TY  - JOUR
A1  - Davis, Lea K.
A1  - Yu, Dongmei
A1  - Keenan, Clare L.
A1  - Gamazon, Eric R.
A1  - Konkashbaev, Anuar I.
A1  - Derks, Eske M.
A1  - Neale, Benjamin M.
A1  - Yang, Jian
A1  - Lee, S. Hong
A1  - Evans, Patrick
A1  - Barr, Cathy L.
A1  - Bellodi, Laura
A1  - Benarroch, Fortu
A1  - Berrio, Gabriel Bedoya
A1  - Bienvenu, Oscar J.
A1  - Bloch, Michael H.
A1  - Blom, Rianne M.
A1  - Bruun, Ruth D.
A1  - Budman, Cathy L.
A1  - Camarena, Beatriz
A1  - Campbell, Desmond
A1  - Cappi, Carolina
A1  - Cardona Silgado, Julio C.
A1  - Cath, Danielle C.
A1  - Cavallini, Maria C.
A1  - Chavira, Denise A.
A1  - Chouinard, Sylvian
A1  - Conti, David V.
A1  - Cook, Edwin H.
A1  - Coric, Vladimir
A1  - Cullen, Bernadette A.
A1  - Deforce, Dieter
A1  - Delorme, Richard
A1  - Dion, Yves
A1  - Edlund, Christopher K.
A1  - Egberts, Karin
A1  - Falkai, Peter
A1  - Fernandez, Thomas V.
A1  - Gallagher, Patience J.
A1  - Garrido, Helena
A1  - Geller, Daniel
A1  - Girard, Simon L.
A1  - Grabe, Hans J.
A1  - Grados, Marco A.
A1  - Greenberg, Benjamin D.
A1  - Gross-Tsur, Varda
A1  - Haddad, Stephen
A1  - Heiman, Gary A.
A1  - Hemmings, Sian M. J.
A1  - Hounie, Ana G.
A1  - Illmann, Cornelia
A1  - Jankovic, Joseph
A1  - Jenike, Micheal A.
A1  - Kennedy, James L.
A1  - King, Robert A.
A1  - Kremeyer, Barbara
A1  - Kurlan, Roger
A1  - Lanzagorta, Nuria
A1  - Leboyer, Marion
A1  - Leckman, James F.
A1  - Lennertz, Leonhard
A1  - Liu, Chunyu
A1  - Lochner, Christine
A1  - Lowe, Thomas L.
A1  - Macciardi, Fabio
A1  - McCracken, James T.
A1  - McGrath, Lauren M.
A1  - Restrepo, Sandra C. Mesa
A1  - Moessner, Rainald
A1  - Morgan, Jubel
A1  - Muller, Heike
A1  - Murphy, Dennis L.
A1  - Naarden, Allan L.
A1  - Ochoa, William Cornejo
A1  - Ophoff, Roel A.
A1  - Osiecki, Lisa
A1  - Pakstis, Andrew J.
A1  - Pato, Michele T.
A1  - Pato, Carlos N.
A1  - Piacentini, John
A1  - Pittenger, Christopher
A1  - Pollak, Yehunda
A1  - Rauch, Scott L.
A1  - Renner, Tobias J.
A1  - Reus, Victor I.
A1  - Richter, Margaret A.
A1  - Riddle, Mark A.
A1  - Robertson, Mary M.
A1  - Romero, Roxana
A1  - Rosàrio, Maria C.
A1  - Rosenberg, David
A1  - Rouleau, Guy A.
A1  - Ruhrmann, Stephan
A1  - Ruiz-Linares, Andreas
A1  - Sampaio, Aline S.
A1  - Samuels, Jack
A1  - Sandor, Paul
A1  - Sheppard, Broke
A1  - Singer, Harvey S.
A1  - Smit, Jan H.
A1  - Stein, Dan J.
A1  - Strengman, E.
A1  - Tischfield, Jay A.
A1  - Valencia Duarte, Ana V.
A1  - Vallada, Homero
A1  - Van Nieuwerburgh, Flip
A1  - Veenstra-VanderWeele, Jeremy
A1  - Walitza, Susanne
A1  - Wang, Ying
A1  - Wendland, Jens R.
A1  - Westenberg, Herman G. M.
A1  - Shugart, Yin Yao
A1  - Miguel, Euripedes C.
A1  - McMahon, William
A1  - Wagner, Michael
A1  - Nicolini, Humberto
A1  - Posthuma, Danielle
A1  - Hanna, Gregory L.
A1  - Heutink, Peter
A1  - Denys, Damiaan
A1  - Arnold, Paul D.
A1  - Oostra, Ben A.
A1  - Nestadt, Gerald
A1  - Freimer, Nelson B.
A1  - Pauls, David L.
A1  - Wray, Naomi R.
A1  - Stewart, S. Evelyn
A1  - Mathews, Carol A.
A1  - Knowles, James A.
A1  - Cox, Nancy J.
A1  - Scharf, Jeremiah M.
T1  - Partitioning the Heritability of Tourette Syndrome and Obsessive Compulsive Disorder Reveals Differences in Genetic Architecture
JF  - PLoS Genetics
N2  - The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
KW  - TIC disorders
KW  - missing heritability
KW  - complex diseases
KW  - neuropsychiatric disorders
KW  - common SNPS
KW  - gilles
KW  - family
KW  - brain
KW  - expression
KW  - autism
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127377
SN  - 1553-7390
VL  - 9
IS  - 10
ER  - 
TY  - JOUR
A1  - Viljur, Mari‐Liis
A1  - Abella, Scott R.
A1  - Adámek, Martin
A1  - Alencar, Janderson Batista Rodrigues
A1  - Barber, Nicholas A.
A1  - Beudert, Burkhard
A1  - Burkle, Laura A.
A1  - Cagnolo, Luciano
A1  - Campos, Brent R.
A1  - Chao, Anne
A1  - Chergui, Brahim
A1  - Choi, Chang‐Yong
A1  - Cleary, Daniel F. R.
A1  - Davis, Thomas Seth
A1  - Dechnik‐Vázquez, Yanus A.
A1  - Downing, William M.
A1  - Fuentes‐Ramirez, Andrés
A1  - Gandhi, Kamal J. K.
A1  - Gehring, Catherine
A1  - Georgiev, Kostadin B.
A1  - Gimbutas, Mark
A1  - Gongalsky, Konstantin B.
A1  - Gorbunova, Anastasiya Y.
A1  - Greenberg, Cathryn H.
A1  - Hylander, Kristoffer
A1  - Jules, Erik S.
A1  - Korobushkin, Daniil I.
A1  - Köster, Kajar
A1  - Kurth, Valerie
A1  - Lanham, Joseph Drew
A1  - Lazarina, Maria
A1  - Leverkus, Alexandro B.
A1  - Lindenmayer, David
A1  - Marra, Daniel Magnabosco
A1  - Martín‐Pinto, Pablo
A1  - Meave, Jorge A.
A1  - Moretti, Marco
A1  - Nam, Hyun‐Young
A1  - Obrist, Martin K.
A1  - Petanidou, Theodora
A1  - Pons, Pere
A1  - Potts, Simon G.
A1  - Rapoport, Irina B.
A1  - Rhoades, Paul R.
A1  - Richter, Clark
A1  - Saifutdinov, Ruslan A.
A1  - Sanders, Nathan J.
A1  - Santos, Xavier
A1  - Steel, Zachary
A1  - Tavella, Julia
A1  - Wendenburg, Clara
A1  - Wermelinger, Beat
A1  - Zaitsev, Andrey S.
A1  - Thorn, Simon
T1  - The effect of natural disturbances on forest biodiversity: an ecological synthesis
JF  - Biological Reviews
N2  - Disturbances alter biodiversity via their specific characteristics, including severity and extent in the landscape, which act at different temporal and spatial scales. Biodiversity response to disturbance also depends on the community characteristics and habitat requirements of species. Untangling the mechanistic interplay of these factors has guided disturbance ecology for decades, generating mixed scientific evidence of biodiversity responses to disturbance. Understanding the impact of natural disturbances on biodiversity is increasingly important due to human‐induced changes in natural disturbance regimes. In many areas, major natural forest disturbances, such as wildfires, windstorms, and insect outbreaks, are becoming more frequent, intense, severe, and widespread due to climate change and land‐use change. Conversely, the suppression of natural disturbances threatens disturbance‐dependent biota. Using a meta‐analytic approach, we analysed a global data set (with most sampling concentrated in temperate and boreal secondary forests) of species assemblages of 26 taxonomic groups, including plants, animals, and fungi collected from forests affected by wildfires, windstorms, and insect outbreaks. The overall effect of natural disturbances on α‐diversity did not differ significantly from zero, but some taxonomic groups responded positively to disturbance, while others tended to respond negatively. Disturbance was beneficial for taxonomic groups preferring conditions associated with open canopies (e.g. hymenopterans and hoverflies), whereas ground‐dwelling groups and/or groups typically associated with shady conditions (e.g. epigeic lichens and mycorrhizal fungi) were more likely to be negatively impacted by disturbance. Across all taxonomic groups, the highest α‐diversity in disturbed forest patches occurred under moderate disturbance severity, i.e. with approximately 55% of trees killed by disturbance. We further extended our meta‐analysis by applying a unified diversity concept based on Hill numbers to estimate α‐diversity changes in different taxonomic groups across a gradient of disturbance severity measured at the stand scale and incorporating other disturbance features. We found that disturbance severity negatively affected diversity for Hill number q = 0 but not for q = 1 and q = 2, indicating that diversity–disturbance relationships are shaped by species relative abundances. Our synthesis of α‐diversity was extended by a synthesis of disturbance‐induced change in species assemblages, and revealed that disturbance changes the β‐diversity of multiple taxonomic groups, including some groups that were not affected at the α‐diversity level (birds and woody plants). Finally, we used mixed rarefaction/extrapolation to estimate biodiversity change as a function of the proportion of forests that were disturbed, i.e. the disturbance extent measured at the landscape scale. The comparison of intact and naturally disturbed forests revealed that both types of forests provide habitat for unique species assemblages, whereas species diversity in the mixture of disturbed and undisturbed forests peaked at intermediate values of disturbance extent in the simulated landscape. Hence, the relationship between α‐diversity and disturbance severity in disturbed forest stands was strikingly similar to the relationship between species richness and disturbance extent in a landscape consisting of both disturbed and undisturbed forest habitats. This result suggests that both moderate disturbance severity and moderate disturbance extent support the highest levels of biodiversity in contemporary forest landscapes.
KW  - natural disturbance
KW  - diversity–disturbance relationship
KW  - disturbance severity
KW  - disturbance extent
KW  - intermediate disturbance hypothesis
KW  - forest communities
KW  - α‐diversity
KW  - β‐diversity
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287168
VL  - 97
IS  - 5
SP  - 1930
EP  - 1947
ER  - 
TY  - JOUR
A1  - Ziegler, C.
A1  - Richter, J.
A1  - Mahr, M.
A1  - Gajewska, A.
A1  - Schiele, M.A.
A1  - Gehrmann, A.
A1  - Schmidt, B.
A1  - Lesch, K.-P.
A1  - Lang, T.
A1  - Helbig-Lang, S.
A1  - Pauli, P.
A1  - Kircher, T.
A1  - Reif, A.
A1  - Rief, W.
A1  - Vossbeck-Elsebusch, A.N.
A1  - Arolt, V.
A1  - Wittchen, H.-U.
A1  - Hamm, A.O.
A1  - Deckert, J.
A1  - Domschke, K.
T1  - MAOA gene hypomethylation in panic disorder-reversibility of an epigenetic risk pattern by psychotherapy
JF  - Translational Psychiatry
N2  - Epigenetic signatures such as methylation of the monoamine oxidase A (MAOA) gene have been found to be altered in panic disorder (PD). Hypothesizing temporal plasticity of epigenetic processes as a mechanism of successful fear extinction, the present psychotherapy-epigenetic study for we believe the first time investigated MAOA methylation changes during the course of exposure-based cognitive behavioral therapy (CBT) in PD. MAOA methylation was compared between N=28 female Caucasian PD patients (discovery sample) and N=28 age- and sex-matched healthy controls via direct sequencing of sodium bisulfite-treated DNA extracted from blood cells. MAOA methylation was furthermore analyzed at baseline (T0) and after a 6-week CBT (T1) in the discovery sample parallelized by a waiting time in healthy controls, as well as in an independent sample of female PD patients (N=20). Patients exhibited lower MAOA methylation than healthy controls (P<0.001), and baseline PD severity correlated negatively with MAOA methylation (P=0.01). In the discovery sample, MAOA methylation increased up to the level of healthy controls along with CBT response (number of panic attacks; T0-T1: +3.37±2.17%), while non-responders further decreased in methylation (-2.00±1.28%; P=0.001). In the replication sample, increases in MAOA methylation correlated with agoraphobic symptom reduction after CBT (P=0.02-0.03). The present results support previous evidence for MAOA hypomethylation as a PD risk marker and suggest reversibility of MAOA hypomethylation as a potential epigenetic correlate of response to CBT. The emerging notion of epigenetic signatures as a mechanism of action of psychotherapeutic interventions may promote epigenetic patterns as biomarkers of lasting extinction effects.
KW  - Adult
KW  - Case-Control Studies
KW  - Cognitive Therapy
KW  - DNA Methylation
KW  - Epigenesis
KW  - Genetic
KW  - Female
KW  - Humans
KW  - Monoamine Oxidase/genetics
KW  - Panic Disorder/genetics
KW  - Panic Disorder/therapy
KW  - Sequence Analysis
KW  - DNA
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164422
IS  - 6
ER  - 
TY  - JOUR
A1  - Hegi, M. E.
A1  - Ulrich, D.
A1  - Sagelsdorff, P.
A1  - Richter, C.
A1  - Lutz, Werner K.
T1  - No measurable increase  in thymidine glycol or 8-hydroxydeoxyguanosine in liver DNA of rats treated with nafenopin or choline-devoid low-methionine diet
N2  - Male rats were treated for 2 months with 1000 ppm nafenopin in the diet or for 4 or 7 days with a choline-devoid low-methionine diet. DNA was isolated from the livers and analyzed for the presence of cis-thymidine glycol-3'-phosphate (cis-dTGp) by 32P-postlabeling and for the Ievel of 8-hydroxy-deoxyguanosine (8-0H-dG) by electrochemical detection (ECD). In no DNA sample was the Ievel of cis-dTGp above the Iimit of detection of 1 modified thymidine per 106 nucleotides. With 8-0H-dG, a background Ievel of this modification of 20 8-0H-dG per 106 nucleosides was found in liver DNA of control rats, which was not affected by either treatment. It is postulated for thymidine glycol that a potential increase was below the Iimit of detection or was rapidly repaired in vivo and that the steady-state Ievel of endogenous 8-hydroxydeoxyguanosine appears not tobe influenced by the treatments chosen.
KW  - Toxikologie
KW  - Oxygen radical
KW  - DNA
KW  - Genotoxicity
KW  - Rat liver peroxisome
KW  - Choline deficiency
KW  - Thymidine glycol
KW  - 8-Hydroxy-deoxyguanosine
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-60790
ER  - 
TY  - RPRT
A1  - Schüssler, Ulrich
A1  - von Gehlen, K.
A1  - Matthes, S.
A1  - Okrusch, Martin
A1  - Richter, P.
A1  - Röhr, C.
T1  - Ultramafische Einschaltungen in Metabasiten der KTB-Vorbohrung
N2  - No abstract available
KW  - Kontinentales Tiefbohrprogramm
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-39206
ER  - 
TY  - JOUR
A1  - Straube, B.
A1  - Reif, A.
A1  - Richter, J.
A1  - Lueken, U.
A1  - Weber, H.
A1  - Arolt, V.
A1  - Jansen, A.
A1  - Zwanzger, P.
A1  - Domschke, K.
A1  - Pauli, P.
A1  - Konrad, C.
A1  - Gerlach, A. L.
A1  - Lang, T.
A1  - Fydrich, T.
A1  - Alpers, G. W.
A1  - Stroehle, A.
A1  - Wittmann, A.
A1  - Pfleiderer, B.
A1  - Wittchen, H.-U.
A1  - Hamm, A.
A1  - Deckert, J.
A1  - Kircher, T.
T1  - The functional - 1019C/G HTR1A polymorphism and mechanisms of fear
JF  - Translational Psychiatry
N2  - Serotonin receptor 1A gene (HTR1A) knockout mice show pronounced defensive behaviour and increased fear conditioning to ambiguous conditioned stimuli. Such behaviour is a hallmark of pathological human anxiety, as observed in panic disorder with agoraphobia (PD/AG). Thus, variations in HTR1A might contribute to neurophysiological differences within subgroups of PD/AG patients. Here, we tested this hypothesis by combining genetic with behavioural techniques and neuroimaging. In a clinical multicentre trial, patients with PD/AG received 12 sessions of manualized cognitive-behavioural therapy (CBT) and were genotyped for HTR1A rs6295. In four subsamples of this multicentre trial, exposure behaviour (n = 185), defensive reactivity measured using a behavioural avoidance test (BAT; before CBT: n = 245; after CBT: n = 171) and functional magnetic resonance imaging (fMRI) data during fear conditioning were acquired before and after CBT (n = 39). HTR1A risk genotype (GG) carriers more often escaped during the BAT before treatment. Exploratory fMRI results suggest increased activation of the amygdala in response to threat as well as safety cues before and after treatment in GG carriers. Furthermore, GG carriers demonstrated reduced effects of CBT on differential conditioning in regions including the bilateral insulae and the anterior cingulate cortex. Finally, risk genotype carriers demonstrated reduced self-initiated exposure behaviour to aversive situations. This study demonstrates the effect of HTR1A variation on defensive behaviour, amygdala activity, CBT-induced neural plasticity and normalization of defence behaviour in PD/AG. Our results, therefore, translate evidence from animal studies to humans and suggest a central role for HTR1A in differentiating subgroups of patients with anxiety disorders.
KW  - randomized-controlled trial
KW  - panic disorder
KW  - 5-HT1A receptor
KW  - defensive reactivity
KW  - major depression
KW  - cognitive-behavioral therapy
KW  - receptor gene polymorphism
KW  - C(-1019)G polymorphism
KW  - anxiety disorders
KW  - serotonin(1A) receptor
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-114369
SN  - 2158-3188
VL  - 4
ER  - 
TY  - JOUR
A1  - von Gehlen, K.
A1  - Matthes, S.
A1  - Okrusch, Martin
A1  - Richter, P.
A1  - Röhr, C.
A1  - Schüssler, Ulrich
T1  - Metapyroxenite in der KTB-Vorbohrung
N2  - No abstract available.
KW  - Kontinentales Tiefbohrprogramm der Bundesrepublik Deutschland
Y1  - 1990
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-87539
ER  - 
TY  - JOUR
A1  - Jiang, Yuxiang
A1  - Oron, Tal Ronnen
A1  - Clark, Wyatt T.
A1  - Bankapur, Asma R.
A1  - D'Andrea, Daniel
A1  - Lepore, Rosalba
A1  - Funk, Christopher S.
A1  - Kahanda, Indika
A1  - Verspoor, Karin M.
A1  - Ben-Hur, Asa
A1  - Koo, Da Chen Emily
A1  - Penfold-Brown, Duncan
A1  - Shasha, Dennis
A1  - Youngs, Noah
A1  - Bonneau, Richard
A1  - Lin, Alexandra
A1  - Sahraeian, Sayed M. E.
A1  - Martelli, Pier Luigi
A1  - Profiti, Giuseppe
A1  - Casadio, Rita
A1  - Cao, Renzhi
A1  - Zhong, Zhaolong
A1  - Cheng, Jianlin
A1  - Altenhoff, Adrian
A1  - Skunca, Nives
A1  - Dessimoz, Christophe
A1  - Dogan, Tunca
A1  - Hakala, Kai
A1  - Kaewphan, Suwisa
A1  - Mehryary, Farrokh
A1  - Salakoski, Tapio
A1  - Ginter, Filip
A1  - Fang, Hai
A1  - Smithers, Ben
A1  - Oates, Matt
A1  - Gough, Julian
A1  - Törönen, Petri
A1  - Koskinen, Patrik
A1  - Holm, Liisa
A1  - Chen, Ching-Tai
A1  - Hsu, Wen-Lian
A1  - Bryson, Kevin
A1  - Cozzetto, Domenico
A1  - Minneci, Federico
A1  - Jones, David T.
A1  - Chapman, Samuel
A1  - BKC, Dukka
A1  - Khan, Ishita K.
A1  - Kihara, Daisuke
A1  - Ofer, Dan
A1  - Rappoport, Nadav
A1  - Stern, Amos
A1  - Cibrian-Uhalte, Elena
A1  - Denny, Paul
A1  - Foulger, Rebecca E.
A1  - Hieta, Reija
A1  - Legge, Duncan
A1  - Lovering, Ruth C.
A1  - Magrane, Michele
A1  - Melidoni, Anna N.
A1  - Mutowo-Meullenet, Prudence
A1  - Pichler, Klemens
A1  - Shypitsyna, Aleksandra
A1  - Li, Biao
A1  - Zakeri, Pooya
A1  - ElShal, Sarah
A1  - Tranchevent, Léon-Charles
A1  - Das, Sayoni
A1  - Dawson, Natalie L.
A1  - Lee, David
A1  - Lees, Jonathan G.
A1  - Sillitoe, Ian
A1  - Bhat, Prajwal
A1  - Nepusz, Tamás
A1  - Romero, Alfonso E.
A1  - Sasidharan, Rajkumar
A1  - Yang, Haixuan
A1  - Paccanaro, Alberto
A1  - Gillis, Jesse
A1  - Sedeño-Cortés, Adriana E.
A1  - Pavlidis, Paul
A1  - Feng, Shou
A1  - Cejuela, Juan M.
A1  - Goldberg, Tatyana
A1  - Hamp, Tobias
A1  - Richter, Lothar
A1  - Salamov, Asaf
A1  - Gabaldon, Toni
A1  - Marcet-Houben, Marina
A1  - Supek, Fran
A1  - Gong, Qingtian
A1  - Ning, Wei
A1  - Zhou, Yuanpeng
A1  - Tian, Weidong
A1  - Falda, Marco
A1  - Fontana, Paolo
A1  - Lavezzo, Enrico
A1  - Toppo, Stefano
A1  - Ferrari, Carlo
A1  - Giollo, Manuel
A1  - Piovesan, Damiano
A1  - Tosatto, Silvio C. E.
A1  - del Pozo, Angela
A1  - Fernández, José M.
A1  - Maietta, Paolo
A1  - Valencia, Alfonso
A1  - Tress, Michael L.
A1  - Benso, Alfredo
A1  - Di Carlo, Stefano
A1  - Politano, Gianfranco
A1  - Savino, Alessandro
A1  - Rehman, Hafeez Ur
A1  - Re, Matteo
A1  - Mesiti, Marco
A1  - Valentini, Giorgio
A1  - Bargsten, Joachim W.
A1  - van Dijk, Aalt D. J.
A1  - Gemovic, Branislava
A1  - Glisic, Sanja
A1  - Perovic, Vladmir
A1  - Veljkovic, Veljko
A1  - Almeida-e-Silva, Danillo C.
A1  - Vencio, Ricardo Z. N.
A1  - Sharan, Malvika
A1  - Vogel, Jörg
A1  - Kansakar, Lakesh
A1  - Zhang, Shanshan
A1  - Vucetic, Slobodan
A1  - Wang, Zheng
A1  - Sternberg, Michael J. E.
A1  - Wass, Mark N.
A1  - Huntley, Rachael P.
A1  - Martin, Maria J.
A1  - O'Donovan, Claire
A1  - Robinson, Peter N.
A1  - Moreau, Yves
A1  - Tramontano, Anna
A1  - Babbitt, Patricia C.
A1  - Brenner, Steven E.
A1  - Linial, Michal
A1  - Orengo, Christine A.
A1  - Rost, Burkhard
A1  - Greene, Casey S.
A1  - Mooney, Sean D.
A1  - Friedberg, Iddo
A1  - Radivojac, Predrag
A1  - Veljkovic, Nevena
T1  - An expanded evaluation of protein function prediction methods shows an improvement in accuracy
JF  - Genome Biology
N2  - Background
A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging.

Results
We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2.

Conclusions
The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent.
KW  - Protein function prediction
KW  - Disease gene prioritization
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-166293
VL  - 17
IS  - 184
ER  - 
TY  - JOUR
A1  - Richter, K.
A1  - Mathes, V.
A1  - Fronius, M.
A1  - Althaus, M.
A1  - Hecker, A.
A1  - Krasteva-Christ, G.
A1  - Padberg, W.
A1  - Hone, A. J.
A1  - McIntosh, J. M.
A1  - Zakrzewicz, A.
A1  - Grau, V.
T1  - Phosphocholine - an agonist of metabotropic but not of ionotropic functions of α9-containing nicotinic acetylcholine receptors
JF  - Scientific Reports
N2  - We demonstrated previously that phosphocholine and phosphocholine-modified macromolecules efficiently inhibit ATP-dependent release of interleukin-1β from human and murine monocytes by a mechanism involving nicotinic acetylcholine receptors (nAChR). Interleukin-1β is a potent pro-inflammatory cytokine of innate immunity that plays pivotal roles in host defence. Control of interleukin-1β release is vital as excessively high systemic levels cause life threatening inflammatory diseases. In spite of its structural similarity to acetylcholine, there are no other reports on interactions of phosphocholine with nAChR. In this study, we demonstrate that phosphocholine inhibits ion-channel function of ATP receptor P2X7 in monocytic cells via nAChR containing α9 and α10 subunits. In stark contrast to choline, phosphocholine does not evoke ion current responses in Xenopus laevis oocytes, which heterologously express functional homomeric nAChR composed of α9 subunits or heteromeric receptors containing α9 and α10 subunits. Preincubation of these oocytes with phosphocholine, however, attenuated choline-induced ion current changes, suggesting that phosphocholine may act as a silent agonist. We conclude that phophocholine activates immuno-modulatory nAChR expressed by monocytes but does not stimulate canonical ionotropic receptor functions.
KW  - phosphocholine
KW  - interleukin-1β
KW  - nicotinic acetylcholine receptors
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167655
VL  - 6
IS  - 28660
ER  - 
TY  - JOUR
A1  - Sommer, Kim K.
A1  - Amr, Ali
A1  - Bavendiek, Udo
A1  - Beierle, Felix
A1  - Brunecker, Peter
A1  - Dathe, Henning
A1  - Eils, Jürgen
A1  - Ertl, Maximilian
A1  - Fette, Georg
A1  - Gietzelt, Matthias
A1  - Heidecker, Bettina
A1  - Hellenkamp, Kristian
A1  - Heuschmann, Peter
A1  - Hoos, Jennifer D. E.
A1  - Kesztyüs, Tibor
A1  - Kerwagen, Fabian
A1  - Kindermann, Aljoscha
A1  - Krefting, Dagmar
A1  - Landmesser, Ulf
A1  - Marschollek, Michael
A1  - Meder, Benjamin
A1  - Merzweiler, Angela
A1  - Prasser, Fabian
A1  - Pryss, Rüdiger
A1  - Richter, Jendrik
A1  - Schneider, Philipp
A1  - Störk, Stefan
A1  - Dieterich, Christoph
T1  - Structured, harmonized, and interoperable integration of clinical routine data to compute heart failure risk scores
JF  - Life
N2  - Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care.
KW  - medical informatics initiative
KW  - HiGHmed
KW  - medical data integration center
KW  - clinical routine data
KW  - heart failure
KW  - risk prediction scores
KW  - semantic interoperability
KW  - openEHR
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275239
SN  - 2075-1729
VL  - 12
IS  - 5
ER  - 
TY  - JOUR
A1  - Zaho, Huaying
A1  - Ghirlando, Rodolfo
A1  - Alfonso, Carlos
A1  - Arisaka, Fumio
A1  - Attali, Ilan
A1  - Bain, David L.
A1  - Bakhtina, Marina M.
A1  - Becker, Donald F.
A1  - Bedwell, Gregory J.
A1  - Bekdemir, Ahmet
A1  - Besong, Tabot M. D.
A1  - Birck, Catherine
A1  - Brautigam, Chad A.
A1  - Brennerman, William
A1  - Byron, Olwyn
A1  - Bzowska, Agnieszka
A1  - Chaires, Jonathan B.
A1  - Chaton, Catherine T.
A1  - Coelfen, Helmbut
A1  - Connaghan, Keith D.
A1  - Crowley, Kimberly A.
A1  - Curth, Ute
A1  - Daviter, Tina
A1  - Dean, William L.
A1  - Diez, Ana I.
A1  - Ebel, Christine
A1  - Eckert, Debra M.
A1  - Eisele, Leslie E.
A1  - Eisenstein, Edward
A1  - England, Patrick
A1  - Escalante, Carlos
A1  - Fagan, Jeffrey A.
A1  - Fairman, Robert
A1  - Finn, Ron M.
A1  - Fischle, Wolfgang
A1  - Garcia de la Torre, Jose
A1  - Gor, Jayesh
A1  - Gustafsson, Henning
A1  - Hall, Damien
A1  - Harding, Stephen E.
A1  - Hernandez Cifre, Jose G.
A1  - Herr, Andrew B.
A1  - Howell, Elizabeth E.
A1  - Isaac, Richard S.
A1  - Jao, Shu-Chuan
A1  - Jose, Davis
A1  - Kim, Soon-Jong
A1  - Kokona, Bashkim
A1  - Kornblatt, Jack A.
A1  - Kosek, Dalibor
A1  - Krayukhina, Elena
A1  - Krzizike, Daniel
A1  - Kusznir, Eric A.
A1  - Kwon, Hyewon
A1  - Larson, Adam
A1  - Laue, Thomas M.
A1  - Le Roy, Aline
A1  - Leech, Andrew P.
A1  - Lilie, Hauke
A1  - Luger, Karolin
A1  - Luque-Ortega, Juan R.
A1  - Ma, Jia
A1  - May, Carrie A.
A1  - Maynard, Ernest L.
A1  - Modrak-Wojcik, Anna
A1  - Mok, Yee-Foong
A1  - Mücke, Norbert
A1  - Nagel-Steger, Luitgard
A1  - Narlikar, Geeta J.
A1  - Noda, Masanori
A1  - Nourse, Amanda
A1  - Obsil, Thomas
A1  - Park, Chad K
A1  - Park, Jin-Ku
A1  - Pawelek, Peter D.
A1  - Perdue, Erby E.
A1  - Perkins, Stephen J.
A1  - Perugini, Matthew A.
A1  - Peterson, Craig L.
A1  - Peverelli, Martin G.
A1  - Piszczek, Grzegorz
A1  - Prag, Gali
A1  - Prevelige, Peter E.
A1  - Raynal, Bertrand D. E.
A1  - Rezabkova, Lenka
A1  - Richter, Klaus
A1  - Ringel, Alison E.
A1  - Rosenberg, Rose
A1  - Rowe, Arthur J.
A1  - Rufer, Arne C.
A1  - Scott, David J.
A1  - Seravalli, Javier G.
A1  - Solovyova, Alexandra S.
A1  - Song, Renjie
A1  - Staunton, David
A1  - Stoddard, Caitlin
A1  - Stott, Katherine
A1  - Strauss, Holder M.
A1  - Streicher, Werner W.
A1  - Sumida, John P.
A1  - Swygert, Sarah G.
A1  - Szczepanowski, Roman H.
A1  - Tessmer, Ingrid
A1  - Toth, Ronald T.
A1  - Tripathy, Ashutosh
A1  - Uchiyama, Susumu
A1  - Uebel, Stephan F. W.
A1  - Unzai, Satoru
A1  - Gruber, Anna Vitlin
A1  - von Hippel, Peter H.
A1  - Wandrey, Christine
A1  - Wang, Szu-Huan
A1  - Weitzel, Steven E
A1  - Wielgus-Kutrowska, Beata
A1  - Wolberger, Cynthia
A1  - Wolff, Martin
A1  - Wright, Edward
A1  - Wu, Yu-Sung
A1  - Wubben, Jacinta M.
A1  - Schuck, Peter
T1  - A Multilaboratory Comparison of Calibration Accuracy and the Performance of External References in Analytical Ultracentrifugation
JF  - PLoS ONE
N2  - Analytical ultracentrifugation (AUC) is a first principles based method to determine absolute sedimentation coefficients and buoyant molar masses of macromolecules and their complexes, reporting on their size and shape in free solution. The purpose of this multi-laboratory study was to establish the precision and accuracy of basic data dimensions in AUC and validate previously proposed calibration techniques. Three kits of AUC cell assemblies containing radial and temperature calibration tools and a bovine serum albumin (BSA) reference sample were shared among 67 laboratories, generating 129 comprehensive data sets. These allowed for an assessment of many parameters of instrument performance, including accuracy of the reported scan time after the start of centrifugation, the accuracy of the temperature calibration, and the accuracy of the radial magnification. The range of sedimentation coefficients obtained for BSA monomer in different instruments and using different optical systems was from 3.655 S to 4.949 S, with a mean and standard deviation of (4.304\(\pm\)0.188) S (4.4%). After the combined application of correction factors derived from the external calibration references for elapsed time, scan velocity, temperature, and radial magnification, the range of s-values was reduced 7-fold with a mean of 4.325 S and a 6-fold reduced standard deviation of \(\pm\)0.030 S (0.7%). In addition, the large data set provided an opportunity to determine the instrument-to-instrument variation of the absolute radial positions reported in the scan files, the precision of photometric or refractometric signal magnitudes, and the precision of the calculated apparent molar mass of BSA monomer and the fraction of BSA dimers. These results highlight the necessity and effectiveness of independent calibration of basic AUC data dimensions for reliable quantitative studies.
KW  - fluorescence-detected sedimentation
KW  - size exclusion chromatography
KW  - field flow fractionation
KW  - spinco ultracentrifuge
KW  - aggregation
KW  - bead models
KW  - velocity
KW  - hydrodynamics
KW  - biopharmaceuticals
KW  - proteins
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151903
VL  - 10
IS  - 5
ER  -