TY  - JOUR
A1  - Liu, Han
A1  - Chen, Chunhai
A1  - Gao, Zexia
A1  - Min, Jiumeng
A1  - Gu, Yongming
A1  - Jian, Jianbo
A1  - Jiang, Xiewu
A1  - Cai, Huimin
A1  - Ebersberger, Ingo
A1  - Xu, Meng
A1  - Zhang, Xinhui
A1  - Chen, Jianwei
A1  - Luo, Wei
A1  - Chen, Boxiang
A1  - Chen, Junhui
A1  - Liu, Hong
A1  - Li, Jiang
A1  - Lai, Ruifang
A1  - Bai, Mingzhou
A1  - Wei, Jin
A1  - Yi, Shaokui
A1  - Wang, Huanling
A1  - Cao, Xiaojuan
A1  - Zhou, Xiaoyun
A1  - Zhao, Yuhua
A1  - Wei, Kaijian
A1  - Yang, Ruibin
A1  - Liu, Bingnan
A1  - Zhao, Shancen
A1  - Fang, Xiaodong
A1  - Schartl, Manfred
A1  - Qian, Xueqiao
A1  - Wang, Weimin
T1  - The draft genome of blunt snout bream (Megalobrama amblycephala) reveals the development of intermuscular bone and adaptation to herbivorous diet
JF  - GigaScience
N2  - The blunt snout bream Megalobrama amblycephala is the economically most important cyprinid fish species. As an herbivore, it can be grown by eco-friendly and resource-conserving aquaculture. However, the large number of intermuscular bones in the trunk musculature is adverse to fish meat processing and consumption. As a first towards optimizing this aquatic livestock, we present a 1.116-Gb draft genome of M. amblycephala, with 779.54 Mb anchored on 24 linkage groups. Integrating spatiotemporal transcriptome analyses, we show that intermuscular bone is formed in the more basal teleosts by intramembranous ossification and may be involved in muscle contractibility and coordinating cellular events. Comparative analysis revealed that olfactory receptor genes, especially of the beta type, underwent an extensive expansion in herbivorous cyprinids, whereas the gene for the umami receptor T1R1 was specifically lost in M. amblycephala. The composition of gut microflora, which contributes to the herbivorous adaptation of M. amblycephala, was found to be similar to that of other herbivores. As a valuable resource for the improvement of M. amblycephala livestock, the draft genome sequence offers new insights into the development of intermuscular bone and herbivorous adaptation.
KW  - Megalobrama amblycephala
KW  - whole genome
KW  - herbivorous diet
KW  - intermuscular bone
KW  - transcriptome
KW  - gut microflora
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170844
VL  - 6
IS  - 7
ER  - 
TY  - JOUR
A1  - Zhang, Yonghong
A1  - Zheng, Lanlan
A1  - Zheng, Yan
A1  - Zhou, Chao
A1  - Huang, Ping
A1  - Xiao, Xiao
A1  - Zhao, Yongheng
A1  - Hao, Xincai
A1  - Hu, Zhubing
A1  - Chen, Qinhua
A1  - Li, Hongliang
A1  - Wang, Xuanbin
A1  - Fukushima, Kenji
A1  - Wang, Guodong
A1  - Li, Chen
T1  - Assembly and Annotation of a Draft Genome of the Medicinal Plant Polygonum cuspidatum
JF  - Frontiers in Plant Science
N2  - Polygonum cuspidatum (Japanese knotweed, also known as Huzhang in Chinese), a plant that produces bioactive components such as stilbenes and quinones, has long been recognized as important in traditional Chinese herbal medicine. To better understand the biological features of this plant and to gain genetic insight into the biosynthesis of its natural products, we assembled a draft genome of P. cuspidatum using Illumina sequencing technology. The draft genome is ca. 2.56 Gb long, with 71.54% of the genome annotated as transposable elements. Integrated gene prediction suggested that the P. cuspidatum genome encodes 55,075 functional genes, including 6,776 gene families that are conserved in the five eudicot species examined and 2,386 that are unique to P. cuspidatum. Among the functional genes identified, 4,753 are predicted to encode transcription factors. We traced the gene duplication history of P. cuspidatum and determined that it has undergone two whole-genome duplication events about 65 and 6.6 million years ago. Roots are considered the primary medicinal tissue, and transcriptome analysis identified 2,173 genes that were expressed at higher levels in roots compared to aboveground tissues. Detailed phylogenetic analysis demonstrated expansion of the gene family encoding stilbene synthase and chalcone synthase enzymes in the phenylpropanoid metabolic pathway, which is associated with the biosynthesis of resveratrol, a pharmacologically important stilbene. Analysis of the draft genome identified 7 abscisic acid and water deficit stress-induced protein-coding genes and 14 cysteine-rich transmembrane module genes predicted to be involved in stress responses. The draft de novo genome assembly produced in this study represents a valuable resource for the molecular characterization of medicinal compounds in P. cuspidatum, the improvement of this important medicinal plant, and the exploration of its abiotic stress resistance.
KW  - genome assembly
KW  - resveratrol biosynthesis
KW  - whole-genome duplication
KW  - medicinal plant
KW  - stress tolerance
KW  - Polygonum  cuspidatum
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189279
SN  - 1664-462X
VL  - 10
ER  - 
TY  - JOUR
A1  - Chen, Xing
A1  - Meng, Guoyun
A1  - Liao, Guanming
A1  - Rauch, Florian
A1  - He, Jiang
A1  - Friedrich, Alexandra
A1  - Marder, Todd B.
A1  - Wang, Nan
A1  - Chen, Pangkuan
A1  - Wang, Suning
A1  - Yin, Xiaodong
T1  - Highly Emissive 9-Borafluorene Derivatives: Synthesis, Photophysical Properties and Device Fabrication
JF  - Chemistry—A European Journal
N2  - A series of 9-borafluorene derivatives, functionalised with electron-donating groups, have been prepared. Some of these 9-borafluorene compounds exhibit strong yellowish emission in solution and in the solid state with relatively high quantum yields (up to 73.6 % for FMesB-Cz as a neat film). The results suggest that the highly twisted donor groups suppress charge transfer, but the intrinsic photophysical properties of the 9-borafluorene systems remain. The new compounds showed enhanced stability towards the atmosphere, and exhibited excellent thermal stability, revealing their potential for application in materials science. Organic light-emitting diode (OLED) devices were fabricated with two of the highly emissive compounds, and they exhibited strong yellow-greenish electroluminescence, with a maximum luminance intensity of >22 000 cd m\(^{-2}\). These are the first two examples of 9-borafluorene derivatives being used as light-emitting materials in OLED devices, and they have enabled us to achieve a balance between maintaining their intrinsic properties while improving their stability.
KW  - boron heterocycles
KW  - photophysics
KW  - organic light-emitting diodes
KW  - luminescence
KW  - density functional calculations
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-256738
VL  - 27
IS  - 20
ER  - 
TY  - JOUR
A1  - Zhao, De-Wei
A1  - Yu, Mang
A1  - Hu, Kai
A1  - Wang, Wei
A1  - Yang, Lei
A1  - Wang, Ben-Jie
A1  - Gao, Xiao-Hong
A1  - Guo, Yong-Ming
A1  - Xu, Yong-Qing
A1  - Wei, Yu-Shan
A1  - Tian, Si-Miao
A1  - Yang, Fan
A1  - Wang, Nan
A1  - Huang, Shi-Bo
A1  - Xie, Hui
A1  - Wei, Xiao-Wei
A1  - Jiang, Hai-Shen
A1  - Zang, Yu-Qiang
A1  - Ai, Jun
A1  - Chen, Yuan-Liang
A1  - Lei, Guang-Hua
A1  - Li, Yu-Jin
A1  - Tian, Geng
A1  - Li, Zong-Sheng
A1  - Cao, Yong
A1  - Ma, Li
T1  - Prevalence of Nontraumatic Osteonecrosis of the Femoral Head and its Associated Risk Factors in the Chinese Population: Results from a Nationally Representative Survey
JF  - Chinese Medical Journal
N2  - Background: Nontraumatic osteonecrosis of the femoral head (NONFH) is a debilitating disease that represents a significant financial burden for both individuals and healthcare systems. Despite its significance, however, its prevalence in the Chinese general population remains unknown. This study aimed to investigate the prevalence of NONFH and its associated risk factors in the Chinese population. 
Methods: A nationally representative survey of 30,030 respondents was undertaken from June 2012 to August 2013. All participants underwent a questionnaire investigation, physical examination of hip, and bilateral hip joint X-ray and/or magnetic resonance imaging examination. Blood samples were taken after overnight fasting to test serum total cholesterol, triglyceride, and high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels. We then used multivariate logistic regression analysis to investigate the associations between various metabolic, demographic, and lifestyle-related variables and NONFH. 
Results: NONFH was diagnosed in 218 subjects (0.725%) and the estimated NONFH cases were 8.12 million among Chinese people aged 15 years and over. The prevalence of NONFH was significantly higher in males than in females (1.02% vs. 0.51%, \(\chi^2\) = 24.997, P < 0.001). Among NONFH patients, North residents were subjected to higher prevalence of NONFH than that of South residents (0.85% vs. 0.61%, \(\chi^2\) = 5.847, P = 0.016). Our multivariate regression analysis showed that high blood levels of triglycerides, total cholesterol, LDL-cholesterol, and non-HDL-cholesterol, male, urban residence, family history of osteonecrosis of the femoral head, heavy smoking, alcohol abuse and glucocorticoid intake, overweight, and obesity were all significantly associated with an increased risk of NONFH. 
Conclusions: Our findings highlight that NONFH is a significant public health challenge in China and underscore the need for policy measures on the national level. Furthermore, NONFH shares a number of risk factors with atherosclerosis.
KW  - nontraumatic osteonecrosis of the femoral head
KW  - risk factors
KW  - idiopathic osteonecrosis
KW  - early-stage osteonecrosis
KW  - implantation
KW  - bone
KW  - marrow
KW  - follow-up
KW  - intake
KW  - avascular necrosis
KW  - occupational-status
KW  - cigarette smoking
KW  - alcohol
KW  - prevalence
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-138482
VL  - 128
IS  - 21
ER  - 
TY  - JOUR
A1  - Couch, Fergus J.
A1  - Wang, Xianshu
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Olswold, Curtis
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Fredericksen, Zachary
A1  - Barrowdale, Daniel
A1  - Dennis, Joe
A1  - Gaudet, Mia M.
A1  - Dicks, Ed
A1  - Kosel, Matthew
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Lee, Adam
A1  - Bacot, Françios
A1  - Vincent, Daniel
A1  - Hogervorst, Frans B. L.
A1  - Peock, Susan
A1  - Stoppa-Lyonnet, Dominique
A1  - Jakubowska, Anna
A1  - Radice, Paolo
A1  - Schmutzler, Rita Katharina
A1  - Domchek, Susan M.
A1  - Piedmonte, Marion
A1  - Singer, Christian F.
A1  - Friedman, Eitan
A1  - Thomassen, Mads
A1  - Hansen, Thomas V. O.
A1  - Neuhausen, Susan L.
A1  - Szabo, Csilla I.
A1  - Blanco, Ingnacio
A1  - Greene, Mark H.
A1  - Karlan, Beth Y.
A1  - Garber, Judy
A1  - Phelan, Catherine M.
A1  - Weitzel, Jeffrey N.
A1  - Montagna, Marco
A1  - Olah, Edith
A1  - Andrulis, Irene L.
A1  - Godwin, Andrew K.
A1  - Yannoukakos, Drakoulis
A1  - Goldgar, David E.
A1  - Caldes, Trinidad
A1  - Nevanlinna, Heli
A1  - Osorio, Ana
A1  - Terry, Mary Beth
A1  - Daly, Mary B.
A1  - van Rensburg, Elisabeth J.
A1  - Hamann, Ute
A1  - Ramus, Susan J.
A1  - Toland, Amanda Ewart
A1  - Caligo, Maria A.
A1  - Olopade, Olufunmilayo I.
A1  - Tung, Nadine
A1  - Claes, Kathleen
A1  - Beattie, Mary S.
A1  - Southey, Melissa C.
A1  - Imyanitov, Evgeny N.
A1  - Tischkowitz, Marc
A1  - Janavicius, Ramunas
A1  - John, Esther M.
A1  - Kwong, Ava
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Balmaña, Judith
A1  - Barkardottir, Rosa B.
A1  - Arun, Banu K.
A1  - Rennert, Gad
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Campbell, Ian
A1  - van der Hout, Annemarie H.
A1  - van Deurzen, Carolien H. M.
A1  - Seynaeve, Caroline
A1  - Garcia, Encarna B. Gómez
A1  - van Leeuwen, Flora E.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Gille, Johannes J. P.
A1  - Ausems, Magreet G. E. M.
A1  - Blok, Marinus J.
A1  - Ligtenberg, Marjolinjin J. L.
A1  - Rookus, Matti A.
A1  - Devilee, Peter
A1  - Verhoef, Senno
A1  - van Os, Theo A. M.
A1  - Wijnen, Juul T.
A1  - Frost, Debra
A1  - Ellis, Steve
A1  - Fineberg, Elena
A1  - Platte, Radke
A1  - Evans, D. Gareth
A1  - Izatt, Luise
A1  - Eeles, Rosalind A.
A1  - Adlard, Julian
A1  - Eccles, Diana M.
A1  - Cook, Jackie
A1  - Brewer, Carole
A1  - Douglas, Fiona
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Side, Lucy E.
A1  - Donaldson, Alan
A1  - Houghton, Catherine
A1  - Rogers, Mark T.
A1  - Dorkins, Huw
A1  - Eason, Jacqueline
A1  - Gregory, Helen
A1  - McCann, Emma
A1  - Murray, Alex
A1  - Calender, Alain
A1  - Hardouin, Agnès
A1  - Berthet, Pascaline
A1  - Delnatte, Capucine
A1  - Nogues, Catherine
A1  - Lasset, Christine
A1  - Houdayer, Claude
A1  - Leroux,, Dominique
A1  - Rouleau, Etienne
A1  - Prieur, Fabienne
A1  - Damiola, Francesca
A1  - Sobol, Hagay
A1  - Coupier, Isabelle
A1  - Venat-Bouvet, Laurence
A1  - Castera, Laurent
A1  - Gauthier-Villars, Marion
A1  - Léoné, Mélanie
A1  - Pujol, Pascal
A1  - Mazoyer, Sylvie
A1  - Bignon, Yves-Jean
A1  - Zlowocka-Perlowska, Elzbieta
A1  - Gronwald, Jacek
A1  - Lubinski,, Jan
A1  - Durda, Katarzyna
A1  - Jaworska, Katarzyna
A1  - Huzarski, Tomasz
A1  - Spurdle, Amanda B.
A1  - Viel, Alessandra
A1  - Peissel, Bernhard
A1  - Bonanni, Bernardo
A1  - Melloni, Guilia
A1  - Ottini, Laura
A1  - Papi, Laura
A1  - Varesco, Liliana
A1  - Tibiletti, Maria Grazia
A1  - Peterlongo, Paolo
A1  - Volorio, Sara
A1  - Manoukian, Siranoush
A1  - Pensotti, Valeria
A1  - Arnold, Norbert
A1  - Engel, Christoph
A1  - Deissler, Helmut
A1  - Gadzicki, Dorothea
A1  - Gehrig, Andrea
A1  - Kast, Karin
A1  - Rhiem, Kerstin
A1  - Meindl, Alfons
A1  - Niederacher, Dieter
A1  - Ditsch, Nina
A1  - Plendl, Hansjoerg
A1  - Preisler-Adams, Sabine
A1  - Engert, Stefanie
A1  - Sutter, Christian
A1  - Varon-Mateeva, Raymenda
A1  - Wappenschmidt, Barbara
A1  - Weber, Bernhard H. F.
A1  - Arver, Brita
A1  - Stenmark-Askmalm, Marie
A1  - Loman, Niklas
A1  - Rosenquist, Richard
A1  - Einbeigi, Zakaria
A1  - Nathanson, Katherine L.
A1  - Rebbeck, Timothy R.
A1  - Blank, Stephanie V.
A1  - Cohn, David E.
A1  - Rodriguez, Gustavo C.
A1  - Small, Laurie
A1  - Friedlander, Michael
A1  - Bae-Jump, Victoria L.
A1  - Fink-Retter, Anneliese
A1  - Rappaport, Christine
A1  - Gschwantler-Kaulich, Daphne
A1  - Pfeiler, Georg
A1  - Tea, Muy-Kheng
A1  - Lindor, Noralane M.
A1  - Kaufman, Bella
A1  - Paluch, Shani Shimon
A1  - Laitman, Yael
A1  - Skytte, Anne-Bine
A1  - Gerdes, Anne-Marie
A1  - Pedersen, Inge Sokilde
A1  - Moeller, Sanne Traasdahl
A1  - Kruse, Torben A.
A1  - Jensen, Uffe Birk
A1  - Vijai, Joseph
A1  - Sarrel, Kara
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Ozcelik, Hilmi
A1  - Ejlertsen, Bent
A1  - Nielsen, Finn C.
A1  - Jønson, Lars
A1  - Andersen, Mette K.
A1  - Ding, Yuan Chun
A1  - Steele, Linda
A1  - Foretova, Lenka
A1  - Teulé, Alex
A1  - Lazaro, Conxi
A1  - Brunet, Joan
A1  - Pujana, Miquel Angel
A1  - Mai, Phuong L.
A1  - Loud, Jennifer T.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - Orsulic, Sandra
A1  - Narod, Steven A.
A1  - Herzog, Josef
A1  - Sand, Sharon R.
A1  - Tognazzo, Silvia
A1  - Agata, Simona
A1  - Vaszko, Tibor
A1  - Weaver, Joellen
A1  - Stravropoulou, Alexandra V.
A1  - Buys, Saundra S.
A1  - Romero, Atocha
A1  - de la Hoya, Miguel
A1  - Aittomäki, Kristiina
A1  - Muranen, Taru A.
A1  - Duran, Mercedes
A1  - Chung, Wendy K.
A1  - Lasa, Adriana
A1  - Dorfling, Cecilia M.
A1  - Miron, Alexander
A1  - Benitez, Javier
A1  - Senter, Leigha
A1  - Huo, Dezheng
A1  - Chan, Salina B.
A1  - Sokolenko, Anna P.
A1  - Chiquette, Jocelyne
A1  - Tihomirova, Laima
A1  - Friebel, Tara M.
A1  - Agnarsson, Bjarne A.
A1  - Lu, Karen H.
A1  - Lejbkowicz, Flavio
A1  - James, Paul A.
A1  - Hall, Per
A1  - Dunning, Alison M.
A1  - Tessier, Daniel
A1  - Cunningham, Julie
A1  - Slager, Susan L.
A1  - Chen, Wang
A1  - Hart, Steven
A1  - Stevens, Kristen
A1  - Simard, Jacques
A1  - Pastinen, Tomi
A1  - Pankratz, Vernon S.
A1  - Offit, Kenneth
A1  - Easton, Douglas F.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
T1  - Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
JF  - PLOS Genetics
N2  - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
KW  - common variants
KW  - susceptibility alleles
KW  - genetic variants
KW  - modifiers
KW  - ZNF365
KW  - investigators
KW  - population
KW  - consortium
KW  - selection
KW  - subtypes
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127947
SN  - 1553-7404
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Yan, Yan
A1  - Hong, Ni
A1  - Chen, Tiansheng
A1  - Li, Mingyou
A1  - Wang, Tiansu
A1  - Guan, Guijun
A1  - Qiao, Yongkang
A1  - Chen, Songlin
A1  - Schartl, Manfred
A1  - Li, Chang-Ming
A1  - Hong, Yunhan
T1  - p53 Gene Targeting by Homologous Recombination in Fish ES Cells
JF  - PLoS One
N2  - Background: Gene targeting (GT) provides a powerful tool for the generation of precise genetic alterations in embryonic stem (ES) cells to elucidate gene function and create animal models for human diseases. This technology has, however, been limited to mouse and rat. We have previously established ES cell lines and procedures for gene transfer and selection for homologous recombination (HR) events in the fish medaka (Oryzias latipes). 
Methodology and Principal Findings: Here we report HR-mediated GT in this organism. We designed a GT vector to disrupt the tumor suppressor gene p53 (also known as tp53). We show that all the three medaka ES cell lines, MES1 similar to MES3, are highly proficient for HR, as they produced detectable HR without drug selection. Furthermore, the positive-negative selection (PNS) procedure enhanced HR by similar to 12 folds. Out of 39 PNS-resistant colonies analyzed, 19 (48.7%) were positive for GT by PCR genotyping. When 11 of the PCR-positive colonies were further analyzed, 6 (54.5%) were found to be bona fide homologous recombinants by Southern blot analysis, sequencing and fluorescent in situ hybridization. This produces a high efficiency of up to 26.6% for p53 GT under PNS conditions. We show that p53 disruption and long-term propagation under drug selection conditions do not compromise the pluripotency, as p53-targeted ES cells retained stable growth, undifferentiated phenotype, pluripotency gene expression profile and differentiation potential in vitro and in vivo. 
Conclusions: Our results demonstrate that medaka ES cells are proficient for HR-mediated GT, offering a first model organism of lower vertebrates towards the development of full ES cell-based GT technology.
KW  - mouse
KW  - in-vitro
KW  - drug selection
KW  - chimera formation
KW  - medakafish oryzias latipes
KW  - embryonic stem-cells
KW  - zebrafish
KW  - differentiation
KW  - cultures
KW  - pluripotency
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133416
VL  - 8
IS  - 3
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  - Luo, Yueming
A1  - Ling, Chuanren
A1  - Liu, Yangchen
A1  - Deng, Chong
A1  - Waaga-Gasser, Ana Maria
A1  - Chen, Minggui
A1  - He, Zehui
A1  - Chen, Erhui
A1  - Wei, Lin
A1  - Luo, Shimiao
A1  - Gong, Xiaozhen
A1  - Ye, Hong
A1  - Zhu, Jing
A1  - Song, Shan
A1  - Wang, Qiuting
A1  - Li, Shunmin
A1  - Gasser, Martin
A1  - Lin, Meizhen
T1  - The Beneficial Role of Auricular Point Pressure in Insomnia and Anxiety in Isolated COVID-19 Patients
JF  - Evidence-Based Complementary and Alternative Medicine
N2  - Background 
Coronavirus disease 2019 (COVID-19) causes psychological distress and can have a negative impact on the general mental health and rehabilitation in affected patients under currently implemented isolation guidelines. Auricular point pressure (APP) as well-established technique in traditional Chinese medicine may help to relieve sleep disturbance and anxiety in COVID-19 patients. 
Methods 
During the early phase of the epidemic/pandemic, patients were enrolled in this study (02/2020 until 03/2020 n = 84). They were strictly isolated on specific wards at the Hubei Provincial Hospital of Integrated Chinese and Western Medicine in Hubei. The retrospective cohort study design included two groups. Group A patients were treated with an auricular point pressure (APP) in addition to standard intensive care medicine while Group B participants (No-APP) received routine nursing measures alone. Treatment outcome was measured using the St. Mary’s Hospital Sleep Questionnaire (SMH) Score and the 7-Item Generalized Anxiety Disorder Scale (GAD-7). Both scores were measured in each patient at baseline and on the discharge day. 
Results 
The SMH score and sleep status changed in APP patients at the end of the treatment period when compared with No-APP patients (P < 0.01). APP-treated patients demonstrated lower GAD-7 scores than No-APP controls (P < 0.01). Further, no significant differences in safety or adverse events between the APP and No-APP groups were observed. Conclusion 
The results from our snapshot study during the early phase of the SARS-CoV-2 epidemic/pandemic suggest that auricular point pressure could be a simple and effective tool to relieve insomnia and situational anxiety in hospitalized patients suffering from COVID-19 and kept under disconcerting conditions of isolation.
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-369658
VL  - 2021
ER  - 
TY  - JOUR
A1  - Ascierto, Maria Libera
A1  - Worschech, Andrea
A1  - Yu, Zhiya
A1  - Adams, Sharon
A1  - Reinboth, Jennifer
A1  - Chen, Nanhai G
A1  - Pos, Zoltan
A1  - Roychoudhuri, Rahul
A1  - Di Pasquale, Giovanni
A1  - Bedognetti, Davide
A1  - Uccellini, Lorenzo
A1  - Rossano, Fabio
A1  - Ascierto, Paolo A
A1  - Stroncek, David F
A1  - Restifo, Nicholas P
A1  - Wang, Ena
A1  - Szalay, Aladar A
A1  - Marincola, Francesco M
T1  - Permissivity of the NCI-60 cancer cell lines to oncolytic Vaccinia Virus GLV-1h68
JF  - BMC Cancer
N2  - Background: 

Oncolytic viral therapy represents an alternative therapeutic strategy for the treatment of cancer. We previously described GLV-1h68, a modified Vaccinia Virus with exclusive tropism for tumor cells, and we observed a cell line-specific relationship between the ability of GLV-1h68 to replicate in vitro and its ability to colonize and eliminate tumor in vivo. 

Methods: 

In the current study we surveyed the in vitro permissivity to GLV-1h68 replication of the NCI-60 panel of cell lines. Selected cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain. In order to identify correlates of permissity to viral infection, we measured transcriptional profiles of the cell lines prior infection. 

Results: 

We observed highly heterogeneous permissivity to VACV infection amongst the cell lines. The heterogeneity of permissivity was independent of tissue with the exception of B cell derivation. Cell lines were also tested for permissivity to another Vaccinia Virus and a vesicular stomatitis virus (VSV) strain and a significant correlation was found suggesting a common permissive phenotype. While no clear transcriptional pattern could be identified as predictor of permissivity to infection, some associations were observed suggesting multifactorial basis permissivity to viral infection. 

Conclusions: 

Our findings have implications for the design of oncolytic therapies for cancer and offer insights into the nature of permissivity of tumor cells to viral infection.
KW  - gene-therapy
KW  - adenovirus
KW  - receptor
KW  - identification
KW  - infection
KW  - CD9
KW  - panel
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141503
VL  - 11
IS  - 451
ER  - 
TY  - JOUR
A1  - Tsai, Yu-Chen
A1  - Grimm, Stefan
A1  - Chao, Ju-Lan
A1  - Wang, Shih-Chin
A1  - Hofmeyer, Kerstin
A1  - Shen, Jie
A1  - Eichinger, Fred
A1  - Michalopoulou, Theoni
A1  - Yao, Chi-Kuang
A1  - Chang, Chih-Hsuan
A1  - Lin, Shih-Han
A1  - Sun, Y. Henry
A1  - Pflugfelder, Gert O.
T1  - Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling
JF  - PLoS ONE
N2  - Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired.
KW  - morphogenetic furrow progression
KW  - cell fate
KW  - compartment boundary
KW  - reporter gene
KW  - compound eye
KW  - gene expression
KW  - retinal differentiation
KW  - acts downstream
KW  - imaginal disk
KW  - glial cells
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143577
VL  - 10
IS  - 3
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  - Wang, Huiqiang
A1  - Chen, Nanhai G.
A1  - Minev, Boris R.
A1  - Szalay, Aladar A.
T1  - Oncolytic vaccinia virus GLV-1h68 strain shows enhanced replication in human breast cancer stem-like cells in comparison to breast cancer cells
JF  - Journal of Translational Medicine
N2  - Background: Recent data suggest that cancer stem cells (CSCs) play an important role in cancer, as these cells possess enhanced tumor-forming capabilities and are responsible for relapses after apparently curative therapies have been undertaken. Hence, novel cancer therapies will be needed to test for both tumor regression and CSC targeting. The use of oncolytic vaccinia virus (VACV) represents an attractive anti-tumor approach and is currently under evaluation in clinical trials. The purpose of this study was to demonstrate whether VACV does kill CSCs that are resistant to irradiation and chemotherapy. 
Methods: Cancer stem-like cells were identified and separated from the human breast cancer cell line GI-101A by virtue of increased aldehyde dehydrogenase 1 (ALDH1) activity as assessed by the ALDEFLUOR assay and cancer stem cell-like features such as chemo-resistance, irradiation-resistance and tumor-initiating were confirmed in cell culture and in animal models. VACV treatments were applied to both ALDEFLUOR-positive cells in cell culture and in xenograft tumors derived from these cells. Moreover, we identified and isolated CD44\(^+\)CD24\(^+\)ESA\(^+\) cells from GI-101A upon an epithelial-mesenchymal transition (EMT). These cells were similarly characterized both in cell culture and in animal models. 
Results: We demonstrated for the first time that the oncolytic VACV GLV-1h68 strain replicated more efficiently in cells with higher ALDH1 activity that possessed stem cell-like features than in cells with lower ALDH1 activity. GLV-1h68 selectively colonized and eventually eradicated xenograft tumors originating from cells with higher ALDH1 activity. Furthermore, GLV-1h68 also showed preferential replication in CD44\(^+\)CD24\(^+\)ESA\(^+\) cells derived from GI-101A upon an EMT induction as well as in xenograft tumors originating from these cells that were more tumorigenic than CD44\(^+\)CD24\(^-\)ESA\(^+\) cells. 
Conclusions: Taken together, our findings indicate that GLV-1h68 efficiently replicates and kills cancer stem-like cells. Thus, GLV-1h68 may become a promising agent for eradicating both primary and metastatic tumors, especially tumors harboring cancer stem-like cells that are resistant to chemo and/or radiotherapy and may be responsible for recurrence of tumors.
KW  - tumors
KW  - therapy
KW  - metastasis
KW  - identification
KW  - lines
KW  - gene expression
KW  - in-vitro propagation
KW  - acute myeloid leukemia
KW  - epithelial-mesenchymal transition
KW  - subpopulation
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130019
VL  - 10
IS  - 167
ER  - 
TY  - JOUR
A1  - Wang, Huiqiang
A1  - Chen, Nanhai G.
A1  - Minev, Boris R.
A1  - Zimmermann, Martina
A1  - Aguilar, Richard J.
A1  - Zhang, Qian
A1  - Sturm, Julia B.
A1  - Fend, Falko
A1  - Yu, Yong A.
A1  - Cappello, Joseph
A1  - Lauer, Ulrich M.
A1  - Szalay, Aladar A.
T1  - Optical Detection and Virotherapy of Live Metastatic Tumor Cells in Body Fluids with Vaccinia Strains
JF  - PLoS ONE
N2  - Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.
KW  - lymph nodes
KW  - cancer treatment
KW  - metastatic tumors
KW  - breast cancer
KW  - blood
KW  - prostate cancer
KW  - ascites
KW  - mouse models
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130059
VL  - 8
IS  - 9
ER  - 
TY  - JOUR
A1  - Kuzkina, Anastasia
A1  - Bargar, Connor
A1  - Schmitt, Daniela
A1  - Rößle, Jonas
A1  - Wang, Wen
A1  - Schubert, Anna-Lena
A1  - Tatsuoka, Curtis
A1  - Gunzler, Steven A.
A1  - Zou, Wen-Quan
A1  - Volkmann, Jens
A1  - Sommer, Claudia
A1  - Doppler, Kathrin
A1  - Chen, Shu G.
T1  - Diagnostic value of skin RT-QuIC in Parkinson's disease: a two-laboratory study
JF  - NPJ Parkinson's Disease
N2  - Skin alpha-synuclein deposition is considered a potential biomarker for Parkinson's disease (PD). Real-time quaking-induced conversion (RT-QuIC) is a novel, ultrasensitive, and efficient seeding assay that enables the detection of minute amounts of alpha-synuclein aggregates. We aimed to determine the diagnostic accuracy, reliability, and reproducibility of alpha-synuclein RT-QuIC assay of skin biopsy for diagnosing PD and to explore its correlation with clinical markers of PD in a two-center inter-laboratory comparison study. Patients with clinically diagnosed PD (n = 34), as well as control subjects (n = 30), underwent skin punch biopsy at multiple sites (neck, lower back, thigh, and lower leg). The skin biopsy samples (198 in total) were divided in half to be analyzed by RT-QuIC assay in two independent laboratories. The a-synuclein RT-QuIC assay of multiple skin biopsies supported the clinical diagnosis of PD with a diagnostic accuracy of 88.9% and showed a high degree of inter-rater agreement between the two laboratories (92.2%). Higher alpha-synuclein seeding activity in RT-QuIC was shown in patients with longer disease duration and more advanced disease stage and correlated with the presence of REM sleep behavior disorder, cognitive impairment, and constipation. The alpha-synuclein RT-QuIC assay of minimally invasive skin punch biopsy is a reliable and reproducible biomarker for Parkinson's disease. Moreover, alpha-synuclein RT-QuIC seeding activity in the skin may serve as a potential indicator of progression as it correlates with the disease stage and certain non-motor symptoms.
KW  - diagnostic markers
KW  - Parkinson's disease
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-260451
VL  - 7
IS  - 1
ER  - 
TY  - JOUR
A1  - Chen, Si
A1  - Waxman, Susannah
A1  - Wang, Chao
A1  - Atta, Sarah
A1  - Loewen, Ralitsa
A1  - Loewen, Nils A.
T1  - Dose-dependent effects of netarsudil, a Rho-kinase inhibitor, on the distal outflow tract
JF  - Graefe's Archive for Clinical and Experimental Ophthalmology
N2  - Purpose
To characterize the effects of netarsudil on the aqueous humor outflow tract distal to the trabecular meshwork (TM). Wehypothesized that netarsudil increases outflow facility in eyes with and without circumferential ab interno trabeculectomy (AIT)that removes the TM.

Methods
Sixty-four porcine anterior segment cultures were randomly assigned to groups with (n= 32) and without circumferential AIT (n= 32). Cultures were exposed to 0.1, 1, and 10μM netarsudil (N= 8 eyes per concentration). For each concentration,IOP and vessel diameters were compared with their respective pretreatment baselines. Outflow tract vessel diameters wereassessed by spectral-domain optical coherence tomography (SDOCT) and rendered in 4D (XYZ time series).

Results
Netarsudil at 1μM reduced IOP both in eyes with TM (−0.60 ± 0.24 mmHg,p= 0.01) and in eyes without TM (−1.79 ±0.42 mmHg,p< 0.01). At this concentration, vessels of the distal outflow tract dilated by 72%. However, at 0.1μMnetarsudilelevated IOP in eyes with TM (1.59 ± 0.36 mmHg,p< 0.001) as well as in eyes without TM (0.23 ± 0.32 mmHg,p<0.001). Vessels of the distal outflow tract constricted by 31%. Similarly, netarsudil at a concentration of 10μM elevated IOP both in eyeswith TM (1.91 ± 0.193,p< 0.001) and in eyes without TM (3.65 ± 0.86 mmHg,p< 0.001). At this concentration, outflow tractvessels constricted by 27%.

Conclusion
In the porcine anterior segment culture, the dose-dependent IOP changes caused by netarsudil matched the diameterchanges of distal outflow tract vessels. Hyper- and hypotensive properties of netarsudil persisted after TM removal
KW  - Rho-kinase inhibitor
KW  - Netarsudil
KW  - Distal outflow trac
KW  - Anterior chamber perfusion model
KW  - Porcine eye
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231893
SN  - 0721-832X
VL  - 258
ER  - 
TY  - JOUR
A1  - Dörk, Thilo
A1  - Peterlongo, Peter
A1  - Mannermaa, Arto
A1  - Bolla, Manjeet K.
A1  - Wang, Qin
A1  - Dennis, Joe
A1  - Ahearn, Thomas
A1  - Andrulis, Irene L.
A1  - Anton-Culver, Hoda
A1  - Arndt, Volker
A1  - Aronson, Kristan J.
A1  - Augustinsson, Annelie
A1  - Beane Freeman, Laura E.
A1  - Beckmann, Matthias W.
A1  - Beeghly-Fadiel, Alicia
A1  - Behrens, Sabine
A1  - Bermisheva, Marina
A1  - Blomqvist, Carl
A1  - Bogdanova, Natalia V.
A1  - Bojesen, Stig E.
A1  - Brauch, Hiltrud
A1  - Brenner, Hermann
A1  - Burwinkel, Barbara
A1  - Canzian, Federico
A1  - Chan, Tsun L.
A1  - Chang-Claude, Jenny
A1  - Chanock, Stephen J.
A1  - Choi, Ji-Yeob
A1  - Christiansen, Hans
A1  - Clarke, Christine L.
A1  - Couch, Fergus J.
A1  - Czene, Kamila
A1  - Daly, Mary B.
A1  - dos-Santos-Silva, Isabel
A1  - Dwek, Miriam
A1  - Eccles, Diana M.
A1  - Ekici, Arif B.
A1  - Eriksson, Mikael
A1  - Evans, D. Gareth
A1  - Fasching, Peter A.
A1  - Figueroa, Jonine
A1  - Flyger, Henrik
A1  - Fritschi, Lin
A1  - Gabrielson, Marike
A1  - Gago-Dominguez, Manuela
A1  - Gao, Chi
A1  - Gapstur, Susan M.
A1  - García-Closas, Montserrat
A1  - García-Sáenz, José A.
A1  - Gaudet, Mia M.
A1  - Giles, Graham G.
A1  - Goldberg, Mark S.
A1  - Goldgar, David E.
A1  - Guenél, Pascal
A1  - Haeberle, Lothar
A1  - Haimann, Christopher A.
A1  - Håkansson, Niclas
A1  - Hall, Per
A1  - Hamann, Ute
A1  - Hartman, Mikael
A1  - Hauke, Jan
A1  - Hein, Alexander
A1  - Hillemanns, Peter
A1  - Hogervorst, Frans B. L.
A1  - Hooning, Maartje J.
A1  - Hopper, John L.
A1  - Howell, Tony
A1  - Huo, Dezheng
A1  - Ito, Hidemi
A1  - Iwasaki, Motoki
A1  - Jakubowska, Anna
A1  - Janni, Wolfgang
A1  - John, Esther M.
A1  - Jung, Audrey
A1  - Kaaks, Rudolf
A1  - Kang, Daehee
A1  - Kapoor, Pooja Middha
A1  - Khusnutdinova, Elza
A1  - Kim, Sung-Won
A1  - Kitahara, Cari M.
A1  - Koutros, Stella
A1  - Kraft, Peter
A1  - Kristensen, Vessela N.
A1  - Kwong, Ava
A1  - Lambrechts, Diether
A1  - Le Marchand, Loic
A1  - Li, Jingmei
A1  - Lindström, Sara
A1  - Linet, Martha
A1  - Lo, Wing-Yee
A1  - Long, Jirong
A1  - Lophatananon, Artitaya
A1  - Lubiński, Jan
A1  - Manoochehri, Mehdi
A1  - Manoukian, Siranoush
A1  - Margolin, Sara
A1  - Martinez, Elena
A1  - Matsuo, Keitaro
A1  - Mavroudis, Dimitris
A1  - Meindl, Alfons
A1  - Menon, Usha
A1  - Milne, Roger L.
A1  - Mohd Taib, Nur Aishah
A1  - Muir, Kenneth
A1  - Mulligan, Anna Marie
A1  - Neuhausen, Susan L.
A1  - Nevanlinna, Heli
A1  - Neven, Patrick
A1  - Newman, William G.
A1  - Offit, Kenneth
A1  - Olopade, Olufunmilayo I.
A1  - Olshan, Andrew F.
A1  - Olson, Janet E.
A1  - Olsson, Håkan
A1  - Park, Sue K.
A1  - Park-Simon, Tjoung-Won
A1  - Peto, Julian
A1  - Plaseska-Karanfilska, Dijana
A1  - Pohl-Rescigno, Esther
A1  - Presneau, Nadege
A1  - Rack, Brigitte
A1  - Radice, Paolo
A1  - Rashid, Muhammad U.
A1  - Rennert, Gad
A1  - Rennert, Hedy S.
A1  - Romero, Atocha
A1  - Ruebner, Matthias
A1  - Saloustros, Emmanouil
A1  - Schmidt, Marjanka K.
A1  - Schmutzler, Rita K.
A1  - Schneider, Michael O.
A1  - Schoemaker, Minouk J.
A1  - Scott, Christopher
A1  - Shen, Chen-Yang
A1  - Shu, Xiao-Ou
A1  - Simard, Jaques
A1  - Slager, Susan
A1  - Smichkoska, Snezhana
A1  - Southey, Melissa C.
A1  - Spinelli, John J.
A1  - Stone, Jennifer
A1  - Surowy, Harald
A1  - Swerdlow, Anthony J.
A1  - Tamimi, Rulla M.
A1  - Tapper, William J.
A1  - Teo, Soo H.
A1  - Terry, Mary Beth
A1  - Toland, Amanda E.
A1  - Tollenaar, Rob A. E. M.
A1  - Torres, Diana
A1  - Torres-Mejía, Gabriela
A1  - Troester, Melissa A.
A1  - Truong, Thérèse
A1  - Tsugane, Shoichiro
A1  - Untch, Michael
A1  - Vachon, Celine M.
A1  - van den Ouweland, Ans M. W.
A1  - van Veen, Elke M.
A1  - Vijai, Joseph
A1  - Wendt, Camilla
A1  - Wolk, Alicja
A1  - Yu, Jyh-Cherng
A1  - Zheng, Wei
A1  - Ziogas, Argyrios
A1  - Ziv, Elad
A1  - Dunnig, Alison
A1  - Pharaoh, Paul D. P.
A1  - Schindler, Detlev
A1  - Devilee, Peter
A1  - Easton, Douglas F.
T1  - Two truncating variants in FANCC and breast cancer risk
JF  - Scientific Reports
N2  - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
KW  - oncology
KW  - risk factors
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222838
VL  - 9
ER  - 
TY  - JOUR
A1  - Biernacka, J. M.
A1  - Sangkuhl, K.
A1  - Jenkins, G.
A1  - Whaley, R. M.
A1  - Barman, P.
A1  - Batzler, A.
A1  - Altman, R. B.
A1  - Arolt, V.
A1  - Brockmöller, J.
A1  - Chen, C. H.
A1  - Domschke, K.
A1  - Hall-Flavin, D. K.
A1  - Hong, C. J.
A1  - Illi, A.
A1  - Ji, Y.
A1  - Kampman, O.
A1  - Kinoshita, T.
A1  - Leinonen, E.
A1  - Liou, Y. J.
A1  - Mushiroda, T.
A1  - Nonen, S.
A1  - Skime, M. K.
A1  - Wang, L.
A1  - Baune, B. T.
A1  - Kato, M.
A1  - Liu, Y. L.
A1  - Praphanphoj, V.
A1  - Stingl, J. C.
A1  - Tsai, S. J.
A1  - Kubo, M.
A1  - Klein, T. E.
A1  - Weinshilboum, R.
T1  - The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response
JF  - Translational Psychiatry
N2  - Response to treatment with selective serotonin reuptake inhibitors (SSRIs) varies considerably between patients. The International SSRI Pharmacogenomics Consortium (ISPC) was formed with the primary goal of identifying genetic variation that may contribute to response to SSRI treatment of major depressive disorder. A genome-wide association study of 4-week treatment outcomes, measured using the 17-item Hamilton Rating Scale for Depression (HRSD-17), was performed using data from 865 subjects from seven sites. The primary outcomes were percent change in HRSD-17 score and response, defined as at least 50% reduction in HRSD-17. Data from two prior studies, the Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomics Study (PGRN-AMPS) and the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study, were used for replication, and a meta-analysis of the three studies was performed (N = 2394). Although many top association signals in the ISPC analysis map to interesting candidate genes, none were significant at the genome-wide level and the associations were not replicated using PGRN-AMPS and STAR*D data. Top association results in the meta-analysis of response included single-nucleotide polymorphisms (SNPs) in the HPRTP4 (hypoxanthine phosphoribosyltransferase pseudogene 4)/VSTM5 (V-set and transmembrane domain containing 5) region, which approached genome-wide significance (P = 5.03E - 08) and SNPs 5' upstream of the neuregulin-1 gene, NRG1 (P = 1.20E - 06). NRG1 is involved in many aspects of brain development, including neuronal maturation and variations in this gene have been shown to be associated with increased risk for mental disorders, particularly schizophrenia. Replication and functional studies of these findings are warranted.
KW  - major depressive disorder
KW  - genetic variation
KW  - schizophrenia
KW  - neuregulin-1
KW  - population
KW  - microcephalin 1
KW  - susceptibility
KW  - metaanalysis
KW  - MCPH1
KW  - loci
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143223
VL  - 5
IS  - e553
ER  - 
TY  - JOUR
A1  - Banks, Sarah
A1  - Millard, Koreen
A1  - Behnamian, Amir
A1  - White, Lori
A1  - Ullmann, Tobias
A1  - Charbonneau, Francois
A1  - Chen, Zhaohua
A1  - Wang, Huili
A1  - Pasher, Jon
A1  - Duffe, Jason
T1  - Contributions of actual and simulated satellite SAR data for substrate type differentiation and shoreline mapping in the Canadian Arctic
JF  - Remote Sensing
N2  - Detailed information on the land cover types present and the horizontal position of the land–water interface is needed for sensitive coastal ecosystems throughout the Arctic, both to establish baselines against which the impacts of climate change can be assessed and to inform response operations in the event of environmental emergencies such as oil spills. Previous work has demonstrated potential for accurate classification via fusion of optical and SAR data, though what contribution either makes to model accuracy is not well established, nor is it clear what shorelines can be classified using optical or SAR data alone. In this research, we evaluate the relative value of quad pol RADARSAT-2 and Landsat 5 data for shoreline mapping by individually excluding both datasets from Random Forest models used to classify images acquired over Nunavut, Canada. In anticipation of the RADARSAT Constellation Mission (RCM), we also simulate and evaluate dual and compact polarimetric imagery for shoreline mapping. Results show that SAR data is needed for accurate discrimination of substrates as user’s and producer’s accuracies were 5–24% higher for models constructed with quad pol RADARSAT-2 and DEM data than models constructed with Landsat 5 and DEM data. Models based on simulated RCM and DEM data achieved significantly lower overall accuracies (71–77%) than models based on quad pol RADARSAT-2 and DEM data (80%), with Wetland and Tundra being most adversely affected. When classified together with Landsat 5 and DEM data, however, model accuracy was less affected by the SAR data type, with multiple polarizations and modes achieving independent overall accuracies within a range acceptable for operational mapping, at 89–91%. RCM is expected to contribute positively to ongoing efforts to monitor change and improve emergency preparedness throughout the Arctic.
KW  - geography
KW  - RADARSAT-2
KW  - RADARSAT Constellation Mission
KW  - Random Forests
KW  - Arctic
KW  - shorelines
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-172630
VL  - 9
IS  - 12
ER  - 
TY  - JOUR
A1  - Li, Ming
A1  - Zhang, Rui
A1  - Fan, Guangyi
A1  - Xu, Wenteng
A1  - Zhou, Qian
A1  - Wang, Lei
A1  - Li, Wensheng
A1  - Pang, Zunfang
A1  - Yu, Mengjun
A1  - Liu, Qun
A1  - Liu, Xin
A1  - Schartl, Manfred
A1  - Chen, Songlin
T1  - Reconstruction of the Origin of a Neo-Y Sex Chromosome and Its Evolution in the Spotted Knifejaw, Oplegnathus punctatus
JF  - Molecular Biology and Evolution
N2  - Sex chromosomes are a peculiar constituent of the genome because the evolutionary forces that fix the primary sex-determining gene cause genic degeneration and accumulation of junk DNA in the heterogametic partner. One of the most spectacular phenomena in sex chromosome evolution is the occurrence of neo-Y chromosomes, which lead to X1X2Y sex-determining systems. Such neo-sex chromosomes are critical for understanding the processes of sex chromosome evolution because they rejuvenate their total gene content. We assembled the male and female genomes at the chromosome level of the spotted knifejaw (Oplegnathus punctatus), which has a cytogenetically recognized neo-Y chromosome. The full assembly and annotation of all three sex chromosomes allowed us to reconstruct their evolutionary history. Contrary to other neo-Y chromosomes, the fusion to X2 is quite ancient, estimated at 48 Ma. Despite its old age and being even older in the X1 homologous region which carries a huge inversion that occurred as early as 55–48 Ma, genetic degeneration of the neo-Y appears to be only moderate. Transcriptomic analysis showed that sex chromosomes harbor 87 genes, which may serve important functions in the testis. The accumulation of such male-beneficial genes, a large inversion on the X1 homologous region and fusion to X2 appear to be the main drivers of neo-Y evolution in the spotted knifejaw. The availability of high-quality assemblies of the neo-Y and both X chromosomes make this fish an ideal model for a better understanding of the variability of sex determination mechanisms and of sex chromosome evolution.
KW  - neo-Y
KW  - evolution;
KW  - spotted knifejaw
KW  - genome
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-364215
VL  - 38
ER  -