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Association between GWAS-identified lung adenocarcinoma susceptibility loci and EGFR mutations in never-smoking Asian women, and comparison with findings from Western populations

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Human molecular genetics 2017年第2期26卷 454-465页

作者： Wei Jie Seow Keitaro Matsuo Chao Agnes Hsiung Kouya Shiraishi Minsun Song Hee Nam Kim Maria Pik Wong Yun-Chul Hong H Dean Hosgood Zhaoming Wang I-Shou Chang Jiu-Cun Wang Nilanjan Chatterjee Margaret Tucker Hu Wei Tetsuya Mitsudomi Wei Zheng Jin Hee Kim Baosen Zhou Neil E Caporaso Demetrius Albanes Min-Ho Shin Lap Ping Chung She-Juan An Ping Wang Hong Zheng Yasushi Yatabe Xu-Chao Zhang Young Tae Kim Xiao-Ou Shu Young-Chul Kim Bryan A Bassig Jiang Chang James Chung Man Ho Bu-Tian Ji Michiaki Kubo Yataro Daigo Hidemi Ito Yukihide Momozawa Kyota Ashikawa Yoichiro Kamatani Takayuki Honda Hiromi Sakamoto Hideo Kunitoh Koji Tsuta Shun-Ichi Watanabe Hiroshi Nokihara Yohei Miyagi Haruhiko Nakayama Shingo Matsumoto Masahiro Tsuboi Koichi Goto Zhihua Yin Jianxin Shi Atsushi Takahashi Akiteru Goto Yoshihiro Minamiya Kimihiro Shimizu Kazumi Tanaka Tangchun Wu Fusheng Wei Jason Y Y Wong Fumihiko Matsuda Jian Su Yeul Hong Kim In-Jae Oh Fengju Song Victor Ho Fun Lee Wu-Chou Su Yuh-Min Chen Gee-Chen Chang Kuan-Yu Chen Ming-Shyan Huang Pan-Chyr Yang Hsien-Chih Lin Yong-Bing Xiang Adeline Seow Jae Yong Park Sun-Seog Kweon Chien-Jen Chen Haixin Li Yu-Tang Gao Chen Wu Biyun Qian Daru Lu Jianjun Liu Hyo-Sung Jeon Chin-Fu Hsiao Jae Sook Sung Ying-Huang Tsai Yoo Jin Jung Huan Guo Zhibin Hu Wen-Chang Wang Charles C Chung Charles Lawrence Laurie Burdett Meredith Yeager Kevin B Jacobs Amy Hutchinson Sonja I Berndt Xingzhou He Wei Wu Junwen Wang Yuqing Li Jin Eun Choi Kyong Hwa Park Sook Whan Sung Li Liu Chang Hyun Kang Lingmin Hu Chung-Hsing Chen Tsung-Ying Yang Jun Xu Peng Guan Wen Tan Chih-Liang Wang Alan Dart Loon Sihoe Ying Chen Yi Young Choi Jen-Yu Hung Jun Suk Kim Ho-Il Yoon Qiuyin Cai Chien-Chung Lin In Kyu Park Ping Xu Jing Dong Christopher Kim Qincheng He Reury-Perng Perng Chih-Yi Chen Roel Vermeulen Junjie Wu Wei-Yen Lim Kun-Chieh Chen John K C Chan Minjie Chu Yao-Jen Li Jihua Li Hongyan Chen Chong-Jen Yu Li Jin Yen-Li Lo Ying-Hsiang Chen Joseph F Fraumeni Jie Liu Taiki Yamaji Yang Yang Belynda Hicks Kathleen Wyatt Shengchao A Li Division of Cancer Epidemiology and Genetics National Cancer Institute Bethesda MD USA. Saw Swee Hock School of Public Health National University of Singapore and National University Health System Singapore. Division of Molecular Medicine Aichi Cancer Center Research Institute Nagoya Japan. Institute of Population Health Sciences National Health Research Institutes Zhunan Taiwan. Division of Genome Biology National Cancer Center Research Institute Tokyo Japan. Department of Statistics Sookmyung Women's University Seoul Republic of Korea. Department of Preventive Medicine Chonnam National University Medical School Gwangju Republic of Korea. Department of Pathology The University of Hong Kong Queen Mary Hospital Hong Kong. Department of Preventive Medicine Seoul National University College of Medicine Seoul Republic of Korea. Department of Epidemiology and Population Health Albert Einstein College of Medicine Bronx NY USA. Department of Computational Biology St. Jude Children's Research Hospital Memphis TN 38105 USA. National Institute of Cancer Research National Health Research Institutes Zhunan Taiwan. Ministry of Education Key Laboratory of Contemporary Anthropology School of Life Sciences Fudan University Shanghai People's Republic of China. State Key Laboratory of Genetic Engineering School of Life Sciences Fudan University Shanghai People's Republic of China. Division of Thoracic Surgery Kinki University School of Medicine Sayama Japan. Division of Epidemiology Department of Medicine Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center Nashville TN USA. Department of Integrative Bioscience & Biotechnology Sejong University Seoul Republic of Korea. Department of Epidemiology School of Public Health China Medical University Shenyang People's Republic of China. Guangdong Lung Cancer Institute Medical Research Center and Cancer Center of Guangdong General Hospital Guangdong Academy of Medical Sciences Guangzhou People's Republic

To evaluate associations by EGFR mutation status for lung adenocarcinoma risk among never-smoking Asian women, we conducted a meta-analysis of 11 loci previously identified in genome-wide association studies (GWAS). Genotyping in an additional 10,780 never-smoking cases and 10,938 never-smoking controls from Asia confirmed associations with eight known single nucleotide polymorphisms (SNPs). Two new signals were observed at genome-wide significance (P < 5 × 10-8), namely, rs7216064 (17q24.3, BPTF), for overall lung adenocarcinoma risk, and rs3817963 (6p21.3, BTNL2) which is specific to cases with EGFR mutations. In further sub-analyses by EGFR status, rs9387478 (ROS1/DCBLD1) and rs2179920 (HLA-DPB1) showed stronger estimated associations in EGFR-positive compared to EGFR-negative cases. Comparison of the overall associations with published results in Western populations revealed that the majority of these findings were distinct, underscoring the importance of distinct contributing factors for smoking and non-smoking lung cancer. Our results extend the catalogue of regions associated with lung adenocarcinoma in non-smoking Asian women and highlight the importance of how the germline could inform risk for specific tumour mutation patterns, which could have important translational implications.

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World Congress Integrative Medicine & Health 2017: Part one: Berlin, Germany. 3-5 May 2017

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BMC Complement Altern Med 2017年第SUPPL 1期17卷 322-322页

作者： Benno Brinkhaus Torkel Falkenberg Aviad Haramati Stefan N. Willich Josephine P. Briggs Merlin Willcox Klaus Linde Töres Theorell Lisa M. Wong Jeffrey Dusek Darong Wu David Eisenberg Bettina Berger Kathi Kemper Beate Stock-Schröer Hedda Sützl-Klein Rosaria Ferreri Gary Kaplan Harald Matthes Gabriele Rotter Elad Schiff Zahi Arnon Eckhard Hahn Christina M. Luberto David Martin Silke Schwarz Diethard Tauschel Andrew Flower Harsha Gramminger Hedwig H. Gupta S. N. Gupta Annette Kerckhoff Christian S. Kessler Andreas Michalsen Eun S. Kim Eun H. Jang Rana Kim Sae B. Jan Martin Mittwede Wiebke Mohme Eran Ben-Arye Massimo Bonucci Bashar Saad Thomas Breitkreuz Elio Rossi Rejin Kebudi Michel Daher Samaher Razaq Nahla Gafer Omar Nimri Mohamed Hablas Gunver Sophia Kienle Noah Samuels Michael Silbermann Lena Bandelin Anna-Lena Lang Eva Wartner Christoph Holtermann Maxwell Binstock Robert Riebau Edin Mujkanovic Holger Cramer Romy Lauche Andres Michalsen Lesley Ward Dominik Irnich Wolfram Stör Geoffrey Burnstock Hans-Georg Schaible Thomas Ots Jost Langhorst Tobias Sundberg Catherina Amarell Melanie Anheyer Marion Eckert Mercedes Ogal Annette Schönauer Birgit Reisenberger Bernhard Brand Dennis Anheyer Gustav Dobos Matthias Kroez Aldo Ammendola Jun J. Mao Claudia Witt Yufei Yang Miriam Oritz Markus Horneber Petra Voiß Alexandra von Rosenstiel Catharina Amarell Friedemann Schad Marc Schläppi Matthias Kröz Arndt Büssing Gil Bar-Sela David Avshalomov Samuel Attias Sian Cotton Miek Jong Mats Jong Christian Scheffer Friedrich Edelhäuser Abdullah AlBedah Myeong Soo Lee Mohamed Khalil Keiko Ogawa Yoshiharu Motoo Junsuke Arimitsu Masao Ogawa Genki Shimizu Rainer Stange Karin Kraft Kenny Kuchta Kenji Watanabe D Bonin Harald Gruber Sabine Koch Urs Pohlmann Christine Caldwell Barbara Krantz Ria Kortum Lily Martin Lisa S. Wieland Ben Kligler Susan Gould-Fogerite Yuqing Zhang John J. Riva Michael Lumpkin Emily Ratner Liu Ping Pei Jian Gesa-Meyer Hamme Xiaosong Mao Han Chouping Sven Schröder Josef Hummelsberger Michael Wullinger Marc Brodzky Chr Institute for Social Medicine Epidemiology and Health Economics Charité – Universitätsmedizin Berlin Berlin Germany Department of Neurobiology Care Sciences and Society Division of Nursing Research Group Integrative Care Karolinska Institutet Stockholm Sweden I C – The Integrative Care Science Center Järna Sweden Department of Biochemistry Molecular and Cellular Biology Georgetown University Medical Center Washington DC USA Department of Medicine Georgetown University Medical Center Washington DC USA NCCIH NIH Bethesda MD USA Department of Primary Care and Population Sciences University of Southampton Aldermoor Health Centre Coxford Rd Southampton 2016 5ST UK Institute of General Practice Technical University Munich Munich Germany Department of Neuroscience Karolinska Institute Stockholm Sweden Stress Research Institute Stockholm University Stockholm Sweden Arts and Humanities Initiative Harvard Medical School Boston MA 02115 USA Psychosomatic medicine Neuropsychology Allina Health Minneapolis MN USA nd Affiliated Hospital of Guangzhou University of Chinese Medicine Guangzhou China Department of Nutrition Harvard University T H Chan School of Public Health Boston MA 02115 USA Department of Health University of Witten/Herdecke Witten/Herdecke Germany OSU Blacklick OH USA Carstens-Foundation and FORUM D-45276 Essen Germany ESIHR (European Society for Integrative Health Care) A-1070 Vienna Austria Hospital Centre of Integrated Medicine Hospital of Pitiglian o ASL SudEst Toscana Grosseto Italy The Kaplan Center for Integrative Medicine Georgetown University McLean VA USA Hospital Havelhöhe Berlin Germany Institute for Social Medicine Epidemiology and Health Economics Charité University Hospital Berlin Germany Internal medicine and Complementary medicine service Bnai Zion Medical Center Haifa Israel Complementary-Integrative Surgery Service Bnai Zion Medical Center Haifa Israel The Emek Yezreel Academic College Yezreel Valley Israel Medicine

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Unwinding and rewinding the nucleosome inner turn: Force dependence of the kinetic rate constants

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Physical Review E 2013年第1期87卷 012710-012710页

作者： S. G. J. Mochrie A. H. Mack D. J. Schlingman R. Collins M. Kamenetska L. Regan Integrated Graduate Program in Physical and Engineering Biology Yale University New Haven Connecticut 06520 USA Department of Applied Physics Yale University New Haven Connecticut 06520 USA Department of Physics Yale University New Haven Connecticut 06520 USA Department of Molecular Biophysics and Biochemistry Yale University New Haven Connecticut 06520 USA Department of Chemistry Yale University New Haven Connecticut 06520 USA

A simple model for the force-dependent unwinding and rewinding rates of the nucleosome inner turn is constructed and quantitatively compared to the results of recent measurements [A. H. Mack et al., J. Mol. Biol. 423, 687 (2012)]. First, a coarse-grained model for the histone-DNA free-energy landscape that incorporates both an elastic free-energy barrier and specific histone-DNA bonds is developed. Next, a theoretical expression for the rate of transitions across a piecewise linear free-energy landscape with multiple minima and maxima is presented. Then, the model free-energy landscape, approximated as a piecewise linear function, and the theoretical expression for the transition rates are combined to construct a model for the force-dependent unwinding and rewinding rates of the nucleosome inner turn. Least-mean-squares fitting of the model rates to the rates observed in recent experiments rates demonstrates that this model is able to well describe the force-dependent unwinding and rewinding rates of the nucleosome inner turn, observed in the recent experiments, except at the highest forces studied, where an additional ad hoc term is required to describe the data, which may be interpreted as an indication of an alternate high-force nucleosome disassembly pathway, that bypasses simple unwinding. The good agreement between the measurements and the model at lower forces demonstrates that both specific histone-DNA contacts and an elastic free-energy barrier play essential roles for nucleosome winding and unwinding, and quantifies their relative contributions.

关键词： CHROMATIN HISTONES LEAST squares CHEMICAL bonds ANALYSIS of DNA

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Practical axial optical trapping

Practical axial optical trapping

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作者： MacK, A.H. Schlingman, D.J. Regan, L. Mochrie, S.G.J. Integrated Graduate Program in Physical and Engineering Biology Yale University New Haven CT 06511 United States Department of Applied Physics Yale University New Haven CT 06511 United States Department of Molecular Biophysics and Biochemistry Yale University New Haven CT 06511 United States Department of Chemistry Yale University New Haven CT 06511 United States Department of Physics Yale University New Haven CT 06511 United States

We describe a new method for calibrating optical trapping measurements in which tension is applied in the direction of the laser beam to a molecule tethered between a surface and an optically trapped bead. Specifically, we present a generally-applicable procedure for converting from the measured scattering intensity and the measured stage displacement to applied tension and bead-coverslip separation, using measurements of the light intensity scattered from an untethered, trapped bead. Our calibration accounts for a number of effects, including aberrations and the interference of forward-reflected bead-scattered light with the trapping beam. To demonstrate the accuracy of our method, we show measurements of the DNA force-versus-extension relation using a range of laser intensities, and show that these measurements match the expected extensible wormlike-chain (WLC) behavior. Finally, we also demonstrate a force-clamp, in which the tension in a tether is held fixed while the extension varies as a result of molecular events. © 2012 American Institute of Physics.

关键词： Equipment

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Optimization of surface plasmon resonance based assay for investigating T-antigen helicase activity

Journal of Biotech Research

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Journal of Biotech Research 2010年第1期2卷 56-66页

作者： Plyler, Jason R. Sanjar, Fatemeh Howard, Rhonda Araki, Naoko David, Wendi M. Department of Chemistry and Biochemistry Texas State University-San Marcos 601 University Drive San Marcos TX 78666 United States Integrated Multidisciplinary Graduate Program UT Health Science Center San Antonio TX 78229 United States

Due to the increasing number of helicases shown to unwind quadruplex DNA structures in addition to duplex DNA, the biological significance of this activity is currently under investigation. One limitation of traditional gel analysis of helicase activity is the inability to effectively monitor unwinding of intramolecular G-quadruplex DNA substrates. Optimization of our novel SPR-based assay for monitoring the helicase activity of simian virus 40 (SV40) large T-antigen (T-ag) was undertaken to explore limitations and improvements in the ability to investigate G-quadruplex helicase activity. Although T-ag helicase was used, the assay is general in nature. An improved method for assessing unwinding of intramolecular G-quadruplex DNA substrates was developed.

关键词： Antigens

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Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN

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Nature Biotechnology 2010年第3期28卷 271-274页

作者： Foust, Kevin D. Wang, Xueyong McGovern, Vicki L. Braun, Lyndsey Bevan, Adam K. Haidet, Amanda M. Le, Thanh T. Morales, Pablo R. Rich, Mark M. Burghes, Arthur H. M. Kaspar, Brian K. Center for Gene Therapy Research Institute at Nationwide Children's Hospital Columbus OH United States Wright State University Dayton OH United States Department of Molecular and Cellular Biochemistry United States Integrated Biomedical Graduate Program Ohio State University Columbus OH United States Mannheimer Foundation Inc. Homestead FL United States

Spinal muscular atrophy (SMA), the most common autosomal recessive neurodegenerative disease affecting children, results in impaired motor neuron function. Despite knowledge of the pathogenic role of decreased survival motor neuron (SMN) protein levels, efforts to increase SMN have not resulted in a treatment for patients. We recently demonstrated that self-complementary adeno-associated virus 9 (scAAV9) can infect ∼60% of motor neurons when injected intravenously into neonatal mice. Here we use scAAV9-mediated postnatal day 1 vascular gene delivery to replace SMN in SMA pups and rescue motor function, neuromuscular physiology and life span. Treatment on postnatal day 5 results in partial correction, whereas postnatal day 10 treatment has little effect, suggesting a developmental period in which scAAV9 therapy has maximal benefit. Notably, we also show extensive scAAV9-mediated motor neuron transduction after injection into a newborn cynomolgus macaque. This demonstration that scAAV9 traverses the blood-brain barrier in a nonhuman primate emphasizes the clinical potential of scAAV9 gene therapy for SMA. © 2010 Nature America, Inc. All rights reserved.

关键词： Gene therapy

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Cover Picture: Influence of Plasma Stimulation on Si Nanowire Nucleation and Orientation Dependence (Adv. Mater. 18/2007)

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Advanced Materials 2007年第18期19卷

作者： P. Aella S. Ingole W. T. Petuskey S. T. Picraux School of Materials Arizona State University Tempe AZ 85287 (USA) Department of Chemistry and Biochemistry Science and Engineering of Materials Graduate Program Arizona State University Tempe AZ 85287 (USA) Center for Integrated Nanotechnologies Los Alamos National Laboratory Los Alamos NM 87545 (USA)

On p. 2603, Tom Picraux and co‐workers report on the use of plasma excitation to strongly enhance the nucleation of Si nanowires by the vapor–liquid–solid growth method. This control allows the preferential formation of very small diameter [110] oriented nanowires, as well as significant enhancements in low temperature nanowire growth.

关键词： Nanowires, inorganic Plasmas Silicon Synthesis

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A GATA-1-Regulated microRNA Cluster That Is Essential for Erythropoiesis.

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Blood 2007年第11期110卷 378-378页

作者： Louis C. Dore Camila O. dos Santos Julio Amigo Christine Dorman Weisheng Wu Ross C. Hardison Barry H. Paw Mitchell J. Weiss Integrated Graduate Program Feinberg School of Medicine Northwestern University Chicago IL USA Division of Hematology Children's Hospital of Philadelphia Philadelphia PA USA Division of Hematology Department of Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA Department of Biochemistry and Molecular Biology Pennsylvania State University University Park PA USA

The nuclear factor GATA-1 controls erythropoiesis by regulating transcription of numerous protein-encoding genes. Here we show that GATA-1 also activates the expression of a critical erythroid microRNA (miR) locus. MicroRNAs regulate gene expression and tissue differentiation by binding the 3′ untranslated regions of mRNA transcripts to inhibit their translation or stability. We used an oligonucleotide-based microarray to analyze miR expression in G1E cells, a GATA-1-null erythroid line that undergoes terminal maturation when GATA-1 activity is restored. We identified 8 miRs that are significantly upregulated during GATA-1-induced erythroid maturation. Two of the most highly induced miRs, 144 and 451, are encoded in tandem on mouse chromosome 11 and are transcribed on the same primary microRNA transcript. Northern blot studies showed that the miR144/451 locus is strongly induced by GATA-1 and specifically expressed at high levels in human and murine erythroid precursors. Bioinformatic analysis of the miR144/451 locus identified a conserved region containing three closely-spaced GATA binding motifs located about 2.7 kb upstream of the transcriptional start. In erythroid cells, this region exhibits enhancer activity and binds GATA-1 and its cofactor FOG-1, as determined by chromatin immunoprecipitation studies. MicroRNAs 144 and 451 are conserved between mammals and zebrafish, facilitating further in vivo studies. Whole mount in situ hybridization of zebrafish embryos showed both miRs to be exclusively expressed in the developing blood islands (intermediate cell mass) at 24h post-fertilization (hpf), colocalizing with gata-1 and β -globinE1 expression. Both miRs are deficient in the gata-1 null mutant, vlad tepes , consistent with their epistatic relationship to gata-1 . Transient inactivation of miR-451 function using anti-sense morpholino oligomers selectively ablated hemoglobin staining cells in embryos at 48 hpf. These morphant embryos also exhibited dramatically

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