TY  - JOUR
A1  - Blättner, Sebastian
A1  - Das, Sudip
A1  - Paprotka, Kerstin
A1  - Eilers, Ursula
A1  - Krischke, Markus
A1  - Kretschmer, Dorothee
A1  - Remmele, Christian W.
A1  - Dittrich, Marcus
A1  - Müller, Tobias
A1  - Schuelein-Voelk, Christina
A1  - Hertlein, Tobias
A1  - Mueller, Martin J.
A1  - Huettel, Bruno
A1  - Reinhardt, Richard
A1  - Ohlsen, Knut
A1  - Rudel, Thomas
A1  - Fraunholz, Martin J.
T1  - Staphylococcus aureus Exploits a Non-ribosomal Cyclic Dipeptide to Modulate Survival within Epithelial Cells and Phagocytes
JF  - PLoS Pathogens
N2  - Community-acquired (CA) Staphylococcus aureus cause various diseases even in healthy individuals. Enhanced virulence of CA-strains is partly attributed to increased production of toxins such as phenol-soluble modulins (PSM). The pathogen is internalized efficiently by mammalian host cells and intracellular S. aureus has recently been shown to contribute to disease. Upon internalization, cytotoxic S. aureus strains can disrupt phagosomal membranes and kill host cells in a PSM-dependent manner. However, PSM are not sufficient for these processes. Here we screened for factors required for intracellular S. aureus virulence. We infected escape reporter host cells with strains from an established transposon mutant library and detected phagosomal escape rates using automated microscopy. We thereby, among other factors, identified a non-ribosomal peptide synthetase (NRPS) to be required for efficient phagosomal escape and intracellular survival of S. aureus as well as induction of host cell death. By genetic complementation as well as supplementation with the synthetic NRPS product, the cyclic dipeptide phevalin, wild-type phenotypes were restored. We further demonstrate that the NRPS is contributing to virulence in a mouse pneumonia model. Together, our data illustrate a hitherto unrecognized function of the S. aureus NRPS and its dipeptide product during S. aureus infection.
KW  - cell death
KW  - cytotoxicity
KW  - Staphylococcus aureus
KW  - host cells
KW  - neutrophils
KW  - macrophages
KW  - transposable elements
KW  - epithelial cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-180380
VL  - 12
IS  - 9
ER  - 
TY  - JOUR
A1  - Zahnert, Thomas
A1  - Löwenheim, Hubert
A1  - Beutner, Dirk
A1  - Hagen, Rudolf
A1  - Ernst, Arneborg
A1  - Pau, Hans-Wilhelm
A1  - Zehlicke, Thorsten
A1  - Kühne, Hilke
A1  - Friese, Natascha
A1  - Tropitzsch, Anke
A1  - Lüers, Jan-Christoffer
A1  - Mlynski, Robert
A1  - Todt, Ingo
A1  - Hüttenbrink, Karl-Bernd
T1  - Multicenter Clinical Trial of Vibroplasty Couplers to Treat Mixed/Conductive Hearing Loss: First Results
JF  - Audiology and Neurotology
N2  - Objective: To evaluate the safety and effectiveness of round window (RW), oval window (OW), CliP and Bell couplers for use with an active middle ear implant. Methods: This is a multicenter, long-term, prospective trial with consecutive enrollment, involving 6 university hospitals in Germany. Bone conduction, air conduction, implant-aided warble-tone thresholds and Freiburger monosyllable word recognition scores were compared with unaided preimplantation results in 28 moderate-to-profound hearing-impaired patients after 12 months of follow-up. All patients had previously undergone failed reconstruction surgeries (up to 5 or more). In a subset of patients, additional speech tests at 12 months postoperatively were used to compare the aided with the unaided condition after implantation with the processor switched off. An established quality-of-life questionnaire for hearing aids was used to determine patient satisfaction. Results: Postoperative bone conduction remained stable. Mean functional gain for all couplers was 37 dB HL (RW = 42 dB, OW = 35 dB, Bell = 38 dB, CliP = 27 dB). The mean postoperative Freiburger monosyllable score was 71% at 65 dB SPL. The postimplantation mean SRT<sub>50</sub> (speech reception in quiet for 50% understanding of words in sentences) improved on average by 23 dB over unaided testing and signal-to-noise ratios also improved in all patients. The International Outcome Inventory for Hearing Aids (IOI-HA)quality-of-life questionnaire was scored very positively by all patients. Conclusion: A significant improvement was seen with all couplers, and patients were satisfied with the device at 12 months postoperatively. These results demonstrate that an active implant is an advantage in achieving good hearing benefit in patients with prior failed reconstruction surgery.
KW  - conductive hearing loss
KW  - mixed hearing loss
KW  - vibroplasty
KW  - couplers
KW  - middle ear implant
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199129
SN  - 1420-3030
SN  - 1421-9700
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 21
IS  - 4
ER  - 
TY  - JOUR
A1  - Schmid, Michael
A1  - Steinlein, Claus
A1  - Winking, Heinz
T1  - Multicolor Spectral Analyses of Mitotic and Meiotic Mouse Chromosomes Involved in Multiple Robertsonian Translocations. I. The CD/Cremona Hybrid Strain
JF  - Cytogenetic and Genome Research
N2  - Multicolor spectral analysis (spectral karyotyping) was applied to mitotic and male diakinetic chromosomes of hybrid mice carrying a unique system of 18 autosomal Robertsonian translocation chromosomes with alternating arm homologies. Only the autosomes 19 and the XY sex chromosomes are excluded from these Robertsonian translocations. The translocations, previously identified by conventional banding analyses, could be verified by spectral karyotyping. Besides the Robertsonian translocations, no other interchromosomal rearrangements were detected. In diakineses of male meiosis, the 18 metacentric Robertsonian translocation chromosomes form a very large meiotic ‘superring'. The predictable, specific order of the chromosomes along this ‘superring' was completely confirmed by multicolor spectral analysis. In the majority of diakineses analyzed, the free autosomal bivalent 19 and the XY sex bivalent form a conspicuous complex which tightly associates with the 12;14 Robertsonian translocation chromosome in the ‘superring'.
KW  - meiotic ‘superring’
KW  - mouse
KW  - Robertsonian translocation chromosomes
KW  - spectral karyotyping
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199013
SN  - 1424-8581
SN  - 1424-859X
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 147
IS  - 4
ER  - 
TY  - JOUR
A1  - Schmid, Michael
A1  - Steinlein, Claus
T1  - Chromosome Banding in Amphibia. XXXIII. Demonstration of 5-Methylcytosine-Rich Heterochromatin in Anura
JF  - Cytogenetic and Genome Research
N2  - An experimental approach using monoclonal anti-5-methylcytosine (5-MeC) antibodies and indirect immunofluorescence was elaborated for detecting 5-MeC-rich chromosome regions in anuran chromosomes. This technique was applied to mitotic metaphases of 6 neotropical frog species belonging to 6 genera and 4 families. The hypermethylation patterns were compared with a variety of banding patterns obtained by conventional banding techniques. The hypermethylated DNA sequences are species-specific and located exclusively in constitutive heterochromatin. They are found in centromeric, pericentromeric, telomeric, and interstitial positions of the chromosomes and adjacent to nucleolus organizer regions. 5-MeC-rich DNA sequences can be embedded both in AT- and GC-rich repetitive DNA. The experimental parameters that have major influence on the reproducibility and quality of the anti-5-MeC antibody labeling are discussed.
KW  - Anura
KW  - heterochromatin
KW  - hypermethylated DNA
KW  - immunofluorescence
KW  - 5-Methylcytosine
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-199022
SN  - 1424-8581
SN  - 1424-859X
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 148
IS  - 1
ER  - 
TY  - JOUR
A1  - Dengler, Julius
A1  - Maldaner, Nicolai
A1  - Gläsker, Sven
A1  - Endres, Matthias
A1  - Wagner, Martin
A1  - Malzahn, Uwe
A1  - Heuschmann, Peter U.
A1  - Vajkoczy, Peter
T1  - Outcome of Surgical or Endovascular Treatment of Giant Intracranial Aneurysms, with Emphasis on Age, Aneurysm Location, and Unruptured Aneuryms - A Systematic Review and Meta-Analysis
JF  - Cerebrovascular Diseases
N2  - Background: Designing treatment strategies for unruptured giant intracranial aneurysms (GIA) is difficult as evidence of large clinical trials is lacking. We examined the outcome following surgical or endovascular GIA treatment focusing on patient age, GIA location and unruptured GIA. Methods: Medline and Embase were searched for studies reporting on GIA treatment outcome published after January 2000. We calculated the proportion of good outcome (PGO) for all included GIA and for unruptured GIA by meta-analysis using a random effects model. Results: We included 54 studies containing 64 study populations with 1,269 GIA at a median follow-up time (FU-T) of 26.4 months (95% CI 10.8-42.0). PGO was 80.9% (77.4-84.4) in the analysis of all GIA compared to 81.2% (75.3-86.1) in the separate analysis of unruptured GIA. For each year added to patient age, PGO decreased by 0.8%, both for all GIA and unruptured GIA. For all GIA, surgical treatment resulted in a PGO of 80.3% (95% CI 76.0-84.6) compared to 84.2% (78.5-89.8, p = 0.27) after endovascular treatment. In unruptured GIA, PGO was 79.7% (95% CI 71.5-87.8) after surgical treatment and 84.9% (79.1-90.7, p = 0.54) after endovascular treatment. PGO was lower in high quality studies and in studies presenting aggregate instead of individual patient data. In unruptured GIA, the OR for good treatment outcome was 5.2 (95% CI 2.0-13.0) at the internal carotid artery compared to 0.1 (0.1-0.3, p < 0.1) in the posterior circulation. Patient sex, FU-T and prevalence of ruptured GIA were not associated with PGO. Conclusions: We found that the chances of good outcome after surgical or endovascular GIA treatment mainly depend on patient age and aneurysm location rather than on the type of treatment conducted. Our analysis may inform future research on GIA.
KW  - surgical aneurysm treatment
KW  - giant intracranial aneurysm
KW  - endovascular treatment
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196792
SN  - 1015-9770
SN  - 1421-9786
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 41
IS  - 3-4
ER  - 
TY  - JOUR
A1  - Almanzar, Giovanni
A1  - Klein, Matthias
A1  - Schmalzing, Marc
A1  - Hilligardt, Deborah
A1  - El Hajj, Nady
A1  - Kneitz, Hermann
A1  - Wild, Vanessa
A1  - Rosenwald, Andreas
A1  - Benoit, Sandrine
A1  - Hamm, Henning
A1  - Tony, Hans-Peter
A1  - Haaf, Thomas
A1  - Goebeler, Matthias
A1  - Prelog, Martina
T1  - Disease Manifestation and Inflammatory Activity as Modulators of Th17/Treg Balance and RORC/FoxP3 Methylation in Systemic Sclerosis
JF  - International Archives of Allergy and Immunology
N2  - Background: There is much evidence that T cells are strongly involved in the pathogenesis of localized and systemic forms of scleroderma (SSc). A dysbalance between FoxP3+ regulatory CD4+ T cells (Tregs) and inflammatory T-helper (Th) 17 cells has been suggested. Methods: The study aimed (1) to investigate the phenotypical and functional characteristics of Th17 and Tregs in SSc patients depending on disease manifestation (limited vs. diffuse cutaneous SSc, dcSSc) and activity, and (2) the transcriptional level and methylation status of Th17- and Treg-specific transcription factors. Results: There was a concurrent accumulation of circulating peripheral IL-17-producing CCR6+ Th cells and FoxP3+ Tregs in patients with dcSSc. At the transcriptional level, Th17- and Treg-associated transcription factors were elevated in SSc. A strong association with high circulating Th17 and Tregs was seen with early, active, and severe disease presentation. However, a diminished suppressive function on autologous lymphocytes was found in SSc-derived Tregs. Significant relative hypermethylation was seen at the gene level for RORC1 and RORC2 in SSc, particularly in patients with high inflammatory activity. Conclusions: Besides the high transcriptional activity of T cells, attributed to Treg or Th17 phenotype, in active SSc disease, Tregs may be insufficient to produce high amounts of IL-10 or to control proliferative activity of effector T cells in SSc. Our results suggest a high plasticity of Tregs strongly associated with the Th17 phenotype. Future directions may focus on enhancing Treg functions and stabilization of the Treg phenotype.
KW  - methylation
KW  - systemic sclerosis
KW  - suppression
KW  - Tregs
KW  - Th17
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196577
SN  - 1018-2438
SN  - 1423-0097
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 171
IS  - 2
ER  - 
TY  - JOUR
A1  - Schmid, Michael
A1  - Steinlein, Claus
T1  - Chromosome Banding in Amphibia. XXXIV. Intrachromosomal Telomeric DNA Sequences in Anura
JF  - Cytogenetic and Genome Research
N2  - The mitotic chromosomes of 4 anuran species were examined by various classical banding techniques and by fluorescence in situ hybridization using a (TTAGGG)\(_n\) repeat. Large intrachromosomal telomeric sequences (ITSs) were demonstrated in differing numbers and chromosome locations. A detailed comparison of the present results with numerous published and unpublished data allowed a consistent classification of the various categories of large ITSs present in the genomes of anurans and other vertebrates. The classification takes into consideration the total numbers of large ITSs in the karyotypes, their chromosomal locations and their specific distribution patterns. A new category of large ITSs was recognized to exist in anuran species. It consists of large clusters of ITSs located in euchromatic chromosome segments, which is in clear contrast to the large ITSs in heterochromatic chromosome regions known in vertebrates. The origin of the different categories of large ITSs in heterochromatic and euchromatic chromosome regions, their mode of distribution in the karyotypes and evolutionary fixation in the genomes, as well as their cytological detection are discussed.
KW  - heterochromatin
KW  - intrachromosomal telomeric sequences
KW  - Anura
KW  - euchromatin
KW  - evolutionary fixation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196693
SN  - 1424-8581
SN  - 1424-859X
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 148
IS  - 2-3
ER  - 
TY  - JOUR
A1  - Schmid, Michael
A1  - Steinlein, Claus
A1  - Lomb, Christian
A1  - Sperling, Karl
A1  - Neitzel, Heidemarie
T1  - 5-Methylcytosine-Rich Heterochromatin in the Indian Muntjac
JF  - Cytogenetic and Genome Research
N2  - Two 5-methylcytosine (5-MeC)-rich heterochromatic regions were demonstrated in metaphase chromosomes of the Indian muntjac by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. The metaphases were obtained from diploid and triploid cell lines. A major region is located in the ‘neck' of the 3;X fusion chromosome and can be detected after denaturation of the chromosomal DNA with UV-light irradiation for 1 h. It is located exactly at the border of the X chromosome and the translocated autosome 3. A minor region is found in the centromeric region of the free autosome 3 after denaturing the chromosomal DNA for 3 h or longer. The structure and possible function of the major hypermethylated region as barrier against spreading of the X-inactivation process into the autosome 3 is discussed.
KW  - heterochromatin
KW  - immunofluorescence
KW  - Indian muntjac
KW  - 5-Methylcytosine
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196701
SN  - 1424-8581
SN  - 1424-859X
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 147
IS  - 4
ER  - 
TY  - JOUR
A1  - Schmid, Michael
A1  - Steinlein, Claus
A1  - Yano, Cassia F.
A1  - Cioffi, Marcelo B.
T1  - Hypermethylated Chromosome Regions in Nine Fish Species with Heteromorphic Sex Chromosomes
JF  - Cytogenetic and Genome Research
N2  - Sites and amounts of 5-methylcytosine (5-MeC)-rich chromosome regions were detected in the karyotypes of 9 Brazilian species of Characiformes fishes by indirect immunofluorescence using a monoclonal anti-5-MeC antibody. These species, belonging to the genera Leporinus, Triportheus and Hoplias, are characterized by highly differentiated and heteromorphic ZW and XY sex chromosomes. In all species, the hypermethylated regions are confined to constitutive heterochromatin. The number and chromosome locations of hypermethylated heterochromatic regions in the karyotypes are constant and species-specific. Generally, heterochromatic regions that are darkly stained by the C-banding technique are distinctly hypermethylated, but several of the brightly fluorescing hypermethylated regions merely exhibit moderate or faint C-banding. The ZW and XY sex chromosomes of all 9 analyzed species also show species-specific heterochromatin hypermethylation patterns. The analysis of 5-MeC-rich chromosome regions contributes valuable data for comparative cytogenetics of closely related species and highlights the dynamic process of differentiation operating in the repetitive DNA fraction of sex chromosomes.
KW  - heterochromatin
KW  - heteromorphic sex chromosomes
KW  - hypermethylation
KW  - immunofluorescence
KW  - 5-Methylcytosine
KW  - fish
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196710
SN  - 1424-8581
SN  - 1424-859X
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 147
IS  - 2-3
ER  - 
TY  - JOUR
A1  - Vaiopoulos, Aristeidis G.
A1  - Kanakis, Meletios A.
A1  - Kapsimali, Violetta
A1  - Vaiopoulos, Georgios
A1  - Kaklamanis, Phedon G.
A1  - Zouboulis, Christos C.
T1  - Juvenile Adamantiades-Behçet disease
JF  - Dermatology
N2  - Adamantiades-Behçet disease (ABD) is a chronic, multisystemic, recurrent, inflammatory vascular disorder of unknown etiology. Patients with symptoms initially appearing at the age of 16 or less are considered as cases of juvenile-onset ABD (JABD). JABD is relatively rare compared to ABD of adults, and only case reports and case studies have been published regarding this subtype of the disease. Epidemiology, clinical features, diagnosis and treatment of JABD are discussed in this review.
KW  - Aphthae
KW  - Childhood
KW  - Epidemiological study
KW  - Genitoanal region
KW  - Adamantiades-Behçet disease
KW  - Behçet’s disease
KW  - Uveitis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196616
SN  - 1018-8665
SN  - 1421-9832
N1  - This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.
VL  - 232
IS  - 2
SP  - 129
EP  - 136
ER  - 
TY  - JOUR
A1  - Verma, Pramod Kumar
A1  - Steinbacher, Andreas
A1  - Schmiedel, Alexander
A1  - Nuernberger, Patrick
A1  - Brixner, Tobias
T1  - Excited-state intramolecular proton transfer of 2-acetylindan-1,3-dione studied by ultrafast absorption and fluorescence spectroscopy
JF  - Structural Dynamics
N2  - We employ transient absorption from the deep-UV to the visible region and fluorescence upconversion to investigate the photoinduced excited-state intramolecular proton-transfer dynamics in a biologically relevant drug molecule, 2-acetylindan-1,3-dione. The molecule is a ß-diketone which in the electronic ground state exists as exocyclic enol with an intramolecular H-bond. Upon electronic excitation at 300 nm, the first excited state of the exocyclic enol is initially populated, followed by ultrafast proton transfer (≈160 fs) to form the vibrationally hot endocyclic enol. Subsequently, solvent-induced vibrational relaxation takes place (≈10 ps) followed by decay (≈390 ps) to the corresponding ground state.
KW  - time resolved spectroscopy
KW  - ground states
KW  - fluorescence spectra
KW  - absorption spectra
KW  - ultraviolet light
KW  - hydrogen bonding
KW  - excited states
KW  - reaction mechanisms
KW  - fluorescence
KW  - solvents
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181301
VL  - 3
ER  - 
TY  - JOUR
A1  - Münst, Bernhard
A1  - Thier, Marc Christian
A1  - Winnemöller, Dirk
A1  - Helfen, Martina
A1  - Thummer, Rajkumar P.
A1  - Edenhofer, Frank
T1  - Nanog induces suppression of senescence through downregulation of p27\(^{KIP1}\) expression
JF  - Journal of Cell Science
N2  - A comprehensive analysis of the molecular network of cellular factors establishing and maintaining pluripotency as well as self renewal of pluripotent stem cells is key for further progress in understanding basic stem cell biology. Nanog is necessary for the natural induction of pluripotency in early mammalian development but dispensable for both its maintenance and its artificial induction. To gain further insight into the molecular activity of Nanog, we analyzed the outcomes of Nanog gain-of-function in various cell models employing a recently developed biologically active recombinant cell-permeant protein, Nanog-TAT. We found that Nanog enhances the proliferation of both NIH 3T3 and primary fibroblast cells. Nanog transduction into primary fibroblasts results in suppression of senescence-associated beta-galactosidase activity. Investigation of cell cycle factors revealed that transient activation of Nanog correlates with consistent downregulation of the cell cycle inhibitor p27\(^{KIP1}\) (also known as CDKN1B). By performing chromatin immunoprecipitation analysis, we confirmed bona fide Nanog-binding sites upstream of the p27\(^{KIP1}\) gene, establishing a direct link between physical occupancy and functional regulation. Our data demonstrates that Nanog enhances proliferation of fibroblasts through transcriptional regulation of cell cycle inhibitor p27 gene.
KW  - Embryonic stem cell
KW  - Protein transduction
KW  - Pluripotency
KW  - Senescence
KW  - Cell reprogramming
KW  - p27(KIP1)
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190761
VL  - 129
IS  - 5
ER  - 
TY  - JOUR
A1  - Ehnert, Ina
A1  - Parsa, Sepideh
A1  - Roper, Ian
A1  - Wagner, Marcus
A1  - Muller-Camen, Michael
T1  - Reporting on sustainability and HRM: a comparative study of sustainability reporting practices by the world's largest companies
JF  - International Journal of Human Resource Management
N2  - As a response to the growing public awareness on the importance of organisational contributions to sustainable development, there is an increased incentive for corporations to report on their sustainability activities. In parallel with this has been the development of Sustainable HRM' which embraces a growing body of practitioner and academic literature connecting the notions of corporate sustainability to HRM. The aim of this article is to analyse corporate sustainability reporting amongst the world's largest companies and to assess the HRM aspects of sustainability within these reports in comparison to environmental aspects of sustainable management and whether organisational attributes - principally country-of-origin - influences the reporting of such practices. A focus in this article is the extent to which the reporting of various aspects of sustainability may reflect dominant models of corporate governance in the country in which a company is headquartered. The findings suggest, first and against expectations, that the overall disclosure on HRM-related performance is not lower than that on environmental performance. Second, companies report more on their internal workforce compared to their external workforce. Finally, international differences, in particular those between companies headquartered in liberal market economies and coordinated market economies, are not as apparent as expected.
KW  - Human Resource Management
KW  - comparative HRM
KW  - global reporting initiative
KW  - sustainability reporting
KW  - Sustainable HRM
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191141
VL  - 27
IS  - 1
ER  - 
TY  - JOUR
A1  - Daryaee, Fereidoon
A1  - Chang, Andrew
A1  - Schiebel, Johannes
A1  - Lu, Yang
A1  - Zhang, Zhuo
A1  - Kapilashrami, Kanishk
A1  - Walker, Stephen G.
A1  - Kisker, Caroline
A1  - Sotriffer, Christoph A.
A1  - Fisher, Stewart L.
A1  - Tonge, Peter J.
T1  - Correlating drug-target kinetics and in vivo pharmacodynamics: long residence time inhibitors of the FabI enoyl-ACP reductase
JF  - Chemical Science
N2  - Drug-target kinetics enable time-dependent changes in target engagement to be quantified as a function of drug concentration. When coupled to drug pharmacokinetics (PK), drug-target kinetics can thus be used to predict in vivo pharmacodynamics (PD). Previously we described a mechanistic PK/PD model that successfully predicted the antibacterial activity of an LpxC inhibitor in a model of Pseudomonas aeruginosa infection. In the present work we demonstrate that the same approach can be used to predict the in vivo activity of an enoyl-ACP reductase (FabI) inhibitor in a model of methicillin-resistant Staphylococcus aureus (MRSA) infection. This is significant because the LpxC inhibitors are cidal, whereas the FabI inhibitors are static. In addition P. aeruginosa is a Gram-negative organism whereas MRSA is Gram-positive. Thus this study supports the general applicability of our modeling approach across antibacterial space.
KW  - Staphylococcus aureus
KW  - antibacterial activity
KW  - LpxC inhibitors
KW  - enoyl-ACP reductase inhibitors
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191218
VL  - 7
IS  - 9
ER  - 
TY  - JOUR
A1  - El Hajj, Nady
A1  - Dittrich, Marcus
A1  - Böck, Julia
A1  - Kraus, Theo F. J.
A1  - Nanda, Indrajit
A1  - Müller, Tobias
A1  - Seidmann, Larissa
A1  - Tralau, Tim
A1  - Galetzka, Danuta
A1  - Schneider, Eberhard
A1  - Haaf, Thomas
T1  - Epigenetic dysregulation in the developing Down syndrome cortex
JF  - Epigenetics
N2  - Using Illumina 450K arrays, 1.85% of all analyzed CpG sites were significantly hypermethylated and 0.31% hypomethylated in fetal Down syndrome (DS) cortex throughout the genome. The methylation changes on chromosome 21 appeared to be balanced between hypo- and hyper-methylation, whereas, consistent with prior reports, all other chromosomes showed 3-11times more hyper- than hypo-methylated sites. Reduced NRSF/REST expression due to upregulation of DYRK1A (on chromosome 21q22.13) and methylation of REST binding sites during early developmental stages may contribute to this genome-wide excess of hypermethylated sites. Upregulation of DNMT3L (on chromosome 21q22.4) could lead to de novo methylation in neuroprogenitors, which then persists in the fetal DS brain where DNMT3A and DNMT3B become downregulated. The vast majority of differentially methylated promoters and genes was hypermethylated in DS and located outside chromosome 21, including the protocadherin gamma (PCDHG) cluster on chromosome 5q31, which is crucial for neural circuit formation in the developing brain. Bisulfite pyrosequencing and targeted RNA sequencing showed that several genes of PCDHG subfamilies A and B are hypermethylated and transcriptionally downregulated in fetal DS cortex. Decreased PCDHG expression is expected to reduce dendrite arborization and growth in cortical neurons. Since constitutive hypermethylation of PCDHG and other genes affects multiple tissues, including blood, it may provide useful biomarkers for DS brain development and pharmacologic targets for therapeutic interventions.
KW  - trisomy 21
KW  - DNA methylation
KW  - Down syndrome
KW  - fetal brain development
KW  - frontal cortex
KW  - protocadherin gamma cluster
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191239
VL  - 11
IS  - 8
ER  - 
TY  - JOUR
A1  - Bratengeier, Klaus
A1  - Holubyev, Kostyantyn
T1  - Anisotropy of dose contributions-an instrument to upgrade real time IMRT and VMAT adaptation?
JF  - Medical Physics
N2  - Purpose: 
To suggest a definition of dose deposition anisotropy for the purpose of ad hoc adaptation of intensity modulated arc therapy (IMRT) and volumetric arc therapy (VMAT), particularly in the vicinity of important organs at risk (OAR), also for large deformations. 

Methods: 
Beam's-eye-view (BEV) based fluence warping is a standard adaptation method with disadvantages for strongly varying OAR shapes. 2-Step-adaptation overcomes these difficulties by a deeper analysis of the 3D properties of adaptation processes, but requires separate arcs for every OAR to spare, which makes it impractical for cases with multiple OARs. The authors aim to extend the 2-Step method to arbitrary intensity modulated plan by analyzing the anisotropy of dose contributions. Anisotropy was defined as a second term of Fourier transformation of gantry angle dependent dose contributions. For a cylindrical planning target volume (PTV) surrounding an OAR of varying diameter, the anisotropy and the dose-normalized anisotropy were analyzed for several scenarios of optimized fluence distributions. 2-Step adaptation to decreasing and increasing OAR diameter was performed, and compared to a usual fluence based adaptation method. For two clinical cases, prostate and neck, the VMAT was generated and the behavior of anisotropy was qualitatively explored for deformed organs at risk. #

Results: 
Dose contribution anisotropy in the PTV peaks around nearby OARs. The thickness of the "anisotropy wall" around OAR increases for increasing OAR radius, as also does the width of 2-Step dose saturating fluence peak adjacent to the OAR K. Bratengeier et al., "A comparison between 2-Step IMRT and conventional IMRT planning," Radiother. Oncol. 84, 298-306 (2007)]. Different optimized beam fluence profiles resulted in comparable radial dependence of normalized anisotropy. As predicted, even for patient cases, anisotropy was inflated even more than increasing diameters of OAR. 

Conclusions: 
For cylindrically symmetric cases, the dose distribution anisotropy defined in the present work implicitly contains adaptation-relevant information about 3D relationships between PTV and OAR and degree of OAR sparing. For more complex realistic cases, it shows the predicted behavior qualitatively. The authors claim to have found a first component for advancing a 2-Step adaptation to a universal adaptation algorithm based on the BEV projection of the dose anisotropy. Further planning studies to explore the potential of anisotropy for adaptation algorithms using phantoms and clinical cases of differing complexity will follow.
KW  - modulated arc therapy
KW  - 2-step IMRT
KW  - radiation-therapy
KW  - online adaption
KW  - prostate-cancer
KW  - plans
KW  - IMAT
KW  - tracking
KW  - radiotherapy
KW  - adaption
KW  - IMRT
KW  - VMAT
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186833
VL  - 43
IS  - 11
ER  - 
TY  - JOUR
A1  - Dotterweich, Julia
A1  - Schlegelmilch, Katrin
A1  - Keller, Alexander
A1  - Geyer, Beate
A1  - Schneider, Doris
A1  - Zeck, Sabine
A1  - Tower, Robert J. J.
A1  - Ebert, Regina
A1  - Jakob, Franz
A1  - Schütze, Norbert
T1  - Contact of myeloma cells induces a characteristic transcriptome signature in skeletal precursor cells-implications for myeloma bone disease
JF  - Bone
N2  - Physical interaction of skeletal precursors with multiple myeloma cells has been shown to suppress their osteogenic potential while favoring their tumor-promoting features. Although several transcriptome analyses of myeloma patient-derived mesenchymal stem cells have displayed differences compared to their healthy counterparts, these analyses insufficiently reflect the signatures mediated by tumor cell contact, vary due to different methodologies, and lack results in lineage-committed precursors. To determine tumor cell contact-mediated changes on skeletal precursors, we performed transcriptome analyses of mesenchymal stem cells and osteogenic precursor cells cultured in contact with the myeloma cell line INA-6. Comparative analyses confirmed dysregulation of genes which code for known disease-relevant factors and additionally revealed upregulation of genes that are associated with plasma cell homing, adhesion, osteoclastogenesis, and angiogenesis. Osteoclast-derived coupling factors, a dysregulated adipogenic potential, and an imbalance in favor of anti-anabolic factors may play a role in the hampered osteoblast differentiation potential of mesenchymal stem cells. Angiopoietin-Like 4 (ANGPTL4) was selected from a list of differentially expressed genes as a myeloma cell contact-dependent target in skeletal precursor cells which warranted further functional analyses. Adhesion assays with full-length ANGPTL4-coated plates revealed a potential role of this protein in INA6 cell attachment. This study expands knowledge of the myeloma cell contact-induced signature in the stromal compartment of myelomatous bones and thus offers potential targets that may allow detection and treatment of myeloma bone disease at an early stage.
KW  - marrow stromal cells
KW  - Endothelial growth-factor
KW  - precedes multiple-myeloma
KW  - monoclonial gammopathy
KW  - in-vitro
KW  - mesenchymal stem-cells
KW  - undetermined significance
KW  - angiogenic cytokines
KW  - peripheral-blood
KW  - gene-expression
KW  - Multiple myeloma
KW  - Bone disease
KW  - Angiopoietin-like 4
KW  - Gene expression profiling
KW  - Mesenchymal stem cells
KW  - Osteogenic precursor cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186688
VL  - 93
ER  - 
TY  - JOUR
A1  - Scharaw, Sandra
A1  - Iskar, Murat
A1  - Ori, Alessandro
A1  - Boncompain, Gaelle
A1  - Laketa, Vibor
A1  - Poser, Ina
A1  - Lundberg, Emma
A1  - Perez, Franck
A1  - Beck, Martin
A1  - Bork, Peer
A1  - Pepperkok, Rainer
T1  - The endosomal transcriptional regulator RNF11 integrates degradation and transport of EGFR
JF  - Journal of Cell Biology
N2  - Stimulation of cells with epidermal growth factor (EGF) induces internalization and partial degradation of the EGF receptor (EGFR) by the endo-lysosomal pathway. For continuous cell functioning, EGFR plasma membrane levels are maintained by transporting newly synthesized EGFRs to the cell surface. The regulation of this process is largely unknown. In this study, we find that EGF stimulation specifically increases the transport efficiency of newly synthesized EGFRs from the endoplasmic reticulum to the plasma membrane. This coincides with an up-regulation of the inner coat protein complex II (COP II) components SEC23B, SEC24B, and SEC24D, which we show to be specifically required for EGFR transport. Up-regulation of these COP II components requires the transcriptional regulator RNF11, which localizes to early endosomes and appears additionally in the cell nucleus upon continuous EGF stimulation. Collectively, our work identifies a new regulatory mechanism that integrates the degradation and transport of EGFR in order to maintain its physiological levels at the plasma membrane.
KW  - Epidermal growth-factor
KW  - finger protein 11
KW  - receptor tyrosine kinases
KW  - early secretory pathway
KW  - breast-cancer
KW  - brefeldin-a
KW  - E3 ligase
KW  - trafficking
KW  - export
KW  - endoplasmic-reticulum
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186731
VL  - 215
IS  - 4
ER  - 
TY  - JOUR
A1  - Dekant, Wolfgang
A1  - Bridges, James
T1  - Assessment of reproductive and developmental effects of DINP, DnHP and DCHP using quantitative weight of evidence
JF  - Regulatory Toxicology and Pharmacology
N2  - Quantitative weight of evidence (QWoE) methodology utilizes detailed scoring sheets to assess the quality/reliability of each publication on toxicity of a chemical and gives numerical scores for quality and observed toxicity. This QWoE-methodology was applied to the reproductive toxicity data on diisononylphthalate (DINP), di-n-hexylphthalate (DnHP), and dicyclohexylphthalate (DCHP) to determine if the scientific evidence for adverse effects meets the requirements for classification as reproductive toxicants. The scores for DINP were compared to those when applying the methodology DCHP and DnHP that have harmonized classifications. Based on the quality/reliability scores, application of the QWoE shows that the three databases are of similar quality; but effect scores differ widely. Application of QWoE to DINP studies resulted in an overall score well below the benchmark required to trigger classification. For DCHP, the QWoE also results in low scores. The high scores from the application of the QWoE methodology to the toxicological data for DnHP represent clear evidence for adverse effects and justify a classification of DnHP as category 1B for both development and fertility. The conclusions on classification based on the QWoE are well supported using a narrative assessment of consistency and biological plausibility.
KW  - n-hexyl phthalate
KW  - male rats
KW  - dicyclohexyl phthalate
KW  - Diisononyl phthalate
KW  - in-vivo
KW  - 2-Generation reproduction
KW  - testosterone production
KW  - sexual development
KW  - risk-assesment
KW  - fetal testis
KW  - weight of evidence
KW  - classification and labeling
KW  - reproductive and developmental toxicity
KW  - quantitative assessments
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186750
VL  - 81
ER  - 
TY  - JOUR
A1  - Münch, Miriam
A1  - Hsin, Chih-Hsuan
A1  - Ferber, Elena
A1  - Berger, Susanne
A1  - Müller, Martin J.
T1  - Reactive electrophilic oxylipins trigger a heat stress-like response through HSFA1 transcription factors
JF  - Journal of Experimental Botany
N2  - Electrophilic oxylipins trigger a heat-shock-like response in the absence of heat through the canonical heat-shock transcription factor A1, thereby helping to cope with stresses associated with protein damage.Abiotic and biotic stresses are often characterized by an induction of reactive electrophile species (RES) such as the jasmonate 12-oxo-phytodienoic acid (OPDA) or the structurally related phytoprostanes. Previously, RES oxylipins have been shown massively to induce heat-shock-response (HSR) genes including HSP101 chaperones. Moreover, jasmonates have been reported to play a role in basal thermotolerance. We show that representative HSR marker genes are strongly induced by RES oxylipins through the four master regulator transcription factors HSFA1a, b, d, and e essential for short-term adaptation to heat stress in Arabidopsis. When compared with Arabidopsis seedlings treated at the optimal acclimation temperature of 37 A degrees C, the exogenous application of RES oxylipins at 20 A degrees C induced a much weaker induction of HSP101 at both the gene and protein expression levels which, however, was not sufficient to confer short-term acquired thermotolerance. Moreover, jasmonate-deficient mutant lines displayed a wild-type-like HSR and were not compromised in acquiring thermotolerance. Hence, the OPDA- and RES oxylipin-induced HSR is not sufficient to protect seedlings from severe heat stress but may help plants to cope better with stresses associated with protein unfolding by inducing a battery of chaperones in the absence of heat.
KW  - arabidopsis-thaliana
KW  - shock response
KW  - gene-expression
KW  - model
KW  - acquired thermotolerance
KW  - 12-oxo-phytodienoic acid
KW  - thermotolerance
KW  - plants
KW  - detoxification
KW  - acquisition
KW  - activation
KW  - heat stress
KW  - jasmonates
KW  - phytoprostanes
KW  - reactive electrophilic species
KW  - unfolded protein response
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186766
VL  - 67
IS  - 21
ER  - 
TY  - JOUR
A1  - Joensuu, Johanna
A1  - Altimir, Nuria
A1  - Hakola, Hannele
A1  - Rostás, Michael
A1  - Raivonen, Maarit
A1  - Vestenius, Mika
A1  - Aaltonen, Hermanni
A1  - Riederer, Markus
A1  - Bäck, Jaana
T1  - Role of needle surface waxes in dynamic exchange of mono- and sesquiterpenes
JF  - Atmospheric Chemistry and Physics
N2  - Biogenic volatile organic compounds (BVOCs) produced by plants have a major role in atmospheric chemistry. The different physicochemical properties of BVOCs affect their transport within and out of the plant as well as their reactions along the way. Some of these compounds may accumulate in or on the waxy surface layer of conifer needles and participate in chemical reactions on or near the foliage surface. The aim of this work was to determine whether terpenes, a key category of BVOCs produced by trees, can be found on the epicuticles of Scots pine (Pinus sylvestris L.) and, if so, how they compare with the terpenes found in shoot emissions of the same tree. We measured shoot-level emissions of pine seedlings at a remote outdoor location in central Finland and subsequently analysed the needle surface waxes for the same compounds. Both emissions and wax extracts were clearly dominated by monoterpenes, but the proportion of sesquiterpenes was higher in the wax extracts. There were also differences in the terpene spectra of the emissions and the wax extracts. The results, therefore, support the existence of BVOC associated to the epicuticular waxes. We briefly discuss the different pathways for terpenes to reach the needle surfaces and the implications for air chemistry.
KW  - needle surface waxes
KW  - biogenic volatile organic compounds
KW  - Pinus sylvestris L.
KW  - atmospheric chemistry
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171324
VL  - 16
IS  - 12
ER  - 
TY  - JOUR
A1  - Lorenz, Sonja
A1  - Bhattacharyya, Moitrayee
A1  - Feiler, Christian
A1  - Rape, Michael
A1  - Kuriyan, John
T1  - Crystal Structure of a Ube2S-Ubiquitin Conjugate
JF  - PLoS ONE
N2  - Protein ubiquitination occurs through the sequential formation and reorganization of specific protein-protein interfaces. Ubiquitin-conjugating (E2) enzymes, such as Ube2S, catalyze the formation of an isopeptide linkage between the C-terminus of a “donor” ubiquitin and a primary amino group of an “acceptor” ubiquitin molecule. This reaction involves an intermediate, in which the C-terminus of the donor ubiquitin is thioester-bound to the active site cysteine of the E2 and a functionally important interface is formed between the two proteins. A docked model of a Ube2S-donor ubiquitin complex was generated previously, based on chemical shift mapping by NMR, and predicted contacts were validated in functional studies. We now present the crystal structure of a covalent Ube2S-ubiquitin complex. The structure contains an interface between Ube2S and ubiquitin in trans that resembles the earlier model in general terms, but differs in detail. The crystallographic interface is more hydrophobic than the earlier model and is stable in molecular dynamics (MD) simulations. Remarkably, the docked Ube2S-donor complex converges readily to the configuration seen in the crystal structure in 3 out of 8 MD trajectories. Since the crystallographic interface is fully consistent with mutational effects, this indicates that the structure provides an energetically favorable representation of the functionally critical Ube2S-donor interface.
KW  - crystal structure
KW  - protein ubiquitination
KW  - Ubiquitin-conjugating (E2) enzymes
KW  - Ube2S
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167265
VL  - 11
IS  - 2
ER  - 
TY  - JOUR
A1  - Bahník, Štěpán
A1  - Strack, Fritz
T1  - Overlap of accessible information undermines the anchoring effect
JF  - Judgment and Decision Making
N2  - According to the Selective Accessibility Model of anchoring, the comparison question in the standard anchoring paradigm activates information that is congruent with an anchor. As a consequence, this information will be more likely to become the basis for the absolute judgment which will therefore be assimilated toward the anchor. However, if the activated information overlaps with information that is elicited by the absolute judgment itself, the preceding comparative judgment should not exert an incremental effect and should fail to result in an anchoring effect. The present studies find this result when the comparative judgment refers to a general category and the absolute judgment refers to a subset of the general category that was activated by the anchor value. For example, participants comparing the average annual temperature in New York City to a high 102 °F judged the average winter, but not summer temperature to be higher than participants making no comparison. On the other hand, participants comparing the annual temperature to a low –4 °F judged the average summer, but not winter temperature to be lower than control participants. This pattern of results was shown also in another content domain. It is consistent with the Selective Accessibility Model but difficult to reconcile with other main explanations of the anchoring effect.
KW  - anchoring
KW  - judgment
KW  - heuristics and biases
KW  - selective accessibility
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169287
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Bekes, Inga
A1  - Friedl, Thomas W. P.
A1  - Köhler, Tanja
A1  - Möbus, Volker
A1  - Janni, Wolfgang
A1  - Wöckel, Achim
A1  - Wulff, Christine
T1  - Does VEGF facilitate local tumor growth and spread into the abdominal cavity by suppressing endothelial cell adhesion, thus increasing vascular peritoneal permeability followed by ascites production in ovarian cancer?
JF  - Molecular Cancer
N2  - Background

Ovarian cancer is mostly associated with pathologically regulated permeability of peritoneal vessels, leading to ascites. Here, we investigated the molecular regulation of endothelial permeability by the vascular endothelial growth factor (VEGF) and both tight and adherens junction proteins (VE-cadherin and claudin 5) with regards to the tumor biology of different ovarian cancer types.

Methods

Serum and ascites samples before and after surgery, as well as peritoneal biopsies of 68 ovarian cancer patients and 20 healthy controls were collected. In serum and ascites VEGF protein was measured by ELISA. In peritoneal biopsies co-localization of VE-cadherin and claudin 5 was investigated using immunohistochemical dual staining. In addition, the gene expression of VE-cadherin and claudin 5 was quantified by Real-time PCR. Differences in VEGF levels, VE-cadherin and claudin 5 gene expression were analyzed in relation to various tumor characteristics (tumor stage, grading, histological subtypes, resection status after surgery) and then compared to controls. Furthermore, human primary ovarian cancer cells were co-cultured with human umbilical vein endothelial cells (HUVEC) and changes in VE-cadherin and claudin 5 were investigated after VEGF inhibition.

Results

VEGF was significantly increased in tumor patients in comparison to controls and accumulates in ascites. The highest VEGF levels were found in patients diagnosed with advanced tumor stages, with tumors of poor differentiation, or in the group of solid / cystic-solid tumors. Patients with residual tumor after operation showed significantly higher levels of VEGF both before and after surgery as compared to tumor-free resected patients. Results of an immunohistochemical double-staining experiment indicated co-localization of VE-cadherin and claudin 5 in the peritoneal vasculature. Compared to controls, expression of VE-cadherin and claudin 5 was significantly suppressed in peritoneal vessels of tumor patients, but there were no significant differences regarding VE-cadherin and claudin 5 expression in relation to different tumor characteristics. A significant positive correlation was found between VE-cadherin and claudin 5 expression. VEGF inhibition in vitro was associated with significant increase in VE-cadherin and claudin 5.

Conclusions

Our results indicate that increased peritoneal permeability in ovarian cancer is due to down-regulation of adhesion proteins via tumor derived VEGF. Advanced ovarian cancer with aggressive tumor biology may be associated with early dysregulation of vascular permeability leading to ascites. These patients may benefit from therapeutic VEGF inhibition.
KW  - ovarian cancer
KW  - vascular permeability
KW  - ascites
KW  - VEGF
KW  - claudin 5
KW  - VE-cadherin
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-169298
VL  - 15
IS  - 13
ER  - 
TY  - JOUR
A1  - Huang, Guozheng
A1  - Schramm, Simon
A1  - Heilmann, Jörg
A1  - Biedermann, David
A1  - Kren, Vladimír
A1  - Decker, Michael
T1  - Unconventional application of the Mitsunobu reaction: Selective flavonolignan dehydration yielding hydnocarpins
JF  - Beilstein Journal of Organic Chemistry
N2  - Various Mitsunobu conditions were investigated for a series of flavonolignans (silybin A, silybin B, isosilybin A, and silychristin A) to achieve either selective esterification in position C-23 or dehydration in a one-pot reaction yielding the biologically important enantiomers of hydnocarpin D, hydnocarpin and isohydnocarpin, respectively. This represents the only one-pot semi-synthetic method to access these flavonolignans in high yields.
KW  - Mitsunobu
KW  - dehydration
KW  - flavonoid
KW  - hydnocarpin
KW  - silybin
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160986
VL  - 12
ER  - 
TY  - JOUR
A1  - Zinner, C.
A1  - Krueger, M.
A1  - Reed, J. L.
A1  - Kohl-Bareis, M.
A1  - Holmberg, H. C.
A1  - Sperlich, B.
T1  - Exposure to a combination of heat and hyperoxia during cycling at submaximal intensity does not alter thermoregulatory responses
JF  - Biology of Sport
N2  - In this study, we tested the hypothesis that breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) while exercising in a hot environment exerts negative effects on the total tissue level of haemoglobin concentration (tHb); core (T\(_{core}\)) and skin (T\(_{skin}\)) temperatures; muscle activity; heart rate; blood concentration of lactate; pH; partial pressure of oxygen (P\(_a\)O\(_2\)) and carbon dioxide; arterial oxygen saturation (S\(_a\)O\(_2\)); and perceptual responses. Ten well-trained male athletes cycled at submaximal intensity at 21°C or 33°C in randomized order: first for 20 min while breathing normal air (FinO\(_2\) = 0.21) and then 10 min with F\(_{in}\)O\(_2\) = 0.40 (HOX). At both temperatures, S\(_a\)O\(_2\) and P\(_a\)O\(_2\), but not tHb, were increased by HOX. Tskin and perception of exertion and thermal discomfort were higher at 33°C than 21°C (p < 0.01), but independent of F\(_{in}\)O\(_2\). T\(_{core}\) and muscle activity were the same under all conditions (p > 0.07). Blood lactate and heart rate were higher at 33°C than 21°C. In conclusion, during 30 min of submaximal cycling at 21°C or 33°C, T\(_{core}\), T\(_{skin}\) and T\(_{body}\), tHb, muscle activity and ratings of perceived exertion and thermal discomfort were the same under normoxic and hyperoxic conditions. Accordingly, breathing hyperoxic air (F\(_{in}\)O\(_2\) = 0.40) did not affect thermoregulation under these conditions.
KW  - heat stress
KW  - hyperthermia
KW  - skin blood flow
KW  - thermoregulation
KW  - vasoconstriction
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-160993
VL  - 33
IS  - 1
ER  - 
TY  - JOUR
A1  - Joukhadar, R.
A1  - Wöckel, A.
A1  - Herr, D.
A1  - Paulus, V.
A1  - Radosa, J.
A1  - Hamza, A.
A1  - Solomayer, E.
A1  - Baum, S.
T1  - Challenges of Longevity: Safety of Vaginal and Laparoscopic Urogynecological Procedures in Septuagenarians and Older Patients
JF  - BioMed Research International
N2  - Introduction. Pelvic organ prolapse (POP) and urinary incontinence (UI) have increasing prevalence in the elderly population. The aim of this study was to compare the comorbidities of these procedures between <70 y/o and ≥70 y/o patients. Materials and Methods. In our retrospective study over a period of 2.5 years, 407 patients had received an urogynecological procedure. All patients with POP were treated by reconstructive surgery. Complications were reported using the standardized classification of Clavien-Dindo (CD). The study can be assigned to stage 2b Exploration IDEAL (Idea, Development, Exploration, Assessment, Long-term study)-system of surgical innovation. Results. Operation time, blood loss, and intraoperative complications have not been more frequent in the elderly, whereas hospital stay was significantly longer in ≥70 y/o patients. Regarding postoperative complications, we noticed that ≥70 y/o patients had an almost threefold risk to develop mild early postoperative complications compared to younger patients (OR: 2.86; 95% CI: 1.76–4.66). On the contrary, major complications were not more frequent. No case of life-threatening complication or the need for blood transfusion was reported. Conclusion. After urogynecological procedures, septuagenarians and older patients are more likely to develop mild postoperative complications but not more intraoperative or severe postoperative complications compared to younger patients.
KW  - gynecologic surgical procedures/methods
KW  - postoperative complications/epidemiology
KW  - vagina/surgery
KW  - pelvic organ prolapse/surgery
KW  - middle Aged
KW  - laparoscopy/methods
KW  - uterine prolapse/surgery
KW  - urinary incontinence/surgery
KW  - surgical Mesh
KW  - retrospective Studies
KW  - age factors
KW  - aged
KW  - aged 80 and over
KW  - female
KW  - reconstructive surgical procedures/methods
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-161005
VL  - 2016
IS  - Article ID 5184595
ER  - 
TY  - JOUR
A1  - Isaias, Ioannis U.
A1  - Trujillo, Paula
A1  - Summers, Paul
A1  - Marotta, Giorgio
A1  - Mainardi, Luca
A1  - Pezzoli, Gianni
A1  - Zecca, Luigi
A1  - Costa, Antonella
T1  - Neuromelanin Imaging and Dopaminergic Loss in Parkinson's Disease
JF  - Frontiers in Aging Neuroscience
N2  - Parkinson's disease (PD) is a progressive neurodegenerative disorder in which the major pathologic substrate is a loss of dopaminergic neurons from the substantia nigra. Our main objective was to determine the correspondence between changes in the substantia nigra, evident in neuromelanin and iron sensitive magnetic resonance imaging (MRI), and dopaminergic striatal innervation loss in patients with PD. Eighteen patients and 18 healthy control subjects were included in the study. Using neuromelanin-MRI, we measured the volume of the substantia nigra and the contrast-to-noise-ratio between substantia nigra and a background region. The apparent transverse relaxation rate and magnetic susceptibility of the substantia nigra were calculated from dual-echo MRI. Striatal dopaminergic innervation was measured as density of dopamine transporter (DAT) by means of single-photon emission computed tomography and [123I] N-ω-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) tropane. Patients showed a reduced volume of the substantia nigra and contrast-to-noise-ratio and both positively correlated with the corresponding striatal DAT density. The apparent transverse relaxation rate and magnetic susceptibility values of the substantia nigra did not differ between patients and healthy controls. The best predictor of DAT reduction was the volume of the substantia nigra. Clinical and imaging correlations were also investigated for the locus coeruleus. Our results suggest that neuromelanin-MRI can be used for quantifying substantia nigra pathology in PD where it closely correlates with dopaminergic striatal innervation loss. Longitudinal studies should further explore the role of Neuromelanin-MRI as an imaging biomarker of PD, especially for subjects at risk of developing the disease.
KW  - MRI
KW  - neuromelanin
KW  - dopamine
KW  - Parkinson's disease
KW  - FP-CIT SPECT
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164046
VL  - 8
IS  - 196
ER  - 
TY  - THES
A1  - Lorenzin, Francesca
T1  - Regulation of transcription by MYC - DNA binding and target genes
T1  - Transkriptionelle Regulation durch MYC - DNA-Bindung und Zielgene
N2  - MYC is a transcription factor, whose expression is elevated or deregulated in many human cancers (up to 70%) and is often associated with aggressive and poorly differentiated tumors. Although MYC is extensively studied, discrepancies have emerged about how this transcription factor works. In primary lymphocytes, MYC promotes transcriptional amplification of virtually all genes with an open promoter, whereas in tumor cells MYC regulates specific sets of genes that have significant prognostic value. Furthermore, the set of target genes that distinguish MYC’s physiological function from the pathological/oncogenic one, whether it exists or not, has not been fully understood yet.
In this study, it could be shown that MYC protein levels within a cell and promoter affinity (determined by E-box presence or interaction with other proteins) of target genes toward MYC are important factors that influence MYC activity. At low levels, MYC can amplify a certain transcriptional program, which includes high affinity binding sites, whereas at high levels MYC leads to the specific up- and down regulation of genes with low affinity. Moreover, the promoter affinity characterizes different sets of target genes which can be distinguished in the physiological or oncogenic MYC signatures. 
MYC-mediated repression requires higher MYC levels than activation and formation of a complex with MIZ1 is necessary for inhibiting expression of a subset of MYC target genes.
N2  - MYC ist ein Transkriptionsfaktor, dessen Expression in vielen humanen Tumoren (bis zu 70 %) erhöht oder dereguliert ist. Die Tumore, in denen viel MYC hergestellt wird, zeichnen sich durch einen geringen Differenzierungsgrad aus und verhalten sich sehr aggressiv. Obwohl das biologische Verhalten des MYC Proteins intensiv untersucht wurde, sind unterschiedliche Modelle, wie dieser Transkriptionsfaktor funktioniert, entwickelt worden. In primären Lymphozyten verstärkt MYC die Expression fast aller Gene mit offener Chromatinstruktur, während MYC in Tumorzellen spezifische Gengruppten reguliert, deren Expression mit der Prognose von Patienten korreliert. Es ist also unklar, ob sich die Zielgene der physiologischen Funktion von Myc von den oncogenen/pathophysiologischen Zielgenen unterscheidet und um welche Gene es sich bei letzteren handelt. 
In dieser Arbeit konnte gezeigt werden, dass Expressionsniveau  von MYC und unterschiedliche Promotoraffinitäten zu MYC (charakterisiert durch den Ebox-Gehalt und Interaktionen zu anderen Proteinen) wichtig für die Aktivität des MYC Proteins sind. So kann Myc bei niedrigen Konzentrationen ein bestimmtes transkriptionelles Programm amplifizieren, das sich aus hochaffinen Promotoren zusammensetzt. Bei hohen Konzentrationen hingegen führt MYC zur transkriptionellen Aktivierung und Repression bestimmter Zielgengruppen, die sich durch niedrige Affinität zu MYC auszeichnen. Somit ist die Promotoraffinität ein Parameter, der physiologische von oncogenen MYC Signaturen trennen kann. Darüberhinaus konnte gezeigt werden, dass MYC-vermittelte Repression höhere MYC Mengen benötigt, als MYC-vermittelte Transaktivierung und die Komplexbildung mit MIZ1 für die Repression einer Gruppe an MYC Zielgenen nötig ist.
KW  - MYC
KW  - Transcription
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150766
ER  - 
TY  - CHAP
A1  - Schmitz, Barbara
T1  - Space, Borders and Boundaries in the Letter of Aristeas
T2  - Borders : Terminologies, Ideologies, and Performances
N2  - No abstract available.
KW  - Aristeas
KW  - Ad Philocratem
KW  - Aristeas-Brief
KW  - Letter of Aristeas
KW  - Aristeas, Epistolographus : Ad Philocratem
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151285
UR  - https://www.mohr.de/en/book/borders-terminologies-ideologies-and-performances-9783161543760
SN  - 978-3-16-154375-3
PB  - Mohr Siebeck
CY  - Tübingen
ER  - 
TY  - JOUR
A1  - Tiede, Jennifer
A1  - Grafe, Silke
T1  - Media Pedagogy in German and US Teacher Education
JF  - Communicar
N2  - Varios estudios de investigación y de práctica llegan a la conclusión de que la pedagogía de los medios debe integrarse en la formación de profesores para que estos futuros docentes puedan utilizar los medios de comunicación en sus clases con eficacia y éxito. Sin embargo, estos resultados no se reflejan en los programas universitarios vigentes, de manera que en algunas instituciones los profesores en formación pueden llegar al término de sus estudios sin haber abordado cuestiones de educación en medios. Para comprender, evaluar y más adelante mejorar la situación actual de la formación del profesorado en el ámbito de la pedagogía de los medios se necesitan extensas investigaciones. Teniendo en cuenta esta situación, el siguiente artículo presenta un resumen del «statu quo» de las competencias en pedagogía de los medios de los futuros profesores, centrándose en los ejemplos de Alemania y EEUU. Para crear una base presentamos diferentes modelos de competencias pedagógicas mediáticas de ambos países e intentaremos responder a la pregunta si estas competencias son promovidas por los programas de formación del profesorado. Después, se describirán el método y resultados seleccionados de un estudio que midió las competencias en pedagogía de los medios de estudiantes de ambos países, estudio basado en un modelo generalizador de competencias pedagógicas mediáticas que conectan la investigación alemana e internacional en este campo. La perspectiva internacional comparada ayuda a extender perspectivas y comprender diferencias y similitudes. Los datos de este estudio sirven para identificar diferentes formas de integrar la pedagogía de los medios de comunicación en la formación del profesorado. Además, se pueden sacar conclusiones sobre las consecuencias que implican estos procesos para profesores en formación y sus competencias mediáticas.
N2  - Various research works and practitioners conclude that media pedagogy should be integrated in teacher education in order to enable future teachers to use media for their lessons effectively and successfully. However, this realization is not necessarily reflected in actual university curricula, as preservice teachers at some places can still finish their studies without ever dealing with media pedagogical issues. To understand, assess and eventually improve the status of media pedagogical teacher education, comprehensive research is required. Against this background, the following article seeks to present a theory-based and empirical overview of the status quo of preservice teachers’ pedagogical media competencies focusing Germany and the USA exemplarily. To form a basis, different models of pedagogical media competencies from both countries will be introduced and the extent to which these competencies have become part of teacher education programs and related studies will be summarised. Afterwards, method and selected results of a study will be described where the skills in question were measured with students from both countries, based on a comprehensive model of pedagogical media competencies that connects German and international research in this field. The international comparative perspective will help broaden the viewpoint and understand differences, but also similarities. These data serve to identify different ways of integrating media pedagogy into teacher training and draw conclusions on the consequences these processes entail for preservice teachers and their pedagogical media competencies.
T2  - Pedagogía mediática en la formación de profesores de Alemania y EEUU
KW  - enseñanzapor por competencias
KW  - currículum
KW  - análisis transnacional
KW  - investigación de currículo universitario
KW  - currículo de la educación en medios
KW  - alfabetización mediática
KW  - educación en medios
KW  - pedagogía
KW  - formación de profesorado
KW  - investigación
KW  - media literacy
KW  - media education
KW  - pedagogy
KW  - preservice teacher education
KW  - competency based teaching
KW  - curricula
KW  - research
KW  - crossnational analysis
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162600
VL  - XXIV
IS  - 49
ER  - 
TY  - JOUR
A1  - Kaluza, Benjamin F.
A1  - Wallace, Helen
A1  - Heard, Tim A.
A1  - Klein, Aelxandra-Maria
A1  - Leonhardt, Sara D.
T1  - Urban gardens promote bee foraging over natural habitats and plantations
JF  - Ecology and Evolution
N2  - Increasing human land use for agriculture and housing leads to the loss of natural habitat and to widespread declines in wild bees. Bee foraging dynamics and fitness depend on the availability of resources in the surrounding landscape, but how precisely landscape related resource differences affect bee foraging patterns remains unclear. To investigate how landscape and its interaction with season and weather drive foraging and resource intake in social bees, we experimentally compared foraging activity, the allocation of foragers to different resources (pollen, nectar, and resin) and overall resource intake in the Australian stingless bee Tetragonula carbonaria (Apidae, Meliponini). Bee colonies were monitored in different seasons over two years. We compared foraging patterns and resource intake between the bees' natural habitat (forests) and two landscapes differently altered by humans (suburban gardens and agricultural macadamia plantations). We found foraging activity as well as pollen and nectar forager numbers to be highest in suburban gardens, intermediate in forests and low in plantations. Foraging patterns further differed between seasons, but seasonal variations strongly differed between landscapes. Sugar and pollen intake was low in plantations, but contrary with our predictions, it was even higher in gardens than in forests. In contrast, resin intake was similar across landscapes. Consequently, differences in resource availability between natural and altered landscapes strongly affect foraging patterns and thus resource intake in social bees. While agricultural monocultures largely reduce foraging success, suburban gardens can increase resource intake well above rates found in natural habitats of bees, indicating that human activities can both decrease and increase the availability of resources in a landscape and thus reduce or enhance bee fitness.
KW  - urbanization
KW  - anthropogenic activities
KW  - climate factors
KW  - meliponines
KW  - resource availability
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-162713
VL  - 6
IS  - 5
ER  - 
TY  - JOUR
A1  - Seydelmann, Nora
A1  - Liu, Dan
A1  - Krämer, Johannes
A1  - Drechsler, Christiane
A1  - Hu, Kai
A1  - Nordbeck, Peter
A1  - Schneider, Andreas
A1  - Störk, Stefan
A1  - Bijnens, Bart
A1  - Ertl, Georg
A1  - Wanner, Christoph
A1  - Weidemann, Frank
T1  - High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease
JF  - Journal of the American Heart Association
N2  - Background
High‐sensitivity troponin (hs‐TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs‐TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow‐up study to assess longitudinal hs‐TNT changes relative to fibrosis and cardiomyopathy progression.

Methods and Results
For the prospective analysis, hs‐TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry‐associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs‐TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs‐TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56–302.59]; P=0.002); patients with elevated baseline hs‐TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1–3.3] %; follow‐up, 3.2 [2.3–4.9] %; P<0.001) and slightly elevated hs‐TNT (baseline, 44.7 [30.1–65.3] ng/L; follow‐up, 49.1 [27.6–69.5] ng/L; P=0.116) during follow‐up. Left ventricular wall thickness and EF of patients with elevated hs‐TNT were decreased during follow‐up, indicating potential cardiomyopathy progression.

Conclusions
hs‐TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs‐TNT could be helpful for staging and follow‐up of Fabry patients.
KW  - biomarker
KW  - cardiomyopathy
KW  - fabry disease
KW  - myocardial fibrosis
KW  - troponin T
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165682
VL  - 5
IS  - e002839
ER  - 
TY  - JOUR
A1  - Albers, Gregory W.
A1  - Bernstein, Richard A.
A1  - Brachmann, Johannes
A1  - Camm, John
A1  - Easton, J. Donald
A1  - Fromm, Peter
A1  - Goto, Shinya
A1  - Granger, Christopher B.
A1  - Hohnloser, Stefan H.
A1  - Hylek, Elaine
A1  - Jaffer, Amir K.
A1  - Krieger, Derk W.
A1  - Passman, Rod
A1  - Pines, Jesse M.
A1  - Reed, Shelby D.
A1  - Rothwell, Peter M.
A1  - Kowey, Peter R.
T1  - Heart Rhythm Monitoring Strategies for Cryptogenic Stroke: 2015 Diagnostics and Monitoring Stroke Focus Group Report
JF  - Journal of the American Heart Association
N2  - No abstract available.
KW  - anticoagulants
KW  - atrial fibrillation
KW  - diagnosis
KW  - electrocardiography
KW  - insertable cardiac monitor
KW  - stroke prevention
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165709
VL  - 5
IS  - e00294
ER  - 
TY  - JOUR
A1  - Wawra, Stephan
A1  - Fesel, Philipp
A1  - Widmer, Heidi
A1  - Timm, Malte
A1  - Seibel, Jürgen
A1  - Leson, Lisa
A1  - Kesseler, Leona
A1  - Nostadt, Robin
A1  - Hilbert, Magdalena
A1  - Langen, Gregor
A1  - Zuccaro, Alga
T1  - The fungal-specific beta-glucan-binding lectin FGB1 alters cell-wall composition and suppresses glucan-triggered immunity in plants
JF  - Nature Communications
N2  - β-glucans are well-known modulators of the immune system in mammals but little is known about β-glucan triggered immunity in planta. Here we show by isothermal titration calorimetry, circular dichroism spectroscopy and nuclear magnetic resonance spectroscopy that the FGB1 gene from the root endophyte Piriformospora indica encodes for a secreted fungal-specific β-glucan-binding lectin with dual function. This lectin has the potential to both alter fungal cell wall composition and properties, and to efficiently suppress β-glucan-triggered immunity in different plant hosts, such as Arabidopsis, barley and Nicotiana benthamiana. Our results hint at the existence of fungal effectors that deregulate innate sensing of β-glucan in plants.
KW  - Effectors in plant pathology
KW  - Fungal host response
KW  - Lectins
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165945
VL  - 7
ER  - 
TY  - JOUR
A1  - Knorr, Johannes
A1  - Sokkar, Pandian
A1  - Schott, Sebastian
A1  - Costa, Paolo
A1  - Thiel, Walter
A1  - Sander, Wolfram
A1  - Sanchez-Garcia, Elsa
A1  - Nuernberger, Patrick
T1  - Competitive solvent-molecule interactions govern primary processes of diphenylcarbene in solvent mixtures
JF  - Nature Communications
N2  - Photochemical reactions in solution often proceed via competing reaction pathways
comprising intermediates that capture a solvent molecule. A disclosure of the underlying
reaction mechanisms is challenging due to the rapid nature of these processes and the
intricate identification of how many solvent molecules are involved. Here combining
broadband femtosecond transient absorption and quantum mechanics/molecular mechanics
simulations, we show for one of the most reactive species, diphenylcarbene, that the
decision-maker is not the nearest solvent molecule but its neighbour. The hydrogen bonding
dynamics determine which reaction channels are accessible in binary solvent mixtures at
room temperature. In-depth analysis of the amount of nascent intermediates corroborates
the importance of a hydrogen-bonded complex with a protic solvent molecule, in striking
analogy to complexes found at cryogenic temperatures. Our results show that adjacent
solvent molecules take the role of key abettors rather than bystanders for the fate of the
reactive intermediate.
KW  - Reaction kinetics and dynamics
KW  - Photochemistry
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165954
VL  - 7
ER  - 
TY  - JOUR
A1  - Mitchell, Jonathan S.
A1  - Li, Ni
A1  - Weinhold, Niels
A1  - Försti, Asta
A1  - Ali, Mina
A1  - van Duin, Mark
A1  - Thorleifsson, Gudmar
A1  - Johnson, David C.
A1  - Chen, Bowang
A1  - Halvarsson, Britt-Marie
A1  - Gudbjartsson, Daniel F.
A1  - Kuiper, Rowan
A1  - Stephens, Owen W.
A1  - Bertsch, Uta
A1  - Broderick, Peter
A1  - Campo, Chiara
A1  - Einsele, Hermann
A1  - Gregory, Walter A.
A1  - Gullberg, Urban
A1  - Henrion, Marc
A1  - Hillengass, Jens
A1  - Hoffmann, Per
A1  - Jackson, Graham H.
A1  - Johnsson, Ellinor
A1  - Jöud, Magnus
A1  - Kristinsson, Sigurdur Y.
A1  - Lenhoff, Stig
A1  - Lenive, Oleg
A1  - Mellqvist, Ulf-Henrik
A1  - Migliorini, Gabriele
A1  - Nahi, Hareth
A1  - Nelander, Sven
A1  - Nickel, Jolanta
A1  - Nöthen, Markus M.
A1  - Rafnar, Thorunn
A1  - Ross, Fiona M.
A1  - da Silva Filho, Miguel Inacio
A1  - Swaminathan, Bhairavi
A1  - Thomsen, Hauke
A1  - Turesson, Ingemar
A1  - Vangsted, Annette
A1  - Vogel, Ulla
A1  - Waage, Anders
A1  - Walker, Brian A.
A1  - Wihlborg, Anna-Karin
A1  - Broyl, Annemiek
A1  - Davies, Faith E.
A1  - Thorsteinsdottir, Unnur
A1  - Langer, Christian
A1  - Hansson, Markus
A1  - Kaiser, Martin
A1  - Sonneveld, Pieter
A1  - Stefansson, Kari
A1  - Morgan, Gareth J.
A1  - Goldschmidt, Hartmut
A1  - Hemminki, Kari
A1  - Nilsson, Björn
A1  - Houlston, Richard S.
T1  - Genome-wide association study identifies multiple susceptibility loci for multiple myeloma
JF  - Nature Communications
N2  - Multiple myeloma (MM) is a plasma cell malignancy with a significant heritable basis. Genome-wide association studies have transformed our understanding of MM predisposition, but individual studies have had limited power to discover risk loci. Here we perform a meta-analysis of these GWAS, add a new GWAS and perform replication analyses resulting in 9,866 cases and 239,188 controls. We confirm all nine known risk loci and discover eight new loci at 6p22.3 (rs34229995, P=1.31 × 10−8), 6q21 (rs9372120, P=9.09 × 10−15), 7q36.1 (rs7781265, P=9.71 × 10−9), 8q24.21 (rs1948915, P=4.20 × 10−11), 9p21.3 (rs2811710, P=1.72 × 10−13), 10p12.1 (rs2790457, P=1.77 × 10−8), 16q23.1 (rs7193541, P=5.00 × 10−12) and 20q13.13 (rs6066835, P=1.36 × 10−13), which localize in or near to JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1. These findings provide additional support for a polygenic model of MM and insight into the biological basis of tumour development.
KW  - Cancer genetics
KW  - Genome-wide association studies
KW  - Myeloma
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165983
VL  - 7
ER  - 
TY  - JOUR
A1  - Van Haute, Lindsey
A1  - Dietmann, Sabine
A1  - Kremer, Laura
A1  - Hussain, Shobbir
A1  - Pearce, Sarah F.
A1  - Powell, Christopher A.
A1  - Rorbach, Joanna
A1  - Lantaff, Rebecca
A1  - Blanco, Sandra
A1  - Sauer, Sascha
A1  - Kotzaeridou, Urania
A1  - Hoffmann, Georg F.
A1  - Memari, Yasin
A1  - Kolb-Kokocinski, Anja
A1  - Durbin, Richard
A1  - Mayr, Johannes A.
A1  - Frye, Michaela
A1  - Prokisch, Holger
A1  - Minczuk, Michal
T1  - Deficient methylation and formylation of mt-tRNA(Met) wobble cytosine in a patient carrying mutations in NSUN3
JF  - Nature Communications
N2  - Epitranscriptome modifications are required for structure and function of RNA and defects in these pathways have been associated with human disease. Here we identify the RNA target for the previously uncharacterized 5-methylcytosine (m5C) methyltransferase NSun3 and link m5C RNA modifications with energy metabolism. Using whole-exome sequencing, we identified loss-of-function mutations in NSUN3 in a patient presenting with combined mitochondrial respiratory chain complex deficiency. Patient-derived fibroblasts exhibit severe defects in mitochondrial translation that can be rescued by exogenous expression of NSun3. We show that NSun3 is required for deposition of m5C at the anticodon loop in the mitochondrially encoded transfer RNA methionine (mt-tRNAMet). Further, we demonstrate that m5C deficiency in mt-tRNAMet results in the lack of 5-formylcytosine (f5C) at the same tRNA position. Our findings demonstrate that NSUN3 is necessary for efficient mitochondrial translation and reveal that f5C in human mitochondrial RNA is generated by oxidative processing of m5C.
KW  - Methylation
KW  - RNA
KW  - Transferases
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165998
VL  - 7
ER  - 
TY  - JOUR
A1  - Kernreiter, T.
A1  - Governale, M.
A1  - Zülicke, U.
A1  - Hankiewicz, E. M.
T1  - Anomalous Spin Response and Virtual-Carrier-Mediated Magnetism in a Topological Insulator
JF  - Physical Review X
N2  - We present a comprehensive theoretical study of the static spin response in HgTe quantum wells, revealing distinctive behavior for the topologically nontrivial inverted structure. Most strikingly, the q=0 (long-wavelength) spin susceptibility of the undoped topological-insulator system is constant and equal to the value found for the gapless Dirac-like structure, whereas the same quantity shows the typical decrease with increasing band gap in the normal-insulator regime. We discuss ramifications for the ordering of localized magnetic moments present in the quantum well, both in the insulating and electron-doped situations. The spin response of edge states is also considered, and we extract effective Landé g factors for the bulk and edge electrons. The variety of counterintuitive spin-response properties revealed in our study arises from the system’s versatility in accessing situations where the charge-carrier dynamics can be governed by ordinary Schrödinger-type physics; it mimics the behavior of chiral Dirac fermions or reflects the material’s symmetry-protected topological order.
KW  - spin response
KW  - magnetism
KW  - nanophysics
KW  - topological insulators
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166582
VL  - 6
IS  - 021010
ER  - 
TY  - JOUR
A1  - Kim, Seonghoon
A1  - Zhang, Bo
A1  - Wang, Zhaorong
A1  - Fischer, Julian
A1  - Brodbeck, Sebastian
A1  - Kamp, Martin
A1  - Schneider, Christian
A1  - Höfling, Sven
A1  - Deng, Hui
T1  - Coherent Polariton Laser
JF  - Physical Review X
N2  - The semiconductor polariton laser promises a new source of coherent light, which, compared to conventional semiconductor photon lasers, has input-energy threshold orders of magnitude lower. However, intensity stability, a defining feature of a coherent state, has remained poor. Intensity noise many times the shot noise of a coherent state has persisted, attributed to multiple mechanisms that are difficult to separate in conventional polariton systems. The large intensity noise, in turn, limits the phase coherence. Thus, the capability of the polariton laser as a source of coherence light is limited. Here, we demonstrate a polariton laser with shot-noise-limited intensity stability, as expected from a fully coherent state. This stability is achieved by using an optical cavity with high mode selectivity to enforce single-mode lasing, suppress condensate depletion, and establish gain saturation. Moreover, the absence of spurious intensity fluctuations enables the measurement of a transition from exponential to Gaussian decay of the phase coherence of the polariton laser. It suggests large self-interaction energies in the polariton condensate, exceeding the laser bandwidth. Such strong interactions are unique to matter-wave lasers and important for nonlinear polariton devices. The results will guide future development of polariton lasers and nonlinear polariton devices.
KW  - polariton laser
KW  - condensed matter physics
KW  - photonics
KW  - quantum physics
KW  - coherent light
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166597
VL  - 6
IS  - 011026
ER  - 
TY  - JOUR
A1  - Isles, Anthony R.
A1  - Ingason, Andrés
A1  - Lowther, Chelsea
A1  - Walters, James
A1  - Gawlick, Micha
A1  - Stöber, Gerald
A1  - Rees, Elliott
A1  - Martin, Joanna
A1  - Little, Rosie B.
A1  - Potter, Harry
A1  - Georgieva, Lyudmila
A1  - Pizzo, Lucilla
A1  - Ozaki, Norio
A1  - Aleksic, Branko
A1  - Kushima, Itaru
A1  - Ikeda, Masashi
A1  - Iwata, Nakao
A1  - Levinson, Douglas F.
A1  - Gejman, Pablo V.
A1  - Shi, Jianxin
A1  - Sanders, Alan R.
A1  - Duan, Jubao
A1  - Willis, Joseph
A1  - Sisodiya, Sanjay
A1  - Costain, Gregory
A1  - Werge, Thomas M.
A1  - Degenhardt, Franziska
A1  - Giegling, Ina
A1  - Rujescu, Dan
A1  - Hreidarsson, Stefan J.
A1  - Saemundsen, Evald
A1  - Ahn, Joo Wook
A1  - Ogilvie, Caroline
A1  - Girirajan, Santhosh D.
A1  - Stefansson, Hreinn
A1  - Stefansson, Kari
A1  - O'Donovan, Michael C.
A1  - Owen, Michael J.
A1  - Bassett, Anne
A1  - Kirov, George
T1  - Parental Origin of Interstitial Duplications at 15q11.2-q13.3 in Schizophrenia and Neurodevelopmental Disorders
JF  - PLoS Genetics
N2  - Duplications at 15q11.2-q13.3 overlapping the Prader-Willi/Angelman syndrome (PWS/AS) region have been associated with developmental delay (DD), autism spectrum disorder (ASD) and schizophrenia (SZ). Due to presence of imprinted genes within the region, the parental origin of these duplications may be key to the pathogenicity. Duplications of maternal origin are associated with disease, whereas the pathogenicity of paternal ones is unclear. To clarify the role of maternal and paternal duplications, we conducted the largest and most detailed study to date of parental origin of 15q11.2-q13.3 interstitial duplications in DD, ASD and SZ cohorts. We show, for the first time, that paternal duplications lead to an increased risk of developing DD/ASD/multiple congenital anomalies (MCA), but do not appear to increase risk for SZ. The importance of the epigenetic status of 15q11.2-q13.3 duplications was further underlined by analysis of a number of families, in which the duplication was paternally derived in the mother, who was unaffected, whereas her offspring, who inherited a maternally derived duplication, suffered from psychotic illness. Interestingly, the most consistent clinical characteristics of SZ patients with 15q11.2-q13.3 duplications were learning or developmental problems, found in 76% of carriers. Despite their lower pathogenicity, paternal duplications are less frequent in the general population with a general population prevalence of 0.0033% compared to 0.0069% for maternal duplications. This may be due to lower fecundity of male carriers and differential survival of embryos, something echoed in the findings that both types of duplications are de novo in just over 50% of cases. Isodicentric chromosome 15 (idic15) or interstitial triplications were not observed in SZ patients or in controls. Overall, this study refines the distinct roles of maternal and paternal interstitial duplications at 15q11.2-q13.3, underlining the critical importance of maternally expressed imprinted genes in the contribution of Copy Number Variants (CNVs) at this interval to the incidence of psychotic illness. This work will have tangible benefits for patients with 15q11.2-q13.3 duplications by aiding genetic counseling.
KW  - interstitial duplications
KW  - schizophrenia
KW  - developmental delay
KW  - autism spectrum disorder
KW  - parental origin
KW  - genetics
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166706
VL  - 12
IS  - 5
ER  - 
TY  - JOUR
A1  - Vendelova, Emilia
A1  - de Lima, Jeferson Camargo
A1  - Lorenzatto, Karina Rodrigues
A1  - Monteiro, Karina Mariante
A1  - Mueller, Thomas
A1  - Veepaschit, Jyotishman
A1  - Grimm, Clemens
A1  - Brehm, Klaus
A1  - Hrčková, Gabriela
A1  - Lutz, Manfred B.
A1  - Ferreira, Henrique B.
A1  - Nono, Justin Komguep
T1  - Proteomic Analysis of Excretory-Secretory Products of Mesocestoides corti Metacestodes Reveals Potential Suppressors of Dendritic Cell Functions
JF  - PLoS Neglected Tropical Diseases
N2  - Accumulating evidences have assigned a central role to parasite-derived proteins in immunomodulation. Here, we report on the proteomic identification and characterization of immunomodulatory excretory-secretory (ES) products from the metacestode larva (tetrathyridium) of the tapeworm Mesocestoides corti (syn. M. vogae). We demonstrate that ES products but not larval homogenates inhibit the stimuli-driven release of the pro-inflammatory, Th1-inducing cytokine IL-12p70 by murine bone marrow-derived dendritic cells (BMDCs). Within the ES fraction, we biochemically narrowed down the immunosuppressive activity to glycoproteins since active components were lipid-free, but sensitive to heat- and carbohydrate-treatment. Finally, using bioassay-guided chromatographic analyses assisted by comparative proteomics of active and inactive fractions of the ES products, we defined a comprehensive list of candidate proteins released by M. corti tetrathyridia as potential suppressors of DC functions. Our study provides a comprehensive library of somatic and ES products and highlight some candidate parasite factors that might drive the subversion of DC functions to facilitate the persistence of M. corti tetrathyridia in their hosts.
KW  - proteomic analysis
KW  - excretory-secretory
KW  - Mesocestoides corti
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166742
VL  - 10
IS  - 10
ER  - 
TY  - JOUR
A1  - Shi, Yaoyao
A1  - Kuai, Yue
A1  - Lei, Lizhen
A1  - Weng, Yuanyuan
A1  - Berberich-Siebelt, Friederike
A1  - Zhang, Xinxia
A1  - Wang, Jinjie
A1  - Zhou, Yuan
A1  - Jiang, Xin
A1  - Ren, Guoping
A1  - Pan, Hongyang
A1  - Mao, Zhengrong
A1  - Zhou, Ren
T1  - The feedback loop of LITAF and BCL6 is involved in regulating apoptosis in B cell non-Hodgkin's-lymphoma
JF  - Oncotarget
N2  - 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.
KW  - LITAF
KW  - BCL6
KW  - apoptosis
KW  - lymphoma
KW  - B-cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166500
VL  - 7
IS  - 47
ER  - 
TY  - JOUR
A1  - Vučićević, Dubravka
A1  - Gehre, Maja
A1  - Dhamija, Sonam
A1  - Friis-Hansen, Lennart
A1  - Meierhofer, David
A1  - Sauer, Sascha
A1  - Ørom, Ulf Andersson
T1  - The long non-coding RNA PARROT is an upstream regulator of c-Myc and affects proliferation and translation
JF  - Oncotarget
N2  - 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.
KW  - PARROT
KW  - c-Myc
KW  - long ncRNA
KW  - upstream regulator
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166519
VL  - 7
IS  - 23
ER  - 
TY  - JOUR
A1  - Eisenhardt, Anja E.
A1  - Sprenger, Adrian
A1  - Röring, Michael
A1  - Herr, Ricarda
A1  - Weinberg, Florian
A1  - Köhler, Martin
A1  - Braun, Sandra
A1  - Orth, Joachim
A1  - Diedrich, Britta
A1  - Lanner, Ulrike
A1  - Tscherwinski, Natalja
A1  - Schuster, Simon
A1  - Dumaz, Nicolas
A1  - Schmidt, Enrico
A1  - Baumeister, Ralf
A1  - Schlosser, Andreas
A1  - Dengjel, Jörn
A1  - Brummer, Tilman
T1  - Phospho-proteomic analyses of B-Raf protein complexes reveal new regulatory principles
JF  - Oncotarget
N2  - B-Raf represents a critical physiological regulator of the Ras/RAF/MEK/ERK-pathway and a pharmacological target of growing clinical relevance, in particular in oncology. To understand how B-Raf itself is regulated, we combined mass spectrometry with genetic approaches to map its interactome in MCF-10A cells as well as in B-Raf deficient murine embryonic fibroblasts (MEFs) and B-Raf/Raf-1 double deficient DT40 lymphoma cells complemented with wildtype or mutant B-Raf expression vectors. Using a multi-protease digestion approach, we identified a novel ubiquitination site and provide a detailed B-Raf phospho-map. Importantly, we identify two evolutionary conserved phosphorylation clusters around T401 and S419 in the B-Raf hinge region. SILAC labelling and genetic/biochemical follow-up revealed that these clusters are phosphorylated in the contexts of oncogenic Ras, sorafenib induced Raf dimerization and in the background of the V600E mutation. We further show that the vemurafenib sensitive phosphorylation of the T401 cluster occurs in trans within a Raf dimer. Substitution of the Ser/Thr-residues of this cluster by alanine residues enhances the transforming potential of B-Raf, indicating that these phosphorylation sites suppress its signaling output. Moreover, several B-Raf phosphorylation sites, including T401 and S419, are somatically mutated in tumors, further illustrating the importance of phosphorylation for the regulation of this kinase.
KW  - BRAF
KW  - proteomics
KW  - phosphorylation
KW  - sorafenib
KW  - protein-protein interaction
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166529
VL  - 7
IS  - 18
ER  - 
TY  - JOUR
A1  - Chenari, Hossein Mahmoudi
A1  - Seibel, Christoph
A1  - Hauschild, Dirk
A1  - Reinert, Friedrich
A1  - Abdollahian, Hossein
T1  - Titanium Dioxide Nanoparticles: Synthesis, X-Ray Line Analysis and Chemical Composition Study
JF  - Materials Research
N2  - TiO2 nanoparticleshave been synthesized by the sol-gel method using titanium alkoxide and isopropanolas a precursor. The structural properties and chemical composition of the TiO2 nanoparticles were studied usingX-ray diffraction, scanning electron microscopy, and X-ray photoelectron spectroscopy.The X-ray powder diffraction pattern confirms that the particles are mainly composed of the anatase phase with the preferential orientation along [101] direction. The physical parameters such as strain, stress and energy density were investigated from the Williamson- Hall (W-H) plot assuming a uniform deformation model (UDM), and uniform deformation energy density model (UDEDM). The W-H analysis shows an anisotropic nature of the strain in nanopowders. The scanning electron microscopy image shows clear TiO2 nanoparticles with particle sizes varying from 60 to 80nm. The results of mean particle size of TiO2 nanoparticles show an inter correlation with the W-H analysis and SEM results. Our X-ray photoelectron spectroscopy spectra show that nearly a complete amount of titanium has reacted to TiO2
KW  - TiO\(_2\)
KW  - Nanoparticles
KW  - X-ray analysis
KW  - SEM
KW  - XPS
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165807
VL  - 19
IS  - 6
ER  - 
TY  - JOUR
A1  - Dingemans, Josef
A1  - Monsieurs, Pieter
A1  - Yu, Sung-Huan
A1  - Crabbé, Aurélie
A1  - Förstner, Konrad U.
A1  - Malfroot, Anne
A1  - Cornelis, Pierre
A1  - Van Houdt, Rob
T1  - Effect of Shear Stress on Pseudomonas aeruginosa Isolated from the Cystic Fibrosis Lung
JF  - mBio
N2  - Chronic colonization of the lungs by Pseudomonas aeruginosa is one of the major causes of morbidity and mortality in cystic fibrosis (CF) patients. To gain insights into the characteristic biofilm phenotype of P. aeruginosa in the CF lungs, mimicking the CF lung environment is critical. We previously showed that growth of the non-CF-adapted P. aeruginosa PAO1 strain in a rotating wall vessel, a device that simulates the low fluid shear (LS) conditions present in the CF lung, leads to the formation of in-suspension, self-aggregating biofilms. In the present study, we determined the phenotypic and transcriptomic changes associated with the growth of a highly adapted, transmissible P. aeruginosa CF strain in artificial sputum medium under LS conditions. Robust self-aggregating biofilms were observed only under LS conditions. Growth under LS conditions resulted in the upregulation of genes involved in stress response, alginate biosynthesis, denitrification, glycine betaine biosynthesis, glycerol metabolism, and cell shape maintenance, while genes involved in phenazine biosynthesis, type VI secretion, and multidrug efflux were downregulated. In addition, a number of small RNAs appeared to be involved in the response to shear stress. Finally, quorum sensing was found to be slightly but significantly affected by shear stress, resulting in higher production of autoinducer molecules during growth under high fluid shear (HS) conditions. In summary, our study revealed a way to modulate the behavior of a highly adapted P. aeruginosa CF strain by means of introducing shear stress, driving it from a biofilm lifestyle to a more planktonic lifestyle.
KW  - biology
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165821
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Drgonova, Jana
A1  - Walther, Donna
A1  - Hartstein, G Luke
A1  - Bukhari, Mohammad O
A1  - Baumann, Michael H
A1  - Katz, Jonathan
A1  - Hall, F Scott
A1  - Arnold, Elizabeth R
A1  - Flax, Shaun
A1  - Riley, Anthony
A1  - Rivero, Olga
A1  - Lesch, Klaus-Peter
A1  - Troncoso, Juan
A1  - Ranscht, Barbara
A1  - Uhl, George R
T1  - Cadherin 13: Human cis-Regulation and Selectively Altered Addiction Phenotypes and Cerebral Cortical Dopamine in Knockout Mice
JF  - Molecular Medicine
N2  - The Cadherin 13 (CDH13) gene encodes a cell adhesion molecule likely to influence development and connections of brain circuits that modulate addiction, locomotion and cognition, including those that involve midbrain dopamine neurons. Human CDH13 mRNA expression differs by more than 80% in postmortem cerebral cortical samples from individuals with different CDH13 genotypes, supporting examination of mice with altered CDH13 expression as models for common human variation at this locus. Constitutive CDH13 knockout mice display evidence for changed cocaine reward: shifted dose response relationship in tests of cocaine-conditioned place preference using doses that do not alter cocaine-conditioned taste aversion. Reduced adult CDH13 expression in conditional knockouts also alters cocaine reward in ways that correlate with individual differences in cortical CDH13 mRNA levels. In control and comparison behavioral assessments, knockout mice display modestly quicker acquisition of rotarod and water maze tasks, with a trend toward faster acquisition of 5-choice serial reaction time tasks that otherwise displayed no genotype-related differences. They display significant differences in locomotion in some settings, with larger effects in males. In assessments of brain changes that might contribute to these behavioral differences, there are selective alterations of dopamine levels, dopamine/metabolite ratios, dopaminergic fiber densities and mRNA encoding the activity dependent transcription factor npas4 in cerebral cortex of knockout mice. These novel data and previously reported human associations of CDH13 variants with addiction, individual differences in responses to stimulant administration and attention deficit hyperactivity disorder (ADHD) phenotypes suggest that levels of CDH13 expression, through mechanisms likely to include effects on mesocortical dopamine, influence stimulant reward and may contribute modestly to cognitive and locomotor phenotypes relevant to ADHD.
KW  - Cadherin (CDH13)
KW  - CDH13 mRNA
KW  - Attention Deficit Hyperactivity Disorder (ADHD)
KW  - CDH13 Expression
KW  - Human CDH13
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-165842
VL  - 22
ER  - 
TY  - JOUR
A1  - van de Kerkhof, Nora WA
A1  - Fekkes, Durk
A1  - van der Heijden, Frank MMA
A1  - Hoogendijk, Witte JG
A1  - Stöber, Gerald
A1  - Egger, Jos IM
A1  - Verhoeven, Willem MA
T1  - Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia
JF  - Neuropsychiatric Disease and Treatment
N2  - 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.
KW  - cycloid psychoses
KW  - schizophrenia
KW  - glutamate
KW  - glycine
KW  - tryptophan
KW  - neuroplasticity
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166255
VL  - 12
ER  - 
TY  - JOUR
A1  - Hargart, F
A1  - Roy-Choudhury, K
A1  - John, T
A1  - Portalupi, S L
A1  - Schneider, C
A1  - Höfling, S
A1  - Kamp, M
A1  - Hughes, S
A1  - Michler, P
T1  - Probing different regimes of strong field light-matter interaction with semiconductor quantum dots and few cavity photons
JF  - New Journal of Physics
N2  - In this work we present an extensive experimental and theoretical investigation of different regimes of strong field light–matter interaction for cavity-driven quantum dot (QD) cavity systems. The electric field enhancement inside a high-Q micropillar cavity facilitates exceptionally strong interaction with few cavity photons, enabling the simultaneous investigation for a wide range of QD-laser detuning. In case of a resonant drive, the formation of dressed states and a Mollow triplet sideband splitting of up to 45 μeV is measured for amean cavity photon number <n\(_c\)>\(\leq\) 1. In the asymptotic limit of the linear ACStark effect we systematically investigate the power and detuning dependence of more than 400 QDs. Some QD-cavity systems exhibit an unexpected anomalous Stark shift, which can be explained by an extended dressed 4-levelQDmodel.Weprovide a detailed analysis of the QD-cavity systems properties enabling this novel effect. The experimental results are successfully reproduced using a polaron master equation approach for the QD-cavity system, which includes the driving laser field, exciton-cavity and exciton-phonon interactions
KW  - light–matter interaction
KW  - quantum dots
KW  - AC Stark effect
KW  - dressed states
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166278
VL  - 18
ER  -