@article{LendersHennermannKurschatetal.2016, author = {Lenders, Malte and Hennermann, Julia B. and Kurschat, Christine and Rolfs, Arndt and Canaan-K{\"u}hl, Sima and Sommer, Claudia and {\"U}{\c{c}}eyler, Nurcan and Kampmann, Christoph and Karabul, Nesrin and Giese, Anne-Katrin and Duning, Thomas and Stypmann, J{\"o}rg and Kr{\"a}mer, Johannes and Weidemann, Frank and Brand, Stefan-Martin and Wanner, Christoph and Brand, Eva}, title = {Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease}, series = {Orphanet Journal of Rare Diseases}, volume = {11}, journal = {Orphanet Journal of Rare Diseases}, number = {88}, doi = {10.1186/s13023-016-0473-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166543}, year = {2016}, abstract = {Background The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines. Methods Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed. Results Fifty-five percent of females were on enzyme replacement therapy (ERT), according to recent European FD guidelines. Thirty-three percent of females were untreated although criteria for ERT initiation were fulfilled. In general, the presence of left ventricular hypertrophy (LVH) seemed to impact more on ERT initiation than impaired renal function. In ERT-na{\"i}ve females RAAS blockers were more often prescribed if LVH was present rather than albuminuria. Affected females with missense mutations showed a similar disease burden compared to females with nonsense mutations. Elevated plasma lyso-Gb3 levels in ERT-na{\"i}ve females seem to be a marker of disease burden, since patients showed comparable incidences of organ manifestations even if they were ~8 years younger than females with normal lyso-Gb3 levels. Conclusion The treatment of the majority of females with FD in Germany is in line with the current European FD guidelines. However, a relevant number of females remain untreated despite organ involvement, necessitating a careful reevaluation of these females.}, language = {en} } @article{WenteSchroederBuckardetal.2016, author = {Wente, Sarah and Schr{\"o}der, Simone and Buckard, Johannes and B{\"u}ttel, Hans-Martin and von Deimling, Florian and Diener, Wilfried and H{\"a}ussler, Martin and H{\"u}bschle, Susanne and Kinder, Silvia and Kurlemann, Gerhard and Kretzschmar, Christoph and Lingen, Michael and Maroske, Wiebke and Mundt, Dirk and S{\´a}nchez-Albisua, Iciar and Seeger, J{\"u}rgen and Toelle, Sandra P. and Boltshauser, Eugen and Brockmann, Knut}, title = {Nosological delineation of congenital ocular motor apraxia type Cogan: an observational study}, series = {Orphanet Journal of Rare Diseases}, volume = {11}, journal = {Orphanet Journal of Rare Diseases}, number = {104}, doi = {10.1186/s13023-016-0486-z}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166534}, year = {2016}, abstract = {Background The nosological assignment of congenital ocular motor apraxia type Cogan (COMA) is still controversial. While regarded as a distinct entity by some authorities including the Online Mendelian Inheritance in Man catalog of genetic disorders, others consider COMA merely a clinical symptom. Methods We performed a retrospective multicenter data collection study with re-evaluation of clinical and neuroimaging data of 21 previously unreported patients (8 female, 13 male, ages ranging from 2 to 24 years) diagnosed as having COMA. Results Ocular motor apraxia (OMA) was recognized during the first year of life and confined to horizontal pursuit in all patients. OMA attenuated over the years in most cases, regressed completely in two siblings, and persisted unimproved in one individual. Accompanying clinical features included early onset ataxia in most patients and cognitive impairment with learning disability (n = 6) or intellectual disability (n = 4). Re-evaluation of MRI data sets revealed a hitherto unrecognized molar tooth sign diagnostic for Joubert syndrome in 11 patients, neuroimaging features of Poretti-Boltshauser syndrome in one case and cerebral malformation suspicious of a tubulinopathy in another subject. In the remainder, MRI showed vermian hypo-/dysplasia in 4 and no abnormalities in another 4 patients. There was a strong trend to more severe cognitive impairment in patients with Joubert syndrome compared to those with inconclusive MRI, but otherwise no significant difference in clinical phenotypes between these two groups. Conclusions Systematical renewed analysis of neuroimaging data resulted in a diagnostic reappraisal in the majority of patients with early-onset OMA in the cohort reported here. This finding poses a further challenge to the notion of COMA constituting a separate entity and underlines the need for an expert assessment of neuroimaging in children with COMA, especially if they show cognitive impairment.}, language = {en} } @article{EisenhardtSprengerRoeringetal.2016, author = {Eisenhardt, Anja E. and Sprenger, Adrian and R{\"o}ring, Michael and Herr, Ricarda and Weinberg, Florian and K{\"o}hler, Martin and Braun, Sandra and Orth, Joachim and Diedrich, Britta and Lanner, Ulrike and Tscherwinski, Natalja and Schuster, Simon and Dumaz, Nicolas and Schmidt, Enrico and Baumeister, Ralf and Schlosser, Andreas and Dengjel, J{\"o}rn and Brummer, Tilman}, title = {Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles}, series = {Oncotarget}, volume = {7}, journal = {Oncotarget}, number = {18}, doi = {10.18632/oncotarget.8427}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166529}, pages = {26628-26652}, year = {2016}, abstract = {B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1 double deficient DT40 lymphoma cells complemented with wildtype or mutant B-Raf expression vectors. Using a multi-protease digestion approach, we identified a novel ubiquitination site and provide a detailed B-Raf phospho-map. Importantly, we identify two evolutionary conserved phosphorylation clusters around T401 and S419 in the B-Raf hinge region. SILAC labelling and genetic/biochemical follow-up revealed that these clusters are phosphorylated in the contexts of oncogenic Ras, sorafenib induced Raf dimerization and in the background of the V600E mutation. We further show that the vemurafenib sensitive phosphorylation of the T401 cluster occurs in trans within a Raf dimer. Substitution of the Ser/Thr-residues of this cluster by alanine residues enhances the transforming potential of B-Raf, indicating that these phosphorylation sites suppress its signaling output. Moreover, several B-Raf phosphorylation sites, including T401 and S419, are somatically mutated in tumors, further illustrating the importance of phosphorylation for the regulation of this kinase.}, language = {en} } @article{VučićevićGehreDhamijaetal.2016, author = {Vučićević, Dubravka and Gehre, Maja and Dhamija, Sonam and Friis-Hansen, Lennart and Meierhofer, David and Sauer, Sascha and {\O}rom, Ulf Andersson}, title = {The long non-coding RNA PARROT is an upstream regulator of c-Myc and affects proliferation and translation}, series = {Oncotarget}, volume = {7}, journal = {Oncotarget}, number = {23}, doi = {10.18632/oncotarget.8985}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166519}, pages = {33934-33947}, year = {2016}, abstract = {Long non-coding RNAs are important regulators of gene expression and signaling pathways. The expression of long ncRNAs is dysregulated in cancer and other diseases. The identification and characterization of long ncRNAs is often challenging due to their low expression level and localization to chromatin. Here, we identify a functional long ncRNA, PARROT (Proliferation Associated RNA and Regulator Of Translation) transcribed by RNA polymerase II and expressed at a relatively high level in a number of cell lines. The PARROT long ncRNA is associated with proliferation in both transformed and normal cell lines. We characterize the long ncRNA PARROT as an upstream regulator of c-Myc affecting cellular proliferation and translation using RNA sequencing and mass spectrometry following depletion of the long ncRNA. PARROT is repressed during senescence of human mammary epithelial cells and overexpressed in some cancers, suggesting an important association with proliferation through regulation of c-Myc. With this study, we add to the knowledge of cytoplasmic functional long ncRNAs and extent the long ncRNA-Myc regulatory network in transformed and normal cells.}, language = {en} } @article{ShiKuaiLeietal.2016, author = {Shi, Yaoyao and Kuai, Yue and Lei, Lizhen and Weng, Yuanyuan and Berberich-Siebelt, Friederike and Zhang, Xinxia and Wang, Jinjie and Zhou, Yuan and Jiang, Xin and Ren, Guoping and Pan, Hongyang and Mao, Zhengrong and Zhou, Ren}, title = {The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma}, series = {Oncotarget}, volume = {7}, journal = {Oncotarget}, number = {47}, doi = {10.18632/oncotarget.12680}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166500}, pages = {77444-77456}, year = {2016}, abstract = {Dysregulation of the apoptotic pathway is widely recognized as a key step in lymphomagenesis. Notably, LITAF was initially identified as a p53-inducible gene, subsequently implicated as a tumor suppressor. Our previous study also showed LITAF to be methylated in 89.5\% B-NHL samples. Conversely, deregulated expression of BCL6 is a pathogenic event in many lymphomas. Interestingly, our study found an oppositional expression of LITAF and BCL6 in B-NHL. In addition, LITAF was recently identified as a novel target gene of BCL6. Therefore, we sought to explore the feedback loop between LITAF and BCL6 in B-NHL. Here, our data for the first time show that LITAF can repress expression of BCL6 by binding to Region A (-87 to +65) containing a putative LITAF-binding motif (CTCCC) within the BCL6 promoter. Furthermore, the regulation of BCL6 targets (PRDM1 or c-Myc) by LITAF may be associated with B-cell differentiation. Results also demonstrate that ectopic expression of LITAF induces cell apoptosis, activated by releasing cytochrome c, cleaving PARP and caspase 3 in B-NHL cells whereas knockdown of LITAF robustly protected cells from apoptosis. Interestingly, BCL6, in turn, could reverse cell apoptosis mediated by LITAF. Collectively, our findings provide a novel apoptotic regulatory pathway in which LITAF, as a transcription factor, inhibits the expression of BCL6, which leads to activation of the intrinsic mitochondrial pathway and tumor apoptosis. Our study is expected to provide a possible biomarker as well as a target for clinical therapies to promote tumor cell apoptosis.}, language = {en} } @article{SchneiderCoronaSpoeringetal.2016, author = {Schneider, Anna and Corona, Angela and Sp{\"o}ring, Imke and Jordan, Mareike and Buchholz, Bernd and Maccioni, Elias and Di Santo, Roberto and Bodem, Jochen and Tramontano, Enzo and W{\"o}hrl, Birgitta M.}, title = {Biochemical characterization of a multi-drug resistant HIV-1 subtype AG reverse transcriptase: antagonism of AZT discrimination and excision pathways and sensitivity to RNase H inhibitors}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {5}, doi = {10.1093/nar/gkw060}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166423}, pages = {2310-2322}, year = {2016}, abstract = {We analyzed a multi-drug resistant (MR) HIV-1 reverse transcriptase (RT), subcloned from a patient-derived subtype CRF02_AG, harboring 45 amino acid exchanges, amongst them four thymidine analog mutations (TAMs) relevant for high-level AZT (azidothymidine) resistance by AZTMP excision (M41L, D67N, T215Y, K219E) as well as four substitutions of the AZTTP discrimination pathway (A62V, V75I, F116Y and Q151M). In addition, K65R, known to antagonize AZTMP excision in HIV-1 subtype B was present. Although MR-RT harbored the most significant amino acid exchanges T215Y and Q151M of each pathway, it exclusively used AZTTP discrimination, indicating that the two mechanisms are mutually exclusive and that the Q151M pathway is obviously preferred since it confers resistance to most nucleoside inhibitors. A derivative was created, additionally harboring the TAM K70R and the reversions M151Q as well as R65K since K65R antagonizes excision. MR-R65K-K70R-M151Q was competent of AZTMP excision, whereas other combinations thereof with only one or two exchanges still promoted discrimination. To tackle the multi-drug resistance problem, we tested if the MR-RTs could still be inhibited by RNase H inhibitors. All MR-RTs exhibited similar sensitivity toward RNase H inhibitors belonging to different inhibitor classes, indicating the importance of developing RNase H inhibitors further as anti-HIV drugs.}, language = {en} } @article{CuiSchlesingerSchoenhalsetal.2016, author = {Cui, Huanhuan and Schlesinger, Jenny and Schoenhals, Sophia and Tonjes, Martje and Dunkel, Ilona and Meierhofer, David and Cano, Elena and Schulz, Kerstin and Berger, Michael F. and Haack, Timm and Abdelilah-Seyfried, Salim and Bulyk, Martha L. and Sauer, Sascha and Sperling, Silke R.}, title = {Phosphorylation of the chromatin remodeling factor DPF3a induces cardiac hypertrophy through releasing HEY repressors from DNA}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {6}, doi = {10.1093/nar/gkv1244}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166391}, pages = {2538-2553}, year = {2016}, abstract = {DPF3 (BAF45c) is a member of the BAF chromatin remodeling complex. Two isoforms have been described, namely DPF3a and DPF3b. The latter binds to acetylated and methylated lysine residues of histones. Here, we elaborate on the role of DPF3a and describe a novel pathway of cardiac gene transcription leading to pathological cardiac hypertrophy. Upon hypertrophic stimuli, casein kinase 2 phosphorylates DPF3a at serine 348. This initiates the interaction of DPF3a with the transcriptional repressors HEY, followed by the release of HEY from the DNA. Moreover, BRG1 is bound by DPF3a, and is thus recruited to HEY genomic targets upon interaction of the two components. Consequently, the transcription of downstream targets such as NPPA and GATA4 is initiated and pathological cardiac hypertrophy is established. In human, DPF3a is significantly up-regulated in hypertrophic hearts of patients with hypertrophic cardiomyopathy or aortic stenosis. Taken together, we show that activation of DPF3a upon hypertrophic stimuli switches cardiac fetal gene expression from being silenced by HEY to being activated by BRG1. Thus, we present a novel pathway for pathological cardiac hypertrophy, whose inhibition is a long-term therapeutic goal for the treatment of the course of heart failure.}, language = {en} } @article{SchwarzTamuriKultysetal.2016, author = {Schwarz, Roland F. and Tamuri, Asif U. and Kultys, Marek and King, James and Godwin, James and Florescu, Ana M. and Schultz, J{\"o}rg and Goldman, Nick}, title = {ALVIS: interactive non-aggregative visualization and explorative analysis of multiple sequence alignments}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {8}, doi = {10.1093/nar/gkw022}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166374}, pages = {e77}, year = {2016}, abstract = {Sequence Logos and its variants are the most commonly used method for visualization of multiple sequence alignments (MSAs) and sequence motifs. They provide consensus-based summaries of the sequences in the alignment. Consequently, individual sequences cannot be identified in the visualization and covariant sites are not easily discernible. We recently proposed Sequence Bundles, a motif visualization technique that maintains a one-to-one relationship between sequences and their graphical representation and visualizes covariant sites. We here present Alvis, an open-source platform for the joint explorative analysis of MSAs and phylogenetic trees, employing Sequence Bundles as its main visualization method. Alvis combines the power of the visualization method with an interactive toolkit allowing detection of covariant sites, annotation of trees with synapomorphies and homoplasies, and motif detection. It also offers numerical analysis functionality, such as dimension reduction and classification. Alvis is user-friendly, highly customizable and can export results in publication-quality figures. It is available as a full-featured standalone version (http://www.bitbucket.org/rfs/alvis) and its Sequence Bundles visualization module is further available as a web application (http://science-practice.com/projects/sequence-bundles).}, language = {en} } @article{LetunicBork2016, author = {Letunic, Ivica and Bork, Peer}, title = {Interactive tree of life (iTOL) v3: an online tool for the display and annotation of phylogenetic and other trees}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {W1}, doi = {10.1093/nar/gkw290}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166181}, pages = {W242-W245}, year = {2016}, abstract = {Interactive Tree Of Life (http://itol.embl.de) is a web-based tool for the display, manipulation and annotation of phylogenetic trees. It is freely available and open to everyone. The current version was completely redesigned and rewritten, utilizing current web technologies for speedy and streamlined processing. Numerous new features were introduced and several new data types are now supported. Trees with up to 100,000 leaves can now be efficiently displayed. Full interactive control over precise positioning of various annotation features and an unlimited number of datasets allow the easy creation of complex tree visualizations. iTOL 3 is the first tool which supports direct visualization of the recently proposed phylogenetic placements format. Finally, iTOL's account system has been redesigned to simplify the management of trees in user-defined workspaces and projects, as it is heavily used and currently handles already more than 500,000 trees from more than 10,000 individual users.}, language = {en} } @article{TeloracPrykhozhijSchoeneetal.2016, author = {Telorac, Jonas and Prykhozhij, Sergey V. and Sch{\"o}ne, Stefanie and Meierhofer, David and Sauer, Sascha and Thomas-Chollier, Morgane and Meijsing, Sebastiaan H.}, title = {Identification and characterization of DNA sequences that prevent glucocorticoid receptor binding to nearby response elements}, series = {Nucleic Acids Research}, volume = {44}, journal = {Nucleic Acids Research}, number = {13}, doi = {10.1093/nar/gkw203}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166330}, pages = {6142-6156}, year = {2016}, abstract = {Out of the myriad of potential DNA binding sites of the glucocorticoid receptor (GR) found in the human genome, only a cell-type specific minority is actually bound, indicating that the presence of a recognition sequence alone is insufficient to specify where GR binds. Cooperative interactions with other transcription factors (TFs) are known to contribute to binding specificity. Here, we reasoned that sequence signals preventing GR recruitment to certain loci provide an alternative means to confer specificity. Motif analyses uncovered candidate Negative Regulatory Sequences (NRSs) that interfere with genomic GR binding. Subsequent functional analyses demonstrated that NRSs indeed prevent GR binding to nearby response elements. We show that NRS activity is conserved across species, found in most tissues and that they also interfere with the genomic binding of other TFs. Interestingly, the effects of NRSs appear not to be a simple consequence of changes in chromatin accessibility. Instead, we find that NRSs interact with proteins found at sub-nuclear structures called paraspeckles and that these proteins might mediate the repressive effects of NRSs. Together, our studies suggest that the joint influence of positive and negative sequence signals partition the genome into regions where GR can bind and those where it cannot.}, language = {en} } @article{AlmadeJongJelusicetal.2016, author = {Alma, Harma and de Jong, Corina and Jelusic, Danijel and Wittmann, Michael and Schuler, Michael and Flokstra-de Blok, Bertine and Kocks, Janwillem and Schultz, Konrad and van der Molen, Thys}, title = {Health status instruments for patients with COPD in pulmonary rehabilitation: defining a minimal clinically important difference}, series = {npj Primary Care Respiration Medicine}, volume = {26}, journal = {npj Primary Care Respiration Medicine}, number = {16041}, doi = {10.1038/npjpcrm.2016.41}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166327}, year = {2016}, abstract = {The minimal clinically important difference (MCID) defines to what extent change on a health status instrument is clinically relevant, which aids scientists and physicians in measuring therapy effects. This is the first study that aimed to establish the MCID of the Clinical chronic obstructive pulmonary disease (COPD) Questionnaire (CCQ), the COPD Assessment Test (CAT) and the St George's Respiratory Questionnaire (SGRQ) in the same pulmonary rehabilitation population using multiple approaches. In total, 451 COPD patients participated in a 3-week Pulmonary Rehabilitation (PR) programme (58 years, 65\% male, 43 pack-years, GOLD stage II/III/IV 50/39/11\%). Techniques used to assess the MCID were anchor-based approaches, including patient-referencing, criterion-referencing and questionnaire-referencing, and the distribution-based methods standard error of measurement (SEM), 1.96SEM and half standard deviation (0.5s.d.). Patient- and criterion-referencing led to MCID estimates of 0.56 and 0.62 (CCQ); 3.12 and 2.96 (CAT); and 8.40 and 9.28 (SGRQ). Questionnaire-referencing suggested MCID ranges of 0.28-0.61 (CCQ), 1.46-3.08 (CAT) and 6.86-9.47 (SGRQ). The SEM, 1.96SEM and 0.5s.d. were 0.29, 0.56 and 0.46 (CCQ); 3.28, 6.43 and 2.80 (CAT); 5.20, 10.19 and 6.06 (SGRQ). Pooled estimates were 0.52 (CCQ), 3.29 (CAT) and 7.91 (SGRQ) for improvement. MCID estimates differed depending on the method used. Pooled estimates suggest clinically relevant improvements needing to exceed 0.40 on the CCQ, 3.00 on the CAT and 7.00 on the SGRQ for moderate to very severe COPD patients. The MCIDs of the CAT and SGRQ in the literature might be too low, leading to overestimation of treatment effects for patients with COPD.}, language = {en} } @article{RedlichLingnauHolzingeretal.2016, author = {Redlich, Christoph and Lingnau, Benjamin and Holzinger, Steffen and Schlottmann, Elisabeth and Kreinberg, S{\"o}ren and Schneider, Christian and Kamp, Martin and H{\"o}fling, Sven and Wolters, Janik and Reitzenstein, Stephan and L{\"u}dge, Kathy}, title = {Mode-switching induced super-thermal bunching in quantum-dot microlasers}, series = {New Journal of Physics}, volume = {18}, journal = {New Journal of Physics}, number = {063011}, doi = {10.1088/1367-2630/18/6/063011}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166286}, year = {2016}, abstract = {The super-thermal photon bunching in quantum-dot (QD) micropillar lasers is investigated both experimentally and theoretically via simulations driven by dynamic considerations. Using stochastic multi-mode rate equations we obtain very good agreement between experiment and theory in terms of intensity profiles and intensity-correlation properties of the examined QD micro-laser's emission. Further investigations of the time-dependent emission show that super-thermal photon bunching occurs due to irregular mode-switching events in the bimodal lasers. Our bifurcation analysis reveals that these switchings find their origin in an underlying bistability, such that spontaneous emission noise is able to effectively perturb the two competing modes in a small parameter region. We thus ascribe the observed high photon correlation to dynamical multistabilities rather than quantum mechanical correlations.}, language = {en} } @article{HargartRoyChoudhuryJohnetal.2016, author = {Hargart, F and Roy-Choudhury, K and John, T and Portalupi, S L and Schneider, C and H{\"o}fling, S and Kamp, M and Hughes, S and Michler, P}, title = {Probing different regimes of strong field light-matter interaction with semiconductor quantum dots and few cavity photons}, series = {New Journal of Physics}, volume = {18}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/aa5198}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166278}, year = {2016}, abstract = {In this work we present an extensive experimental and theoretical investigation of different regimes of strong field light-matter interaction for cavity-driven quantum dot (QD) cavity systems. The electric field enhancement inside a high-Q micropillar cavity facilitates exceptionally strong interaction with few cavity photons, enabling the simultaneous investigation for a wide range of QD-laser detuning. In case of a resonant drive, the formation of dressed states and a Mollow triplet sideband splitting of up to 45 μeV is measured for amean cavity photon number \(\leq\) 1. In the asymptotic limit of the linear ACStark effect we systematically investigate the power and detuning dependence of more than 400 QDs. Some QD-cavity systems exhibit an unexpected anomalous Stark shift, which can be explained by an extended dressed 4-levelQDmodel.Weprovide a detailed analysis of the QD-cavity systems properties enabling this novel effect. The experimental results are successfully reproduced using a polaron master equation approach for the QD-cavity system, which includes the driving laser field, exciton-cavity and exciton-phonon interactions}, language = {en} } @article{vandeKerkhofFekkesvanderHeijdenetal.2016, author = {van de Kerkhof, Nora WA and Fekkes, Durk and van der Heijden, Frank MMA and Hoogendijk, Witte JG and St{\"o}ber, Gerald and Egger, Jos IM and Verhoeven, Willem MA}, title = {Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia}, series = {Neuropsychiatric Disease and Treatment}, volume = {12}, journal = {Neuropsychiatric Disease and Treatment}, doi = {10.2147/NDT.S101317}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166255}, pages = {1927-1933}, year = {2016}, abstract = {Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia. Eighty patients referred for psychotic disorders were assessed with the Comprehensive Assessment of Symptoms and History, and (both at inclusion and after 6 weeks of antipsychotic treatment) with the Positive and Negative Syndrome Scale and Clinical Global Impression. From 58 completers, 33 patients were diagnosed with schizophrenia and ten with CP according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Leonhard criteria, respectively. Fifteen patients were diagnosed with other disorders within the psychosis spectrum. At both time points, blood levels of the dopamine metabolite homovanillic acid, brain-derived neurotrophic factor, and amino acids related to glutamate neurotransmission were measured and compared with a matched control sample. Patients with CP showed a significantly better response to antipsychotic treatment as compared to patients with schizophrenia. In CP, glycine levels were elevated and tryptophan levels were lowered as compared to schizophrenia. Glutamate levels were increased in both patient groups as compared to controls. These results, showing marked differences in both treatment outcome and glutamate-related variable parameters, may point at better neuroplasticity in CP, necessitating demarcation of this subgroup within the psychosis spectrum.}, language = {en} } @article{StoeckelEsserGameretal.2016, author = {Stoeckel, M. Cornelia and Esser, Roland W. and Gamer, Matthias and B{\"u}chel, Christian and von Leupoldt, Andreas}, title = {Brain Responses during the Anticipation of Dyspnea}, series = {Neural Plasticity}, volume = {2016}, journal = {Neural Plasticity}, number = {6434987}, doi = {10.1155/2016/6434987}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166238}, year = {2016}, abstract = {Dyspnea is common in many cardiorespiratory diseases. Already the anticipation of this aversive symptom elicits fear in many patients resulting in unfavorable health behaviors such as activity avoidance and sedentary lifestyle. This study investigated brain mechanisms underlying these anticipatory processes. We induced dyspnea using resistive-load breathing in healthy subjects during functional magnetic resonance imaging. Blocks of severe and mild dyspnea alternated, each preceded by anticipation periods. Severe dyspnea activated a network of sensorimotor, cerebellar, and limbic areas. The left insular, parietal opercular, and cerebellar cortices showed increased activation already during dyspnea anticipation. Left insular and parietal opercular cortex showed increased connectivity with right insular and anterior cingulate cortex when severe dyspnea was anticipated, while the cerebellum showed increased connectivity with the amygdala. Notably, insular activation during dyspnea perception was positively correlated with midbrain activation during anticipation. Moreover, anticipatory fear was positively correlated with anticipatory activation in right insular and anterior cingulate cortex. The results demonstrate that dyspnea anticipation activates brain areas involved in dyspnea perception. The involvement of emotion-related areas such as insula, anterior cingulate cortex, and amygdala during dyspnea anticipation most likely reflects anticipatory fear and might underlie the development of unfavorable health behaviors in patients suffering from dyspnea.}, language = {en} } @article{BenoitAdelmanReinhardtetal.2016, author = {Benoit, Joshua B. and Adelman, Zach N. and Reinhardt, Klaus and Dolan, Amanda and Poelchau, Monica and Jennings, Emily C. and Szuter, Elise M. and Hagan, Richard W. and Gujar, Hemant and Shukla, Jayendra Nath and Zhu, Fang and Mohan, M. and Nelson, David R. and Rosendale, Andrew J. and Derst, Christian and Resnik, Valentina and Wernig, Sebastian and Menegazzi, Pamela and Wegener, Christian and Peschel, Nicolai and Hendershot, Jacob M. and Blenau, Wolfgang and Predel, Reinhard and Johnston, Paul R. and Ioannidis, Panagiotis and Waterhouse, Robert M. and Nauen, Ralf and Schorn, Corinna and Ott, Mark-Christoph and Maiwald, Frank and Johnston, J. Spencer and Gondhalekar, Ameya D. and Scharf, Michael E. and Raje, Kapil R. and Hottel, Benjamin A. and Armis{\´e}n, David and Crumi{\`e}re, Antonin Jean Johan and Refki, Peter Nagui and Santos, Maria Emilia and Sghaier, Essia and Viala, S{\`e}verine and Khila, Abderrahman and Ahn, Seung-Joon and Childers, Christopher and Lee, Chien-Yueh and Lin, Han and Hughes, Daniel S.T. and Duncan, Elizabeth J. and Murali, Shwetha C. and Qu, Jiaxin and Dugan, Shannon and Lee, Sandra L. and Chao, Hsu and Dinh, Huyen and Han, Yi and Doddapaneni, Harshavardhan and Worley, Kim C. and Muzny, Donna M. and Wheeler, David and Panfilio, Kristen A. and Jentzsch, Iris M. Vargas and Jentzsch, IMV and Vargo, Edward L. and Booth, Warren and Friedrich, Markus and Weirauch, Matthew T. and Anderson, Michelle A.E. and Jones, Jeffery W. and Mittapalli, Omprakash and Zhao, Chaoyang and Zhou, Jing-Jiang and Evans, Jay D. and Attardo, Geoffrey M. and Robertson, Hugh M. and Zdobnov, Evgeny M. and Ribeiro, Jose M.C. and Gibbs, Richard A. and Werren, John H. and Palli, Subba R. and Schal, Coby and Richards, Stephen}, title = {Unique features of a global human ectoparasite identified through sequencing of the bed bug genome}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, number = {10165}, doi = {10.1038/ncomms10165}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166221}, year = {2016}, abstract = {The bed bug, Cimex lectularius, has re-established itself as a ubiquitous human ectoparasite throughout much of the world during the past two decades. This global resurgence is likely linked to increased international travel and commerce in addition to widespread insecticide resistance. Analyses of the C. lectularius sequenced genome (650 Mb) and 14,220 predicted protein-coding genes provide a comprehensive representation of genes that are linked to traumatic insemination, a reduced chemosensory repertoire of genes related to obligate hematophagy, host-symbiont interactions, and several mechanisms of insecticide resistance. In addition, we document the presence of multiple putative lateral gene transfer events. Genome sequencing and annotation establish a solid foundation for future research on mechanisms of insecticide resistance, human-bed bug and symbiont-bed bug associations, and unique features of bed bug biology that contribute to the unprecedented success of C. lectularius as a human ectoparasite.}, language = {en} } @article{ConradAlbrechtRodriguesdeMeloCostaetal.2016, author = {Conrad, Thomas and Albrecht, Anne-Susann and Rodrigues de Melo Costa, Veronica and Sauer, Sascha and Meierhofer, David and Andersson {\O}rom, Ulf}, title = {Serial interactome capture of the human cell nucleus}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, number = {11212}, doi = {10.1038/ncomms11212}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166172}, year = {2016}, abstract = {Novel RNA-guided cellular functions are paralleled by an increasing number of RNA-binding proteins (RBPs). Here we present 'serial RNA interactome capture' (serIC), a multiple purification procedure of ultraviolet-crosslinked poly(A)-RNA-protein complexes that enables global RBP detection with high specificity. We apply serIC to the nuclei of proliferating K562 cells to obtain the first human nuclear RNA interactome. The domain composition of the 382 identified nuclear RBPs markedly differs from previous IC experiments, including few factors without known RNA-binding domains that are in good agreement with computationally predicted RNA binding. serIC extends the number of DNA-RNA-binding proteins (DRBPs), and reveals a network of RBPs involved in p53 signalling and double-strand break repair. serIC is an effective tool to couple global RBP capture with additional selection or labelling steps for specific detection of highly purified RBPs.}, language = {en} } @article{JahnkeGiesAssmannetal.2016, author = {Jahnke, Frank and Gies, Christopher and Aßmann, Marc and Bayer, Manfred and Leymann, H.A.M. and Foerster, Alexander and Wiersig, Jan and Schneider, Christian and Kamp, Martin and H{\"o}fling, Sven}, title = {Giant photon bunching, superradiant pulse emission and excitation trapping in quantum-dot nanolasers}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, number = {11540}, doi = {10.1038/ncomms11540}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166144}, year = {2016}, abstract = {Light is often characterized only by its classical properties, like intensity or coherence. When looking at its quantum properties, described by photon correlations, new information about the state of the matter generating the radiation can be revealed. In particular the difference between independent and entangled emitters, which is at the heart of quantum mechanics, can be made visible in the photon statistics of the emitted light. The well-studied phenomenon of superradiance occurs when quantum-mechanical correlations between the emitters are present. Notwithstanding, superradiance was previously demonstrated only in terms of classical light properties. Here, we provide the missing link between quantum correlations of the active material and photon correlations in the emitted radiation. We use the superradiance of quantum dots in a cavity-quantum electrodynamics laser to show a direct connection between superradiant pulse emission and distinctive changes in the photon correlation function. This directly demonstrates the importance of quantum-mechanical correlations and their transfer between carriers and photons in novel optoelectronic devices.}, language = {en} } @article{GoebelPankratzAsaridouetal.2016, author = {G{\"o}bel, Kerstin and Pankratz, Susann and Asaridou, Chloi-Magdalini and Herrmann, Alexander M. and Bittner, Stefan and Merker, Monika and Ruck, Tobias and Glumm, Sarah and Langhauser, Friederike and Kraft, Peter and Krug, Thorsten F. and Breuer, Johanna and Herold, Martin and Gross, Catharina C. and Beckmann, Denise and Korb-Pap, Adelheid and Schuhmann, Michael K. and Kuerten, Stefanie and Mitroulis, Ioannis and Ruppert, Clemens and Nolte, Marc W. and Panousis, Con and Klotz, Luisa and Kehrel, Beate and Korn, Thomas and Langer, Harald F. and Pap, Thomas and Nieswandt, Bernhard and Wiendl, Heinz and Chavakis, Triantafyllos and Kleinschnitz, Christoph and Meuth, Sven G.}, title = {Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, number = {11626}, doi = {10.1038/ncomms11626}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165503}, year = {2016}, abstract = {Aberrant immune responses represent the underlying cause of central nervous system (CNS) autoimmunity, including multiple sclerosis (MS). Recent evidence implicated the crosstalk between coagulation and immunity in CNS autoimmunity. Here we identify coagulation factor XII (FXII), the initiator of the intrinsic coagulation cascade and the kallikrein-kinin system, as a specific immune cell modulator. High levels of FXII activity are present in the plasma of MS patients during relapse. Deficiency or pharmacologic blockade of FXII renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by reduced numbers of interleukin-17A-producing T cells. Immune activation by FXII is mediated by dendritic cells in a CD87-dependent manner and involves alterations in intracellular cyclic AMP formation. Our study demonstrates that a member of the plasmatic coagulation cascade is a key mediator of autoimmunity. FXII inhibition may provide a strategy to combat MS and other immune-related disorders.}, language = {en} } @article{DomschkeZwanzgerRehbeinetal.2016, author = {Domschke, Katharina and Zwanzger, Peter and Rehbein, Maimu A and Steinberg, Christian and Knoke, Kathrin and Dobel, Christian and Klinkenberg, Isabelle and Kugel, Harald and Kersting, Anette and Arolt, Volker and Pantev, Christo and Junghofer, Markus}, title = {Magnetoencephalographic correlates of emotional processing in major depression before and after pharmacological treatment}, series = {International Journal of Neuropsychopharmacology}, volume = {19}, journal = {International Journal of Neuropsychopharmacology}, number = {2}, doi = {10.1093/ijnp/pyv093}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-149873}, pages = {pyv093}, year = {2016}, abstract = {Background: In major depressive disorder (MDD), electrophysiological and imaging studies suggest reduced neural activity in the parietal and dorsolateral prefrontal cortex regions. In the present study, neural correlates of emotional processing in MDD were analyzed for the first time in a pre-/post-treatment design by means of magnetoencephalography (MEG), allowing for detecting temporal dynamics of brain activation. Methods: Twenty-five medication-free Caucasian in-patients with MDD and 25 matched controls underwent a baseline MEG session with passive viewing of pleasant, unpleasant, and neutral pictures. Fifteen patients were followed-up with a second MEG session after 4 weeks of antidepressant monopharmacotherapy with mirtazapine. The corresponding controls received no intervention between the measurements. The clinical course of depression was assessed using the Hamilton Depression scale. Results: Prior to treatment, an overall neocortical hypoactivation during emotional processing, particularly at the parietal regions and areas at the right temporoparietal junction, as well as abnormal valence-specific reactions at the right parietal and bilateral dorsolateral prefrontal cortex (dlPFC) regions were observed in patients compared to controls. These effects occurred <150ms, suggesting dysfunctional processing of emotional stimuli at a preconscious level. Successful antidepressant treatment resulted in a normalization of the hypoactivation at the right parietal and right temporoparietal regions. Accordingly, both dlPFC regions revealed an increase of activity after therapy. Conclusions: The present study provides neurophysiological evidence for dysfunctional emotional processing in a fronto-parieto-temporal network, possibly contributing to the pathogenesis of MDD. These activation patterns might have the potential to serve as biomarkers of treatment success.}, language = {en} }