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Buxbaum, Joseph D. ; Bolshakova, Nadia ; Brownfeld, Jessica M. ; Anney, Richard J. L. ; Bender, Patrick ; Bernier, Raphael ; Cook, Edwin H. ; Coon, Hilary ; Cuccaro, Michael L. ; Freitag, Christine M. ; Hallmayer, Joachim ; Geschwind, Daniel H. ; Klauck, Sabine M. ; Nurnberger, John I. ; Oliveira, Guiomar ; Pinto, Dalila ; Poustka, Fritz ; Scherer, Stephen W. ; Shih, Andy ; Sutcliffe, James S. ; Szatmari, Peter ; Vicente, Astrid M. ; Vieland, Veronica J. ; Gallagher, Louise
Background: There is an urgent need for expanding and enhancing autism spectrum disorder (ASD) samples, in order to better understand causes of ASD.
Methods: In a unique public-private partnership, 13 sites with extensive experience in both the assessment and diagnosis of ASD embarked on an ambitious, 2-year program to collect samples for genetic and phenotypic research and begin analyses on these samples. The program was called The Autism Simplex Collection (TASC). TASC sample collection began in 2008 and was completed in 2010, and included nine sites from North America and four sites from Western Europe, as well as a centralized Data Coordinating Center.
Results: Over 1,700 trios are part of this collection, with DNA from transformed cells now available through the National Institute of Mental Health (NIMH). Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule-Generic (ADOS-G) measures are available for all probands, as are standardized IQ measures, Vineland Adaptive Behavioral Scales (VABS), the Social Responsiveness Scale (SRS), Peabody Picture Vocabulary Test (PPVT), and physical measures (height, weight, and head circumference). At almost every site, additional phenotypic measures were collected, including the Broad Autism Phenotype Questionnaire (BAPQ) and Repetitive Behavior Scale-Revised (RBS-R), as well as the non-word repetition scale, Communication Checklist (Children's or Adult), and Aberrant Behavior Checklist (ABC). Moreover, for nearly 1,000 trios, the Autism Genome Project Consortium (AGP) has carried out Illumina 1 M SNP genotyping and called copy number variation (CNV) in the samples, with data being made available through the National Institutes of Health (NIH). Whole exome sequencing (WES) has been carried out in over 500 probands, together with ancestry matched controls, and this data is also available through the NIH. Additional WES is being carried out by the Autism Sequencing Consortium (ASC), where the focus is on sequencing complete trios. ASC sequencing for the first 1,000 samples (all from whole-blood DNA) is complete and data will be released in 2014. Data is being made available through NIH databases (database of Genotypes and Phenotypes (dbGaP) and National Database for Autism Research (NDAR)) with DNA released in Dist 11.0. Primary funding for the collection, genotyping, sequencing and distribution of TASC samples was provided by Autism Speaks and the NIH, including the National Institute of Mental Health (NIMH) and the National Human Genetics Research Institute (NHGRI).
Conclusions: TASC represents an important sample set that leverages expert sites. Similar approaches, leveraging expert sites and ongoing studies, represent an important path towards further enhancing available ASD samples.
Zepf, Florian Daniel ; Rao, Pradeep ; Runions, Kevin ; Stewart, Richard M. ; Moore, Julia K. ; Wong, Janice W. Y. ; Linden, Maike ; Sungurtekin, Idil ; Glass, Franziska ; Gut, Linda ; Peetz, Dirk ; Hintereder, Gudrun ; Schaab, Michael ; Poustka, Fritz ; Wöckel, Lars
Background: Research has implicated that changes in zinc (Zn) metabolism may be associated with the biological underpinnings of eating disorders, in particular anorexia nervosa. However, to date research on the role of Zn in patients with bulimia nervosa (BN) is scarce.
Objective: We aimed to explore serum Zn concentrations in young patients with BN, with a focus on the stage of the disorder, comparing acutely ill and recovered patients with BN with healthy controls.
Methods: Serum Zn concentrations were obtained from healthy controls and from acutely ill and remitted young patients with BN. Mean duration of remission was 4.0±3.5 years.
Results: Remitted patients showed elevated serum Zn concentrations when compared to controls (Cohen’s d=2.022), but concentrations were still in the normal range. Acutely ill patients also had higher serum Zn levels when compared to controls (all values still being within the reference range, Cohen’s d=0.882). There was no difference between acutely ill and remitted patients with BN in serum Zn concentrations. Of note, remitted patients had a significantly higher body weight when compared to the other two groups. Overall, there were no significant differences in dietary preferences with regard to Zn containing foods between the groups.
Conclusion: The present study provides preliminary evidence that the underlying factors for changes in Zn serum concentrations in young patients with BN do not vary with regard to the stage of illness (acute versus remitted BN). Further prospective research is needed in order to disentangle the possible interplay between serum Zn status and bulimic eating behaviors.
Voskamp, Alke ; Fritz, Susanne A. ; Köcke, Anna Valerie ; Biber, Matthias ; Nogueira-Brockmeyer, Timo ; Bertzky, Bastian ; Forrest, Matthew ; Goldstein, Allie ; Henderson, Scott ; Hickler, Thomas ; Hof, Christian ; Kastner, Thomas ; Lang, Stefanie ; Manning, Peter ; Mascia, Michael B. ; McFadden, Ian R. ; Niamir, Aidin ; Noon, Monica ; O’Donell, Brian ; Opel, Mark ; Schwede, Georg ; West, Peyton ; Schenck, Christof ; Böhning-Gaese, Katrin
The establishment and maintenance of protected areas (PAs) is viewed as a key action in delivering post-2020 biodiversity targets. PAs often need to meet multiple objectives, ranging from biodiversity protection to ecosystem service provision and climate change mitigation, but available land and conservation funding is limited. Therefore, optimizing resources by selecting the most beneficial PAs is vital. Here, we advocate for a flexible and transparent approach to selecting protected areas based on multiple objectives, and illustrate this with a decision support tool on a global scale. The tool allows weighting and prioritization of different conservation objectives according to user-specified preferences, as well as real-time comparison of the selected areas that result from such different priorities. We apply the tool across 1347 terrestrial PAs and highlight frequent trade-offs among different objectives, e.g., between species protection and ecosystem integrity. Outputs indicate that decision makers frequently face trade-offs among conflicting objectives. Nevertheless, we show that transparent decision-support tools can reveal synergies and trade-offs associated with PA selection, thereby helping to illuminate and resolve land-use conflicts embedded in divergent societal and political demands and values.
Ablikim, Medina ; Achasov, Mikhail N. ; Adlarson, Patrik ; Ahmed, Samer ; Albrecht, Michael ; Aliberti, Riccardo ; Amoroso, Antonio ; An, M. R. ; An, Qi ; Bai, X. H. ; Bai, Yu ; Bakina, Olga ; Baldini Ferroli, Rinaldo ; Balossino, Ilaria ; Ban, Yong ; Begzsuren, Khurelbaatar ; Berger, Niklaus ; Bertani, Monica ; Bettoni, Diego ; Bianchi, Fabrizio ; Bloms, Johannes ; Bortone, Alberto ; Boyko, Igor R. ; Briere, Roy A. ; Cai, Hao ; Cai, Xiao ; Calcaterra, Alessandro ; Cao, G. F. ; Cao, N. ; Çetin, Serkant Ali ; Chang, Jinfan ; Chang, W. L. ; Chelkov, Gueorgui A. ; Chen, D. Y. ; Chen, G. ; Chen, Hesheng ; Chen, M. L. ; Chen, S. J. ; Chen, X. R. ; Chen, Yuanbo ; Chen, Z. J. ; Cheng, W. S. ; Cibinetto, Gianluigi ; Cossio, Fabio ; Cui, X. F. ; Dai, Hongliang ; Dai, Xinchen ; Dbeyssi, Alaa ; Boer, Remco E. de ; Dedovich, Dmitri V. ; Deng, Ziyan ; Denig, Achim ; Denysenko, Igor ; Destefanis, Marco Giovanni Maria ; De Mori, Francesca ; Ding, Yanchun ; Dong, C. ; Dong, J. ; Dong, Liaoyuan ; Dong, Mingyi ; Dong, X. ; Du, Shuxian ; Fan, Y. L. ; Fang, J. ; Fang, Shuangshi ; Fang, Y. ; Farinelli, Riccardo ; Fava, Luciano ; Feldbauer, Florian ; Felici, Giulietto ; Feng, C. Q. ; Feng, J. H. ; Fritsch, Miriam ; Fu, Chengdong ; Gao, Y. ; Gao, Y. ; Gao, Y. ; Gao, Y. G. ; Garzia, Isabella ; Ge, P. T. ; Geng, C. ; Gersabeck, Evelina ; Gilman, A. ; Götzen, Klaus ; Gong, L. ; Gong, Wenxuan ; Gradl, Wolfgang ; Greco, M. ; Gu, L. M. ; Gu, Minhao ; Gu, S. ; Gu, Y. T. ; Guan, C. Y. ; Guo, Aiqiang ; Guo, L. B. ; Guo, R. P. ; Guo, Yuping ; Guskov, Alexey ; Han, T. T. ; Han, W. Y. ; Hao, Xiqing ; Harris, Frederick Allan ; He, K. L. ; Heinsius, Fritz-Herbert ; Heinz, C. H. ; Held, T. ; Heng, Yuekun ; Herold, Christoph ; Himmelreich, Mathilde ; Holtmann, Tobias ; Hou, G. Y. ; Hou, Y. R. ; Hou, Zhilong ; Hu, Haiming ; Hu, J. F. ; Hu, T. ; Hu, Y. ; Huang, G. S. ; Huang, L. Q. ; Huang, X. T. ; Huang, Y. P. ; Huang, Z. ; Hussain, Tahir ; Hüsken, Nils ; Ikegami Andersson, Walter ; Imoehl, William ; Irshad, M. ; Jaeger, S. ; Janchiv, S. ; Ji, Quan ; Ji, Qingping ; Ji, X. B. ; Ji, X. L. ; Ji, Y. Y. ; Jiang, H. B. ; Jiang, Xiaoshan ; Jiao, J. B. ; Jiao, Z. ; Jin, Shan ; Jin, Y. ; Jing, M. Q. ; Johansson, Tord ; Kalantar-Nayestanaki, Nasser ; Kang, X. S. ; Kappert, Rosa ; Kavatsyuk, Myroslav O. ; Ke, B. C. ; Keshk, I. K. ; Khoukaz, Alfons ; Kiese, P. ; Kiuchi, R. ; Kliemt, Ralf ; Koch, L. ; Kolcu, Onur Bugra ; Kopf, Bertram ; Kuemmel, M. ; Küßner, Meike ; Kupsc, Andrzej ; Kurth, M. G. ; Kühn, Wolfgang ; Lane, John Jake ; Lange, Jens Sören ; Larin, Paul ; Lavania, Anita ; Lavezzi, Lia ; Lei, Z. H. ; Leithoff, Hans Heinrich ; Lellmann, Max ; Lenz, Thomas ; Li, C. ; Li, C. H. ; Li, Cheng ; Li, D. M. ; Li, F. ; Li, G. ; Li, H. ; Li, H. ; Li, Haibo ; Li, H. J. ; Li, J. L. ; Li, J. Q. ; Li, J. S. ; Li, Ke ; Li, L. K. ; Li, Lei ; Li, P. R. ; Li, S. Y. ; Li, Weidong ; Li, Weiguo ; Li, X. H. ; Li, Xing Long ; Li, Xiaoyu ; Li, Z. Y. ; Liang, H. ; Liang, H. ; Liang, H. ; Liang, Y. F. ; Liang, Y. T. ; Liao, G. R. ; Liao, L. Z. ; Libby, J. ; Lin, C. X. ; Liu, B. J. ; Liu, C. X. ; Liu, D. ; Liu, Fu-Hu ; Liu, Fang ; Liu, Feng ; Liu, H. B. ; Liu, H. M. ; Liu, Huanhuan ; Liu, Huihui ; Liu, J. B. ; Liu, J. L. ; Liu, J. Y. ; Liu, K. ; Liu, K. Y. ; Liu, L. ; Liu, M. H. ; Liu, P. L. ; Liu, Q. ; Liu, Q. ; Liu, S. B. ; Liu, Shuai ; Liu, T. ; Liu, W. M. ; Liu, X. ; Liu, Y. ; Liu, Y. B. ; Liu, Zhen-An ; Liu, Z. Q. ; Lou, Xinchou ; Lu, F. X. ; Lu, H. J. ; Lu, J. D. ; Lu, Junguang ; Lu, X. L. ; Lu, Y. ; Lu, Yunpeng ; Luo, Chenglin ; Luo, M. X. ; Luo, P. W. ; Luo, Tao ; Luo, X. L. ; Lyu, Xiao-Rui ; Ma, Fengcai ; Ma, Hailong ; Ma, Lianliang ; Ma, M. M. ; Ma, Qiumei ; Ma, R. Q. ; Ma, R. T. ; Ma, X. X. ; Ma, Xiaoyan ; Maas, Frank E. ; Maggiora, Marco ; Maldaner, Stephan ; Malde, Sneha ; Malik, Qadeer Afzal ; Mangoni, Alessio ; Mao, Yajun ; Mao, Zepu ; Marcello, Simonetta ; Meng, Z. X. ; Messchendorp, Johannes Gerhardus ; Mezzadri, Giulio ; Min, T. J. ; Mitchell, Ryan Edward ; Mo, Xiaohu ; Mo, Y. J. ; Muchnoi, Nikolai Yu. ; Muramatsu, Hajime ; Nakhoul, Simon ; Nefedov, Yury ; Nerling, Frank ; Nikolaev, Ivan Borisovich ; Ning, Z. ; Nisar, Shabana ; Olsen, Stephen L. ; Ouyang, Qun ; Pacetti, Simone ; Pan, Xiang ; Pan, Y. ; Pathak, A. ; Pathak, A. ; Patteri, Piero ; Pelizäus, Marc ; Peng, H. P. ; Peters, Klaus ; Pettersson, J. ; Ping, J. L. ; Ping, R. G. ; Poling, Ronald ; Prasad, Vindhyawasini ; Qi, H. ; Qi, H. R. ; Qi, K. H. ; Qi, Ming ; Qi, T. Y. ; Qian, S. ; Qian, W. B. ; Qian, Z. ; Qiao, Congfeng ; Qin, L. Q. ; Qin, X. P. ; Qin, X. S. ; Qin, Zhonghua ; Qiu, Jinfa ; Qu, S. Q. ; Rashid, K. H. ; Ravindran, Krishnakumar ; Redmer, Christoph Florian ; Rivetti, Angelo ; Rodin, Viktor ; Da Rocha Rolo, Manuel Dionisio ; Rong, Gang ; Rosner, Christoph ; Rump, Marcel Andre ; Sang, H. S. ; Sarantsev, Andrei V. ; Schelhaas, Yasemin ; Schnier, Claudius ; Schönning, Karin ; Scodeggio, Marco ; Shan, D. C. ; Shan, Wei ; Shan, Xinyu ; Shangguan, J. F. ; Shao, M. ; Shen, C. P. ; Shen, H. F. ; Shen, P. X. ; Shen, X. Y. ; Shi, H. C. ; Shi, R. S. ; Shi, X. ; Shi, X. D. ; Song, J. J. ; Song, W. M. ; Song, Y. X. ; Sosio, Stefano ; Spataro, Stefano ; Su, K. X. ; Su, P. P. ; Sui, F. F. ; Sun, Gongxing ; Sun, H. K. ; Sun, J. F. ; Sun, L. ; Sun, S. S. ; Sun, T. ; Sun, W. Y. ; Sun, W. Y. ; Sun, X. ; Sun, Y. J. ; Sun, Y. K. ; Sun, Y. Z. ; Sun, Z. T. ; Tan, Y. H. ; Tan, Y. X. ; Tang, C. J. ; Tang, G. Y. ; Tang, J. ; Teng, J. X. ; Thoren, Viktor ; Tian, W. H. ; Tian, Y. T. ; Uman, Ismail ; Wang, B. ; Wang, C. W. ; Wang, D. Y. ; Wang, H. J. ; Wang, H. P. ; Wang, K. ; Wang, L. L. ; Wang, M. ; Wang, M. Z. ; Wang, Meng ; Wang, W. ; Wang, W. H. ; Wang, W. P. ; Wang, X. ; Wang, X. F. ; Wang, X. L. ; Wang, Y. ; Wang, Y. ; Wang, Y. D. ; Wang, Y. F. ; Wang, Y. Q. ; Wang, Y. Y. ; Wang, Z. ; Wang, Zongyuan ; Wang, Ziyi ; Wang, Zongyuan ; Wei, D. H. ; Weidner, Frederik ; Wen, Shuopin ; White, D. J. ; Wiedner, Ulrich ; Wilkinson, Guy ; Wolke, Magnus ; Wollenberg, Leonard ; Wu, J. F. ; Wu, L. H. ; Wu, L. J. ; Wu, X. ; Wu, Z. ; Xia, Lei ; Xiao, H. ; Xiao, S. Y. ; Xiao, Zhenjun ; Xie, X. H. ; Xie, Y. G. ; Xie, Y. H. ; Xing, T. Y. ; Xu, Guofa ; Xu, Q. J. ; Xu, W. ; Xu, Xinping ; Xu, Y. C. ; Yan, F. ; Yan, L. ; Yan, W. B. ; Yan, W. C. ; Yan, Xu ; Yang, H. J. ; Yang, Hongxun ; Yang, L. ; Yang, S. L. ; Yang, Yongxu ; Yang, Yifan ; Yang, Zhi ; Ye, M. ; Ye, Minghan ; Yin, J. H. ; You, Z. Y. ; Yu, Boxiang ; Yu, C. X. ; Yu, G. ; Yu, J. S. ; Yu, T. ; Yuan, Chang-Zheng ; Yuan, L. ; Yuan, X. Q. ; Yuan, Y. ; Yuan, Z. Y. ; Yue, C. X. ; Zafar, A. A. ; Zeng, X. Zeng ; Zeng, Y. ; Zhang, A. Q. ; Zhang, B. X. ; Zhang, Guangyi ; Zhang, Haitao ; Zhang, H. H. ; Zhang, H. H. ; Zhang, Hongyu ; Zhang, J. J. ; Zhang, J. L. ; Zhang, J. Q. ; Zhang, J. W. ; Zhang, Jianyong ; Zhang, J. Z. ; Zhang, Jianyu ; Zhang, Jiawei ; Zhang, L. M. ; Zhang, L. Q. ; Zhang, Lei ; Zhang, S. ; Zhang, S. F. ; Zhang, Shulei ; Zhang, X. D. ; Zhang, X. Y. ; Zhang, Y. ; Zhang, Y. T. ; Zhang, Y. H. ; Zhang, Yan ; Zhang, Yao ; Zhang, Z. H. ; Zhang, Z. Y. ; Zhao, G. ; Zhao, J. ; Zhao, J. Y. ; Zhao, J. Z. ; Zhao, Lei ; Zhao, Ling ; Zhao, Ming-Gang ; Zhao, Q. ; Zhao, Shujun ; Zhao, Yubin ; Zhao, Y. X. ; Zhao, Zhengguo ; Zhemchugov, Alexey ; Zheng, B. ; Zheng, Jianping ; Zheng, Y. ; Zheng, Y. H. ; Zhong, B. ; Zhong, C. ; Zhou, L. P. ; Zhou, Q. ; Zhou, X. ; Zhou, X. K. ; Zhou, X. R. ; Zhou, X. Y. ; Zhu, A. N. ; Zhu, Jianhui ; Zhu, K. ; Zhu, Kejun ; Zhu, S. H. ; Zhu, T. J. ; Zhu, W. J. ; Zhu, W. J. ; Zhu, Y. C. ; Zhu, Zian ; Zou, B. S. ; Zou, Jiaheng
By analyzing 6.32 fb − 1 of e+ e− annihilation data collected at the center-of-mass energies between 4.178 and 4.226 GeV with the BESIII detector, we determine the branching fraction of the leptonic decay D + s → τ + ντ, with τ+ → π + π0¯ντ, to be B D + s → τ + ν τ = (5.29 ± 0.25 stat ± 0.20 syst) %. We estimate the product of the Cabibbo-Kobayashi-Maskawa matrix element |Vcs|and the D + s decay constant f D + s to be f D + s|Vcs| = (244.8 ± 5.8 stat ± 4.8syst) MeV, using the known values of the τ + and D + s masses as well as the D + s lifetime, together with our branching fraction measurement. Combining the value of |Vcs| obtained from a global fit in the standard model and f D + s from lattice quantum chromodynamics, we obtain f D + s = (251.6 ± 5.9 stat ± 4.9syst) MeV and |Vcs| = 0.980 ± 0.023 stat ± 0.019 syst. Using the branching fraction of B D + s → μ + νμ = (5.35±0.21)×10−3, we obtain the ratio of the branching fractions B D + s → τ + ντ/B D +s → μ+νμ = 9.89±0.71, which is consistent with the standard model prediction of lepton flavor universality.
Lawes, Michael J. ; Fisher, Diana O. ; Johnson, Chris N. ; Blomberg, Simon P. ; Frank, Anke S. K. ; Fritz, Susanne A. ; McCallum, Hamish ; Van Der Wal, Jeremy ; Abbott, Brett N. ; Legge, Sarah ; Letnic, Mike ; Thomas, Colette R. ; Thurgate, Nikki ; Fisher, Alaric ; Gordon, Iain J. ; Kutt, Alex
Australia has experienced dramatic declines and extinctions of its native rodent species over the last 200 years, particularly in southern Australia. In the tropical savanna of northern Australia significant declines have occurred only in recent decades. The later onset of these declines suggests that the causes may differ from earlier declines in the south. We examine potential regional effects (northern versus southern Australia) on biological and ecological correlates of range decline in Australian rodents. We demonstrate that rodent declines have been greater in the south than in the tropical north, are strongly influenced by phylogeny, and are consistently greater for species inhabiting relatively open or sparsely vegetated habitat. Unlike in marsupials, where some species have much larger body size than rodents, body mass was not an important predictor of decline in rodents. All Australian rodent species are within the prey-size range of cats (throughout the continent) and red foxes (in the south). Contrary to the hypothesis that mammal declines are related directly to ecosystem productivity (annual rainfall), our results are consistent with the hypothesis that disturbances such as fire and grazing, which occur in non-rainforest habitats and remove cover used by rodents for shelter, nesting and foraging, increase predation risk. We agree with calls to introduce conservation management that limits the size and intensity of fires, increases fire patchiness and reduces grazing impacts at ecological scales appropriate for rodents. Controlling feral predators, even creating predator-free reserves in relatively sparsely-vegetated habitats, is urgently required to ensure the survival of rodent species, particularly in northern Australia where declines are not yet as severe as those in the south.
Wolking, Stefan ; Schulz, Herbert ; Nies, Anne T ; McCormack, Mark ; Schäffeler, Elke ; Auce, Pauls ; Avbersek, Andreja ; Becker, Felicitas ; Klein, Karl Martin ; Krenn, Martin ; Møller, Rikke S. ; Nikanorova, Marina ; Weckhuysen, Sarah ; Cavalleri, Gianpiero L. ; Delanty, Norman ; Depondt, Chantal ; Johnson, Michael R. ; Koeleman, Bobby P. C. ; Kunz, Wolfram S. ; Marson, Anthony G. ; Sander, Josemir W. ; Sills, Graeme J. ; Striano, Pasquale ; Zara, Federico J. ; Zimprich, Fritz ; Weber, Yvonne G. ; Krause, Roland ; Sisodiya, Sanjay M. ; Schwab, Matthias ; Sander, Thomas ; Lerche, Holger
Aim: Pharmacoresistance is a major burden in epilepsy treatment. We aimed to identify genetic biomarkers in response to specific antiepileptic drugs (AEDs) in genetic generalized epilepsies (GGE). Materials & methods: We conducted a genome-wide association study (GWAS) of 3.3 million autosomal SNPs in 893 European subjects with GGE – responsive or nonresponsive to lamotrigine, levetiracetam and valproic acid. Results: Our GWAS of AED response revealed suggestive evidence for association at 29 genomic loci (p <10-5) but no significant association reflecting its limited power. The suggestive associations highlight candidate genes that are implicated in epileptogenesis and neurodevelopment. Conclusion: This first GWAS of AED response in GGE provides a comprehensive reference of SNP associations for hypothesis-driven candidate gene analyses in upcoming pharmacogenetic studies.
Protein signatures of oxidative stress response in a patient specific cell line model for autism
(2014)
Geburtig-Chiocchetti, Andreas ; Haslinger, Denise ; Boesch, Maximilian ; Karl, Thomas ; Wiemann, Stefan ; Freitag, Christine M. ; Poustka, Fritz ; Scheibe, Burghardt ; Bauer, Johann W. ; Hintner, Helmut ; Breitenbach, Michael ; Kellermann, Josef ; Lottspeich, Friedrich ; Klauck, Sabine M. ; Breitenbach-Koller, Lore
Background: Known genetic variants can account for 10% to 20% of all cases with autism spectrum disorders (ASD). Overlapping cellular pathomechanisms common to neurons of the central nervous system (CNS) and in tissues of peripheral organs, such as immune dysregulation, oxidative stress and dysfunctions in mitochondrial and protein synthesis metabolism, were suggested to support the wide spectrum of ASD on unifying disease phenotype. Here, we studied in patient-derived lymphoblastoid cell lines (LCLs) how an ASD-specific mutation in ribosomal protein RPL10 (RPL10[H213Q]) generates a distinct protein signature. We compared the RPL10[H213Q] expression pattern to expression patterns derived from unrelated ASD patients without RPL10[H213Q] mutation. In addition, a yeast rpl10 deficiency model served in a proof-of-principle study to test for alterations in protein patterns in response to oxidative stress.
Methods: Protein extracts of LCLs from patients, relatives and controls, as well as diploid yeast cells hemizygous for rpl10, were subjected to two-dimensional gel electrophoresis and differentially regulated spots were identified by mass spectrometry. Subsequently, Gene Ontology database (GO)-term enrichment and network analysis was performed to map the identified proteins into cellular pathways.
Results: The protein signature generated by RPL10[H213Q] is a functionally related subset of the ASD-specific protein signature, sharing redox-sensitive elements in energy-, protein- and redox-metabolism. In yeast, rpl10 deficiency generates a specific protein signature, harboring components of pathways identified in both the RPL10[H213Q] subjects' and the ASD patients' set. Importantly, the rpl10 deficiency signature is a subset of the signature resulting from response of wild-type yeast to oxidative stress.
Conclusions: Redox-sensitive protein signatures mapping into cellular pathways with pathophysiology in ASD have been identified in both LCLs carrying the ASD-specific mutation RPL10[H213Q] and LCLs from ASD patients without this mutation. At pathway levels, this redox-sensitive protein signature has also been identified in a yeast rpl10 deficiency and an oxidative stress model. These observations point to a common molecular pathomechanism in ASD, characterized in our study by dysregulation of redox balance. Importantly, this can be triggered by the known ASD-RPL10[H213Q] mutation or by yet unknown mutations of the ASD cohort that act upstream of RPL10 in differential expression of redox-sensitive proteins.
Ablikim, Medina ; Achasov, Mikhail N. ; Adlarson, Patrik ; Ahmed, Samer ; Albrecht, Malte ; Amoroso, Antonio ; An, Qi ; Anita ; Bai, Yu ; Bakina, Olga ; Baldini Ferroli, Rinaldo ; Balossino, Ilaria ; Ban, Yong ; Begzsuren, Khurelbaatar ; Bennett, Jake V. ; Berger, Niklaus ; Bertani, Monica ; Bettoni, Diego ; Bianchi, Fabrizio ; Biernat, Jacek ; Bloms, Johannes ; Bortone, Alberto ; Boyko, Igor R. ; Briere, Roy A. ; Cai, Hao ; Cai, Xiao ; Calcaterra, Alessandro ; Cao, G. F. ; Cao, N. ; Çetin, Serkant Ali ; Chang, Jinfan ; Chang, W. L. ; Chelkov, Gueorgui A. ; Chen, D. Y. ; Chen, G. ; Chen, Hesheng ; Chen, M. L. ; Chen, S. J. ; Chen, X. R. ; Chen, Yuanbo ; Cheng, W. ; Cibinetto, Gianluigi ; Cossio, Fabio ; Cui, X. F. ; Dai, Hongliang ; Dai, J. P. ; Dai, Xinchen ; Dbeyssi, Alaa ; de Boer, R. B. ; Dedovich, Dmitri V. ; Deng, Ziyan ; Denig, Achim ; Denysenko, Igor ; Destefanis, Marco Giovanni Maria ; De Mori, Francesca ; Ding, Yanchun ; Dong, C. ; Dong, J. ; Dong, Liaoyuan ; Dong, Mingyi ; Du, Shuxian ; Fang, J. ; Fang, Shuangshi ; Fang, Y. ; Farinelli, Riccardo ; Fava, Luciano ; Feldbauer, Florian ; Felici, Giulietto ; Feng, C. Q. ; Fritsch, Miriam ; Fu, Chengdong ; Fu, Y. ; Gao, X. L. ; Gao, Y. ; Gao, Y. ; Gao, Y. G. ; Garzia, Isabella ; Gersabeck, Evelina ; Gilman, A. ; Götzen, Klaus ; Gong, L. ; Gong, Wenxuan ; Gradl, Wolfgang ; Greco, M. ; Gu, L. M. ; Gu, Minhao ; Gu, S. ; Gu, Y. T. ; Guan, C. Y. ; Guo, Aiqiang ; Guo, L. B. ; Guo, R. P. ; Guo, Yuping ; Guo, Yuping ; Guskov, Alexey ; Han, S. ; Han, T. T. ; Han, T. Z. ; Hao, Xiqing ; Harris, Frederick Allan ; He, K. L. ; Heinsius, Fritz-Herbert ; Held, T. ; Heng, Yuekun ; Himmelreich, Mathilde ; Holtmann, Tobias ; Hou, Y. R. ; Hou, Zhilong ; Hu, Haiming ; Hu, J. F. ; Hu, T. ; Hu, Y. ; Huang, G. S. ; Huang, L. Q. ; Huang, X. T. ; Huang, Z. ; Huesken, Nils ; Hussain, Tahir ; Ikegami Andersson, Walter ; Imoehl, William ; Irshad, M. ; Jaeger, S. ; Janchiv, S. ; Ji, Quan ; Ji, Qingping ; Ji, X. B. ; Ji, X. L. ; Jiang, H. B. ; Jiang, Xiaoshan ; Jiang, X. Y. ; Jiao, J. B. ; Jiao, Z. ; Jin, Shan ; Jin, Y. ; Johansson, Tord ; Kalantar-Nayestanaki, Nasser ; Kang, X. S. ; Kappert, Rosa ; Kavatsyuk, Myroslav O. ; Ke, B. C. ; Keshk, I. K. ; Khoukaz, Alfons ; Kiese, P. ; Kiuchi, R. ; Kliemt, Ralf ; Koch, L. ; Kolcu, Onur Bugra ; Kopf, Bertram ; Kuemmel, M. ; Küßner, Meike ; Kupsc, Andrzej ; Kurth, M. G. ; Kühn, Wolfgang ; Lane, John Jake ; Lange, Jens Sören ; Larin, Paul ; Lavezzi, Lia ; Leithoff, Hans Heinrich ; Lellmann, Max ; Lenz, Thomas ; Li, C. ; Li, C. H. ; Li, Cheng ; Li, D. M. ; Li, F. ; Li, G. ; Li, Haibo ; Li, H. J. ; Li, J. L. ; Li, J. Q. ; Li, Ke ; Li, L. K. ; Li, Lei ; Li, P. L. ; Li, P. R. ; Li, S. Y. ; Li, Weidong ; Li, Weiguo ; Li, X. H. ; Li, Xing Long ; Li, Z. B. ; Li, Z. Y. ; Liang, H. ; Liang, H. ; Liang, Y. F. ; Liang, Y. T. ; Liao, L. Z. ; Libby, J. ; Lin, C. X. ; Liu, B. ; Liu, B. J. ; Liu, C. X. ; Liu, D. ; Liu, D. Y. ; Liu, Fu-Hu ; Liu, Fang ; Liu, Feng ; Liu, H. B. ; Liu, H. M. ; Liu, Huanhuan ; Liu, Huihui ; Liu, J. B. ; Liu, J. Y. ; Liu, K. ; Liu, K. Y. ; Liu, Ke ; Liu, L. ; Liu, L. Y. ; Liu, Q. ; Liu, S. B. ; Liu, T. ; Liu, X. ; Liu, Y. B. ; Liu, Zhen-An ; Liu, Z. Q. ; Long, Y. F. ; Lou, Xinchou ; Lu, H. J. ; Lu, J. D. ; Lu, Junguang ; Lu, X. L. ; Lu, Y. ; Lu, Yunpeng ; Luo, Chenglin ; Luo, M. X. ; Luo, P. W. ; Luo, T. ; Luo, X. L. ; Lusso, S. ; Lyu, Xiao-Rui ; Ma, Fengcai ; Ma, H. L. ; Ma, Lianliang ; Ma, M. M. ; Ma, Qiumei ; Ma, R. Q. ; Ma, R. T. ; Ma, X. N. ; Ma, X. X. ; Ma, Xiaoyan ; Ma, Y. M. ; Maas, Frank E. ; Maggiora, Marco ; Maldaner, Stephan ; Malde, Sneha ; Malik, Qadeer Afzal ; Mangoni, Alessio ; Mao, Yajun ; Mao, Zepu ; Marcello, Simonetta ; Meng, Z. X. ; Messchendorp, Johannes Gerhardus ; Mezzadri, Giulio ; Min, T. J. ; Mitchell, Ryan Edward ; Mo, Xiaohu ; Mo, Y. J. ; Muchnoi, Nikolai Yu. ; Muramatsu, Hajime ; Nakhoul, Simon ; Nefedov, Yury ; Nerling, Frank ; Nikolaev, Ivan Borisovich ; Ning, Z. ; Nisar, Shabana ; Olsen, Stephen L. ; Ouyang, Qun ; Pacetti, Simone ; Pan, Y. ; Papenbrock, Michael ; Pathak, A. ; Patteri, Piero ; Pelizäus, Marc ; Peng, H. P. ; Peters, Klaus ; Pettersson, J. ; Ping, J. L. ; Ping, R. G. ; Pitka, A. ; Poling, Ronald ; Prasad, Vindhyawasini ; Qi, H. ; Qi, H. R. ; Qi, Ming ; Qi, T. Y. ; Qian, S. ; Qian, W.-B. ; Qiao, Congfeng ; Qin, L. Q. ; Qin, X. P. ; Qin, X. S. ; Qin, Zhonghua ; Qiu, Jinfa ; Qu, S. Q. ; Rashid, K. H. ; Ravindran, Krishnakumar ; Redmer, Christoph Florian ; Rivetti, Angelo ; Rodin, Viktor ; Da Rocha Rolo, Manuel Dionisio ; Rong, Gang ; Rosner, Christoph ; Rump, Marcel Andre ; Sarantsev, Andrei V. ; Savrié, Mauro ; Schelhaas, Yasemin ; Schnier, Claudius ; Schönning, Karin ; Shan, Wei ; Shan, Xinyu ; Shao, M. ; Shen, C. P. ; Shen, P. X. ; Shen, X. Y. ; Shi, H. C. ; Shi, R. S. ; Shi, X. ; Shi, X. D. ; Song, J. J. ; Song, Q. Q. ; Song, Y. X. ; Sosio, Stefano ; Spataro, Stefano ; Sui, F. F. ; Sun, Gongxing ; Sun, J. F. ; Sun, L. ; Sun, S. S. ; Sun, T. ; Sun, W. Y. ; Sun, Y. J. ; Sun, Y. K. ; Sun, Y. Z. ; Sun, Z. T. ; Tan, Y. X. ; Tang, C. J. ; Tang, G. Y. ; Tang, J. ; Thoren, Viktor ; Tsednee, B. ; Uman, Ismail ; Wang, B. ; Wang, B. L. ; Wang, C. W. ; Wang, D. Y. ; Wang, H. P. ; Wang, K. ; Wang, L. L. ; Wang, M. ; Wang, M. Z. ; Wang, Meng ; Wang, W. P. ; Wang, X. ; Wang, X. F. ; Wang, X. L. ; Wang, Y. ; Wang, Y. ; Wang, Y. D. ; Wang, Y. F. ; Wang, Y. Q. ; Wang, Z. ; Wang, Zongyuan ; Wang, Ziyi ; Wang, Zongyuan ; Weber, T. ; Wei, D. H. ; Weidenkaff, Peter ; Weidner, Frederik ; Wen, H. W. ; Wen, Shuopin ; White, D. J. ; Wiedner, Ulrich ; Wilkinson, Guy ; Wolke, Magnus ; Wollenberg, Leonard ; Wu, J. F. ; Wu, L. H. ; Wu, L. J. ; Wu, X. ; Wu, Z. ; Xia, Lei ; Xiao, H. ; Xiao, S. Y. ; Xiao, Y. J. ; Xiao, Zhenjun ; Xie, X. H. ; Xie, Y. G. ; Xie, Y. H. ; Xing, T. Y. ; Xiong, X. A. ; Xu, Guofa ; Xu, J. J. ; Xu, Q. J. ; Xu, W. ; Xu, Xinping ; Yan, L. ; Yan, L. ; Yan, W. B. ; Yan, W. C. ; Yang, H. J. ; Yang, Hongxun ; Yang, L. ; Yang, R. X. ; Yang, S. L. ; Yang, Y. H. ; Yang, Yongxu ; Yang, Yifan ; Yang, Zhi ; Ye, M. ; Ye, Minghan ; Yin, J. H. ; You, Z. Y. ; Yu, Boxiang ; Yu, C. X. ; Yu, G. ; Yu, J. S. ; Yu, T. ; Yuan, Chang-Zheng ; Yuan, W. ; Yuan, X. Q. ; Yuan, Y. ; Yue, C. X. ; Yüncü, Alperen ; Zafar, A. A. ; Zeng, Y. ; Zhang, B. X. ; Zhang, Guangyi ; Zhang, H. H. ; Zhang, Hongyu ; Zhang, J. L. ; Zhang, J. Q. ; Zhang, J. W. ; Zhang, Jianyong ; Zhang, J. Z. ; Zhang, Jianyu ; Zhang, Jiawei ; Zhang, L. ; Zhang, Lei ; Zhang, S. ; Zhang, S. F. ; Zhang, T. J. ; Zhang, X. Y. ; Zhang, Y. ; Zhang, Y. H. ; Zhang, Y. T. ; Zhang, Yan ; Zhang, Yao ; Zhang, Yi ; Zhang, Z. H. ; Zhang, Z. Y. ; Zhao, G. ; Zhao, J. ; Zhao, J. Y. ; Zhao, J. Z. ; Zhao, Lei ; Zhao, Ling ; Zhao, Ming-Gang ; Zhao, Q. ; Zhao, Shujun ; Zhao, Yubin ; Zhao Zhao, Y. X. ; Zhao, Zhengguo ; Zhemchugov, Alexey ; Zheng, B. ; Zheng, Jianping ; Zheng, Y. ; Zheng, Y. H. ; Zhong, B. ; Zhong, C. ; Zhou, L. P. ; Zhou, Q. ; Zhou, X. ; Zhou, X. K. ; Zhou, X. R. ; Zhu, A. N. ; Zhu, Jianhui ; Zhu, K. ; Zhu, Kejun ; Zhu, S. H. ; Zhu, W. J. ; Zhu, X. L. ; Zhu, Y. C. ; Zhu, Zian ; Zou, B. S. ; Zou, Jiaheng
We report a measurement of the observed cross sections of e+ e− → J/ψX based on 3.21 fb − 1 of data accumulated at energies from 3.645 to 3.891 GeV with the BESIII detector operated at the BEPCII collider. In analysis of the cross sections, we measured the decay branching fractions of B(ψ(3686) → J/ψX) = (64.4 ± 0.6 ± 1.6)% and B(ψ(3770) → J/ψX) = (0.5 ± 0.2 ± 0.1)% for the first time. The energy-dependent line shape of these cross sections cannot be well described by two Breit-Wigner (BW) amplitudes of the expected decays ψ (3686) → J/ψX and ψ(3770) → J/ψX. Instead, it can be better described with one more BW amplitude of the decay R(3760)→ J/ψX. Under this assumption, we extracted the R (3760) mass M R (3760 ) = 3766.2 ± 3.8 ± 0.4 MeV/c2, total width Γ tot R ( 3760 ) = 22.2 ± 5.9 ± 1.4 MeV, and product of leptonic width and decay branching fraction
ΓeeR(3760) B[R(3760) → J/ψX] = (79.4 ± 85.5 ± 11.7) eV. The significance of the R(3760) is 5.3σ. The first uncertainties of these measured quantities are from fits to the cross sections and second systematic.
Radeloff, Daniel ; Ciaramidaro, Angela ; Siniatchkin, Michael ; Hainz, Daniela ; Schlitt, Sabine ; Weber, Bernhard ; Poustka, Fritz ; Bölte, Sven ; Walter, Henrik ; Freitag, Christine M.
Autism spectrum disorder and schizophrenia share a substantial number of etiologic and phenotypic characteristics. Still, no direct comparison of both disorders has been performed to identify differences and commonalities in brain structure. In this voxel based morphometry study, 34 patients with autism spectrum disorder, 21 patients with schizophrenia and 26 typically developed control subjects were included to identify global and regional brain volume alterations. No global gray matter or white matter differences were found between groups. In regional data, patients with autism spectrum disorder compared to typically developed control subjects showed smaller gray matter volume in the amygdala, insula, and anterior medial prefrontal cortex. Compared to patients with schizophrenia, patients with autism spectrum disorder displayed smaller gray matter volume in the left insula. Disorder specific positive correlations were found between mentalizing ability and left amygdala volume in autism spectrum disorder, and hallucinatory behavior and insula volume in schizophrenia. Results suggest the involvement of social brain areas in both disorders. Further studies are needed to replicate these findings and to quantify the amount of distinct and overlapping neural correlates in autism spectrum disorder and schizophrenia.