cyanolichens Peltula patellata and P. richardsii, several other lichen species and 12 cyanobacterial species were found in the biological soil crusts sampled. The chlorolichen BSCs already gained positive net photosynthesis with high air humidity alone, while the cyanolichen types did not, but showed smaller CO2-uptake depression after water suprasaturation. Such specific net photosynthesis responses to mode of hydration and to crust water content seem to correlate with precipitation characteristics of their habitat. Conclusions: Species specific photosynthetic performance related to activation of respiration and net photosynthesis as well as to crust water content help to explain niche occupation and species composition of BSCs. Different functional types have to be considered when they have a patchy distribution. KW - patchiness KW - cyanobacterium KW - desert soil KW - dominance KW - lichen KW - photosynthesis KW - reactivation KW - soil crust KW - Baja California [(PNN) Mexico] KW - Mexico [North America] KW - Sonoran Desert KW - cyanobacteria KW - peltula patellata KW - placidium KW - psora decipiens Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131878 VL - 2 IS - 6 ER - TY - JOUR A1 - Camago-Molina, J.E. A1 - O'Leary, B. A1 - Porod, W. A1 - Staub, F. T1 - Vevacious: a tool for finding the global minima of one-loop effective potentials with many scalars JF - European Physical Journal C N2 - Several extensions of the Standard Model of particle physics contain additional scalars implying a more complex scalar potential compared to that of the Standard Model. In general these potentials allow for charge- and/or color-breaking minima besides the desired one with correctly broken SU(2) L ×U(1) Y . Even if one assumes that a metastable local minimum is realized, one has to ensure that its lifetime exceeds that of our universe. We introduce a new program called Vevacious which takes a generic expression for a one-loop effective potential energy function and finds all the tree-level extrema, which are then used as the starting points for gradient-based minimization of the one-loop effective potential. The tunneling time from a given input vacuum to the deepest minimum, if different from the input vacuum, can be calculated. The parameter points are given as files in the SLHA format (though is not restricted to supersymmetric models), and new model files can be easily generated automatically by the Mathematica package SARAH. This code uses HOM4PS2 to find all the minima of the tree-level potential, PyMinuit to follow gradients to the minima of the one-loop potential, and CosmoTransitions to calculate tunneling times. KW - True Vacuum KW - One-loop Effective Potential KW - Saddle Point KW - Minimal Surface Tension KW - CMSSM Point KW - SM Gauge Group KW - Renormalization Scale KW - Landau Gauge KW - Homotopy Continuation Method KW - Gauge-dependent Quantity KW - False Vacuum KW - Spectrum Generator KW - SLHA File KW - Tunneling Time KW - Charged Scalar Field Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132110 VL - 73 IS - 2588 ER -