TY  - JOUR
A1  - Böhler, Elmar
A1  - Creignou, Nadia
A1  - Galota, Matthias
A1  - Reith, Steffen
A1  - Schnoor, Henning
A1  - Vollmer, Heribert
T1  - Complexity Classifications for Different Equivalence and Audit Problems for Boolean Circuits
JF  - Logical Methods in Computer Science
N2  - We study Boolean circuits as a representation of Boolean functions and conskier different equivalence, audit, and enumeration problems. For a number of restricted sets of gate types (bases) we obtain efficient algorithms, while for all other gate types we show these problems are at least NP-hard.
KW  - hierarchy
KW  - satisfiability problems
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131121
VL  - 8
IS  - 3:27
SP  - 1
EP  - 25
ER  - 
TY  - JOUR
A1  - Matlach, Juliane
A1  - Hoffmann, Niels
A1  - Freiberg, Florentina J.
A1  - Grehn, Franz
A1  - Klink, Thomas
T1  - Comparative study of trabeculectomy using single sutures versus releasable sutures
JF  - Clinical ophthalmology
N2  - BACKGROUND: The purpose of this study was to compare the outcomes of trabeculectomy using single sutures or releasable sutures.
METHODS: This retrospective study analyzed the medical records of 61 patients who had undergone trabeculectomy using single sutures (n = 33, 54.1%) or releasable sutures (n = 28, 45.9%). The scleral flap was secured with a mean 3.9 (range 3-5) single sutures in 33 patients and with three releasable sutures in 28 patients. Primary outcomes were the success rate, based on intraocular pressure and medication usage, and the frequency of complications and post-surgical interventions. The criteria used to determine complete success were, first, intraocular pressure < 18 mmHg and, second, <=21 mmHg and >=20% intraocular pressure reduction without glaucoma medication.
RESULTS: All patients had an intraocular pressure <= 21 mmHg; 87.5% in the single suture group and 92.6% in the releasable suture group had an intraocular pressure < 18 mmHg at 24 months. There was a highly significant reduction in intraocular pressure to baseline values in both groups at the last visit. Applying the first criterion, complete success was achieved in 57.6% of patients with single sutures and 71.4% with releasable sutures, and based on the second criterion, 66.7% and 71.4%, respectively. No significant difference was found between the groups with regard to intraocular pressure, or success or complication rates.
CONCLUSION: The results of trabeculectomy using single sutures or releasable sutures are equivalent. Therefore, the choice of suture technique should be based on individual patient requirements and surgeon experience.
KW  - laser suture lysis
KW  - releasable suture
KW  - glaucoma surgery
KW  - trabeculectomy
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123715
N1  - This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.
VL  - 6
ER  - 
TY  - JOUR
A1  - Schokraie, Elham
A1  - Warnken, Uwe
A1  - Hotz-Wagenblatt, Agnes
A1  - Grohme, Markus A.
A1  - Hengherr, Steffen
A1  - Förster, Frank
A1  - Schill, Ralph O.
A1  - Frohme, Marcus
A1  - Dandekar, Thomas
A1  - Schnölzer, Martina
T1  - Comparative proteome analysis of Milnesium tardigradum in early embryonic state versus adults in active and anhydrobiotic state
JF  - PLoS One
N2  - Tardigrades have fascinated researchers for more than 300 years because of their extraordinary capability to undergo cryptobiosis and survive extreme environmental conditions. However, the survival mechanisms of tardigrades are still poorly understood mainly due to the absence of detailed knowledge about the proteome and genome of these organisms. Our study was intended to provide a basis for the functional characterization of expressed proteins in different states of tardigrades. High-throughput, high-accuracy proteomics in combination with a newly developed tardigrade specific protein database resulted in the identification of more than 3000 proteins in three different states: early embryonic state and adult animals in active and anhydrobiotic state. This comprehensive proteome resource includes protein families such as chaperones, antioxidants, ribosomal proteins, cytoskeletal proteins, transporters, protein channels, nutrient reservoirs, and developmental proteins. A comparative analysis of protein families in the different states was performed by calculating the exponentially modified protein abundance index which classifies proteins in major and minor components. This is the first step to analyzing the proteins involved in early embryonic development, and furthermore proteins which might play an important role in the transition into the anhydrobiotic state.
KW  - life-span regulation
KW  - genes
KW  - Yolk protein
KW  - water stress
KW  - expression
KW  - tolerance
KW  - richtersius coronifer
KW  - superoxide-dismutase
KW  - caenorhabditis elegans
KW  - arabidopsis thaliana
KW  - vitellogenin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134447
VL  - 7
IS  - 9
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  - van Koolwijk, Leonieke M. E.
A1  - Ramdas, Wishal D.
A1  - Ikram, M. Kamran
A1  - Jansonius, Nomdo M.
A1  - Pasutto, Francesca
A1  - Hys, Pirro G.
A1  - Macgregor, Stuart
A1  - Janssen, Sarah F.
A1  - Hewitt, Alex W.
A1  - Viswanathan, Ananth C.
A1  - ten Brink, Jacoline B.
A1  - Hosseini, S. Mohsen
A1  - Amin, Najaf
A1  - Despriet, Dominiek D. G.
A1  - Willemse-Assink, Jacqueline J. M.
A1  - Kramer, Rogier
A1  - Rivadeneira, Fernando
A1  - Struchalin, Maksim
A1  - Aulchenko, Yurii S.
A1  - Weisschuh, Nicole
A1  - Zenkel, Matthias
A1  - Mardin, Christian Y.
A1  - Gramer, Eugen
A1  - Welge-Lüssen, Ulrich
A1  - Montgomery, Grant W.
A1  - Carbonaro, Francis
A1  - Young, Terri L.
A1  - Bellenguez, Céline
A1  - McGuffin, Peter
A1  - Foster, Paul J.
A1  - Topouzis, Fotis
A1  - Mitchell, Paul
A1  - Wang, Jie Jin
A1  - Wong, Tien Y.
A1  - Czudowska, Monika A.
A1  - Hofman, Albert
A1  - Uitterlinden, Andre G.
A1  - Wolfs, Roger C. W.
A1  - de Jong, Paulus T. V. M.
A1  - Oostra, Ben A.
A1  - Paterson, Andrew D.
A1  - Mackey, David A.
A1  - Bergen, Arthur A. B.
A1  - Reis, Andre
A1  - Hammond, Christopher J.
A1  - Vingerling, Johannes R.
A1  - Lemij, Hans G.
A1  - Klaver, Caroline C. W.
A1  - van Duijn, Cornelia M.
T1  - Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma
JF  - PLoS Genetics
N2  - Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4 x 10\(^{-8}\)), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6 x 10\(^{-8}\)). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4 x 10\(^{-2}\) for rs11656696 and p = 9.1 x 10\(^{-4}\) for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.
KW  - expression
KW  - goldmann applanation tonometer
KW  - central corneal thickness
KW  - genome-wide scan
KW  - beaver-dam eye
KW  - to-disc ratio
KW  - onset
KW  - association
KW  - identification
KW  - population
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131378
VL  - 8
IS  - 5
ER  - 
TY  - JOUR
A1  - Kreissl, Michael C.
A1  - Hänscheid, Heribert
A1  - Löhr, Mario
A1  - Verburg, Frederik A.
A1  - Schiller, Markus
A1  - Lassmann, Michael
A1  - Reiners, Christoph
A1  - Samnick, Samuel S.
A1  - Buck, Andreas K.
A1  - Flentje, Michael
A1  - Sweeney, Reinhart A.
T1  - Combination of peptide receptor radionuclide therapy with fractionated external beam radiotherapy for treatment of advanced symptomatic meningioma
N2  - Background: External beam radiotherapy (EBRT) is the treatment of choice for irresectable meningioma. Due to the strong expression of somatostatin receptors, peptide receptor radionuclide therapy (PRRT) has been used in advanced cases. We assessed the feasibility and tolerability of a combination of both treatment modalities in advanced symptomatic meningioma. Methods: 10 patients with irresectable meningioma were treated with PRRT (177Lu-DOTA0,Tyr3 octreotate or - DOTA0,Tyr3 octreotide) followed by external beam radiotherapy (EBRT). EBRT performed after PRRT was continued over 5–6 weeks in IMRT technique (median dose: 53.0 Gy). All patients were assessed morphologically and by positron emission tomography (PET) before therapy and were restaged after 3–6 months. Side effects were evaluated according to CTCAE 4.0. Results: Median tumor dose achieved by PRRT was 7.2 Gy. During PRRT and EBRT, no side effects>CTCAE grade 2 were noted. All patients reported stabilization or improvement of tumor-associated symptoms, no morphologic tumor progression was observed in MR-imaging (median follow-up: 13.4 months). The median pre-therapeutic SUVmax in the meningiomas was 14.2 (range: 4.3–68.7). All patients with a second PET after combined PRRT + EBRT showed an increase in SUVmax (median: 37%; range: 15%–46%) to a median value of 23.7 (range: 8.0–119.0; 7 patients) while PET-estimated volume generally decreased to 81 ± 21% of the initial volume. Conclusions: The combination of PRRT and EBRT is feasible and well tolerated. This approach represents an attractive strategy for the treatment of recurring or progressive symptomatic meningioma, which should be further evaluated.
KW  - Medizin
KW  - PRRT
KW  - Peptide receptor radionuclide therapy
KW  - Meningioma
KW  - Radiotherapy
KW  - EBRT
KW  - Combination
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75540
ER  - 
TY  - JOUR
A1  - Müller, Joachim
A1  - Brill, Stefan
A1  - Hagen, Rudolf
A1  - Moeltner, Alexander
A1  - Brockmeier, Steffi-Johanna
A1  - Stark, Thomas
A1  - Helbig, Silke
A1  - Maurer, Jan
A1  - Zahnert, Thomas
A1  - Zierhofer, Clemens
A1  - Nopp, Peter
A1  - Anderson, Ilona
T1  - Clinical Trial Results with the MED-EL Fine Structure Processing Coding Strategy in Experienced Cochlear Implant Users
JF  - ORL
N2  - Objectives: To assess the subjective and objective performance of the new fine structure processing strategy (FSP) compared to the previous generation coding strategies CIS+ and HDCIS. Methods: Forty-six adults with a minimum of 6 months of cochlear implant experience were included. CIS+, HDCIS and FSP were compared in speech perception tests in noise, pitch scaling and questionnaires. The randomized tests were performed acutely (interval 1) and again after 3 months of FSP experience (interval 3). The subjective evaluation included questionnaire 1 at intervals 1 and 3, and questionnaire 2 at interval 2, 1 month after interval 1. Results: Comparison between FSP and CIS+ showed that FSP performed at least as well as CIS+ in all speech perception tests, and outperformed CIS+ in vowel and monosyllabic word discrimination. Comparison between FSP and HDCIS showed that both performed equally well in all speech perception tests. Pitch scaling showed that FSP performed at least as well as HDCIS. With FSP, sound quality was at least as good and often better than with HDCIS. Conclusions: Results indicate that FSP performs better than CIS+ in vowel and monosyllabic word understanding. Subjective evaluation demonstrates strong user preferences for FSP when listening to speech and music.
KW  - pitch
KW  - CIS+
KW  - OPUS
KW  - fine structure processing
KW  - cochlear implant
KW  - coding strategy
KW  - speech perception
KW  - music
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196396
SN  - 0301-1569
SN  - 1423-0275
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  - 74
IS  - 4
ER  - 
TY  - JOUR
A1  - Wieching, Anna
A1  - Benser, Jasmin
A1  - Kohlhauser-Vollmuth, Christina
A1  - Weisbrich, Bendikt
A1  - Streng, Andrea
A1  - Liese, Johannes G.
T1  - Clinical characteristics of pediatric hospitalizations associated with 2009 pandemic influenza a (H1N1) in Northern Bavaria, Germany
N2  - Background: The 2009 pandemic influenza A (H1N1) (PIA) virus infected large parts of the pediatric population with a wide clinical spectrum and an initially unknown complication rate. The aims of our study were to define clinical characteristics and outcome of pandemic influenza A (H1N1) 2009-associated hospitalizations (PIAH) in children <18 years of age. All hospitalized cases of children <18 years of age with laboratory-confirmed pandemic influenza A (H1N1) 2009 in the region of Wuerzburg (Northern Bavaria, Germany) between July 2009 and March 2010 were identified. For these children a medical chart review was performed to determine their clinical characteristics and complications. Results: Between July 2009 and March 2010, 94 PIAH (62% males) occurred in children <18 years of age, with a median age of 7 years (IQR: 3–12 years). Underlying diseases and predisposing factors were documented in 40 (43%) children; obesity (n = 12, 30%), asthma (n = 10, 25%) and neurologic disorders (n = 8, 20%) were most frequently reported. Sixteen (17%) children received oxygen supplementation; three (3%) children required mechanical ventilation. Six (6%) children were admitted to an intensive care unit, four of them with underlying chronic diseases. Conclusions: Most PIAH demonstrated a benign course of disease. However, six children (6%) needed treatment at an intensive care unit for severe complications.
KW  - Medizin
KW  - Influenza
KW  - Pediatric
KW  - Infectious disease
KW  - Hospitalization
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75657
ER  - 
TY  - JOUR
A1  - Schwerdtle, Barbara
A1  - Kanis, Julia
A1  - Kahl, Lena
A1  - Kübler, Andrea
A1  - Schlarb, Angelika A.
T1  - Children’s Sleep Comic: development of a new diagnostic tool for children with sleep disorders [original research]
N2  - Background: A solid diagnosis of sleep disorders in children should include both self-ratings and parent ratings. However, there are few standardized self-assessment instruments to meet this need. The Children’s Sleep Comic is an adapted version of the unpublished German questionnaire “Freiburger Kinderschlafcomic” and provides pictures for items and responses. Because the drawings were outdated and allowed only for qualitative analysis, we revised the comic, tested its applicability in a target sample, and suggest a procedure for quantitative analysis. Methods: All items were updated and pictures were newly drawn. We used a sample of 201 children aged 5–10 years to test the applicability of the Children’s Sleep Comic in young children and to run a preliminary analysis. Results: The Children’s Sleep Comic comprises 37 items covering relevant aspects of sleep disorders in children. Application took on average 30 minutes. The procedure was well accepted by the children, as reflected by the absence of any dropouts. First comparisons with established questionnaires indicated moderate correlations. Conclusion: The Children’s Sleep Comic is appropriate for screening sleep behavior and sleep problems in children. The interactive procedure can foster a good relationship between the investigator and the child, and thus establish the basis for successful intervention if necessary.
KW  - Psychologie
KW  - children
KW  - sleep
KW  - sleep disorders
KW  - diagnostic
KW  - assessment
KW  - self-rating
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75722
ER  - 
TY  - JOUR
A1  - Homann, Arne
A1  - Timm, Malte
A1  - Seibel, Jürgen
T1  - Chemo-enzymatic synthesis and in vitro cytokine profiling of tailor-made oligofructosides
N2  - Background It is well known that carbohydrates play fundamental roles in cell signaling and infection processes as well as tumor formation and progression. However, the interaction pathways and cellular receptors targeted by carbohydrates and glycoconjugates remain poorly examined and understood. This lack of research stems, at least to a major part, from accessibility problems of large, branched oligosaccharides. Results To test glycan - cell interactions in vitro, a variety of tailored oligosaccharides was synthesized chemo-enzymatically. Glycosyltransferases from the GRAS organisms Bacillus megaterium (SacB) and Aspergillus niger (Suc1) were used in this study. Substrate engineering of these glycosyltransferases generally acting on sucrose leads to the controlled formation of novel tailored di-, tri- and tetrasaccharides. Already industrially used as prebiotics in functional food, the immunogenic potential of novel oligosaccharides was characterized in this study. A differential secretion of CXCL8 and CCL2 was observed upon oligosaccharide co-cultivation with colorectal epithelial Caco-2 cells. Conclusion Pure carbohydrates are able to stimulate a cytokine response in human endothelial cells in vitro. The type and amount of cytokine secretion depends on the type of co-cultivated oligosaccharide.
KW  - Chemie
KW  - Oligofructoside
KW  - Glycosyltransferase
KW  - Suc1
KW  - Aspergillus niger
KW  - SacB
KW  - Bacillus megaterium
KW  - CXCL8 (IL-8)
KW  - CCL2 (MCP-1)
KW  - Caco-2
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76393
ER  - 
TY  - JOUR
A1  - Drechsler, Johannes
A1  - Groetzinger, Joachim
A1  - Hermanns, Heike M.
T1  - Characterization of the Rat Oncostatin M Receptor Complex Which Resembles the Human, but Differs from the Murine Cytokine Receptor
JF  - PLoS One
N2  - Evaluation of a pathophysiological role of the interleukin-6-type cytokine oncostatin M (OSM) for human diseases has been complicated by the fact that mouse models of diseases targeting either OSM or the OSM receptor (OSMR) complex cannot fully reflect the human situation. This is due to earlier findings that human OSM utilizes two receptor complexes, glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR) (type I) and gp130/OSMR (type II), both with wide expression profiles. Murine OSM on the other hand only binds to the gp130/OSMR (type II) receptor complex with high affinity. Here, we characterize the receptor usage for rat OSM. Using different experimental approaches (knock-down of the OSMR expression by RNA interference, blocking of the LIFR by LIF-05, an antagonistic LIF variant and stably transfected Ba/F3 cells) we can clearly show that rat OSM surprisingly utilizes both, the type I and type II receptor complex, therefore mimicking the human situation. Furthermore, it displays cross-species activities and stimulates cells of human as well as murine origin. Its signaling capacities closely mimic those of human OSM in cell types of different origin in the way that strong activation of the Jak/STAT, the MAP kinase as well as the PI3K/Akt pathways can be observed. Therefore, rat disease models would allow evaluation of the relevance of OSM for human biology.
KW  - in vitro
KW  - leukemia-inhibitory factor
KW  - ciliary neurotrophic factor
KW  - T cell development
KW  - swiss model
KW  - fetal liver
KW  - interleukin-6-type cytokines
KW  - rheumatoid arthritis
KW  - signal transduction
KW  - growth regulator
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133879
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - Drechsler, Johannes
A1  - Grötzinger, Joachim
A1  - Hermanns, Heike M.
T1  - Characterization of the Rat Oncostatin M Receptor Complex Which Resembles the Human, but Differs from the Murine Cytokine Receptor
N2  - Evaluation of a pathophysiological role of the interleukin-6-type cytokine oncostatin M (OSM) for human diseases has been complicated by the fact that mouse models of diseases targeting either OSM or the OSM receptor (OSMR) complex cannot fully reflect the human situation. This is due to earlier findings that human OSM utilizes two receptor complexes, glycoprotein 130 (gp130)/leukemia inhibitory factor receptor (LIFR) (type I) and gp130/OSMR (type II), both with wide expression profiles. Murine OSM on the other hand only binds to the gp130/OSMR (type II) receptor complex with high affinity. Here, we characterize the receptor usage for rat OSM. Using different experimental approaches (knock-down of the OSMR expression by RNA interference, blocking of the LIFR by LIF-05, an antagonistic LIF variant and stably transfected Ba/F3 cells) we can clearly show that rat OSM surprisingly utilizes both, the type I and type II receptor complex, therefore mimicking the human situation. Furthermore, it displays cross-species activities and stimulates cells of human as well as murine origin. Its signaling capacities closely mimic those of human OSM in cell types of different origin in the way that strong activation of the Jak/STAT, the MAP kinase as well as the PI3K/Akt pathways can be observed. Therefore, rat disease models would allow evaluation of the relevance of OSM for human biology.
KW  - Biologie
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-78856
ER  - 
TY  - JOUR
A1  - Alb, Miriam
A1  - Sie, Christopher
A1  - Adam, Christian
A1  - Chen, Suzie
A1  - Becker, Jürgen C.
A1  - Schrama, David
T1  - Cellular and cytokine-dependent immunosuppressive mechanisms of grm1-transgenic murine melanoma
JF  - Cancer Immunology, Immunotherapy
N2  - Grm1-transgenic mice spontaneously develop cutaneous melanoma. This model allowed us to scrutinize the generic immune responses over the course of melanoma development. To this end, lymphocytes obtained from spleens, unrelated lymph nodes and tumor-draining lymph nodes of mice with no evidence of disease, and low or high tumor burden were analyzed ex vivo and in vitro. Thereby, we could demonstrate an increase in the number of activated CD4\(^+\) and CD8+ lymphocytes in the respective organs with increasing tumor burden. However, mainly CD4\(^+\) T cells, which could constitute both T helper as well as immunosuppressive regulatory T cells, but not CD8\(^+\) T cells, expressed activation markers upon in vitro stimulation when obtained from tumor-bearing mice. Interestingly, these cells from tumor-burdened animals were also functionally hampered in their proliferative response even when subjected to strong in vitro stimulation. Further analyses revealed that the increased frequency of regulatory T cells in tumor-bearing mice is an early event present in all lymphoid organs. Additionally, expression of the immunosuppressive cytokines TGF-β1 and IL-10 became more evident with increased tumor burden. Notably, TGF-β1 is strongly expressed in both the tumor and the tumor-draining lymph node, whereas IL-10 expression is more pronounced in the lymph node, suggesting a more complex regulation of IL-10. Thus, similar to the situation in melanoma patients, both cytokines as well as cellular immune escape mechanisms seem to contribute to the observed immunosuppressed state of tumor-bearing grm1-transgenic mice, suggesting that this model is suitable for preclinical testing of immunomodulatory therapeutics.
KW  - regulatory T cell
KW  - melanoma
KW  - immune suppression
KW  - tumor-draining lymph node
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125096
VL  - 61
IS  - 12
ER  - 
TY  - JOUR
A1  - Slanina, Heiko
A1  - Hebling, Sabrina
A1  - Hauck, Christoph R.
A1  - Schubert-Unkmeir, Alexandra
T1  - Cell Invasion by Neisseria meningitidis Requires a Functional Interplay between the Focal Adhesion Kinase, Src and Cortactin
N2  - Entry of Neisseria meningitidis (the meningococcus) into human brain microvascular endothelial cells (HBMEC) is mediated by fibronectin or vitronectin bound to the surface protein Opc forming a bridge to the respective integrins. This interaction leads to cytoskeletal rearrangement and uptake of meningococci. In this study, we determined that the focal adhesion kinase (FAK), which directly associates with integrins, is involved in integrin-mediated internalization of N. meningitidis in HBMEC. Inhibition of FAK activity by the specific FAK inhibitor PF 573882 reduced Opc-mediated invasion of HBMEC more than 90%. Moreover, overexpression of FAK mutants that were either impaired in the kinase activity or were not capable of autophosphorylation or overexpression of the dominant-negative version of FAK (FRNK) blocked integrin-mediated internalization of N. meningitidis. Importantly, FAK-deficient fibroblasts were significantly less invaded by N. meningitidis. Furthermore, N. meningitidis induced tyrosine phosphorylation of several host proteins including the FAK/Src complex substrate cortactin. Inhibition of cortactin expression by siRNA silencing and mutation of critical amino acid residues within cortactin, that encompass Arp2/3 association and dynamin binding, significantly reduced meningococcal invasion into eukaryotic cells suggesting that both domains are critical for efficient uptake of N. meningitidis into eukaryotic cells. Together, these results indicate that N. meningitidis exploits the integrin signal pathway for its entry and that FAK mediates the transfer of signals from activated integrins to the cytoskeleton. A cooperative interplay between FAK, Src and cortactin then enables endocytosis of N. meningitidis into host cells.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75354
ER  - 
TY  - JOUR
A1  - Gaiser, Timo
A1  - Geissinger, Eva
A1  - Schattenberg, Torsten
A1  - Scharf, Hanns-Peter
A1  - Dürken, Matthias
A1  - Dinter, Dietmar
A1  - Rosenwald, Andreas
A1  - Marx, Alexander
T1  - Case report: a unique pediatric case of a primary CD8 expressing ALK-1 positive anaplastic large cell lymphoma of skeletal muscle
JF  - Diagnostic Pathology
N2  - Primary involvement of skeletal muscle is a very rare event in ALK-1 positive anaplastic large cell lymphoma (ALCL). We describe a case of a 10-year old boy presenting with a three week history of pain and a palpable firm swelling at the dorsal aspect of the left thigh. Histological examination of the lesion revealed a tumoral and diffuse polymorphic infiltration of the muscle by large lymphoid cells. Tumor cells displayed eccentric, lobulated "horse shoe" or "kidney-shape" nuclei. The cells showed immunohistochemical positivity for CD30, ALK-1, CD2, CD3, CD7, CD8, and Perforin. Fluorescence in situ hybridization analysis revealed a characteristic rearrangement of the ALK-1 gene in 2p23 leading to the diagnosis of ALK-1 positive ALCL. Chemotherapy according to the ALCL-99-NHL-BFM protocol was initiated and resulted in a complete remission after two cycles. This case illustrates the unusual presentation of a pediatric ALCL in soft tissue with a good response to chemotherapy.
KW  - pediatric lymphoma
KW  - psoas muscle
KW  - classification
KW  - translocation
KW  - features
KW  - gene
KW  - ALK-1
KW  - anaplastic large cell lymphoma
KW  - CD30
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135381
VL  - 7
IS  - 38
ER  - 
TY  - JOUR
A1  - Nordbeck, Peter
A1  - Beer, Meinrad
A1  - Köstler, Herbert
A1  - Ladd, Mark E.
A1  - Quick, Harald H.
A1  - Bauer, Wolfgang R.
A1  - Ritter, Oliver
T1  - Cardiac catheter ablation under real-time magnetic resonance guidance
JF  - European Heart Journal
N2  - One of the main shortcomings of interventional electrophysiology (EP) is its inability to generate sufficient soft tissue contrast for intra-procedural visualization of the myocardium and the surrounding tissue, using conventional imaging techniques. Interventional cardiovascular magnetic resonance imaging (MRI) aims at bringing about significant improvements to the complex and decisive EP interventions far beyond the capabilities of currently available supportive imaging techniques used to surmount the drawbacks of fluoroscopy, as MRI not only allows of precise three-dimensional exposure of the cardiovascular morphology, but also proves to be a promising technique exclusively suitable for direct visualization of arrhythmogenic substrate and therapeutic effects. The major challenge posed by clinical …
KW  - magnetic resonance
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125638
VL  - 33
IS  - 15
ER  - 
TY  - JOUR
A1  - Maiden, Martin C. J.
A1  - Frosch, Matthias
T1  - Can we, should we, eradicate the meningococcus?
JF  - Vaccine
N2  - The eradication of infectious agents is an attractive means of disease control that, to date, has been achieved for only one human pathogen, the smallpox virus. The introduction of vaccines against Neisseria meningitidis into immunisation schedules, and particularly the conjugate polysaccharide vaccines which can interrupt transmission, raises the question of whether disease caused by this obligate human bacterium can be controlled, eliminated, or even eradicated. The limited number of meningococcal serogroups, lack of an animal reservoir, and importance of meningococcal disease are considerations in favour of eradication; however, the commensal nature of most infections, the high diversity of meningococcal populations, and the lack of comprehensive vaccines are all factors that suggest that this is not feasible. Indeed, any such attempt might be harmful by perturbing the human microbiome and its interaction with the immune system. On balance, the control and possible elimination of disease caused by particular disease-associated meningococcal genotypes is a more achievable and worthwhile goal.
KW  - population biology
KW  - epidemiology
KW  - vaccines
KW  - neisseria meningitidis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125646
VL  - 30
IS  - Suppl. 2
ER  - 
TY  - JOUR
A1  - Kessler, Michael
A1  - Hertel, Dietrich
A1  - Jungkunst, Hermann F.
A1  - Kluge, Jürgen
A1  - Abrahamczyk, Stefan
A1  - Bos, Merijn
A1  - Buchori, Damayanti
A1  - Gerold, Gerhard
A1  - Gradstein, S. Robbert
A1  - Köhler, Stefan
A1  - Leuschner, Christoph
A1  - Moser, Gerald
A1  - Pitopang, Ramadhanil
A1  - Saleh, Shahabuddin
A1  - Schulze, Christian H.
A1  - Sporn, Simone G.
A1  - Steffan-Dewenter, Ingolf
A1  - Tjitrosoedirdjo, Sri S.
A1  - Tscharntke, Teja
T1  - Can Joint Carbon and Biodiversity Management in Tropical Agroforestry Landscapes Be Optimized?
JF  - PLoS One
N2  - Managing ecosystems for carbon storage may also benefit biodiversity conservation, but such a potential 'win-win' scenario has not yet been assessed for tropical agroforestry landscapes. We measured above-and below-ground carbon stocks as well as the species richness of four groups of plants and eight of animals on 14 representative plots in Sulawesi, Indonesia, ranging from natural rainforest to cacao agroforests that have replaced former natural forest. The conversion of natural forests with carbon stocks of 227-362 Mg C ha\(^{-1}\) to agroforests with 82-211 Mg C ha\(^{-1}\) showed no relationships to overall biodiversity but led to a significant loss of forest-related species richness. We conclude that the conservation of the forest-related biodiversity, and to a lesser degree of carbon stocks, mainly depends on the preservation of natural forest habitats. In the three most carbon-rich agroforestry systems, carbon stocks were about 60% of those of natural forest, suggesting that 1.6 ha of optimally managed agroforest can contribute to the conservation of carbon stocks as much as 1 ha of natural forest. However, agroforestry systems had comparatively low biodiversity, and we found no evidence for a tight link between carbon storage and biodiversity. Yet, potential win-win agroforestry management solutions include combining high shade-tree quality which favours biodiversity with cacao-yield adapted shade levels.
KW  - forest soils
KW  - stocks
KW  - diversity
KW  - sequestration
KW  - conversion
KW  - balance
KW  - root
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132016
VL  - 7
IS  - 10
ER  - 
TY  - JOUR
A1  - Westermaier, Thomas
A1  - Stetter, Christian
A1  - Raslan, Furat
A1  - Vinc, Giles Hamilton
A1  - Ernestus, Ralf-Ingo
T1  - Brain edema formation correlates with perfusion deficit during the first six hours after experimental subarachnoid hemorrhage in rats
N2  - Background: Severe brain edema is observed in a number of patients suffering from subarachnoid hemorrhage (SAH). Little is known about its pathogenesis and time-course in the first hours after SAH. This study was performed to investigate the development of brain edema and its correlation with brain perfusion after experimental SAH. Methods: Male Sprague–Dawley rats, randomly assigned to one of six groups (n = 8), were subjected to SAH using the endovascular filament model or underwent a sham operation. Animals were sacrificed 15, 30, 60, 180 or 360 minutes after SAH. Intracranial pressure (ICP), mean arterial blood pressure (MABP), cerebral perfusion pressure (CPP) and bilateral local cerebral blood flow (LCBF) were continuously measured. Brain water content (BWC) was determined by the wet/dry-weight method. Results: After SAH, CPP and LCBF rapidly decreased. The decline of LCBF markedly exceeded the decline of CPP and persisted until the end of the observation period. BWC continuously increased. A significant correlation was observed between the BWC and the extent of the perfusion deficit in animals sacrificed after 180 and 360 minutes. Conclusions: The significant correlation with the perfusion deficit after SAH suggests that the development of brain edema is related to the extent of ischemia and acute vasoconstriction in the first hours after SAH.
KW  - Medizin
KW  - Subarachnoid hemorrhage
KW  - Cerebral blood flow
KW  - Brain ischemia
KW  - Brain edema
KW  - Animal models
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75765
ER  - 
TY  - JOUR
A1  - Albert-Weissenberger, Christiane
A1  - Stetter, Christian
A1  - Meuth, Sven G.
A1  - Göbel, Kerstin
A1  - Bader, Michael
A1  - Sirén, Anna-Leena
A1  - Kleinschnitz, Christoph
T1  - Blocking of Bradykinin Receptor B1 Protects from Focal Closed Head Injury in Mice by Reducing Axonal Damage and Astroglia Activation
JF  - Journal of Cerebral Blood Flow and Metabolism
N2  - The two bradykinin receptors B1R and B2R are central components of the kallikrein–kinin system with different expression kinetics and binding characteristics. Activation of these receptors by kinins triggers inflammatory responses in the target organ and in most situations enhances tissue damage. We could recently show that blocking of B1R, but not B2R, protects from cortical cryolesion by reducing inflammation and edema formation. In the present study, we investigated the role of B1R and B2R in a closed head model of focal traumatic brain injury (TBI; weight drop). Increased expression of B1R in the injured hemispheres of wild-type mice was restricted to the later stages after brain trauma, i.e. day 7 (P<0.05), whereas no significant induction could be observed for the B2R (P>0.05). Mice lacking the B1R, but not the B2R, showed less functional deficits on day 3 (P<0.001) and day 7 (P<0.001) compared with controls. Pharmacological blocking of B1R in wild-type mice had similar effects. Reduced axonal injury and astroglia activation could be identified as underlying mechanisms, while inhibition of B1R had only little influence on the local inflammatory response in this model. Inhibition of B1R may become a novel strategy to counteract trauma-induced neurodegeneration.
KW  - R-715
KW  - kinin receptors
KW  - closed head injury
KW  - β-APP
KW  - astrocytes
KW  - TNF-α
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125903
VL  - 32
IS  - 9
ER  - 
TY  - JOUR
A1  - Nass, Maximilian
A1  - Weissbrich, Benedikt
A1  - Huber, Moritz
A1  - Schneider, Elisabeth Marion
A1  - Weiss, Manfred
T1  - BK viremia in critically ill surgical patients with hemorrhagic or septic shock
JF  - BMC Research Notes
N2  - Background
Infections with polyomavirus BK virus (BKV) are a common cause of renal dysfunction after renal transplantation and may also be harmful in surgical patients with shock. The aim of the present study was to determine the frequency of BKV viremia in critically ill surgical patients with septic or hemorrhagic shock, and, if viremia is detectable, whether viremia may be associated with renal dysfunction.
Findings
A total of 125 plasma samples from 44 critically ill surgical patients with septic or hemorrhagic shock were tested by real-time polymerase chain reaction (PCR) for BKV DNA during their stay on the intensive care unit (ICU). BKV viremia occurred in four patients, i.e. in three of the septic and in one of the hemorrhagic shock group. There was no association between viremia and renal dysfunction. All positive samples contained a low viral load (< 500 copies/ml).
Conclusions
Since BK viremia was rarely found and with low viral load only in critically ill surgical patients with shock, it is very unlikely that BK viremia results in BK nephropathy later on.
KW  - acute kidney injury
KW  - BK virus
KW  - polyomavirus
KW  - critically ill
KW  - sepsis
KW  - shock
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124136
VL  - 5
IS  - 100
ER  - 
TY  - JOUR
A1  - Arnold, Nicole
A1  - Braunschweig, Holger
A1  - Damme, Alexander
T1  - Bis(μ-diisopropyl-phosphanido-\(κ^2\)P:P)bis-[hydrido(triisopropyl-phosphane-κP)platinum(II)]
JF  - Acta crystallographica. Section E, Structure reports online
N2  - In the centrosymmetric molecular structure of the title compound \([Pt_2(C_6H_{14}P)_2H_2)(C_9H_{21}P)_2]\), each \(Pt^{II}\) atom is bound on one side to a phosphane ligand \((PiPr_3)\) and a hydrido ligand. On the other side, it is bound to two phosphanide ligands \((μ-PiPr_2)\), which engage a bridging position between the two \(Pt^{II}\) atoms, forming a distorted square-planar structure motif. The PtPt distance is 3.6755(2)Å. A comparable molecular structure was observed for bis-(μ-di-tert-butyl-phosphanido)bis-[hydrido(triethyl-phosphane)platinum(II)] [Itazaki et al. (2004 ). Organometallics, 23, 1610-1621].
KW  - data-to-parameter ratio = 22.3
KW  - mean σ(C–C) = 0.004 Å
KW  - single-crystal X-ray study
KW  - T = 100 K
KW  - R factor = 0.018
KW  - wR factor = 0.038
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123723
VL  - E68
ER  - 
TY  - JOUR
A1  - Gerlach, Manfred
A1  - Maetzler, Walter
A1  - Broich, Karl
A1  - Hampel, Harald
A1  - Rems, Lucas
A1  - Reum, Torsten
A1  - Riederer, Peter
A1  - Stäffler, Albrecht
A1  - Streffer, Johannes
A1  - Berg, Daniela
T1  - Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics
JF  - Journal of Neural Transmission
N2  - Reliable biomarkers that can be used for early diagnosis and tracking disease progression are the cornerstone of the development of disease-modifying treatments for Parkinson’s disease (PD). The German Society of Experimental and Clinical Neurotherapeutics (GESENT) has convened a Working Group to review the current status of proposed biomarkers of neurodegeneration according to the following criteria and to develop a consensus statement on biomarker candidates for evaluation of disease-modifying therapeutics in PD. The criteria proposed are that the biomarker should be linked to fundamental features of PD neuropathology and mechanisms underlying neurodegeneration in PD, should be correlated to disease progression assessed by clinical rating scales, should monitor the actual disease status, should be pre-clinically validated, and confirmed by at least two independent studies conducted by qualified investigators with the results published in peer-reviewed journals. To date, available data have not yet revealed one reliable biomarker to detect early neurodegeneration in PD and to detect and monitor effects of drug candidates on the disease process, but some promising biomarker candidates, such as antibodies against neuromelanin, pathological forms of α-synuclein, DJ-1, and patterns of gene expression, metabolomic and protein profiling exist. Almost all of the biomarker candidates were not investigated in relation to effects of treatment, validated in experimental models of PD and confirmed in independent studies.
KW  - disease progression
KW  - biomarkers
KW  - neuroprotection
KW  - disease-modifying therapies
KW  - Parkinson’s disease
KW  - surrogate endpoints
KW  - drug development
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125375
VL  - 119
IS  - 1
ER  - 
TY  - JOUR
A1  - Berendzen, Kenneth W.
A1  - Weiste, Christoph
A1  - Wanke, Dierk
A1  - Kilian, Joachim
A1  - Harter, Klaus
A1  - Dröge-Laser, Wolfgang
T1  - Bioinformatic cis-element analyses performed in Arabidopsis and rice disclose bZIP- and MYB-related binding sites as potential AuxRE-coupling elements in auxin-mediated transcription
N2  - Background: In higher plants, a diverse array of developmental and growth-related processes is regulated by the plant hormone auxin. Recent publications have proposed that besides the well-characterized Auxin Response Factors (ARFs) that bind Auxin Response Elements (AuxREs), also members of the bZIP- and MYB-transcription factor (TF) families participate in transcriptional control of auxin-regulated genes via bZIP Response Elements (ZREs) or Myb Response Elements (MREs), respectively. Results: Applying a novel bioinformatic algorithm, we demonstrate on a genome-wide scale that singular motifs or composite modules of AuxREs, ZREs, MREs but also of MYC2 related elements are significantly enriched in promoters of auxin-inducible genes. Despite considerable, species-specific differences in the genome structure in terms of the GC content, this enrichment is generally conserved in dicot (Arabidopsis thaliana) and monocot (Oryza sativa) model plants. Moreover, an enrichment of defined composite modules has been observed in selected auxin-related gene families. Consistently, a bipartite module, which encompasses a bZIP-associated G-box Related Element (GRE) and an AuxRE motif, has been found to be highly enriched. Making use of transient reporter studies in protoplasts, these findings were experimentally confirmed, demonstrating that GREs functionally interact with AuxREs in regulating auxin-mediated transcription. Conclusions: Using genome-wide bioinformatic analyses, evolutionary conserved motifs have been defined which potentially function as AuxRE-dependent coupling elements to establish auxin-specific expression patterns. Based on these findings, experimental approaches can be designed to broaden our understanding of combinatorial, auxin-controlled gene regulation.
KW  - Arabidopsis
KW  - Cis-elements
KW  - cis-element modules
KW  - Auxin-regulated transcription
KW  - AuxRE
KW  - bZIP
KW  - MYB
KW  - MYC
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75138
ER  - 
TY  - JOUR
A1  - Gross, Henrik
A1  - Hennard, Christine
A1  - Masouris, Ilias
A1  - Cassel, Christian
A1  - Barth, Stephanie
A1  - Stober-Grässer, Ute
A1  - Mamiani, Alfredo
A1  - Moritz, Bodo
A1  - Ostareck, Dirk
A1  - Ostareck-Lederer, Antje
A1  - Neuenkirchen, Nils
A1  - Fischer, Utz
A1  - Deng, Wen
A1  - Leonhardt, Heinrich
A1  - Noessner, Elfriede
A1  - Kremmer, Elisabeth
A1  - Grässer, Friedrich A.
T1  - Binding of the Heterogeneous Ribonucleoprotein K (hnRNP K) to the Epstein-Barr Virus Nuclear Antigen 2 (EBNA2) Enhances Viral LMP2A Expression
JF  - PLoS One
N2  - The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA-antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV-infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties.
KW  - SM proteins
KW  - protein argentine methyltranserase
KW  - motor-neuron protein
KW  - RNA-polymerase-II
KW  - messenger RNA
KW  - C-MYC
KW  - gene expression
KW  - splicing factor
KW  - down regulation
KW  - living cells
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133707
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - El-Keredy, Amira
A1  - Schleyer, Michael
A1  - König, Christian
A1  - Ekim, Aslihan
A1  - Gerber, Bertram
T1  - Behavioural Analyses of Quinine Processing in Choice, Feeding and Learning of Larval Drosophila
JF  - PLoS One
N2  - Gustatory stimuli can support both immediate reflexive behaviour, such as choice and feeding, and can drive internal reinforcement in associative learning. For larval Drosophila, we here provide a first systematic behavioural analysis of these functions with respect to quinine as a study case of a substance which humans report as "tasting bitter". We describe the dose-effect functions for these different kinds of behaviour and find that a half-maximal effect of quinine to suppress feeding needs substantially higher quinine concentrations (2.0 mM) than is the case for internal reinforcement (0.6 mM). Interestingly, in previous studies (Niewalda et al. 2008, Schipanski et al 2008) we had found the reverse for sodium chloride and fructose/sucrose, such that dose-effect functions for those tastants were shifted towards lower concentrations for feeding as compared to reinforcement, arguing that the differences in dose-effect function between these behaviours do not reflect artefacts of the types of assay used. The current results regarding quinine thus provide a starting point to investigate how the gustatory system is organized on the cellular and/or molecular level to result in different behavioural tuning curves towards a bitter tastant.
KW  - honeybees
KW  - chemosensory system
KW  - bitter taste
KW  - melanogaster
KW  - receptor
KW  - reward
KW  - brain
KW  - organization
KW  - architecture
KW  - perception
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130811
VL  - 7
IS  - 7
ER  - 
TY  - JOUR
A1  - Wolff, Alexander
A1  - Rutter, Iganz
T1  - Augmenting the Connectivity of Planar and Geometric Graphs
JF  - Journal of Graph Algorithms and Applications
N2  - In this paper we study connectivity augmentation problems. Given a connected graph G with some desirable property, we want to make G 2-vertex connected (or 2-edge connected) by adding edges such that the resulting graph keeps the property. The aim is to add as few edges as possible. The property that we consider is planarity, both in an abstract graph-theoretic and in a geometric setting, where vertices correspond to points in the plane and edges to straight-line segments.
We show that it is NP-hard to � nd a minimum-cardinality augmentation that makes a planar graph 2-edge connected. For making a planar graph 2-vertex connected this was known. We further show that both problems are hard in the geometric setting, even when restricted to trees. The problems remain hard for higher degrees of connectivity. On the other hand we give polynomial-time algorithms for the special case of convex geometric graphs.
We also study the following related problem. Given a planar (plane geometric) graph G, two vertices s and t of G, and an integer c, how many edges have to be added to G such that G is still planar (plane geometric) and contains c edge- (or vertex-) disjoint s{t paths? For the planar case we give a linear-time algorithm for c = 2. For the plane geometric case we give optimal worst-case bounds for c = 2; for c = 3 we characterize the cases that have a solution.
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-97587
ER  - 
TY  - JOUR
A1  - Chen, Wen
A1  - Gaßner, Birgit
A1  - Börner, Sebastian
A1  - Nikolaev, Viacheslav O.
A1  - Schlegel, Nicolas
A1  - Waschke, Jens
A1  - Steinbronn, Nadine
A1  - Strasser, Ruth
A1  - Kuhn, Michaela
T1  - Atrial natriuretic peptide enhances microvascular albumin permeability by the caveolae-mediated transcellular pathway
JF  - Cardiovascular Research
N2  - Aims 
Cardiac atrial natriuretic peptide (ANP) participates in the maintenance of arterial blood pressure and intravascular volume homeostasis. The hypovolaemic effects of ANP result from coordinated actions in the kidney and systemic microcirculation. Hence, ANP, via its guanylyl cyclase-A (GC-A) receptor and intracellular cyclic GMP as second messenger, stimulates endothelial albumin permeability. Ultimately, this leads to a shift of plasma fluid into interstitial pools. Here we studied the role of caveolae-mediated transendothelial albumin transport in the hyperpermeability effects of ANP.
Methods and results 
Intravital microscopy studies of the mouse cremaster microcirculation showed that ANP stimulates the extravasation of fluorescent albumin from post-capillary venules and causes arteriolar vasodilatation. The hyperpermeability effect was prevented in mice with conditional, endothelial deletion of GC-A (EC GC-A KO) or with deleted caveolin-1 (cav-1), the caveolae scaffold protein. In contrast, the vasodilating effect was preserved. Concomitantly, the acute hypovolaemic action of ANP was abolished in EC GC-A KO and Cav-1−/− mice. In cultured microvascular rat fat pad and mouse lung endothelial cells, ANP stimulated uptake and transendothelial transport of fluorescent albumin without altering endothelial electrical resistance. The stimulatory effect on albumin uptake was prevented in GC-A- or cav-1-deficient pulmonary endothelia. Finally, preparation of caveolin-enriched lipid rafts from mouse lung and western blotting showed that GC-A and cGMP-dependent protein kinase I partly co-localize with Cav-1 in caveolae microdomains.
Conclusion 
ANP enhances transendothelial caveolae-mediated albumin transport via its GC-A receptor. This ANP-mediated cross-talk between the heart and the microcirculation is critically involved in the regulation of intravascular volume.
KW  - caveolin-1
KW  - microvessel permeability
KW  - atrial natriuretic peptide
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126562
N1  - Lizenzhinweis: The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for noncommercial purposes provided that the original authorship is properly and fully attributed; the Journal, Learned Society and Oxford University Press are attributed as the original place of publication with correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated.
VL  - 93
IS  - 1
ER  - 
TY  - JOUR
T1  - ATLAS search for a heavy gauge boson decaying to a charged lepton and a neutrino in pp collisions at √s=7 TeV
JF  - The European Physical Journal C
N2  - The ATLAS detector at the LHC is used to search for high-mass states, such as heavy charged gauge bosons (W′), decaying to a charged lepton (electron or muon) and a neutrino. Results are presented based on the analysis of pp collisions at a center-of-mass energy of 7  TeV corresponding to an integrated luminosity of 4.7 fb\(^{−1}\). No excess beyond Standard Model expectations is observed. A W′ with Sequential Standard Model couplings is excluded at the 95 % credibility level for masses up to 2.55  TeV. Excited chiral bosons (W∗) with equivalent coupling strength are excluded for masses up to 2.42  TeV.
KW  - systematic uncertainty
KW  - muon decay channel
KW  - partial decay width
KW  - simulated signal event
KW  - background cross section
KW  - primary vertex
KW  - sequential standard model
KW  - muon spectrometer
KW  - Cl Lowe limit
KW  - QCD background
KW  - coupling strength
KW  - isolation requirement
KW  - chiral boson
KW  - experimental systematic uncertainty
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128888
VL  - 72
IS  - 2241
ER  - 
TY  - JOUR
A1  - Tomei, Sara
A1  - Adams, Sharon
A1  - Uccellini, Lorenzo
A1  - Bedognetti, Davide
A1  - De Giorgi, Valeria
A1  - Erdenebileg, Narnygerel
A1  - Libera Ascierto, Maria
A1  - Reinboth, Jennifer
A1  - Liu, Qiuzhen
A1  - Bevilacqua, Generoso
A1  - Wang, Ena
A1  - Mazzanti, Chiara
A1  - Marincola, Francesco M.
T1  - Association between HRAS rs12628 and rs112587690 polymorphisms with the risk of melanoma in the North American population
JF  - Medical Oncology
N2  - HRAS belongs to the RAS genes superfamily. RAS genes are important players in several human tumors and the single-nucleotide polymorphism rs12628 has been shown to contribute to the risk of bladder, colon, gastrointestinal, oral, and thyroid carcinoma. We hypothesized that this SNP may affect the risk of cutaneous melanoma as well. HRAS gene contains a polymorphic region (rs112587690), a repeated hexanucleotide -GGGCCT- located in intron 1. Three alleles of this region, P1, P2, and P3, have been identified that contain two, three, and four repeats of the hexanucleotide, respectively. We investigated the clinical impact of these polymorphisms in a case–control study. A total of 141 melanoma patients and 118 healthy donors from the North America Caucasian population were screened for rs12628 and rs112587690 polymorphisms. Genotypes were assessed by capillary sequencing or fragment analysis, respectively, and rs12628 CC and rs112587690 P1P1 genotypes significantly associated with increased melanoma risk (OR = 3.83, p = 0.003; OR = 11.3, p = 0.033, respectively), while rs112587690 P1P3 frequency resulted significantly higher in the control group (OR = 0.5, p = 0.017). These results suggest that rs12628 C homozygosis may be considered a potential risk factor for melanoma development in the North American population possibly through the linkage to rs112587690.
KW  - HRAS
KW  - polymorphism
KW  - melanoma
KW  - rs12628
KW  - rs112587690
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126834
VL  - 29
IS  - 5
ER  - 
TY  - JOUR
A1  - Zwink, Nadine
A1  - Jenetzky, Ekkehart
A1  - Schmiedeke, Eberhard
A1  - Schmidt, Dominik
A1  - Märzheuser, Schmidt
A1  - Grasshoff-Derr, Sabine
A1  - Holland-Cunz, Stefan
A1  - Weih, Sandra
A1  - Hosie, Stuart
A1  - Reifferscheid, Peter
A1  - Ameis, Helen
A1  - Kujath, Christina
A1  - Rissmann, Anke
A1  - Obermayr, Florian
A1  - Schwarzer, Nicole
A1  - Bartels, Enrika
A1  - Reutter, Heiko
A1  - Brenner, Hermann
T1  - Assisted reproductive techniques and the risk of anorectal malformations: a German case-control study
JF  - Orphanet Journal of Rare Diseases
N2  - Background: The use of assisted reproductive techniques (ART) for treatment of infertility is increasing rapidly worldwide. However, various health effects have been reported including a higher risk of congenital malformations. Therefore, we assessed the risk of anorectal malformations (ARM) after in-vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI).
Methods: Data of the German Network for Congenital Uro-REctal malformations (CURE-Net) were compared to nationwide data of the German IVF register and the Federal Statistical Office (DESTATIS). Odds ratios (95% confidence intervals) were determined to quantify associations using multivariable logistic regression accounting for potential confounding or interaction by plurality of births. 
Results: In total, 295 ARM patients born between 1997 and 2011 in Germany, who were recruited through participating pediatric surgeries from all over Germany and the German self-help organisation SoMA, were included. Controls were all German live-births (n = 10,069,986) born between 1997 and 2010. Overall, 30 cases (10%) and 129,982 controls (1%) were born after IVF or ICSI, which translates to an odds ratio (95% confidence interval) of 8.7 (5.9-12.6) between ART and ARM in bivariate analyses. Separate analyses showed a significantly increased risk for ARM after IVF (OR, 10.9; 95% CI, 6.2-19.0; P < 0.0001) as well as after ICSI (OR, 7.5; 95% CI, 4.6-12.2; P < 0.0001). Furthermore, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed strong associations with ART (ORs 4.9, 11.9 and 7.9, respectively). After stratification for plurality of birth, the corresponding odds ratios (95% confidence intervals) were 7.7 (4.6-12.7) for singletons and 4.9 (2.4-10.1) for multiple births. Conclusions: There is a strongly increased risk for ARM among children born after ART. Elevations of risk were seen after both IVF and ICSI. Further, separate analyses of patients with isolated ARM, ARM with associated anomalies and those with a VATER/VACTERL association showed increased risks in each group. An increased risk of ARM was also seen among both singletons and multiple births.
KW  - metaanalysis
KW  - in-vitro fertilization
KW  - reproductive medicine
KW  - anal atresia
KW  - imperforate anus
KW  - anorectal malformation
KW  - birth defects
KW  - prevalence
KW  - assisted reproductive techniques
KW  - congenital malformations
KW  - descriptive epidemiology
KW  - infants born
KW  - children born
KW  - IVF-methods
KW  - technology
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134036
VL  - 7
IS  - 65
ER  - 
TY  - JOUR
A1  - Schreiber, Ulrich
A1  - Klughammer, Christof
A1  - Kolbowski, Jörg
T1  - Assessment of wavelength-dependent parameters of photosynthetic electron transport with a new type of multi-color PAM chlorophyll fluorometer
JF  - Photosynthesis Research
N2  - Technical features of a novel multi-color pulse amplitude modulation (PAM) chlorophyll fluorometer as well as the applied methodology and some typical examples of its practical application with suspensions of Chlorella vulgaris and Synechocystis PCC 6803 are presented. The multi-color PAM provides six colors of pulse-modulated measuring light (peak-wavelengths at 400, 440, 480, 540, 590, and 625 nm) and six colors of actinic light (AL), peaking at 440, 480, 540, 590, 625 and 420–640 nm (white). The AL can be used for continuous illumination, maximal intensity single-turnover pulses, high intensity multiple-turnover pulses, and saturation pulses. In addition, far-red light (peaking at 725 nm) is provided for preferential excitation of PS I. Analysis of the fast fluorescence rise kinetics in saturating light allows determination of the wavelength- and sample-specific functional absorption cross section of PS II, Sigma(II)λ, with which the PS II turnover rate at a given incident photosynthetically active radiation (PAR) can be calculated. Sigma(II)λ is defined for a quasi-dark reference state, thus differing from σPSII used in limnology and oceanography. Vastly different light response curves for Chlorella are obtained with light of different colors, when the usual PAR-scale is used. Based on Sigma(II)λ the PAR, in units of μmol quanta/(m2 s), can be converted into PAR(II) (in units of PS II effective quanta/s) and a fluorescence-based electron transport rate ETR(II) = PAR(II) · Y(II)/Y(II)max can be defined. ETR(II) in contrast to rel.ETR qualifies for quantifying the absolute rate of electron transport in optically thin suspensions of unicellular algae and cyanobacteria. Plots of ETR(II) versus PAR(II) for Chlorella are almost identical using either 440 or 625 nm light. Photoinhibition data are presented suggesting that a lower value of ETR(II)max with 440 nm possibly reflects photodamage via absorption by the Mn-cluster of the oxygen-evolving complex.
KW  - synechocystis
KW  - O–I 1 fluorescence rise
KW  - functional absorption cross section of PS II
KW  - ETR
KW  - chlorella
KW  - PAR
KW  - photoinhibition
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127003
VL  - 113
IS  - 1
ER  - 
TY  - JOUR
A1  - Jazbutyte, Virginija
A1  - Stumpner, Jan
A1  - Redel, Andreas
A1  - Lorenzen, Johan M.
A1  - Roewer, Norbert
A1  - Thum, Thomas
A1  - Kehl, Franz
T1  - Aromatase Inhibition Attenuates Desflurane-Induced Preconditioning against Acute Myocardial Infarction in Male Mouse Heart In Vivo
JF  - PLoS One
N2  - The volatile anesthetic desflurane (DES) effectively reduces cardiac infarct size following experimental ischemia/reperfusion injury in the mouse heart. We hypothesized that endogenous estrogens play a role as mediators of desflurane-induced preconditioning against myocardial infarction. In this study, we tested the hypothesis that desflurane effects local estrogen synthesis by modulating enzyme aromatase expression and activity in the mouse heart. Aromatase metabolizes testosterone to 17b- estradiol (E2) and thereby significantly contributes to local estrogen synthesis. We tested aromatase effects in acute myocardial infarction model in male mice. The animals were randomized and subjected to four groups which were pre-treated with the selective aromatase inhibitor anastrozole (A group) and DES alone (DES group) or in combination (A+DES group) for 15 minutes prior to surgical intervention whereas the control group received 0.9% NaCl (CON group). All animals were subjected to 45 minutes ischemia following 180 minutes reperfusion. Anastrozole blocked DES induced preconditioning and increased infarct size compared to DES alone (37.94615.5% vs. 17.163.62%) without affecting area at risk and systemic hemodynamic parameters following ischemia/reperfusion. Protein localization studies revealed that aromatase was abundant in the murine cardiovascular system with the highest expression levels in endothelial and smooth muscle cells. Desflurane application at pharmacological concentrations efficiently upregulated aromatase expression in vivo and in vitro. We conclude that desflurane efficiently regulates aromatase expression and activity which might lead to increased local estrogen synthesis and thus preserve cellular integrity and reduce cardiac damage in an acute myocardial infarction model.
KW  - smooth muscle cells
KW  - estrogens
KW  - heart
KW  - anesthetics
KW  - immunostaining
KW  - endothelial cells
KW  - gene expression
KW  - myocardial infarction
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151258
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - Kannen, Vinicius
A1  - Hintzsche, Henning
A1  - Zanette, Dalila L.
A1  - Silva Jr., Wilson A.
A1  - Garcia, Sergio B.
A1  - Waaga-Gasser, Anna Maria
A1  - Stopper, Helga
T1  - Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model
N2  - The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G0/G1 phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.
KW  - Medizin
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75879
ER  - 
TY  - JOUR
A1  - Abdelmohsen, Usama Ramadan
A1  - Szesny, Matthias
A1  - Othman, Eman Maher
A1  - Schirmeister, Tanja
A1  - Grond, Stepanie
A1  - Stopper, Helga
A1  - Hentschel, Ute
T1  - Antioxidant and Anti-Protease Activities of Diazepinomicin from the Sponge-Associated Micromonospora Strain RV115
N2  - Diazepinomicin is a dibenzodiazepine alkaloid with an unusual structure among the known microbial metabolites discovered so far. Diazepinomicin was isolated from the marine sponge-associated strain Micromonospora sp. RV115 and was identified by spectroscopic analysis and by comparison to literature data. In addition to its interesting preclinical broad-spectrum antitumor potential, we report here new antioxidant and anti-protease activities for this compound. Using the ferric reducing antioxidant power (FRAP) assay, a strong antioxidant potential of diazepinomicin was demonstrated. Moreover, diazepinomicin showed a significant antioxidant and protective capacity from genomic damage induced by the reactive oxygen species hydrogen peroxide in human kidney (HK-2) and human promyelocytic (HL-60) cell lines. Additionally, diazepinomicin inhibited the proteases rhodesain and cathepsin L at an IC50 of 70–90 μM. It also showed antiparasitic activity against trypomastigote forms of Trypanosoma brucei with an IC50 of 13.5 μM. These results showed unprecedented antioxidant and anti-protease activities of diazepinomicin, thus further highlighting its potential as a future drug candidate.
KW  - Biologie
KW  - diazepinomicin
KW  - anti-protease
KW  - antioxidant
KW  - actinomycetes
KW  - Micromonospora
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-76279
ER  - 
TY  - JOUR
A1  - Zirkel, J.
A1  - Cecil, A.
A1  - Schäfer, F.
A1  - Rahlfs, S.
A1  - Ouedraogo, A.
A1  - Xiao, K.
A1  - Sawadogo, S.
A1  - Coulibaly, B.
A1  - Becker, K.
A1  - Dandekar, T.
T1  - Analyzing Thiol-Dependent Redox Networks in the Presence of Methylene Blue and Other Antimalarial Agents with RT-PCR-Supported in silico Modeling
JF  - Bioinformatics and Biology Insights
N2  - BACKGROUND: In the face of growing resistance in malaria parasites to drugs, pharmacological combination therapies are important. There is accumulating evidence that methylene blue (MB) is an effective drug against malaria. Here we explore the biological effects of both MB alone and in combination therapy using modeling and experimental data.
RESULTS: We built a model of the central metabolic pathways in P. falciparum. Metabolic flux modes and their changes under MB were calculated by integrating experimental data (RT-PCR data on mRNAs for redox enzymes) as constraints and results from the YANA software package for metabolic pathway calculations. Several different lines of MB attack on Plasmodium redox defense were identified by analysis of the network effects. Next, chloroquine resistance based on pfmdr/and pfcrt transporters, as well as pyrimethamine/sulfadoxine resistance (by mutations in DHF/DHPS), were modeled in silico. Further modeling shows that MB has a favorable synergism on antimalarial network effects with these commonly used antimalarial drugs.
CONCLUSIONS: Theoretical and experimental results support that methylene blue should, because of its resistance-breaking potential, be further tested as a key component in drug combination therapy efforts in holoendemic areas.
KW  - methylene blue
KW  - malaria
KW  - elementary mode analysis
KW  - drug
KW  - resistance
KW  - combination therapy
KW  - pathway
KW  - metabolic flux
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123751
N1  - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited.
VL  - 6
ER  - 
TY  - JOUR
A1  - Fernández-Rodríguez, Juana
A1  - Quiles, Francisco
A1  - Blanco, Ignacio
A1  - Teulé, Alex
A1  - Feliubadaló, Lídia
A1  - del Valle, Jesús
A1  - Salinas, Mónica
A1  - Izquierdo, Ángel
A1  - Darder, Esther
A1  - Schindler, Detlev
A1  - Capellá, Gabriel
A1  - Brunet, Joan
A1  - Lázaro, Conxi
A1  - Angel Pujana, Miguel
T1  - Analysis of SLX4/FANCP in non-BRCA1/2-mutated breast cancer families
JF  - BMC Cancer
N2  - Background: Genes that, when mutated, cause Fanconi anemia or greatly increase breast cancer risk encode for proteins that converge on a homology-directed DNA damage repair process. Mutations in the SLX4 gene, which encodes for a scaffold protein involved in the repair of interstrand cross-links, have recently been identified in unclassified Fanconi anemia patients. A mutation analysis of SLX4 in German or Byelorussian familial cases of breast cancer without detected mutations in BRCA1 or BRCA2 has been completed, with globally negative results. 
Methods: The genomic region of SLX4, comprising all exons and exon-intron boundaries, was sequenced in 94 Spanish familial breast cancer cases that match a criterion indicating the potential presence of a highly-penetrant germline mutation, following exclusion of BRCA1 or BRCA2 mutations. 
Results: This mutational analysis revealed extensive genetic variation of SLX4, with 21 novel single nucleotide variants; however, none could be linked to a clear alteration of the protein function. Nonetheless, genotyping 10 variants (nine novel, all missense amino acid changes) in a set of controls (138 women and 146 men) did not detect seven of them. Conclusions: Overall, while the results of this study do not identify clearly pathogenic mutations of SLX4 contributing to breast cancer risk, further genetic analysis, combined with functional assays of the identified rare variants, may be warranted to conclusively assess the potential link with the disease.
KW  - SLX4
KW  - Holliday junction reolvass
KW  - Fanconi-anemia subtype
KW  - susceptibility gene
KW  - helicase BRIP1
KW  - ovarian cancer
KW  - DNA repair
KW  - mutations
KW  - protein
KW  - RAD51C
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131772
VL  - 12
IS  - 84
ER  - 
TY  - JOUR
A1  - Albert-Weißenberger, Christiane
A1  - Várrallyay, Csanád
A1  - Raslan, Furat
A1  - Kleinschnitz, Christoph
A1  - Sirén, Anna-Leena
T1  - An experimental protocol for mimicking pathomechanisms of traumatic brain injury in mice
N2  - Traumatic brain injury (TBI) is a result of an outside force causing immediate mechanical disruption of brain tissue and delayed pathogenic events. In order to examine injury processes associated with TBI, a number of rodent models to induce brain trauma have been described. However, none of these models covers the entire spectrum of events that might occur in TBI. Here we provide a thorough methodological description of a straightforward closed head weight drop mouse model to assess brain injuries close to the clinical conditions of human TBI.
KW  - Medizin
KW  - closed head injury
KW  - traumatic brain injury
KW  - neurobehavioural deficits
KW  - astrocyte
KW  - microglia
KW  - neurons
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75368
ER  - 
TY  - JOUR
A1  - Jäger, Dominik
A1  - Pernitzsch, Sandy R.
A1  - Richter, Andreas S.
A1  - Backofen, Rolf
A1  - Sharma, Cynthia M.
A1  - Schmitz, Ruth A.
T1  - An archaeal sRNA targeting cis- and trans-encoded mRNAs via two distinct domains
JF  - Nucleic Acids Research
N2  - We report on the characterization and target analysis of the small (s) RNA\(_{162}\) in the methanoarchaeon Methanosarcina mazei. Using a combination of genetic approaches, transcriptome analysis and computational predictions, the bicistronic MM2441-MM2440 mRNA encoding the transcription factor MM2441 and a protein of unknown function was identified as a potential target of this sRNA, which due to processing accumulates as three stabile 5' fragments in late exponential growth. Mobility shift assays using various mutants verified that the non-structured single-stranded linker region of sRNA\(_{162}\) (SLR) base-pairs with the MM2440-MM2441 mRNA internally, thereby masking the predicted ribosome binding site of MM2441. This most likely leads to translational repression of the second cistron resulting in dis-coordinated operon expression. Analysis of mutant RNAs in vivo confirmed that the SLR of sRNA\(_{162}\) is crucial for target interactions. Furthermore, our results indicate that sRNA\(_{162}\)-controlled MM2441 is involved in regulating the metabolic switch between the carbon sources methanol and methylamine. Moreover, biochemical studies demonstrated that the 50 end of sRNA\(_{162}\) targets the 5'-untranslated region of the cis-encoded MM2442 mRNA. Overall, this first study of archaeal sRNA/mRNA-target interactions unraveled that sRNA\(_{162}\) acts as an antisense (as) RNA on cis- and trans-encoded mRNAs via two distinct domains, indicating that cis-encoded asRNAs can have larger target regulons than previously anticipated.
KW  - strain
KW  - escherichia coli
KW  - methanosarcina mazei GO1
KW  - methanol methyltransferase isozymes
KW  - small nucleolar RNAs
KW  - acetivorans C2A
KW  - antisense RNAs
KW  - GO1
KW  - transcriptional regulator
KW  - translational initiation
KW  - pyrococcus furiosus
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134972
VL  - 40
IS  - 21
ER  - 
TY  - JOUR
A1  - Klauke, Benedikt
A1  - Winter, Bernward
A1  - Gajewska, Agnes
A1  - Zwanzger, Peter
A1  - Reif, Andreas
A1  - Herrmann, Martin J.
A1  - Dlugos, Andrea
A1  - Warrings, Bodo
A1  - Jacob, Christian
A1  - Mühlberger, Andreas
A1  - Arolt, Volker
A1  - Pauli, Paul
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
T1  - Affect-Modulated Startle: Interactive Influence of Catechol-O-Methyltransferase Val158Met Genotype and Childhood Trauma
JF  - PLoS One
N2  - The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.
KW  - COMT VAL(158)MET polymorphism
KW  - serotonin transporter gene
KW  - life events
KW  - community sample
KW  - acoustic startle
KW  - prepulse inhibition
KW  - panic disorder
KW  - caffeine-induced anxiety
KW  - fear-potentiated startle
KW  - posttraumatic-stress-disorder
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132184
VL  - 7
IS  - 6
ER  - 
TY  - JOUR
A1  - Müller, P.A.
A1  - Bröcker, E.B.
A1  - Klinker, E.
A1  - Stoevesandt, J.
A1  - Benoit, S.
T1  - Adjuvant treatment of recalcitrant Bullous pemphigoid with immunoadsorption
JF  - Dermatology
N2  - Elimination of pathogenic autoantibodies by immunoadsorption (IA) has been described as an effective adjuvant treatment in severe bullous autoimmune diseases, especially in pemphigus. There is much less experience in the treatment of bullous pemphigoid (BP). BP was diagnosed in a 62-year-old Caucasian woman presenting a pruritic rash with multiple tense blisters. Standard treatments with topical and oral corticosteroids, steroid-sparing agents including dapsone, azathioprine, mycophenolate mofetil (MMF) and intravenous immunoglobulins were ineffective or had to be discontinued due to adverse events. An immediate clinical response could be achieved by two treatment cycles of adjuvant protein A immunoadsorption (PA-IA) in addition to continued treatment with MMF (2 g/day) and prednisolone (1 mg/kg/day). Tolerance was excellent. Clinical improvement remained stable after discontinuation of IA and went along with sustained reduction of circulating autoantibodies. Our data demonstrate that PA-IA might be a safe and effective adjuvant treatment in severe and recalcitrant BP.
KW  - Bullous pemphigoid
KW  - Immunoadsorption
KW  - Immunoapheresis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196620
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  - 224
IS  - 3
SP  - 224
EP  - 227
ER  - 
TY  - JOUR
A1  - Neuhaus, Winfried
A1  - Burek, Malgorzata
A1  - Djuzenova, Cholpon C
A1  - Thal, Serge C
A1  - Koepsell, Hermann
A1  - Roewer, Norbert
A1  - Förster, Carola Y
T1  - Addition of NMDA-receptor antagonist MK801 during oxygen/glucose deprivation moderately attenuates the up-regulation of glucose uptake after subsequent reoxygenation in brain endothelial cells
N2  - During stroke the blood–brain barrier (BBB) is damaged which can result in vasogenic brain edema and inflammation. The reduced blood supply leads to decreased delivery of oxygen and glucose to affected areas of the brain. Oxygen and glucose deprivation (OGD) can cause upregulation of glucose uptake of brain endothelial cells. In this letter, we investigated the influence of MK801, a non-competitive inhibitor of the NMDA-receptor, on the regulation of the glucose uptake and of the main glucose transporters glut1 and sglt1 in murine BBB cell line cerebEND during OGD. mRNA expression of glut1 was upregulated 68.7- fold after 6 h OGD, which was significantly reduced by 10 μM MK801 to 28.9-fold. Sglt1 mRNA expression decreased during OGD which was further reduced by MK801. Glucose uptake was significantly increased up to 907% after 6 h OGD and was still higher (210%) after the 20 h reoxygenation phase compared to normoxia. Ten micromolar MK801 during OGD was able to reduce upregulated glucose uptake after OGD and reoxygenation significantly. Presence of several NMDAR subunits was proven on the mRNA level in cerebEND cells. Furthermore, it was shown that NMDAR subunit NR1 was upregulated during OGD and that this was inhibitable by MK801. In conclusion, the addition of MK801 during the OGD phase reduced significantly the glucose uptake after the subsequent reoxygenation phase in brain endothelial cells.
KW  - Blut-Hirn-Schranke
KW  - Schlaganfall
KW  - Glucosetransportproteine
KW  - NMDA-Antagonist
KW  - NMDA-Rezeptor
KW  - blood-brain barrier
KW  - MK801
KW  - NMDAR
KW  - stroke
KW  - glut1
KW  - sglt1
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-67241
ER  - 
TY  - JOUR
A1  - Neubauer, Henning
A1  - Wirth, Clemens
A1  - Ruf, Katharina
A1  - Hebestreit, Helge
A1  - Beer, Meinrad
T1  - Acute Muscle Trauma due to Overexercise in an Otherwise Healthy Patient with Cystic Fibrosis
JF  - Case Reports in Pediatrics
N2  - Cystic fibrosis (CF) is one of the most common inherited diseases and is caused by mutations in the CFTR gene. Although the pulmonary and gastrointestinal manifestations of the disease remain in the focus of treatment, recent studies have shown expression of the CFTR gene product in skeletal muscle cells and observed altered intramuscular \(Ca^{2+}\) release dynamics in CFTR-deficient animal models. Physical exercise is beneficial for maintaining fitness and well-being in CF patients and constitutes one aspect of modern multimodal treatment, which has considerably increased life span and reduced morbidity. We report on a case of acute muscle trauma resulting from excessive dumbbell exercise in a young adult with cystic fibrosis and describe clinical, laboratory and imaging characteristics of acute exercise-induced muscle injury.
KW  - Cystic fibrosis
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123967
VL  - 2012
IS  - 527989
ER  - 
TY  - JOUR
A1  - Hafner, Christian
A1  - Houben, Roland
A1  - Baeurle, Anne
A1  - Ritter, Cathrin
A1  - Schrama, David
A1  - Landthaler, Michael
A1  - Becker, Jürgen C.
T1  - Activation of the PI3K/AKT Pathway in Merkel Cell Carcinoma
JF  - PLoS One
N2  - Merkel cell carcinoma (MCC) is a highly aggressive skin cancer with an increasing incidence. The understanding of the molecular carcinogenesis of MCC is limited. Here, we scrutinized the PI3K/AKT pathway, one of the major pathways activated in human cancer, in MCC. Immunohistochemical analysis of 41 tumor tissues and 9 MCC cell lines revealed high levels of AKT phosphorylation at threonine 308 in 88% of samples. Notably, the AKT phosphorylation was not correlated with the presence or absence of the Merkel cell polyoma virus (MCV). Accordingly, knock-down of the large and small T antigen by shRNA in MCV positive MCC cells did not affect phosphorylation of AKT. We also analyzed 46 MCC samples for activating PIK3CA and AKT1 mutations. Oncogenic PIK3CA mutations were found in 2/46 (4%) MCCs whereas mutations in exon 4 of AKT1 were absent. MCC cell lines demonstrated a high sensitivity towards the PI3K inhibitor LY-294002. This finding together with our observation that the PI3K/AKT pathway is activated in the majority of human MCCs identifies PI3K/AKT as a potential new therapeutic target for MCC patients.
KW  - rare
KW  - T-antigen
KW  - PIK3CA mutations
KW  - squamous cell
KW  - melanoma
KW  - polymavirus
KW  - cancer
KW  - tumors
KW  - akt
KW  - expression
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131398
VL  - 7
IS  - 2
ER  - 
TY  - JOUR
A1  - Stolpmann, K.
A1  - Brinkmann, J.
A1  - Salzmann, S.
A1  - Genkinger, D.
A1  - Fritsche, E.
A1  - Hutzler, C.
A1  - Wajant, H.
A1  - Luch, A.
A1  - Henkler, F.
T1  - Activation of the aryl hydrocarbon receptor sensitises human keratinocytes for CD95L-and TRAIL-induced apoptosis
JF  - Cell Death & Disease
N2  - In this study, we have analysed the apoptotic effects of the ubiquitous environmental toxin benzo[ a] pyrene (BP) in HaCaT cells and human keratinocytes. Although prolonged exposure to BP was not cytotoxic on its own, a strong enhancement of CD95 (Fas)-mediated apoptosis was observed with BP at concentrations activating the aryl hydrocarbon receptor (AhR). Importantly, the ultimately mutagenic BP-metabolite, that is, (+)-anti-BP-7,8-diol-9,10-epoxide (BPDE), failed to enhance CD95-mediated cell death, suggesting that the observed pro-apoptotic effect of BP is neither associated with DNA adducts nor DNA-damage related signalling. CD95-induced apoptosis was also enhanced by beta-naphtoflavone, a well-known agonist of the AhR that does not induce DNA damage, thus suggesting a crucial role for AhR activation. Consistently, BP failed to sensitise for CD95L-induced apoptosis in AhR knockdown HaCaT cells. Furthermore, inhibition of CYP1A1 and/or 1B1 expression did not affect the pro-apoptotic crosstalk. Exposure to BP did not increase expression of CD95, but led to augmented activation of caspase-8. Enhancement of apoptosis was also observed with the TRAIL death receptors that activate caspase-8 and apoptosis by similar mechanisms as CD95. Together, these observations indicate an interference of AhR signalling with the activity of receptor-associated signalling intermediates that are shared by CD95 and TRAIL receptors. Our data thus suggest that AhR agonists can enhance cytokine-mediated adversity upon dermal exposure.
KW  - CD95
KW  - HaCaT cells
KW  - growth-factor receptor
KW  - cell death
KW  - mitochondrial dysfunction
KW  - mediated apoptosis
KW  - FAS
KW  - dermatitis
KW  - pathways
KW  - skin
KW  - progression
KW  - aryl hydrocarbon receptor (AhR)
KW  - apoptosis
KW  - benzo[a]pyrene
KW  - human keratinocytes
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133501
VL  - 3
IS  - e388
ER  - 
TY  - JOUR
A1  - Sweeney, Reinhart A.
A1  - Seubert, Benedikt
A1  - Stark, Silke
A1  - Homann, Vanessa
A1  - Müller, Gerd
A1  - Flentje, Michael
A1  - Guckenbeger, Matthias
T1  - Accuracy and inter-observer variability of 3D versus 4D cone-beam CT based image-guidance in SBRT for lung tumors
N2  - Background: To analyze the accuracy and inter-observer variability of image-guidance (IG) using 3D or 4D cone-beam CT (CBCT) technology in stereotactic body radiotherapy (SBRT) for lung tumors. Materials and methods: Twenty-one consecutive patients treated with image-guided SBRT for primary and secondary lung tumors were basis for this study. A respiration correlated 4D-CT and planning contours served as reference for all IG techniques. Three IG techniques were performed independently by three radiation oncologists (ROs) and three radiotherapy technicians (RTTs). Image-guidance using respiration correlated 4D-CBCT (IG-4D) with automatic registration of the planning 4D-CT and the verification 4D-CBCT was considered gold-standard. Results were compared with two IG techniques using 3D-CBCT: 1) manual registration of the planning internal target volume (ITV) contour and the motion blurred tumor in the 3D-CBCT (IG-ITV); 2) automatic registration of the planning reference CT image and the verification 3D-CBCT (IG-3D). Image quality of 3D-CBCT and 4D-CBCT images was scored on a scale of 1–3, with 1 being best and 3 being worst quality for visual verification of the IGRT results. Results: Image quality was scored significantly worse for 3D-CBCT compared to 4D-CBCT: the worst score of 3 was given in 19 % and 7.1 % observations, respectively. Significant differences in target localization were observed between 4D-CBCT and 3D-CBCT based IG: compared to the reference of IG-4D, tumor positions differed by 1.9 mm± 0.9 mm (3D vector) on average using IG-ITV and by 3.6 mm± 3.2 mm using IG-3D; results of IG-ITV were significantly closer to the reference IG-4D compared to IG-3D. Differences between the 4D-CBCT and 3D-CBCT techniques increased significantly with larger motion amplitude of the tumor; analogously, differences increased with worse 3D-CBCT image quality scores. Inter-observer variability was largest in SI direction and was significantly larger in IG using 3D-CBCT compared to 4D-CBCT: 0.6 mm versus 1.5 mm (one standard deviation). Inter-observer variability was not different between the three ROs compared to the three RTTs. Conclusions: Respiration correlated 4D-CBCT improves the accuracy of image-guidance by more precise target localization in the presence of breathing induced target motion and by reduced inter-observer variability.
KW  - Medizin
KW  - Lung cancer
KW  - Image-guidance
KW  - Cone-beam CT
KW  - Inter-observer variability
KW  - Respiration correlated imaging
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-75698
ER  - 
TY  - JOUR
A1  - Jahn, Daniel
A1  - Schramm, Sabine
A1  - Schnölzer, Martina
A1  - Heilmann, Clemens J.
A1  - de Koster, Chris G.
A1  - Schütz, Wolfgang
A1  - Benavente, Ricardo
A1  - Alsheimer, Manfred
T1  - A truncated lamin A in the Lmna\(^{−/−}\) mouse line: Implications for the understanding of laminopathies
JF  - Nucleus
N2  - During recent years a number of severe clinical syndromes, collectively termed laminopathies, turned out to be caused by various, distinct mutations in the human LMNA gene. Arising from this, remarkable progress has been made to unravel the molecular pathophysiology underlying these disorders. A great benefit in this context was the generation of an A-type lamin deficient mouse line (Lmna\(^{−/−}\)) by Sullivan and others,1 which has become one of the most frequently used models in the field and provided profound insights to many different aspects of A-type lamin function. Here, we report the unexpected finding that these mice express a truncated Lmna gene product on both transcriptional and protein level. Combining different approaches including mass spectrometry, we precisely define this product as a C-terminally truncated lamin A mutant that lacks domains important for protein interactions and post-translational processing. Based on our findings we discuss implications for the interpretation of previous studies using Lmna\(^{−/−}\) mice and the concept of human laminopathies.
KW  - nuclear organization
KW  - A-type lamins
KW  - LMNA mutations
KW  - laminopathies
KW  - nuclear envelope
KW  - nuclear lamina
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127281
VL  - 3
IS  - 5
ER  - 
TY  - JOUR
A1  - Weisschuh, Nicole
A1  - Wissinger, Bernd
A1  - Gramer, Eugen
T1  - A splice site mutation in the PAX6 gene which induces exon skipping causes autosomal dominant inherited aniridia
JF  - Molecular Vision
N2  - Purpose: To identify the underlying genetic cause in a two generation German family diagnosed with isolated aniridia.
Methods: All patients underwent full ophthalmic examination. Mutation screening of the paired box gene 6 (PAX6) was performed by bidirectional Sanger sequencing. A minigene assay was applied to analyze transcript processing of mutant and wildtype PAX6 variants in HEK293 cells.
Results: We identified a PAX6 sequence variant at the splice donor site (+5) of intron 12. This variant has been described before in another family with aniridia but has not been characterized at the transcript level. We could demonstrate that the mutant allele causes the skipping of exon 12 during transcript processing. The mutation is predicted to result in a ‘run on’ translation past the normal translational stop codon.
Conclusions: A splice site mutation resulting in exon skipping was found in a family with autosomal dominant aniridia. The mutation is predicted to result in an enlarged protein with an extra COOH-terminal domain. This very likely affects the transactivation properties of the PAX6 protein.
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124379
VL  - 18
ER  - 
TY  - JOUR
T1  - A search for flavour changing neutral currents in top-quark decays in pp collision data collected with the ATLAS detector at √s=7 TeV
JF  - Journal of High Energy Physics
N2  - A search for flavour changing neutral current (FCNC) processes in top-quark decays by the ATLAS Collaboration is presented. Data collected from pp collisions at the LHC at a centre-of-mass energy of √s=7TeV during 2011, corresponding to an integrated luminosity of 2.1 fb\(^{−1}\), were used. A search was performed for top-quark pair-production events, with one top quark decaying through the t → Zq FCNC (q = u, c) channel, and the other through the Standard Model dominant mode t → W b. Only the decays of the Z boson to charged leptons and leptonic W -boson decays were considered as signal. Consequently, the final-state topology is characterised by the presence of three isolated charged leptons, at least two jets and missing transverse momentum from the undetected neutrino. No evidence for an FCNC signal was found. An upper limit on the t → Zq branching ratio of BR(t → Zq) < 0.73% is set at the 95% confidence level.
KW  - neutral currents
KW  - rare decays
KW  - top physics
KW  - hadron hadron scattering
KW  - flavour changing
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129152
VL  - 9
IS  - 139
ER  - 
TY  - JOUR
T1  - A search for \(t\overline t\) resonances with the ATLAS detector in 2.05 fb\(^{−1}\) of proton-proton collisions at √s=7 TeV
JF  - European Physical Journal C
N2  - A search for top quark pair resonances in final states containing at least one electron or muon has been performed with the ATLAS experiment at the CERN Large Hadron Collider. The search uses a data sample corresponding to an integrated luminosity of 2.05 fb\(^{−1}\), which was recorded in 2011 at a proton-proton centre-of-mass energy of 7 TeV. No evidence for a resonance is found and limits are set on the production cross-section times branching ratio to \(t\overline t\) for narrow and wide resonances. For narrow Z′ bosons, the observed 95 % Bayesian credibility level limits range from 9.3 pb to 0.95 pb for masses in the range of m Z′=500 GeV to m\(_{Z′}\)=1300 GeV. The corresponding excluded mass region for a leptophobic topcolour Z′ boson (Kaluza-Klein gluon excitation in the Randall-Sundrum model) is m\(_{Z′}\)<880 GeV (m\(_{gKK}\)<1130 GeV).
KW  - dilepton invariant mass
KW  - dilepton channel
KW  - jet channel
KW  - top quark mass
KW  - heavy flavour quark
KW  - reconstructed mass spectrum
KW  - muon channel
KW  - single top production
KW  - electron energy deposition
KW  - multijet background
KW  - non-prompt lepton
KW  - light quark jet
KW  - jet sample
KW  - pair invariant mass
KW  - event selcetion cut
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127959
VL  - 72
IS  - 2083
ER  -