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 - De Giorgi, Valeria A1 - Buonaguro, Luigi A1 - Worschech, Andrea A1 - Tornesello, Maria Lina A1 - Izzo, Francesco A1 - Marincola, Francesco M. A1 - Wang, Ena A1 - Buonaguro, Franco M. T1 - Molecular Signatures Associated with HCV-Induced Hepatocellular Carcinoma and Liver Metastasis JF - PLoS ONE N2 - Hepatocellular carcinomas (HCCs) are a heterogeneous group of tumors that differ in risk factors and genetic alterations. In Italy, particularly Southern Italy, chronic hepatitis C virus (HCV) infection represents the main cause of HCC. Using high-density oligoarrays, we identified consistent differences in gene-expression between HCC and normal liver tissue. Expression patterns in HCC were also readily distinguishable from those associated with liver metastases. To characterize molecular events relevant to hepatocarcinogenesis and identify biomarkers for early HCC detection, gene expression profiling of 71 liver biopsies from HCV-related primary HCC and corresponding HCV-positive non-HCC hepatic tissue, as well as gastrointestinal liver metastases paired with the apparently normal peri-tumoral liver tissue, were compared to 6 liver biopsies from healthy individuals. Characteristic gene signatures were identified when normal tissue was compared with HCV-related primary HCC, corresponding HCV-positive non-HCC as well as gastrointestinal liver metastases. Pathway analysis classified the cellular and biological functions of the genes differentially expressed as related to regulation of gene expression and post-translational modification in HCV-related primary HCC; cellular Growth and Proliferation, and Cell-To-Cell Signaling and Interaction in HCV-related non HCC samples; Cellular Growth and Proliferation and Cell Cycle in metastasis. Also characteristic gene signatures were identified of HCV-HCC progression for early HCC diagnosis. Conclusions: A diagnostic molecular signature complementing conventional pathologic assessment was identified. KW - identification KW - hepatitis C virus KW - United States KW - gene expression KW - class I KW - endoplasmic reticulum KW - motile phenotype KW - bladder cancer KW - up-regulation KW - target Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131155 VL - 8 IS - 2 ER - TY - JOUR A1 - Franke, Katharina A1 - Vilne, Baiba A1 - da Costa, Olivia Prazeres A1 - Rudelius, Martina A1 - Peschel, Christian A1 - Oostendorp, Robert A. J. A1 - Keller, Ulrich T1 - In vivo hematopoietic Myc activation directs a transcriptional signature in endothelial cells within the bone marrow microenvironment JF - Oncotarget N2 - Cancer pathogenesis involves tumor-intrinsic genomic aberrations and tumor-cell extrinsic mechanisms such as failure of immunosurveillance and structural and functional changes in the microenvironment. Using Myc as a model oncogene we established a conditional mouse bone marrow transduction/transplantation model where the conditional activation of the oncoprotein Myc expressed in the hematopoietic system could be assessed for influencing the host microenvironment. Constitutive ectopic expression of Myc resulted in rapid onset of a lethal myeloproliferative disorder with a median survival of 21 days. In contrast, brief 4-day Myc activation by means of the estrogen receptor (ER) agonist tamoxifen did not result in gross changes in the percentage/frequency of hematopoietic lineages or hematopoietic stem/progenitor cell (HSPC) subsets, nor did Myc activation significantly change the composition of the non-hematopoietic microenvironment defined by phenotyping for CD31, ALCAM, and Sca-1 expression. Transcriptome analysis of endothelial CD45-Ter119-cells from tamoxifen-treated MycER bone marrow graft recipients revealed a gene expression signature characterized by specific changes in the Rho subfamily pathway members, in the transcription-translation-machinery and in angiogenesis. In conclusion, intra-hematopoietic Myc activation results in significant transcriptome alterations that can be attributed to oncogene-induced signals from hematopoietic cells towards the microenvironment, e. g. endothelial cells, supporting the idea that even pre-leukemic HSPC highjack components of the niche which then could protect and support the cancer-initiating population. KW - stem-cells KW - mutations KW - C-Myc KW - Rho-GTPases KW - niche KW - leukemia KW - target KW - growth KW - cycle KW - apoptosis, Myc KW - microenvironment KW - endothelial cells Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-145844 VL - 6 IS - 26 SP - 21827 EP - 21839 ER - TY - JOUR A1 - Graf, Nicolas A1 - Li, Zhoulei A1 - Herrmann, Ken A1 - Weh, Daniel A1 - Aichler, Michaela A1 - Slawska, Jolanta A1 - Walch, Axel A1 - Peschel, Christian A1 - Schwaiger, Markus A1 - Buck, Andreas K. A1 - Dechow, Tobias A1 - Keller, Ulrich T1 - Positron emission tomographic monitoring of dual phosphatidylinositol-3-kinase and mTOR inhibition in anaplastic large cell lymphoma JF - Oncotargets and Therapy N2 - Background: Dual phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) inhibition offers an attractive therapeutic strategy in anaplastic large cell lymphoma depending on oncogenic nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) signaling. We tested the efficacy of a novel dual PI3K/mTOR inhibitor, NVP-BGT226 (BGT226), in two anaplastic large cell lymphoma cell lines in vitro and in vivo and performed an early response evaluation with positron emission tomography (PET) imaging using the standard tracer, 2-deoxy-2-[F-18] fluoro-D-glucose (FDG) and the thymidine analog, 3'-deoxy-3'-[F-18] fluorothymidine (FLT). Methods: The biological effects of BGT226 were determined in vitro in the NPM-ALK positive cell lines SU-DHL-1 and Karpas299 by 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, propidium iodide staining, and biochemical analysis of PI3K and mTOR downstream signaling. FDG-PET and FLT-PET were performed in immunodeficient mice bearing either SU-DHL-1 or Karpas299 xenografts at baseline and 7 days after initiation of treatment with BGT226. Lymphomas were removed for immunohistochemical analysis of proliferation and apoptosis to correlate PET findings with in vivo treatment effects. Results: SU-DHL-1 cells showed sensitivity to BGT226 in vitro, with cell cycle arrest in G0/G1 phase and an IC50 in the low nanomolar range, in contrast with Karpas299 cells, which were mainly resistant to BGT226. In vivo, both FDG-PET and FLT-PET discriminated sensitive from resistant lymphoma, as indicated by a significant reduction of tumor-to-background ratios on day 7 in treated SU-DHL-1 lymphoma-bearing animals compared with the control group, but not in animals with Karpas299 xenografts. Imaging results correlated with a marked decrease in the proliferation marker Ki67, and a slight increase in the apoptotic marker, cleaved caspase 3, as revealed by immunostaining of explanted lymphoma tissue. Conclusion: Dual PI3K/mTOR inhibition using BGT226 is effective in ALK-positive anaplastic large cell lymphoma and can be monitored with both FDG-PET and FLT-PET early on in the course of therapy. KW - mammalian target of rapamycin KW - phosphatidylinositol-3-kinase KW - lymphoma KW - early response KW - NVP-BGT226 KW - non-hodgkins-lymphoma KW - signaling pathway KW - FDG-PET KW - in-vivo KW - target KW - tumor KW - imaging proliferation KW - inhibition KW - positron emission tomography Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117915 VL - 7 ER - TY - JOUR A1 - Gupta, Shishir K. A1 - Srivastava, Mugdha A1 - Osmanoglu, Oezge A1 - Dandekar, Thomas T1 - Genome-wide inference of the Camponotus floridanus protein-protein interaction network using homologous mapping and interacting domain profile pairs JF - Scientific Reports N2 - Apart from some model organisms, the interactome of most organisms is largely unidentified. High-throughput experimental techniques to determine protein-protein interactions (PPIs) are resource intensive and highly susceptible to noise. Computational methods of PPI determination can accelerate biological discovery by identifying the most promising interacting pairs of proteins and by assessing the reliability of identified PPIs. Here we present a first in-depth study describing a global view of the ant Camponotus floridanus interactome. Although several ant genomes have been sequenced in the last eight years, studies exploring and investigating PPIs in ants are lacking. Our study attempts to fill this gap and the presented interactome will also serve as a template for determining PPIs in other ants in future. Our C. floridanus interactome covers 51,866 non-redundant PPIs among 6,274 proteins, including 20,544 interactions supported by domain-domain interactions (DDIs), 13,640 interactions supported by DDIs and subcellular localization, and 10,834 high confidence interactions mediated by 3,289 proteins. These interactions involve and cover 30.6% of the entire C. floridanus proteome. KW - interaction map KW - drosophila KW - identification KW - evolutionary KW - reliability KW - annotation KW - database KW - target KW - cycle Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229406 VL - 10 IS - 1 ER - TY - THES A1 - Kempkes, Lisa Marleen T1 - EEG Untersuchung zum Zusammenhang zwischen Emotionsverarbeitung und Aufmerksamkeitsprozessen von stark und wenig angstsensitiven Personen T1 - EEG examination about the connection of emotion and attention processing of people with high and low anxiety sensitivity N2 - Gegenstand der vorliegenden Arbeit ist die Untersuchung des Einflusses der Angstsensitivität auf die Emotionsverarbeitung und selektive Aufmerksamkeitsprozesse. Anhand des Angstsensitivitätsindex-3 (ASI-3) wurden die Probanden in stark und wenig angstsensitiv eingeteilt. Der Selbstbeurteilungsfragebogen ASI-3 erfasst in welchem Maß die betreffende Person auf typische angstauslösende Stimuli mit Symptomen reagiert (Kemper, et al., 2009). Bei 53 gesunden, freiwilligen Probanden wurde, während der Präsentation von Bildern mit positiven, negativen und neutralen Inhalt, ein EEG (Elektroenzephalogramm) abgeleitet. In Anlehnung an das Paradigma von Schupp und Kollegen (Schupp, et al., 2007) wurde jede Bildkategorie jeweils in einem Durchgang als Target- und gleichzeitig die beiden anderen Kategorien als Non-Target-Bedingung dargeboten. Außerdem wurde ein Durchgang mit der Anweisung „alle gleich beachten“ (PB-Bedingung) durchgeführt. Die Angstsensitivität beeinflusst den Verlauf des EPN (early posterior negative potential). Bei hoch angstsensitiven Probanden zeigt sich ein stärker negativer Verlauf der EPN-Amplitude als bei wenig Angstsensitiven. Diese Aussage gilt für die Darbietung von neutralen und positiven Bildern bei der PB-Bedingung. Bei Probanden mit hoher Angstsensitivität verläuft sowohl bei der Target-Bedingung als auch bei der Non-Target-Bedingung das EPN signifikant negativer, als bei denjenigen mit niedriger Angstsensitivität. Ebenfalls zeigte sich das EPN-Potential während der Target- und Non-Target-Bedingung bei positiven und neutralen Bildern für hoch angstsensitive Probanden signifikant negativer als bei wenig angstsensitiven Probanden. Im LPP (late positive potential) zeigte sich kein Einfluss der Angstsensitivität auf den Verlauf des Potentials. Keine geschlechtsspezifischen Unterschiede konnten im LPP und EPN festgestellt werden. N2 - The subject of this study is an examination of the influence of anxiety sensitivity on the processing of emotions and selective attention processes. In the present study 53 healthy, voluntary participants have been categorized as highly and little anxiety sensitive according to the anxiety sensitivity index 3 (ASI-3) (Kemper, et al., 2009). The self-evaluation questionnaire ASI-3 determines to which degree the test person reacts with symptoms to typical anxiety-causing stimuli. Event-related brain potentials were measured while subjects viewed images with positive, negative and neutral content. Drawing on Schupp et al’s paradigm each category of images has been displayed at one stage as target condition and the 2 others simultaneously as non-target condition (Schupp, et al., 2007). Also, one stage has been conducted with the subjects being instructed to “regard all equally” (PB-condition). Anxiety sensitivity influences the EPN (early posterior negative potential) waveform. Highly anxiety sensitive subjects displayed an increased negativity of the EPN amplitude than little anxiety sensitive ones. This statement can be made both for neutral and positive images under the PB-condition. The amplitude of the EPN is significantly more negative in subjects with high anxiety sensitivity both in target-condition and non-target-condition when compared to subjects with lower anxiety sensitivity. Similarly, the EPN potential for highly anxiety sensitive subjects during target and non-target condition with positive and neutral images was found to be significantly more negative. In LPP (late positive potential) no influence of anxiety sensitivity on the course of potential could be established. No gender-specific differences have been identified in either LPP or EPN. KW - EEG KW - Emotion KW - Aufmerksamkeit KW - Ereigniskorrelierte Potentiale KW - Angstsensitivitätsindex-3 KW - Angstsensitivität KW - target KW - Anxiety sensitivity KW - Anxiety Sensetivity Index KW - EEG Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-83822 ER - TY - JOUR A1 - Zukher, Inna A1 - Novikova, Maria A1 - Tikhonov, Anton A1 - Nesterchuk, Mikhail V. A1 - Osterman, Ilya A. A1 - Djordjevic, Marko A1 - Sergiev, Petr V. A1 - Sharma, Cynthia M. A1 - Severinov, Konstantin T1 - Ribosome-controlled transcription termination is essential for the production of antibiotic microcin C JF - Nucleic Acids Research N2 - Microcin C (McC) is a peptide-nucleotide antibiotic produced by Escherichia coli cells harboring a plasmid-borne operon mccABCDE. The heptapeptide MccA is converted into McC by adenylation catalyzed by the MccB enzyme. Since MccA is a substrate for MccB, a mechanism that regulates the MccA/MccB ratio likely exists. Here, we show that transcription from a promoter located upstream of mccA directs the synthesis of two transcripts: a short highly abundant transcript containing the mccA ORF and a longer minor transcript containing mccA and downstream ORFs. The short transcript is generated when RNA polymerase terminates transcription at an intrinsic terminator located in the intergenic region between the mccA and mccB genes. The function of this terminator is strongly attenuated by upstream mcc sequences. Attenuation is relieved and transcription termination is induced when ribosome binds to the mccA ORF. Ribosome binding also makes the mccA RNA exceptionally stable. Together, these two effects-ribosome induced transcription termination and stabilization of the message-account for very high abundance of the mccA transcript that is essential for McC production. The general scheme appears to be evolutionary conserved as ribosome-induced transcription termination also occurs in a homologous operon from Helicobacter pylori. KW - escherichia coli KW - messenger-RNA decay KW - translation KW - expression KW - synthetase KW - enterobacteria KW - inhibitors KW - maturation KW - target KW - stability Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114839 SN - 0305-1048 VL - 42 IS - 19 ER -