TY  - JOUR
A1  - Abda, Ebrahim M.
A1  - Krysciak, Dagmar
A1  - Krohn-Molt, Ines
A1  - Mamat, Uwe
A1  - Schmeisser, Christel
A1  - Förstner, Konrad U.
A1  - Schaible, Ulrich E.
A1  - Kohi, Thomas A.
A1  - Nieman, Stefan
A1  - Streit, Wolfgang R.
T1  - Phenotypic Heterogeneity Affects Stenotrophomonas maltophilia K279a Colony Morphotypes and \(\beta\)-Lactamase Expression
JF  - Frontiers in Microbiology
N2  - Phenotypic heterogeneity at the cellular level in response to various stresses, e.g., antibiotic treatment has been reported for a number of bacteria. In a clonal population, cell-to-cell variation may result in phenotypic heterogeneity that is a mechanism to survive changing environments including antibiotic therapy. Stenotrophomonas rnaltophilia has been frequently isolated from cystic fibrosis patients, can cause numerous infections in other organs and tissues, and is difficult to treat due to antibiotic resistances. S. maltophilia K279a produces the Li and L2 beta-lactamases in response to beta-lactam treatment. Here we report that the patient isolate S. rnaltophilia K279a diverges into cellular subpopulations with distinct but reversible morphotypes of small and big colonies when challenged with ampicillin. This observation is consistent with the formation of elongated chains of bacteria during exponential growth phase and the occurrence of mainly rod-shaped cells in liquid media. RNA-seq analysis of small versus big colonies revealed differential regulation of at least seven genes among the colony morphotypes. Among those, bleu and bla(L2) were transcriptionally the most strongly upregulated genes. Promoter fusions of b/a(L1) and b/a(L2) genes indicated that expression of both genes is also subject to high levels of phenotypic heterogeneous expression on a single cell level. Additionally, the comE homolog was found to be differentially expressed in homogenously versus heterogeneously bla(L2) expressing cells as identified by RNA(seq) analysis. Overexpression of cornE in S. maltophilia K279a reduced the level of cells that were in a bla(L2)-ON mode to 1% or lower. Taken together, our data provide strong evidence that S. maltophilia K279a populations develop phenotypic heterogeneity in an ampicillin challenged model. This cellular variability is triggered by regulation networks including b/a(L1), b/a(L2), and comE.
KW  - xanthomonas maltophilia
KW  - gram-negative bacteria
KW  - RNA-seq
KW  - pseudomas aeruginosa
KW  - antibiotic resistance
KW  - colony morphotypes
KW  - beta-lactamases
KW  - K279a
KW  - Stenotrophomonas maltophilia
KW  - phenotypic heterogeneity
KW  - persister cells
KW  - streptococcus pneumoniae
KW  - nosocomial pathogen
KW  - membrane vesicles
KW  - sinorhizobium fredii NGR234
KW  - red fluorescent protein
KW  - escherichia coli
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-136446
VL  - 6
IS  - 1373
ER  - 
TY  - JOUR
A1  - Abdali, Narges
A1  - Younas, Farhan
A1  - Mafakheri, Samaneh
A1  - Pothula, Karunakar R.
A1  - Kleinekathöfer, Ulrich
A1  - Tauch, Andreas
A1  - Benz, Roland
T1  - Identification and characterization of smallest pore-forming protein in the cell wall of pathogenic Corynebacterium urealyticum DSM 7109
JF  - BMC Biochemistry
N2  - Background: Corynebacterium urealyticum, a pathogenic, multidrug resistant member of the mycolata, is known as causative agent of urinary tract infections although it is a bacterium of the skin flora. This pathogenic bacterium shares with the mycolata the property of having an unusual cell envelope composition and architecture, typical for the genus Corynebacterium. The cell wall of members of the mycolata contains channel-forming proteins for the uptake of solutes. Results: In this study, we provide novel information on the identification and characterization of a pore-forming protein in the cell wall of C. urealyticum DSM 7109. Detergent extracts of whole C. urealyticum cultures formed in lipid bilayer membranes slightly cation-selective pores with a single-channel conductance of 1.75 nS in 1 M KCl. Experiments with different salts and non-electrolytes suggested that the cell wall pore of C. urealyticum is wide and water-filled and has a diameter of about 1.8 nm. Molecular modelling and dynamics has been performed to obtain a model of the pore. For the search of the gene coding for the cell wall pore of C. urealyticum we looked in the known genome of C. urealyticum for a similar chromosomal localization of the porin gene to known porH and porA genes of other Corynebacterium strains. Three genes are located between the genes coding for GroEL2 and polyphosphate kinase (PKK2). Two of the genes (cur_1714 and cur_1715) were expressed in different constructs in C. glutamicum Delta porA Delta porH and in porin-deficient BL21 DE3 Omp8 E. coli strains. The results suggested that the gene cur_1714 codes alone for the cell wall channel. The cell wall porin of C. urealyticum termed PorACur was purified to homogeneity using different biochemical methods and had an apparent molecular mass of about 4 kDa on tricine-containing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Conclusions: Biophysical characterization of the purified protein (PorACur) suggested indeed that cur_1714 is the gene coding for the pore-forming protein in C. urealyticum because the protein formed in lipid bilayer experiments the same pores as the detergent extract of whole cells. The study is the first report of a cell wall channel in the pathogenic C. urealyticum.
KW  - cell wall channel
KW  - mycolic acid
KW  - porin
KW  - Corynebacterium urealyticum
KW  - lipid bilayer membrane
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226959
VL  - 19
ER  - 
TY  - JOUR
A1  - Aboagye, B.
A1  - Weber, T.
A1  - Merdian, H. L.
A1  - Bartsch, D.
A1  - Lesch, K. P.
A1  - Waider, J.
T1  - Serotonin deficiency induced after brain maturation rescues consequences of early life adversity
JF  - Scientific Reports
N2  - Brain serotonin (5-HT) system dysfunction is implicated in depressive disorders and acute depletion of 5-HT precursor tryptophan has frequently been used to model the influence of 5-HT deficiency on emotion regulation. Tamoxifen (TAM)-induced Cre/loxP-mediated inactivation of the tryptophan hydroxylase-2 gene (Tph2) was used to investigate the effects of provoked 5-HT deficiency in adult mice (Tph2 icKO) previously subjected to maternal separation (MS). The efficiency of Tph2 inactivation was validated by immunohistochemistry and HPLC. The impact of Tph2 icKO in interaction with MS stress (Tph2 icKOxMS) on physiological parameters, emotional behavior and expression of 5-HT system-related marker genes were assessed. Tph2 icKO mice displayed a significant reduction in 5-HT immunoreactive cells and 5-HT concentrations in the rostral raphe region within four weeks following TAM treatment. Tph2 icKO and MS differentially affected food and water intake, locomotor activity as well as panic-like escape behavior. Tph2 icKO prevented the adverse effects of MS stress and altered the expression of the genes previously linked to stress and emotionality. In conclusion, an experimental model was established to study the behavioral and neurobiological consequences of 5-HT deficiency in adulthood in interaction with early-life adversity potentially affecting brain development and the pathogenesis of depressive disorders.
KW  - emotion
KW  - molecular medicine
KW  - neuroscience
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-258626
SN  - 2045-2322
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Adolf, Christian
A1  - Braun, Leah T.
A1  - Fuss, Carmina T.
A1  - Hahner, Stefanie
A1  - Künzel, Heike
A1  - Handgriff, Laura
A1  - Sturm, Lisa
A1  - Heinrich, Daniel A.
A1  - Schneider, Holger
A1  - Bidlingmaier, Martin
A1  - Reincke, Martin
T1  - Spironolactone reduces biochemical markers of bone turnover in postmenopausal women with primary aldosteronism
JF  - Endocrine
N2  - Context
Primary aldosteronism (PA) is the most frequent form of endocrine hypertension. Besides its deleterious impact on cardiovascular target organ damage, PA is considered to cause osteoporosis.

Patients and methods
We assessed bone turnover in a subset of 36 postmenopausal women with PA. 18 patients had unilateral PA and were treated by adrenalectomy, whereas 18 patients had bilateral PA and received mineralocorticoid receptor antagonist (MRA) therapy respectively. 18 age- and BMI-matched females served as controls. To estimate bone remodeling, we measured the bone turnover markers intact procollagen 1 N-terminal propeptide, bone alkaline phosphatase, osteocalcin and tartrate resistant acid phosphatase 5b in plasma by chemiluminescent immunoassays at time of diagnosis and one year after initiation of treatment.

Study design
Observational longitudinal cohort study.

Setting
Tertiary care hospital.

Results
Compared with controls, patients with PA had mildly elevated osteocalcin at baseline (p = 0.013), while the other bone markers were comparable between both groups. There were no differences between the unilateral and the bilateral PA subgroup. One year after initiation of MRA treatment with spironolactone bone resorption and bone formation markers had significantly decreased in patients with bilateral PA. In contrast, patients adrenalectomized because of unilateral PA showed no significant change of bone turnover markers.

Conclusion
This study shows that aldosterone excess in postmenopausal women with PA is not associated with a relevant increase of bone turnover markers at baseline. However, we observed a significant decrease of bone markers in patients treated with spironolactone, but not in patients treated by adrenalectomy.
KW  - aldosterone
KW  - osteocalcin
KW  - osteoporosis
KW  - hyperparathyroidism
KW  - cortisol
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-315966
SN  - 1355-008X
SN  - 1559-0100
VL  - 69
IS  - 3
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Ageron, M.
A1  - Aharonian, F.
A1  - Aiello, S.
A1  - Albert, A.
A1  - Ameli, F.
A1  - Annasontzis, E.
A1  - Andre, M.
A1  - Androulakis, G.
A1  - Anghinolfi, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Avgitas, T.
A1  - Barbarino, G.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Belhorma, B.
A1  - Belias, A.
A1  - Berbee, A.
A1  - van den Berg, A.
A1  - Bertin, V.
A1  - Beurthey, S.
A1  - van Beeveren, V.
A1  - Beverini, N.
A1  - Biagi, S.
A1  - Biagioni, A.
A1  - Billault, M.
A1  - Bondì, M.
A1  - Bormuth, R.
A1  - Bouhadef, B.
A1  - Bourlis, G.
A1  - Bourret, S.
A1  - Boutonnet, C.
A1  - Bouwhuis, M.
A1  - Bozza, C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Buis, E.
A1  - Busto, J.
A1  - Cacopardo, G.
A1  - Caillat, L.
A1  - Calmai, M.
A1  - Calvo, D.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Cecchini, S.
A1  - Celli, S.
A1  - Champion, C.
A1  - Cherkaoui El Moursli, R.
A1  - Cherubini, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Classen, L.
A1  - Cocimano, R.
A1  - Coelho, J. A. B.
A1  - Coleiro, A.
A1  - Colonges, S.
A1  - Coniglione, R.
A1  - Cordelli, M.
A1  - Cosquer, A.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Cuttone, G.
A1  - D'Amico, A.
A1  - De Bonis, G.
A1  - De Rosa, G.
A1  - De Sio, C.
A1  - Di Capua, F.
A1  - Di Palma, I.
A1  - Díaz García, A. F.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Dorosti-Hasankiadeh, Q.
A1  - Drakopoulou, E.
A1  - Drouhin, D.
A1  - Drury, L.
A1  - Durocher, M.
A1  - Eberl, T.
A1  - Eichie, S.
A1  - van Eijk, D.
A1  - El Bojaddaini, I.
A1  - El Khayati, N.
A1  - Elsaesser, D.
A1  - Enzenhöfer, A.
A1  - Fassi, F.
A1  - Favali, P.
A1  - Fermani, P.
A1  - Ferrara, G.
A1  - Filippidis, C.
A1  - Frascadore, G.
A1  - Fusco, L. A.
A1  - Gal, T.
A1  - Galatà, S.
A1  - Garufi, F.
A1  - Gay, P.
A1  - Gebyehu, M.
A1  - Giordano, V.
A1  - Gizani, N.
A1  - Gracia, R.
A1  - Graf, K.
A1  - Grégoire, T.
A1  - Grella, G.
A1  - Habel, R.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Harissopulos, S.
A1  - Heid, T.
A1  - Heijboer, A.
A1  - Heine, E.
A1  - Henry, S.
A1  - Hernández-Rey, J. J.
A1  - Hevinga, M.
A1  - Hofestädt, J.
A1  - Hugon, C. M. F.
A1  - Illuminati, G.
A1  - James, C. W.
A1  - Jansweijer, P.
A1  - Jongen, M.
A1  - de Jong, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Kappes, A.
A1  - Katz, U. F.
A1  - Keller, P.
A1  - Kieft, G.
A1  - Kießling, D.
A1  - Koffeman, E. N.
A1  - Kooijman, P.
A1  - Kouchner, A.
A1  - Kulikovskiy, V.
A1  - Lahmann, R.
A1  - Lamare, P.
A1  - Leisos, A.
A1  - Leonora, E.
A1  - Lindsey Clark, M.
A1  - Liolios, A.
A1  - Llorenz Alvarez, C. D.
A1  - Lo Presti, D.
A1  - Löhner, H.
A1  - Lonardo, A.
A1  - Lotze, M.
A1  - Loucatos, S.
A1  - Maccioni, E.
A1  - Mannheim, K.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Mariş, O.
A1  - Markou, C.
A1  - Martínez-Mora, J. A.
A1  - Martini, A.
A1  - Mele, R.
A1  - Melis, K. W.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Migneco, E.
A1  - Mijakowski, P.
A1  - Miraglia, A.
A1  - Mollo, C. M.
A1  - Mongelli, M.
A1  - Morganti, M.
A1  - Moussa, A.
A1  - Musico, P.
A1  - Musumeci, M.
A1  - Navas, S.
A1  - Nicoleau, C. A.
A1  - Olcina, I.
A1  - Olivetto, C.
A1  - Orlando, A.
A1  - Papaikonomou, A.
A1  - Papaleo, R.
A1  - Păvălaş, G. E.
A1  - Peek, H.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Pfutzner, M.
A1  - Piattelli, P.
A1  - Pikounis, K.
A1  - Poma, G. E.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Pratolongo, F.
A1  - Pühlhofer, G.
A1  - Pulvirenti, S.
A1  - Quinn, L.
A1  - Racca, C.
A1  - Raffaelli, F.
A1  - Randazzo, N.
A1  - Rapidis, P.
A1  - Razis, P.
A1  - Real, D.
A1  - Resvanis, L.
A1  - Reubelt, J.
A1  - Riccobene, G.
A1  - Rossi, C.
A1  - Rovelli, A.
A1  - Saldaña, M.
A1  - Salvadori, I.
A1  - Samtleben, D. F. E.
A1  - Sánchez García, A.
A1  - Sánchez Losa, A.
A1  - Sanguineti, M.
A1  - Santangelo, A.
A1  - Santonocito, D.
A1  - Sapienza, P.
A1  - Schimmel, F.
A1  - Schmelling, J.
A1  - Sciacca, V.
A1  - Sedita, M.
A1  - Seitz, T.
A1  - Sgura, I.
A1  - Simeone, F.
A1  - Siotis, I.
A1  - Sipala, V.
A1  - Spisso, B.
A1  - Spurio, M.
A1  - Stavropoulos, G.
A1  - Steijger, J.
A1  - Stellacci, S. M.
A1  - Stransky, D.
A1  - Taiuti, M.
A1  - Tayalati, Y.
A1  - Tézier, D.
A1  - Theraube, S.
A1  - Thompson, L.
A1  - Timmer, P.
A1  - Tönnis, C.
A1  - Trasatti, L.
A1  - Trovato, A.
A1  - Tsirigotis, A.
A1  - Tzamarias, S.
A1  - Tzamariudaki, E.
A1  - Vallage, B.
A1  - Van Elewyk, V.
A1  - Vermeulen, J.
A1  - Vicini, P.
A1  - Viola, S.
A1  - Vivolo, D.
A1  - Volkert, M.
A1  - Voulgaris, G.
A1  - Wiggers, L.
A1  - Wilms, J.
A1  - de Wolf, E.
A1  - Zachariadou, K.
A1  - Zornoza, J. D.
A1  - Zúñiga, J.
T1  - Letter of intent for KM3NeT 2.0
JF  - Journal of Physics G-Nuclear and Particle Physics
N2  - The main objectives of the KM3NeT Collaboration are (i) the discovery and subsequent observation of high-energy neutrino sources in the Universe and (ii) the determination of the mass hierarchy of neutrinos. These objectives are strongly motivated by two recent important discoveries, namely: (1) the high-energy astrophysical neutrino signal reported by IceCube and (2) the sizable contribution of electron neutrinos to the third neutrino mass eigenstate as reported by Daya Bay, Reno and others. To meet these objectives, the KM3NeT Collaboration plans to build a new Research Infrastructure consisting of a network of deep-sea neutrino telescopes in the Mediterranean Sea. A phased and distributed implementation is pursued which maximises the access to regional funds, the availability of human resources and the synergistic opportunities for the Earth and sea sciences community. Three suitable deep-sea sites are selected, namely off-shore Toulon (France), Capo Passero (Sicily, Italy) and Pylos (Peloponnese, Greece). The infrastructure will consist of three so-called building blocks. A building block comprises 115 strings, each string comprises 18 optical modules and each optical module comprises 31 photo-multiplier tubes. Each building block thus constitutes a three-dimensional array of photo sensors that can be used to detect the Cherenkov light produced by relativistic particles emerging from neutrino interactions. Two building blocks will be sparsely configured to fully explore the IceCube signal with similar instrumented volume, different methodology, improved resolution and
KW  - neutrino astronomy
KW  - eutrino physics
KW  - deep sea neutrino telescope
KW  - neutrino mass hierarchy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188050
VL  - 43
IS  - 8
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anghinolfi, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Baret, B.
A1  - Barrios-Marti, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Buto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Dekeyser, I.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
T1  - Stacked search for time shifted high energy neutrinos from gamma ray bursts with the ANTARES neutrino telescope
JF  - European Physical Journal C
N2  - A search for high-energy neutrino emission correlated with gamma-ray bursts outside the electromagnetic prompt-emission time window is presented. Using a stacking approach of the time delays between reported gamma-ray burst alerts and spatially coincident muon-neutrino signatures, data from the Antares neutrino telescope recorded between 2007 and 2012 are analysed. One year of public data from the IceCube detector between 2008 and 2009 have been also investigated. The respective timing profiles are scanned for statistically significant accumulations within 40 days of the Gamma Ray Burst, as expected from Lorentz Invariance Violation effects and some astrophysical models. No significant excess over the expected accidental coincidence rate could be found in either of the two data sets. The average strength of the neutrino signal is found to be fainter than one detectable neutrino signal per hundred gamma-ray bursts in the Antares data at 90% confidence level.
KW  - Search window
KW  - Neutrino data
KW  - Neutrino telescope
KW  - Neutrino emission
KW  - Accidental coincidence
KW  - Gamma-ray bursts
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181251
VL  - 77
IS  - 1
ER  - 
TY  - JOUR
A1  - Adrián-Martínez, S.
A1  - Albert, A.
A1  - André, M.
A1  - Anton, G.
A1  - Ardid, M.
A1  - Aubert, J.-J.
A1  - Avgitas, T.
A1  - Baret, B.
A1  - Barrios-Martí, J.
A1  - Basa, S.
A1  - Bertin, V.
A1  - Biagi, S.
A1  - Bormuth, R.
A1  - Bou-Cabo, M.
A1  - Bouwhuis, M.C.
A1  - Bruijn, R.
A1  - Brunner, J.
A1  - Busto, J.
A1  - Capone, A.
A1  - Caramete, L.
A1  - Carr, J.
A1  - Celli, S.
A1  - Chiarusi, T.
A1  - Circella, M.
A1  - Coleiro, A.
A1  - Coniglione, R.
A1  - Costantini, H.
A1  - Coyle, P.
A1  - Creusot, A.
A1  - Deschamps, A.
A1  - De Bonis, G.
A1  - Distefano, C.
A1  - Donzaud, C.
A1  - Dornic, D.
A1  - Drouhin, D.
A1  - Eberl, T.
A1  - El Bojaddaini, I.
A1  - Elsässer, D.
A1  - Enzenhöfer, A.
A1  - Fehn, K.
A1  - Felis, I.
A1  - Fusco, L.A.
A1  - Galatà, S.
A1  - Gay, P.
A1  - Geißelsöder, S.
A1  - Geyer, K.
A1  - Giordano, V.
A1  - Gleixner, A.
A1  - Glotin, H.
A1  - Gracia-Ruiz, R.
A1  - Graf, K.
A1  - Hallmann, S.
A1  - van Haren, H.
A1  - Heijboer, A.J.
A1  - Hello, Y.
A1  - Hernández-Rey, J.-J.
A1  - Hößl, J.
A1  - Hofestädt, J.
A1  - Hugon, C.
A1  - Illuminati, G.
A1  - James, C.W.
A1  - de Jong, M.
A1  - Kadler, M.
A1  - Kalekin, O.
A1  - Katz, U.
A1  - Kießling, D.
A1  - Kouchner, A.
A1  - Kreter, M.
A1  - Kreykenbohm, I.
A1  - Kulikovskiy, V.
A1  - Lachaud, C.
A1  - Lahmann, R.
A1  - Lefèvre, D.
A1  - Leonora, E.
A1  - Loucatos, S.
A1  - Marcelin, M.
A1  - Margiotta, A.
A1  - Marinelli, A.
A1  - Martínez-Mora, J.A.
A1  - Mathieu, A.
A1  - Michael, T.
A1  - Migliozzi, P.
A1  - Moussa, A.
A1  - Mueller, C.
A1  - Nezri, E.
A1  - Păvălaș, G.E.
A1  - Pellegrino, C.
A1  - Perrina, C.
A1  - Piattelli, P.
A1  - Popa, V.
A1  - Pradier, T.
A1  - Racca, C.
A1  - Riccobene, G.
A1  - Roensch, K.
A1  - Saldaña, M.
A1  - Samtleben, D.F.E.
A1  - Sanguineti, M.
A1  - Sapienza, P.
A1  - Schnabel, J.
A1  - Schüssler, F.
A1  - Seitz, T.
A1  - Sieger, C.
A1  - Spurio, M.
A1  - Stolarczyk, Th.
A1  - Sánchez-Losa, A.
A1  - Taiuti, M.
A1  - Trovato, A.
A1  - Tselengidou, M.
A1  - Turpin, D.
A1  - Tönnis, C.
A1  - Vallage, B.
A1  - Vallée, C.
A1  - Van Elewyck, V.
A1  - Vivolo, D.
A1  - Wagner, S.
A1  - Wilms, J.
A1  - Zornoza, J.D.
A1  - Zúñiga, J.
T1  - A search for Secluded Dark Matter in the Sun with the ANTARES neutrino telescope
JF  - Journal of Cosmology and Astroparticle Physics
N2  - A search for Secluded Dark Matter annihilation in the Sun using 2007-2012 data of the ANTARES neutrino telescope is presented. Three different cases are considered: a) detection of dimuons that result from the decay of the mediator, or neutrino detection from: b) mediator that decays into a dimuon and, in turn, into neutrinos, and c) mediator that decays directly into neutrinos. As no significant excess over background is observed, constraints are derived on the dark matter mass and the lifetime of the mediator.
KW  - dark matter experiments
KW  - neutrino detectors
KW  - dark matter detectors
KW  - neutrino astronomy
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189035
VL  - 2016
IS  - 5
ER  - 
TY  - JOUR
A1  - Aeschlimann, Martin
A1  - Bauer, Michael
A1  - Bayer, Daniela
A1  - Brixner, Tobias
A1  - Cunovic, Stefan
A1  - Fischer, Alexander
A1  - Melchior, Pascal
A1  - Pfeiffer, Walter
A1  - Rohmer, Martin
A1  - Schneider, Christian
A1  - Strüber, Christian
A1  - Tuchscherer, Philip
A1  - Voronine, Dimitri V.
T1  - Optimal open-loop near-field control of plasmonic nanostructures
N2  - Optimal open-loop control, i.e. the application of an analytically derived control rule, is demonstrated for nanooptical excitations using polarization-shaped laser pulses. Optimal spatial near-field localization in gold nanoprisms and excitation switching is realized by applying a shift to the relative phase of the two polarization components. The achieved near-field switching confirms theoretical predictions, proves the applicability of predefined control rules in nanooptical light–matter interaction and reveals local mode interference to be an important control mechanism.
KW  - Chemie
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75256
ER  - 
TY  - JOUR
A1  - Aeschlimann, Martin
A1  - Brixner, Tobias
A1  - Cinchetti, Mirko
A1  - Frisch, Benjamin
A1  - Hecht, Bert
A1  - Hensen, Matthias
A1  - Huber, Bernhard
A1  - Kramer, Christian
A1  - Krauss, Enno
A1  - Loeber, Thomas H.
A1  - Pfeiffer, Walter
A1  - Piecuch, Martin
A1  - Thielen, Philip
T1  - Cavity-assisted ultrafast long-range periodic energy transfer between plasmonic nanoantennas
JF  - Light: Science & Applications
N2  - Radiationless energy transfer is at the core of diverse phenomena, such as light harvesting in photosynthesis\(^1\), energy-transfer-based microspectroscopies\(^2\), nanoscale quantum entanglement\(^3\) and photonic-mode hybridization\(^4\). Typically, the transfer is efficient only for separations that are much shorter than the diffraction limit. This hampers its application in optical communication and quantum information processing, which require spatially selective addressing. Here, we demonstrate highly efficient radiationless coherent energy transfer over a distance of twice the excitation wavelength by combining localized and delocalized\(^5\) plasmonic modes. Analogous to the Tavis-Cummings model, two whispering-gallery-mode antennas\(^6\) placed in the foci of an elliptical plasmonic cavity\(^7\) fabricated from single-crystal gold plates act as a pair of oscillators coupled to a common cavity mode. Time-resolved two-photon photoemission electron microscopy (TR 2P-PEEM) reveals an ultrafast long-range periodic energy transfer in accordance with the simulations. Our observations open perspectives for the optimization and tailoring of mesoscopic energy transfer and long-range quantum emitter coupling.
KW  - chemistry
KW  - nanocavities
KW  - nanophotonics and plasmonics
KW  - photonic devices
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173265
VL  - 6
ER  - 
TY  - JOUR
A1  - Ahmad, Ruhel
A1  - Wolber, Wanja
A1  - Eckardt, Sigrid
A1  - Koch, Philipp
A1  - Schmitt, Jessica
A1  - Semechkin, Ruslan
A1  - Geis, Christian
A1  - Heckmann, Manfred
A1  - Brüstle, Oliver
A1  - McLaughlin, John K.
A1  - Sirén, Anna-Leena
A1  - Müller, Albrecht M.
T1  - Functional Neuronal Cells Generated by Human Parthenogenetic Stem Cells
JF  - PLoS One
N2  - Parent of origin imprints on the genome have been implicated in the regulation of neural cell type differentiation. The ability of human parthenogenetic (PG) embryonic stem cells (hpESCs) to undergo neural lineage and cell type-specific differentiation is undefined. We determined the potential of hpESCs to differentiate into various neural subtypes. Concurrently, we examined DNA methylation and expression status of imprinted genes. Under culture conditions promoting neural differentiation, hpESC-derived neural stem cells (hpNSCs) gave rise to glia and neuron-like cells that expressed subtype-specific markers and generated action potentials. Analysis of imprinting in hpESCs and in hpNSCs revealed that maternal-specific gene expression patterns and imprinting marks were generally maintained in PG cells upon differentiation. Our results demonstrate that despite the lack of a paternal genome, hpESCs generate proliferating NSCs that are capable of differentiation into physiologically functional neuron-like cells and maintain allele-specific expression of imprinted genes. Thus, hpESCs can serve as a model to study the role of maternal and paternal genomes in neural development and to better understand imprinting-associated brain diseases.
KW  - methylation
KW  - derivation
KW  - blastocysts
KW  - pluripotent
KW  - differentiation
KW  - lines
KW  - brain development
KW  - in-vitro
KW  - mice
KW  - specification
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130268
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - Aido, Ahmed
A1  - Zaitseva, Olena
A1  - Wajant, Harald
A1  - Buzgo, Matej
A1  - Simaite, Aiva
T1  - Anti-Fn14 antibody-conjugated nanoparticles display membrane TWEAK-like agonism
JF  - Pharmaceutics
N2  - Conventional bivalent IgG antibodies targeting a subgroup of receptors of the TNF superfamily (TNFSF) including fibroblast growth factor-inducible 14 (anti-Fn14) typically display no or only very limited agonistic activity on their own and can only trigger receptor signaling by crosslinking or when bound to Fcγ receptors (FcγR). Both result in proximity of multiple antibody-bound TNFRSF receptor (TNFR) molecules, which enables engagement of TNFR-associated signaling pathways. Here, we have linked anti-Fn14 antibodies to gold nanoparticles to mimic the “activating” effect of plasma membrane-presented FcγR-anchored anti-Fn14 antibodies. We functionalized gold nanoparticles with poly-ethylene glycol (PEG) linkers and then coupled antibodies to the PEG surface of the nanoparticles. We found that Fn14 binding of the anti-Fn14 antibodies PDL192 and 5B6 is preserved upon attachment to the nanoparticles. More importantly, the gold nanoparticle-presented anti-Fn14 antibody molecules displayed strong agonistic activity. Our results suggest that conjugation of monoclonal anti-TNFR antibodies to gold nanoparticles can be exploited to uncover their latent agonism, e.g., for immunotherapeutic applications.
KW  - Fn14
KW  - nanoparticles
KW  - surface modification
KW  - drug-delivery
KW  - anti-TNFRSF receptor (TNFR) antibodies
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-242710
SN  - 1999-4923
VL  - 13
IS  - 7
ER  - 
TY  - JOUR
A1  - Allgaier, Johannes
A1  - Schlee, Winfried
A1  - Langguth, Berthold
A1  - Probst, Thomas
A1  - Pryss, Rüdiger
T1  - Predicting the Gender of Individuals with Tinnitus based on Daily Life Data of the TrackYourTinnitus mHealth Platform
JF  - Scientific Reports
N2  - Tinnitus is an auditory phantom perception in the absence of an external sound stimulation. People with tinnitus often report severe constraints in their daily life. Interestingly, indications exist on gender differences between women and men both in the symptom profile as well as in the response to specific tinnitus treatments. In this paper, data of the TrackYourTinnitus platform (TYT) were analyzed to investigate whether the gender of users can be predicted. In general, the TYT mobile Health crowdsensing platform was developed to demystify the daily and momentary variations of tinnitus symptoms over time. The goal of the presented investigation is a better understanding of gender-related differences in the symptom profiles of users from TYT. Based on two questionnaires of TYT, four machine learning based classifiers were trained and analyzed. With respect to the provided daily answers, the gender of TYT users can be predicted with an accuracy of 81.7%. In this context, worries, difficulties in concentration, and irritability towards the family are the three most important characteristics for predicting the gender. Note that in contrast to existing studies on TYT, daily answers to the worst symptom question were firstly investigated in more detail. It was found that results of this question significantly contribute to the prediction of the gender of TYT users. Overall, our findings indicate gender-related differences in tinnitus and tinnitus-related symptoms. Based on evidence that gender impacts the development of tinnitus, the gathered insights can be considered relevant and justify further investigations in this direction.
KW  - computer science
KW  - machine learning
KW  - psychology
KW  - signs and symptoms
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261753
VL  - 11
IS  - 1
ER  - 
TY  - JOUR
A1  - Allgaier, Johannes
A1  - Schlee, Winfried
A1  - Probst, Thomas
A1  - Pryss, Rüdiger
T1  - Prediction of tinnitus perception based on daily life mHealth data using country origin and season
JF  - Journal of Clinical Medicine
N2  - Tinnitus is an auditory phantom perception without external sound stimuli. This chronic perception can severely affect quality of life. Because tinnitus symptoms are highly heterogeneous, multimodal data analyses are increasingly used to gain new insights. MHealth data sources, with their particular focus on country- and season-specific differences, can provide a promising avenue for new insights. Therefore, we examined data from the TrackYourTinnitus (TYT) mHealth platform to create symptom profiles of TYT users. We used gradient boosting engines to classify momentary tinnitus and regress tinnitus loudness, using country of origin and season as features. At the daily assessment level, tinnitus loudness can be regressed with a mean absolute error rate of 7.9% points. In turn, momentary tinnitus can be classified with an F1 score of 93.79%. Both results indicate differences in the tinnitus of TYT users with respect to season and country of origin. The significance of the features was evaluated using statistical and explainable machine learning methods. It was further shown that tinnitus varies with temperature in certain countries. The results presented show that season and country of origin appear to be valuable features when combined with longitudinal mHealth data at the level of daily assessment.
KW  - tinnitus
KW  - gradient boosting machine
KW  - mobile health
KW  - machine learning
KW  - multimodal data
KW  - explainable machine learning
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281812
SN  - 2077-0383
VL  - 11
IS  - 15
ER  - 
TY  - JOUR
A1  - Alpermann, Björn
A1  - Malzer, Michael
T1  - “In Other News”: China’s International Media Strategy on Xinjiang — CGTN and New China TV on YouTube
JF  - Modern China
N2  - In the Western world China stands accused of severe human rights violations regarding its treatment of the Uyghurs and other predominantly Muslim minorities in its northwestern Xinjiang Uyghur Autonomous Region. This is the first article to systematically analyze the response of China’s international state media to these allegations. By studying the YouTube channels of two leading Chinese state media, China Global Television Network (CGTN) and New China TV (operated by Xinhua News Agency), it presents an indepth understanding of how China’s foreign-facing propaganda works in a crucial case. The quantitative content analysis highlights how China reacted to increasing international (mostly United States) pressure regarding its Xinjiang policies by producing higher volumes of videos and putting out new counternarratives. The qualitative analysis that follows provides in-depth treatment of the most important discourses that Chinese media engage in to salvage the nation’s international image, namely those on development, culture, nature, and terrorism. It finds several ways of countering criticism, ranging from presenting a positive image of China, in line with traditional propaganda guidelines and President Xi Jinping’s assignment to state media to “tell the China story well,” to more innovative approaches. Thus the development narrative becomes more personalized, the discourse on culture supports the “heritagization process” to incorporate minority cultures into a harmonized “Chinese civilization,” representations of nature firmly tie Xinjiang into the discourse of “beautiful China,” the “terror narrative” strategically employs shocking footage in an attempt to gain international “discourse power,” etc. The article provides an up-to-date picture of China’s state media strategy on a highly contentious international issue.
KW  - Xinjiang
KW  - YouTube
KW  - discourse analysis
KW  - Chinese state media
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-314173
UR  - https://journals.sagepub.com/doi/epub/10.1177/00977004231169008
SN  - 1552-6836
ET  - Online first
ER  - 
TY  - JOUR
A1  - Andersen, Jens Peter
A1  - Bøgsted, Martin
A1  - Dybkær, Karen
A1  - Mellqvist, Ulf-Henrik
A1  - Morgan, Gareth J.
A1  - Goldschmidt, Hartmut
A1  - Dimopoulos, Meletios A.
A1  - Einsele, Hermann
A1  - San Miguel, Jesús
A1  - Palumbo, Antonio
A1  - Sonneveld, Pieter
A1  - Johnsen, Hans Erik
T1  - Global myeloma research clusters, output, and citations: a bibliometric mapping and clustering analysis
JF  - PLoS ONE
N2  - Background 
International collaborative research is a mechanism for improving the development of disease-specific therapies and for improving health at the population level. However, limited data are available to assess the trends in research output related to orphan diseases.
 
Methods and Findings 
We used bibliometric mapping and clustering methods to illustrate the level of fragmentation in myeloma research and the development of collaborative efforts. Publication data from Thomson Reuters Web of Science were retrieved for 2005-2009 and followed until 2013. We created a database of multiple myeloma publications, and we analysed impact and co-authorship density to identify scientific collaborations, developments, and international key players over time. The global annual publication volume for studies on multiple myeloma increased from 1,144 in 2005 to 1,628 in 2009, which represents a 43% increase. This increase is high compared to the 24% and 14% increases observed for lymphoma and leukaemia. The major proportion (> 90% of publications) was from the US and EU over the study period. The output and impact in terms of citations, identified several successful groups with a large number of intra-cluster collaborations in the US and EU. The US-based myeloma clusters clearly stand out as the most productive and highly cited, and the European Myeloma Network members exhibited a doubling of collaborative publications from 2005 to 2009, still increasing up to 2013. 

Conclusion and Perspective 
Multiple myeloma research output has increased substantially in the past decade. The fragmented European myeloma research activities based on national or regional groups are progressing, but they require a broad range of targeted research investments to improve multiple myeloma health care.
KW  - multiparametric flow cytometry
KW  - multiple myeloma
KW  - consensus statement
KW  - European experts
KW  - disorders
KW  - therapy
KW  - network
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144214
VL  - 10
IS  - 1
ER  - 
TY  - JOUR
A1  - Andreska, Thomas
A1  - Lüningschrör, Patrick
A1  - Wolf, Daniel
A1  - McFleder, Rhonda L.
A1  - Ayon-Olivas, Maurilyn
A1  - Rattka, Marta
A1  - Drechsler, Christine
A1  - Perschin, Veronika
A1  - Blum, Robert
A1  - Aufmkolk, Sarah
A1  - Granado, Noelia
A1  - Moratalla, Rosario
A1  - Sauer, Markus
A1  - Monoranu, Camelia
A1  - Volkmann, Jens
A1  - Ip, Chi Wang
A1  - Stigloher, Christian
A1  - Sendtner, Michael
T1  - DRD1 signaling modulates TrkB turnover and BDNF sensitivity in direct pathway striatal medium spiny neurons
JF  - Cell Reports
N2  - Highlights
• Dopamine receptor-1 activation induces TrkB cell-surface expression in striatal neurons
• Dopaminergic deficits cause TrkB accumulation and clustering in the ER
• TrkB clusters colocalize with cargo receptor SORCS-2 in direct pathway striatal neurons
• Intracellular TrkB clusters fail to fuse with lysosomes after dopamine depletion

Summary
Disturbed motor control is a hallmark of Parkinson’s disease (PD). Cortico-striatal synapses play a central role in motor learning and adaption, and brain-derived neurotrophic factor (BDNF) from cortico-striatal afferents modulates their plasticity via TrkB in striatal medium spiny projection neurons (SPNs). We studied the role of dopamine in modulating the sensitivity of direct pathway SPNs (dSPNs) to BDNF in cultures of fluorescence-activated cell sorting (FACS)-enriched D1-expressing SPNs and 6-hydroxydopamine (6-OHDA)-treated rats. DRD1 activation causes enhanced TrkB translocation to the cell surface and increased sensitivity for BDNF. In contrast, dopamine depletion in cultured dSPN neurons, 6-OHDA-treated rats, and postmortem brain of patients with PD reduces BDNF responsiveness and causes formation of intracellular TrkB clusters. These clusters associate with sortilin related VPS10 domain containing receptor 2 (SORCS-2) in multivesicular-like structures, which apparently protects them from lysosomal degradation. Thus, impaired TrkB processing might contribute to disturbed motor function in PD.
KW  - motor learning
KW  - cortico-striatal synapse
KW  - basal ganglia
KW  - direct pathway
KW  - DRD1
KW  - dSPN
KW  - BDNF
KW  - TrkB
KW  - synaptic plasticity
KW  - GPCR
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-349932
VL  - 42
IS  - 6
ER  - 
TY  - JOUR
A1  - Anelli, Viviana
A1  - Ordas, Anita
A1  - Kneitz, Susanne
A1  - Sagredo, Leonel Munoz
A1  - Gourain, Victor
A1  - Schartl, Manfred
A1  - Meijer, Annemarie H.
A1  - Mione, Marina
T1  - Ras-Induced miR-146a and 193a Target Jmjd6 to Regulate Melanoma Progression
JF  - Frontiers in Genetics
N2  - Ras genes are among the most commonly mutated genes in human cancer; yet our understanding of their oncogenic activity at the molecular mechanistic level is incomplete. To identify downstream events that mediate ras-induced cellular transformation in vivo, we analyzed global microRNA expression in three different models of Ras-induction and tumor formation in zebrafish. Six microRNAs were found increased in Ras-induced melanoma, glioma and in an inducible model of ubiquitous Ras expression. The upregulation of the microRNAs depended on the activation of the ERK and AKT pathways and to a lesser extent, on mTOR signaling. Two Ras-induced microRNAs (miR-146a and 193a) target Jmjd6, inducing downregulation of its mRNA and protein levels at the onset of Ras expression during melanoma development. However, at later stages of melanoma progression, jmjd6 levels were found elevated. The dynamic of Jmjd6 levels during progression of melanoma in the zebrafish model suggests that upregulation of the microRNAs targeting Jmjd6 may be part of an anti-cancer response. Indeed, triple transgenic fish engineered to express a microRNA-resistant Jmjd6 from the onset of melanoma have increased tumor burden, higher infiltration of leukocytes and shorter melanoma-free survival. Increased JMJD6 expression is found in several human cancers, including melanoma, suggesting that the up-regulation of Jmjd6 is a critical event in tumor progression.
The following link has been created to allow review of record GSE37015: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=jjcrbiuicyyqgpc&acc=GSE37015.
KW  - zebrafish
KW  - cancer models
KW  - microRNA
KW  - Jmjd6
KW  - ras
KW  - melanoma
KW  - miR-146a
KW  - miR-193a
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196963
SN  - 1664-8021
VL  - 9
IS  - 675
ER  - 
TY  - JOUR
A1  - Antoniou, Antonis C.
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Beesley, Jonathan
A1  - Chen, Xiaoqing
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Barrowdale, Daniel
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Caligo, Maria A.
A1  - Loman, Niklas
A1  - Harbst, Katja
A1  - Lindblom, Annika
A1  - Arver, Brita
A1  - Rosenquist, Richard
A1  - Karlsson, Per
A1  - Nathanson, Kate
A1  - Domchek, Susan
A1  - Rebbeck, Tim
A1  - Jakubowska, Anna
A1  - Lubinski, Jan
A1  - Jaworska, Katarzyna
A1  - Durda, Katarzyna
A1  - Zlowowcka-Perłowska, Elżbieta
A1  - Osorio, Ana
A1  - Durán, Mercedes
A1  - Andrés, Raquel
A1  - Benítez, Javier
A1  - Hamann, Ute
A1  - Hogervorst, Frans B.
A1  - van Os, Theo A.
A1  - Verhoef, Senno
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Wijnen, Juul
A1  - Garcia, Encarna B. Gómez
A1  - Ligtenberg, Marjolijn J.
A1  - Kriege, Mieke
A1  - Collée, Margriet
A1  - Ausems, Margreet G. E. M.
A1  - Oosterwijk, Jan C.
A1  - Peock, Susan
A1  - Frost, Debra
A1  - Ellis, Steve D.
A1  - Platte, Radka
A1  - Fineberg, Elena
A1  - Evans, D. Gareth
A1  - Lalloo, Fiona
A1  - Jacobs, Chris
A1  - Eeles, Ros
A1  - Adlard, Julian
A1  - Davidson, Rosemarie
A1  - Cole, Trevor
A1  - Cook, Jackie
A1  - Paterson, Joan
A1  - Douglas, Fiona
A1  - Brewer, Carole
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Walker, Lisa
A1  - Rogers, Mark T.
A1  - Donaldson, Alan
A1  - Dorkins, Huw
A1  - Godwin, Andrew K.
A1  - Bove, Betsy
A1  - Stoppa-Lyonnet, Dominique
A1  - Houdayer, Claude
A1  - Buecher, Bruno
A1  - de Pauw, Antoine
A1  - Mazoyer, Sylvie
A1  - Calender, Alain
A1  - Léoné, Mélanie
A1  - Bressac-de Paillerets, Brigitte
A1  - Caron, Olivier
A1  - Sobol, Hagay
A1  - Frenay, Marc
A1  - Prieur, Fabienne
A1  - Ferrer, Sandra Fert
A1  - Mortemousque, Isabelle
A1  - Buys, Saundra
A1  - Daly, Mary
A1  - Miron, Alexander
A1  - Terry, Mary Beth
A1  - Hopper, John L.
A1  - John, Esther M.
A1  - Southey, Melissa
A1  - Goldgar, David
A1  - Singer, Christian F.
A1  - Fink-Retter, Anneliese
A1  - Muy-Kheng, Tea
A1  - Geschwantler Kaulich, Daphne
A1  - Hansen, Thomas V. O.
A1  - Nielsen, Finn C.
A1  - Barkardottir, Rosa B.
A1  - Gaudet, Mia
A1  - Kirchhoff, Tomas
A1  - Joseph, Vijai
A1  - Dutra-Clarke, Ana
A1  - Offit, Kenneth
A1  - Piedmonte, Marion
A1  - Kirk, Judy
A1  - Cohn, David
A1  - Hurteau, Jean
A1  - Byron, John
A1  - Fiorica, James
A1  - Toland, Amanda E.
A1  - Montagna, Marco
A1  - Oliani, Cristina
A1  - Imyanitov, Evgeny
A1  - Isaacs, Claudine
A1  - Tihomirova, Laima
A1  - Blanco, Ignacio
A1  - Lazaro, Conxi
A1  - Teulé, Alex
A1  - Del Valle, J.
A1  - Gayther, Simon A.
A1  - Odunsi, Kunle
A1  - Gross, Jenny
A1  - Karlan, Beth Y.
A1  - Olah, Edith
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Beattie, Mary S.
A1  - Dorfling, Cecelia M.
A1  - Jansen van Rensburg, Elizabeth
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Schmutzler, Rita K.
A1  - Wappenschmidt, Barbara
A1  - Engel, Christoph
A1  - Meindl, Alfons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Heidemann, Simone
A1  - Niederacher, Dieter
A1  - Preisler-Adams, Sabine
A1  - Gadzicki, Dorothea
A1  - Varon-Mateeva, Raymonda
A1  - Deissler, Helmut
A1  - Gehrig, Andrea
A1  - Sutter, Christian
A1  - Kast, Karin
A1  - Fiebig, Britta
A1  - Schäfer, Dieter
A1  - Caldes, Trinidad
A1  - de la Hoya, Miguel
A1  - Nevanlinna, Heli
A1  - Muranen, Taru A.
A1  - Lespérance, Bernard
A1  - Spurdle, Amanda B.
A1  - Neuhausen, Susan L.
A1  - Ding, Yuan C.
A1  - Wang, Xianshu
A1  - Fredericksen, Zachary
A1  - Pankratz, Vernon S.
A1  - Lindor, Noralane M.
A1  - Peterlongo, Paulo
A1  - Manoukian, Siranoush
A1  - Peissel, Bernard
A1  - Zaffaroni, Daniela
A1  - Bonanni, Bernardo
A1  - Bernard, Loris
A1  - Dolcetti, Riccardo
A1  - Papi, Laura
A1  - Ottini, Laura
A1  - Radice, Paolo
A1  - Greene, Mark H.
A1  - Loud, Jennifer T.
A1  - Andrulis, Irene L.
A1  - Ozcelik, Hilmi
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Thomassen, Mads
A1  - Gerdes, Anne-Marie
A1  - Jensen, Uffe B.
A1  - Skytte, Anne-Bine
A1  - Kruse, Torben A.
A1  - Chenevix-Trench, Georgia
A1  - Couch, Fergus J.
A1  - Simard, Jacques
A1  - Easton, Douglas F.
T1  - Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
JF  - Breast Cancer Research
N2  - Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). 
Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. 
Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10\(^{-4}\)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10\(^{-5}\), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10\(^{-5}\)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). 
Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
KW  - investigators
KW  - genetic modifiers
KW  - mammographic density
KW  - susceptibility loci
KW  - ovarian cancer
KW  - hormone-related protein
KW  - genome-wide association
KW  - tumor subtypes
KW  - alleles
KW  - consortium
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130449
VL  - 14
IS  - R33
ER  - 
TY  - JOUR
A1  - Appeltshauser, Luise
A1  - Brunder, Anna-Michelle
A1  - Heinius, Annika
A1  - Körtvélyessy, Peter
A1  - Wandinger, Klaus-Peter
A1  - Junker, Ralf
A1  - Villmann, Carmen
A1  - Sommer, Claudia
A1  - Leypoldt, Frank
A1  - Doppler, Kathrin
T1  - Antiparanodal antibodies and IgG subclasses in acute autoimmune neuropathy
JF  - Neurology: Neuroimmunology & Neuroinflammation
N2  - Objective
To determine whether IgG subclasses of antiparanodal autoantibodies are related to disease course and treatment response in acute- to subacute-onset neuropathies, we retrospectively screened 161 baseline serum/CSF samples and 66 follow-up serum/CSF samples.

Methods
We used ELISA and immunofluorescence assays to detect antiparanodal IgG and their subclasses and titers in serum/CSF of patients with Guillain-Barre syndrome (GBS), recurrent GBS (R-GBS), Miller-Fisher syndrome, and acute- to subacute-onset chronic inflammatory demyelinating polyradiculoneuropathy (A-CIDP). We evaluated clinical data retrospectively.

Results
We detected antiparanodal autoantibodies with a prevalence of 4.3% (7/161), more often in A-CIDP (4/23, 17.4%) compared with GBS (3/114, 2.6%). Longitudinal subclass analysis in the patients with GBS revealed IgG2/3 autoantibodies against Caspr-1 and against anti-contactin-1/Caspr-1, which disappeared at remission. At disease onset, patients with A-CIDP had IgG2/3 anti-Caspr-1 and anti-contactin-1/Caspr-1 or IgG4 anti-contactin-1 antibodies, IgG3 being associated with good response to IV immunoglobulins (IVIg). In the chronic phase of disease, IgG subclass of one patient with A-CIDP switched from IgG3 to IgG4.

Conclusion
Our data (1) confirm and extend previous observations that antiparanodal IgG2/3 but not IgG4 antibodies can occur in acute-onset neuropathies manifesting as monophasic GBS, (2) suggest association of IgG3 to a favorable response to IVIg, and (3) lend support to the hypothesis that in some patients, an IgG subclass switch from IgG3 to IgG4 may be the correlate of a secondary progressive or relapsing course following a GBS-like onset.
KW  - Guillain-Barre-Syndrome
KW  - inflammatory demyelinating polyradiculoneuropathy
KW  - musk myasthenia gravis
KW  - periperal nerve
KW  - neurofascin
KW  - autoantibodies
KW  - ontactin 1
KW  - biopsies
KW  - binding
KW  - switch
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230079
VL  - 7
IS  - 5
ER  - 
TY  - JOUR
A1  - Arlt, Wiebke
A1  - Biehl, Michael
A1  - Taylor, Angela E.
A1  - Hahner, Stefanie
A1  - Libé, Rossella
A1  - Hughes, Beverly A.
A1  - Schneider, Petra
A1  - Smith, David J.
A1  - Stiekema, Han
A1  - Krone, Nils
A1  - Porfiri, Emilio
A1  - Opocher, Giuseppe
A1  - Bertherat, Jerôme
A1  - Mantero, Franco
A1  - Allolio, Bruno
A1  - Terzolo, Massimo
A1  - Nightingale, Peter
A1  - Shackleton, Cedric H. L.
A1  - Bertagna, Xavier
A1  - Fassnacht, Martin
A1  - Stewart, Paul M.
T1  - Urine Steroid Metabolomics as a Biomarker Tool for Detecting Malignancy in Adrenal Tumors
JF  - The Journal of Clinical Endocrinology & Metabolism
N2  - Context:
Adrenal tumors have a prevalence of around 2% in the general population. Adrenocortical carcinoma (ACC) is rare but accounts for 2–11% of incidentally discovered adrenal masses. Differentiating ACC from adrenocortical adenoma (ACA) represents a diagnostic challenge in patients with adrenal incidentalomas, with tumor size, imaging, and even histology all providing unsatisfactory predictive values.

Objective:
Here we developed a novel steroid metabolomic approach, mass spectrometry-based steroid profiling followed by machine learning analysis, and examined its diagnostic value for the detection of adrenal malignancy.

Design:
Quantification of 32 distinct adrenal derived steroids was carried out by gas chromatography/mass spectrometry in 24-h urine samples from 102 ACA patients (age range 19–84 yr) and 45 ACC patients (20–80 yr). Underlying diagnosis was ascertained by histology and metastasis in ACC and by clinical follow-up [median duration 52 (range 26–201) months] without evidence of metastasis in ACA. Steroid excretion data were subjected to generalized matrix learning vector quantization (GMLVQ) to identify the most discriminative steroids.

Results:
Steroid profiling revealed a pattern of predominantly immature, early-stage steroidogenesis in ACC. GMLVQ analysis identified a subset of nine steroids that performed best in differentiating ACA from ACC. Receiver-operating characteristics analysis of GMLVQ results demonstrated sensitivity = specificity = 90% (area under the curve = 0.97) employing all 32 steroids and sensitivity = specificity = 88% (area under the curve = 0.96) when using only the nine most differentiating markers.

Conclusions:
Urine steroid metabolomics is a novel, highly sensitive, and specific biomarker tool for discriminating benign from malignant adrenal tumors, with obvious promise for the diagnostic work-up of patients with adrenal incidentalomas.
KW  - adrenal cortex hormones
KW  - urine
KW  - adrenal cortex neoplasms
KW  - mass spectrometry
KW  - metabolomics
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-154682
VL  - 96
IS  - 12
SP  - 3775
EP  - 3784
ER  -